NYU Health Sciences Libraries Faculty Bibliography

Guillermo Ignacio Perez-Perez

School of Medicine. Medicine. Infectious Diseases and Immunology; Microbiology. Associate Professor (Research) of Medicine and Microbiology, 2000-
  1. Garza-Gonzalez, E; Perez-Perez, GI; Maldonado-Garza, HJ; Bosques-Padilla, FJ. "A review of helicobacter pylori diagnosis, treatment, and methods to detect eradication". World journal of gastroenterology : WJG. 2014;20(6):1438-1449 (SCOPUS:2-s2.0-84893731367 #841952)       

    Helicobacter pylori (H. pylori) affects nearly half of the world's population and, thus, is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with peptic ulcer disease, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various diagnostic methods exist to detect infection, and the choice of one method or another depends on several factors, such as accessibility, advantages and disadvantages of each method, cost, and the age of patients. Once H. pylori infection is diagnosed, the clinician decides whether treatment is necessity, according to the patient's clinical condition. Typically, eradication of H. pylori is recommended for treatment and prevention of the infection. Cure rates with the standard triple therapy are acceptable, and effective quadruple therapies, sequential therapies, and concomitant therapies have been introduced as key alternatives to treat H. pylori infection. In this work, we review the main diagnostic methods used to identify H. pylori infection and to confirm eradication of infection. In addition, key factors related to treatment are reviewed.
  2. Garza-Gonzalez, Elvira; Perez-Perez, Guillermo Ignacio; Maldonado-Garza, Hector Jesus; Bosques-Padilla, Francisco Javier. "A review of diagnosis, treatment, and methods to detect eradication". World journal of gastroenterology : WJG. 2014 Feb;20(6):1438-1449 (MEDL:24587620 #836732)       

    Helicobacter pylori (H. pylori) affects nearly half of the world's population and, thus, is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with peptic ulcer disease, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various diagnostic methods exist to detect infection, and the choice of one method or another depends on several factors, such as accessibility, advantages and disadvantages of each method, cost, and the age of patients. Once H. pylori infection is diagnosed, the clinician decides whether treatment is necessity, according to the patient's clinical condition. Typically, eradication of H. pylori is recommended for treatment and prevention of the infection. Cure rates with the standard triple therapy are acceptable, and effective quadruple therapies, sequential therapies, and concomitant therapies have been introduced as key alternatives to treat H. pylori infection. In this work, we review the main diagnostic methods used to identify H. pylori infection and to confirm eradication of infection. In addition, key factors related to treatment are reviewed.
  3. Kienesberger, Sabine; Sprenger, Hanna; Wolfgruber, Stella; Halwachs, Bettina; Thallinger, Gerhard G; Perez-Perez, Guillermo I; Blaser, Martin J; Zechner, Ellen L; Gorkiewicz, Gregor. "Comparative Genome Analysis of Campylobacter fetus Subspecies Revealed Horizontally Acquired Genetic Elements Important for Virulence and Niche Specificity". PLoS ONE. 2014;9(1):e85491-e85491 (e85491) (MEDL:24416416 #741182)       

    Campylobacter fetus are important animal and human pathogens and the two major subspecies differ strikingly in pathogenicity. C. fetus subsp. venerealis is highly niche-adapted, mainly infecting the genital tract of cattle. C. fetus subsp. fetus has a wider host-range, colonizing the genital- and intestinal-tract of animals and humans. We report the complete genomic sequence of C. fetus subsp. venerealis 84-112 and comparisons to the genome of C. fetus subsp. fetus 82-40. Functional analysis of genes predicted to be involved in C. fetus virulence was performed. The two subspecies are highly syntenic with 92% sequence identity but C. fetus subsp. venerealis has a larger genome and an extra-chromosomal element. Aside from apparent gene transfer agents and hypothetical proteins, the unique genes in both subspecies comprise two known functional groups: lipopolysaccharide production, and type IV secretion machineries. Analyses of lipopolysaccharide-biosynthesis genes in C. fetus isolates showed linkage to particular pathotypes, and mutational inactivation demonstrated their roles in regulating virulence and host range. The comparative analysis presented here broadens knowledge of the genomic basis of C. fetus pathogenesis and host specificity. It further highlights the importance of surface-exposed structures to C. fetus pathogenicity and demonstrates how evolutionary forces optimize the fitness and host-adaptation of these pathogens.
  4. Mendoza, Eugenia; Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Mera, Robertino; Vilchis, Jenny; Moran, Segundo; Rivera, Octavio; Coria, Rafael; Torres, Javier; Correa, Pelayo; Duque, Ximena. "Present and Past Helicobacter pylori Infection in Mexican School Children". Helicobacter. 2014 Feb;19(1):55-64 (MEDL:24165012 #746432)       

    BACKGROUND: In developing countries, more than 50% of children have serological evidence of Helicobacter pylori infection. However, serological tests for H. pylori did not differentiate between active and past infection. The objectives of this study were to estimate the frequency of active and past H. pylori infection utilizing functional urea breath test (UBT) and serological tests and evaluate factors associated with the infection. METHODS: A total of 675 school children, 6-13 years of age, participated. UBT was performed to detect active H. pylori infection. Blood samples were obtained to determine iron status and Immunoglobulin G (IgG) responses to the H. pylori whole-cell and to Cag A antigens by antigen-specific enzyme-linked immunosorbent assays. Weight, height, and sociodemographic characteristics were recorded. RESULTS: A total of 37.9% (95% Confidence Intervals (CI): 34.2-41.6) of school children had active or past H. pylori infection; of them, 73.8% (CI95% 68.4-79.2) were carrying CagA-positive strain, 26.5% (CI95% 23.2-29.8) had active infection, and 11.4% (95%CI: 9.0-13.8) had evidence of past H. pylori infection. School children with iron deficiency and low height for age had higher risk of H. pylori infection: [OR to active or past infection was 2.30 (CI 95% 1.01-5.23) and to active infection it was 2.64 (CI 95% 1.09-6.44)] compared to school children with normal iron status and height for age or with normal iron status but low height for age or with iron deficiency and normal height for age. CONCLUSIONS: The estimated prevalence of infection depends of the test utilized. Frequency of H. pylori infection and carrying CagA-positive strains was high in this population. Malnutrition was associated with active H. pylori infection.
  5. Alekseyenko, Alexander V; Perez-Perez, Guillermo I; De Souza, Aieska; Strober, Bruce; Gao, Zhan; Bihan, Monika; Li, Kelvin; Methe, Barbara A; Blaser, Martin J. "Community differentiation of the cutaneous microbiota in psoriasis". Microbiome. 2013;1(1):31-31 (MEDL:24451201 #760032)       

    BACKGROUND: Psoriasis is a common chronic inflammatory disease of the skin. We sought to characterize and compare the cutaneous microbiota of psoriatic lesions (lesion group), unaffected contralateral skin from psoriatic patients (unaffected group), and similar skin loci in matched healthy controls (control group) in order to discern patterns that govern skin colonization and their relationship to clinical diagnosis. RESULTS: Using high-throughput 16S rRNA gene sequencing, we assayed the cutaneous bacterial communities of 51 matched triplets and characterized these samples using community data analysis techniques. Intragroup Unifrac beta diversity revealed increasing diversity from control to unaffected to lesion specimens. Likewise, principal coordinates analysis (PCoA) revealed separation of the lesion samples from unaffected and control along the first axis, suggesting that psoriasis is a major contributor to the observed diversity. The taxonomic richness and evenness decreased in both lesion and unaffected communities compared to control. These differences are explained by the combined increased abundance of the four major skin-associated genera (Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus), which present a potentially useful predictor for clinical skin type. Psoriasis samples also showed significant univariate decreases in relative abundances and strong classification performance of Cupriavidus, Flavisolibacter, Methylobacterium, and Schlegelella genera versus controls. The cutaneous microbiota separated into two distinct clusters, which we call cutaneotypes: (1) Proteobacteria-associated microbiota, and (2) Firmicutes-associated and Actinobacteria-associated microbiota. Cutaneotype 2 is enriched in lesion specimens compared to control (odds ratio 3.52 (95% CI 1.44 to 8.98), P <0.01). CONCLUSIONS: Our results indicate that psoriasis induces physiological changes both at the lesion site and at the systemic level, which select for specific differential microbiota among the assayed clinical skin types. These differences in microbial community structure in psoriasis patients are potentially of pathophysiologic and diagnostic significance.
  6. den Hollander, W. J.; Holster, I. L.; van Gilst, B.; van Vuuren, A. J.; Jaddoe, V. W.; Perez-Perez, G. I.; Blaser, M. J.; Moll, H. A.; Kuipers, E. J.. "HELICOBACTER PYLORI COLONIZATION RATE IN CHILDREN IS HIGHLY VARIABLE AMONG DIFFERENT ETHNIC GROUPS IN WESTERN POPULATIONS: THE GENERATION R STUDY [Meeting Abstract]". Helicobacter. 2013 SEP;18 1 1(SI):81-81 (ISI:000324047300020 #557522)    
  7. den Hollander, W. J.; Schalekamp-Timmermans, S.; Holster, I. L.; Jaddoe, V. W.; Perez-Perez, G. I.; Blaser, M. J.; Steegers, E. A. P.; Kuipers, E. J.. "HELICOBACTER PYLORI COLONIZATION AND PREECLAMPSIA: THE GENERATION R STUDY [Meeting Abstract]". Helicobacter. 2013 SEP;18 1 1(SI):115-115 (ISI:000324047300132 #557512)    
  8. den Hollander, W. J.; Sonnenschein-Van der Voort, A. M. M.; Holster, I. L.; Duijts, L.; de Jongste, J. C.; Jaddoe, V. W.; Perez-Perez, G. I.; Blaser, M. J.; Moll, H. A.; Kuipers, E. J.. "MATERNAL HELICOBACTER PYLORI COLONIZATION IS NOT ASSOCIATED WITH ASTHMA SYMPTOMS, AIRWAY INFLAMMATION AND AIRWAY RESISTANCE IN THEIR CHILDREN UNTIL THE AGE OF 6 YEARS: THE GENERATION R STUDY [Meeting Abstract]". Helicobacter. 2013 SEP;18 1 1(SI):116-116 (ISI:000324047300134 #557492)    
  9. Harris S, Paul R; Smythies, Lesley E; Smith, Phillip D; Perez Perez, Guillermo I. "Role of childhood infection in the sequelae of H. pylori disease". Gut microbes. 2013 Nov;4(6):426-438 (MEDL:24275060 #652052)    

    The persistence of Helicobacter pylori infection plays a fundamental role in the development of H. pylori-associated complications. Since the majority of infected persons acquire the bacteria during early childhood, an examination of the immunobiology of H. pylori infection in children compared with that of adults may help identify host factors that contribute to persistent infection. Therefore, we begin our review of the role of persistence in H. pylori disease with an assessment of the clinical features of H. pylori infection in children. We next review the bacterial factors that promote colonization and evasion of host defense mechanisms. We then focus our attention on the early host immunological factors that promote persistence of the infection and its complications in humans and mouse models. We also highlight topics in which further research is needed. An examination of how immunological factors cause divergent manifestations of H. pylori infection in children compared with adults may provide new insight for therapeutic modification or prevention of persistent H. pylori infection and its complications.
  10. Harris, P R; Smythies, L E; Smith, P D; Perez-Perez, G I. "Role of childhood infection in the sequelae of H. Pylori disease". Gut microbes. 2013 06 Nov 2013;4(6):- (EMBASE:2013751206 #712992)      

    The persistence of Helicobacter pylori infection plays a fundamental role in the development of H. pylori-associated complications. Since the majority of infected persons acquire the bacteria during early childhood, an examination of the immunobiology of H. pylori infection in children compared with that of adults may help identify host factors that contribute to persistent infection. Therefore, we begin our review of the role of persistence in H. pylori disease with an assessment of the clinical features of H. pylori infection in children. We next review the bacterial factors that promote colonization and evasion of host defense mechanisms. We then focus our attention on the early host immunological factors that promote persistence of the infection and its complications in humans and mouse models. We also highlight topics in which further research is needed. An examination of how immunological factors cause divergent manifestations of H. pylori infection in children compared with adults may provide new insight for therapeutic modification or prevention of persistent H. pylori infection and its complications. 2013 Landes Bioscience
  11. Hendricks-Munoz, Karen D; Perez-Perez, Guillermo; Xu, Jie; Kim, Yang; Louie, Moi. "Maternal antenatal treatments influence initial oral microbial acquisition in preterm infants". American journal of perinatology. 2013 Jan;30(1):47-52 (MEDL:22814801 #240862)       

    Objective The purpose of this study was to analyze the association of maternal antenatal therapy on initial preterm infant oral microbial acquisition of gut metabolically important bacteria: Firmicutes, Bacteroidetes, Lactobacillus, Bifidobacterium, and Bacteroides species.Study Design Infant oral samples were collected prefeeding at 24 hours and analyzed using group-specific primers by real-time 16S rRNA quantitative polymerase chain reaction with analysis of variance and logistic regression to evaluate effect of antenatal exposure.Results Sixty-five infants <34 weeks' gestational age (GA) were evaluated; mean GA was 28.6 +/- 2.6 (standard deviation) weeks. Infants unexposed to antenatal treatment (n = 5) acquired <1% Firmicutes, which was composed of 100% Lactobacillus species with no detectable Bifidobacterium, Bacteroidetes, or Bacteroides species. Infants exposed to antibiotics (n = 7), acquired fivefold less total bacterial density (TBD) with 45% Firmicutes 1.3% Lactobacillus species, 23.5% Bacteroidetes and rare Bacteroides. Compared with unexposed infants, steroids (n = 26) or steroid and antibiotics (n = 27) exposure led to an eightfold increase in TBD with <1% Lactobacillus species and Bacteroides species 100% and 30%, respectively (p < 0.04). Bifidobacterium was undetectable in all groups.Conclusion Preterm infant exposure to routine maternal antenatal treatments influence early oral microbial acquisition during the primary hours related to establishment of gut commensal bacteria.
  12. Huong, Duong Thu; Zhao, Yanan; Nguyet, Nguyen Thi; Loan, Ta Thi; Binh, Nguyen Thi Thanh; Thinh, Nguyen Van; Hanh, Nguyen Thi Hong; Perez-Perez, Guillermo I; Perlin, David S. "Candida krusei colonization in patients with gastrointestinal diseases". Medical mycology. 2013 Jul;:884-887 (MEDL:23815437 #416902)       

    A total of 135 stomach samples from patients with gastrointestinal diseases and normal controls were examined for Helicobacter pylori infection and Candida colonization. Candida krusei was found in specimens from 20% bleeding, 52% ulcer, and 100% gastritis patients, whereas H. pylori infection rates were 82%, 35% and 30%, respectively, for the same groups of patients. C. krusei was not detected in stomach samples from normal controls.
  13. Redel, Henry; Gao, Zhan; Li, Huilin; Alekseyenko, Alexander V; Zhou, Yanjiao; Perez-Perez, Guillermo I; Weinstock, George; Sodergren, Erica; Blaser, Martin J. "Quantitation and composition of cutaneous microbiota in diabetic and nondiabetic men". Journal of infectious diseases. 2013 Apr;207(7):1105-1114 (MEDL:23300163 #264262)       

    Background. Diabetic foot infections are a leading cause of lower extremity amputations. Our study examines the microbiota of diabetic skin prior to ulcer development or infection. Methods. In a case-control study, outpatient males were recruited at a veterans hospital. Subjects were swabbed at 4 cutaneous sites, 1 on the forearm and 3 on the foot. Quantitative polymerase chain reaction (qPCR) with primers and probes specific for bacteria, Staphylococcus species, Staphylococcus aureus, and fungi were performed on all samples. High-throughput 16S ribosomal RNA (rRNA) sequencing was performed on samples from the forearm and the plantar aspect of the foot. Results. qPCR analysis of swab specimens from 30 diabetic subjects and 30 control subjects showed no differences in total numbers of bacteria or fungi at any sampled site. Increased log concentrations of Staphylococcus aureus, quantified by the number of nuc gene copies, were present in diabetic men on the plantar aspect of the foot. High-throughput 16S rRNA sequencing found that, on the foot, the microbiota in controls (n = 24) was dominated by Staphylococcus species, whereas the microbiota in diabetics (n = 23) was more diverse at the genus level. The forearm microbiota had similar diversity in diabetic and control groups. Conclusions. The feet of diabetic men had decreased populations of Staphylococcus species, increased populations of S. aureus, and increased bacterial diversity, compared with the feet of controls. These ecologic changes may affect the risk for wound infections.
  14. Salazar, Christian R; Sun, Jinghua; Li, Yihong; Francois, Fritz; Corby, Patricia; Perez-Perez, Guillermo; Dasanayake, Ananda; Pei, Zhiheng; Chen, Yu. "Association between Selected Oral Pathogens and Gastric Precancerous Lesions". PLoS ONE. 2013;8(1):e51604-e51604 (e51604) (MEDL:23308100 #211562)       

    We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans) and dental caries (Streptococcus mutans and S. sobrinus). There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR) for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87-2.12), P. gingivalis (OR = 1.12, 0.67-1.88) and T. denticola (OR = 1.34, 0.83-2.12) measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13-5.56) among those with >/= median of percent tooth sites with PD>/=3 mm, compared with no association among those below the median (OR = 0.86, 0.43-1.72). A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03-0.06). Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions.
  15. Statnikov, Alexander; Alekseyenko, Alexander V; Li, Zhiguo; Henaff, Mikael; Perez-Perez, Guillermo I; Blaser, Martin J; Aliferis, Constantin F. "Microbiomic signatures of psoriasis: feasibility and methodology comparison". Scientific reports. 2013 Sep;3:2620-2620 (MEDL:24018484 #529142)       

    Psoriasis is a common chronic inflammatory disease of the skin. We sought to use bacterial community abundance data to assess the feasibility of developing multivariate molecular signatures for differentiation of cutaneous psoriatic lesions, clinically unaffected contralateral skin from psoriatic patients, and similar cutaneous loci in matched healthy control subjects. Using 16S rRNA high-throughput DNA sequencing, we assayed the cutaneous microbiome for 51 such matched specimen triplets including subjects of both genders, different age groups, ethnicities and multiple body sites. None of the subjects had recently received relevant treatments or antibiotics. We found that molecular signatures for the diagnosis of psoriasis result in significant accuracy ranging from 0.75 to 0.89 AUC, depending on the classification task. We also found a significant effect of DNA sequencing and downstream analysis protocols on the accuracy of molecular signatures. Our results demonstrate that it is feasible to develop accurate molecular signatures for the diagnosis of psoriasis from microbiomic data.
  16. Agreus, Lars; Kuipers, Ernst J; Kupcinskas, Limas; Malfertheiner, Peter; Di Mario, Francesco; Leja, Marcis; Mahachai, Varocha; Yaron, Niv; van Oijen, Martijn; Perez Perez, Guillermo; Rugge, Massimo; Ronkainen, Jukka; Salaspuro, Mikko; Sipponen, Pentti; Sugano, Kentaro; Sung, Joseph. "Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers". Scandinavian journal of gastroenterology. 2012 Feb;47(2):136-147 (MEDL:22242613 #746802)       

    BACKGROUND AND AIMS: Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. METHODS: The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. RESULTS: In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. CONCLUSIONS: Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.
  17. Demiray-Gurbuz, E.; Perez-Perez, G.; Olivares, A.; Soyturk, M.; Sarioglu, S.; Simsek, I.; Yilmaz, O.. "PREVALENCE OF VACA ALLELES IN HELICOBACTER PYLORI STRAINS ISOLATED IN TURKEY [Meeting Abstract]". Helicobacter. 2012 SEP;17 1 1(SI):85-85 (ISI:000308581600074 #180191)    
  18. Garza-Gonzalez, Elvira; Rios, Merab; Bosques-Padilla, Francisco J; Francois, Fritz; Cho, Ilseung; Gonzalez, Gloria M; Perez-Perez, Guillermo I. "Immune response against Streptococcus gallolyticus in patients with adenomatous polyps in colon". International journal of cancer. 2012 Nov;131(10):2294-2299 (MEDL:22377818 #180133)       

    Our aim was to examine the humoral immune response against Streptococcus gallolyticus subspecies gallolyticus antigens in individuals subjected to a routine colonoscopy in which colon adenomatous polyps were present or not. Serum samples from 133 individuals with adenomatous polyps and serum samples from 53 individuals with a normal colonoscopy were included. Western blot was performed in all subjects using a whole cell antigen from S. gallolyticus ATCC 9809, and rabbit antisera against the whole cell bacteria was prepared as a control. By analyzing the immune profile of the rabbit-immunized sera by Western-blot, at least 22 proteins were identified as immunogenic in S. gallolyticus. When we evaluated sera from human subjects, two proteins of approximately 30 and 22 kDa were most prominent. Based on this 2-protein band pattern, Western-blot profiles from human subjects were compared. The detection of a protein band of 22 kDa was associated with the presence of adenomatous polyps in colon [odds ratios (OR) 7.98, 95% confidence intervals (CI): 3.54-17.93], p < 0.001. When the presence of the 30 kDa protein alone or both the 22 and 30 kDa proteins were analyzed, the OR increased to 22.37 (95% CI: 3.77-131.64), p < 0.001. The specificity was 84.9 for the presence of the 22 kDa protein, and 98.1 for the presence of the 30 kDa protein alone or both 22 and 30 kDa bands. Serum from individuals with adenomatous polyps recognized two proteins from S. gallolyticus. This result confirmed the possible association of S. gallolyticus with adenomatous polyps in the colon.
  19. Gupta, Vinay; Perez-Perez, Guillermo I; Dorsey, Grant; Rosenthal, Philip J; Blaser, Martin J. "Reply to comment on: The seroprevalence of Helicobacter pylori and its relationship to malaria in Ugandan children [Letter]". Transactions of the Royal Society of Tropical Medicine & Hygiene. 2012 May;106:330-330 (MEDL:22480790 #165583)       
  20. Gupta, Vinay; Perez-Perez, Guillermo I; Dorsey, Grant; Rosenthal, Philip J; Blaser, Martin J. "The seroprevalence of Helicobacter pylori and its relationship to malaria in Ugandan children". Transactions of the Royal Society of Tropical Medicine & Hygiene. 2012 Jan;106(1):35-42 (MEDL:22018600 #165586)       

    Helicobacter pylori epidemiology in sub-Saharan Africa, particularly among children, has been little investigated. A secondary endpoint of our study was to examine for associations between the seroprevalence of H. pylori and the incidence of malaria. We explored H. pylori prevalence by measuring serum IgG antibodies to H. pylori whole cell and cytotoxin-associated gene A (CagA) antigens by ELISA in a longitudinal cohort of 200 Ugandan children, aged 1-10 years at enrollment, in whom malaria incidence was followed over 572 person-years. First-sample seroprevalence for H. pylori -specific IgG (63%) and for the H. pylori protein CagA (78.5%) were both high, and they were positively associated with advancing age (per each 1-year age increase, OR (95% CI): 1.60 (1.39-1.85), P<0.001). We observed nearly universal prevalence of CagA+ H. pylori by the age of 10 years in Kampala and found no evidence that H. pylori-positivity is protective against malaria.
  21. Holster, I Lisanne; Vila, Anne Marie J; Caudri, Daan; den Hoed, Caroline M; Perez-Perez, Guillermo I; Blaser, Martin J; de Jongste, Johan C; Kuipers, Ernst J. "The Impact of Helicobacter pylori on Atopic Disorders in Childhood". Helicobacter. 2012 Jun;17(3):232-237 (MEDL:22515362 #165581)       

    Background: The prevalence of Helicobacter pylori in Western populations has steadily decreased. This has been suggested as one of the factors involved in the recent increase of asthma and allergy. Some studies have reported a negative association between H. pylori and asthma and allergy, but data are inconsistent and there are a few studies in children. Aim: We investigated whether the prevalence of H. pylori was associated with asthma symptoms, allergic rhinitis, and atopic dermatitis in childhood. Methods: We determined IgG anti-H. pylori and CagA antibodies in serum of Dutch children, who took part in the PIAMA birth cohort study. Serum was collected from 545 children, aged 7-9 years (Dutch ethnicity 91.5%). Symptoms of asthma and atopy were assessed by yearly questionnaires. Chi-square tests and logistic regression were used. Results: We found 9%H. pylori and 0.9% CagA seropositivity. Twelve (5.9%) children with reported wheezing ever were H. pylori positive, compared to 37 (10.9%) of the non-wheezers (p = .05). No significant differences in H. pylori prevalence were found between children with or without allergic rhinitis (8.5% vs 9.5%), atopic dermatitis (8.7% vs 9.2%), and physician-diagnosed asthma (7.1% vs 9.4%). Multivariate analysis showed no significant associations between H. pylori seropositivity and wheezing (OR 0.52; 95% CI 0.25-1.06), allergic rhinitis (OR 0.96; 95% CI 0.51-1.81), atopic dermatitis (OR 1.05; 95% CI 0.56-1.98) or physician-diagnosed asthma (OR 0.87; 95% CI 0.37-2.08). Conclusion: We found a borderline significantly lower H. pylori seropositivity in children with wheezing compared to non-wheezers, but no association between H. pylori serum-antibody status and allergic rhinitis, atopic dermatitis, or asthma.
  22. Kienesberger, Sabine; Perez-Perez, Guillermo I; Rivera-Correa, Juan L; Tosado-Acevedo, Rafael; Li, Huilin; Dubois, Andre; Gonzalez-Martinez, Janis A; Dominguez Bello, Maria Gloria; Blaser, Martin J. "Serologic host response to Helicobacter pylori and Campylobacter jejuni in socially housed Rhesus macaques (Macaca mulatta)". Gut pathogens. 2012 Aug;4(1):9-9 (MEDL:22920270 #175980)       

    ABSTRACT: BACKGROUND: Helicobacter pylori are successful colonizers of the human gastric mucosa. Colonization increases the risk of peptic ulcer disease and adenocarcinoma. However, potential benefits of H. pylori colonization include protection against early-onset asthma and against gastrointestinal infections. Campylobacter jejuni are a leading cause of bacterial diarrhea and complications include Guillain-Barre syndrome. Here, we describe the development of reliable serological assays to detect antibodies against those two bacteria in Rhesus macaques and investigated their distribution within a social group of monkeys. METHODS: Two cohorts of monkeys were analyzed. The first cohort consisted of 30 monkeys and was used to establish an enzyme-linked immunosorbent assay (ELISA) for H. pylori antibodies detection. To evaluate colonization of those macaques, stomach biopsies were collected and analyzed for the presence of H. pylori by histology and culture. C. jejuni ELISAs were established using human serum with known C. jejuni antibody status. Next, plasma samples of the 89 macaques (cohort 2) were assayed for antibodies and then statistically analyzed. RESULTS: An H. pylori IgG ELISA, which was 100% specific and 93% sensitive, was established. In contrast, the IgA ELISA was only 82% specific and 61% sensitive. The CagA IgG assay was 100% sensitive and 61% of the macaques were positive. In cohort 2, 62% macaques were H. pylori sero-positive and 52% were CagA positive. The prevalence of H. pylori IgG and CagA IgG increased with monkey age as described for humans. Of the 89 macaques 52% showed IgG against C. jejuni but in contrast to H. pylori, the sero-prevalence was not associated with increasing age. However, there was a drop in the IgG (but not in IgA) mean values between infant and juvenile macaques, similar to trends described in humans. CONCLUSIONS: Rhesus macaques have widespread exposure to H. pylori and C. jejuni, reflecting their social conditions and implying that Rhesus macaques might provide a model to study effects of these two important human mucosal bacteria on a population.
  23. Koshiol, Jill; Flores, Roberto; Lam, Tram K; Taylor, Philip R; Weinstein, Stephanie J; Virtamo, Jarmo; Albanes, Demetrius; Perez-Perez, Guillermo; Caporaso, Neil E; Blaser, Martin J. "Helicobacter pylori seropositivity and risk of lung cancer". PLoS ONE. 2012;7(2):e32106-e32106 (e32106) (MEDL:22384154 #165585)       

    Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori) is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA) antigens, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6) or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7). Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.
  24. Liu, J; Youn, H; Sutton-Ramsey, D; Perez-Perez, G; Leon, D; Ren-Fielding, C; Fielding, G; Kurian, M; Weinshel, E; Francois, F. "Gastric band release rapidly impacts eating behavior, satiety hormones and weight [Meeting Abstract]". American journal of gastroenterology. 2012 October 2012;107:S586-S586 (EMBASE:70895091 #180111)    

    Purpose: Bariatric surgery can achieve sustained weight loss compared to medical management. Among bariatric surgeries, laparoscopic adjustable gastric banding (LAGB) is less-invasive and potentially reversible. LAGB may decrease BMI through restriction of food intake, behavior changes, satiety and digestive hormone levels. The dramatic reduction of appetite observed with LAGB can be ameliorated if the band is underfilled. This effect has not been well evaluated in terms of patient behavior and hormonal changes. Our aim was to assess outcomes related to eating behavior, insulinotropic hormones, and weight change before and after temporary gastric band release. Methods: Adults >= 18 yeaars of age who previously underwent LAGB and achieved successful weight loss were enrolled. All patients underwent standardized evaluation including anthropometric measurements and completion of the Three-Factor Eating Questionnaire (TEFQ-R18) before and after a period of 14 days during which the band was completely loosened. At baseline and follow-up, blood was collected after an overnight fast and 1h after a standard high protein meal, and levels of insulinotropic hormones determined. Results: The mean age of the study cohort (9 women and 6 men) was 42 +/-14 years with mean pre-band adjustment BMI of 32.9 +/- 5.6 and mean waist circumference of 40 +/- 7 inches. All patients had >30% percent reduction in weight within 12-months of the LAGB and demonstrated a lower degree but continued weight loss in the 6-months before study enrollment. Compared to baseline values for the TEFQ-R18, within 2-weeks of loosening the band, cognitive restraint was reduced (11.2 +/- 3 vs. 10.4 +/- 4), while there was a significant increase in both disinhibition (6.4 +/- 3 vs. 9.4 +/- 3, p=0.004) and hunger scores (4.1 +/- 3 vs. 8.0 +/- 3, p=0.004). Compared to baseline, at follow-up insulin output in response to a meal showed a downward trend [Median (IQR) 1,110 (728-1,332) vs. 621 (375-1,325) pg/ml; p=0.21] while leptin was significantly elevated [10,400 (6,030-11,350) vs. 13,700 (10,500-43,900) pg/ml; p=0.001]. Consistent with these findings BMI significantly increased (32.9 +/- 5.6 vs. 34.5 +/- 5.6, p=0.001) along with waist size (40 +/- 7 vs 42 +/- 6, p=0.003). The amount of weight regained within two weeks, returned the cohort to the weight loss level noted at the 12-month post LAGB time point. Conclusion: LAGB adjustment continues to impact eating behavior, satiety hormones, and body weight beyond the initial 12-months following placement. Complete loosening of the LAGB can result in rapid changes in eating behavior, insulinotropic hormones, and significant changes in BMI. Careful adjustment of the band is necessary for continued maintenance of weight loss
  25. Llanes, Rafael; Millan, Leslie M; Escobar, Maria P; Gala, Angela; Capo, Virginia; Feliciano, Onelkis; Gutierrez, Oderay; Llop, Alina; Ponce, Felix; Perez-Perez, Guillermo I. "Low Prevalence of Helicobacter pylori Among Symptomatic Children from a Hospital in Havana, Cuba". Journal of tropical pediatrics. 2012 Jun;58(3):231-234 (MEDL:21752863 #169710)       

    The aims of this study were to assess the prevalence of Helicobacter pylori infection and to introduce a new algorithm to improve its diagnosis in Cuban symptomatic children. One hundred and thirty-three consecutive children with upper gastrointestinal symptoms were studied. Patients were endoscoped and antral biopsies were obtained for rapid urease test (RUT), culture and histology. Prevalence of H. pylori infection was 30.8%. No statistical differences were found concerning demographic, socio-economic factors or chief clinical complaints, between H. pylori-positive and negative children, except for haematemesis, which was significantly higher in infected children (p = 0.003). Histologically, there was statistical association between moderate chronic gastritis in infected children (p = 0.04). Culture and RUT had the highest specificity and sensitivity, respectively. The prevalence of H. pylori infection in Cuban symptomatic children is similar to the one observed in developed countries. Culture and RUT is a useful combination to diagnose H. pylori infection in paediatric patients.
  26. Salazar, Christian R; Francois, Fritz; Li, Yihong; Corby, Patricia; Hays, Rosemary; Leung, Celine; Bedi, Sukhleen; Segers, Stephanie; Queiroz, Erica; Sun, Jinghua; Wang, Beverly; Ho, Hao; Craig, Ronald; Cruz, Gustavo D; Blaser, Martin J; Perez-Perez, Guillermo; Hayes, Richard B; Dasanayake, Ananda; Pei, Zhiheng; Chen, Yu. "Association between oral health and gastric precancerous lesions". Carcinogenesis. 2012 Feb;33(2):399-403 (MEDL:22139442 #156487)       

    Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross-sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared with non-cases, cases were significantly more likely to not floss their teeth [odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.09-7.64], adjusting for age, sex, race, body mass index, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n = 28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases [OR = 2.63, 95% CI: 1.37-5.05 for a standard deviation increase in bleeding sites (equivalent to 19.7%)], independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions.
  27. Torres, Lino E; Gonzalez, Lidice; Melian, Karelia; Alonso, Jordis; Moreno, Arlenis; Hernandez, Mayrin; Reyes, Orlando; Bermudez, Ludisleydis; Campos, Javier; Perez-Perez, Guillermo; Rodriguez, Boris L. "EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains". Biomedica. 2012 Jan-Mar;32(1):23-31 (MEDL:23235784 #746812)       

    INTRODUCTION: It is known that polymorphisms in C-terminal region of CagA influence gastric disease development on Helicobacter pylori infection. Additionally, the geographic distribution of these polymorphisms has been associated with the appearance of more severe gastroduodenal pathologies. Objective. To determine the CagA phosphorylation motifs pattern (EPIYA pattern) in Cuban H. pylori isolates, and to study its association with patient s pathologies. MATERIALS AND METHODS: DNAs from 95 H. pylori cagA-positive strains were used to amplify the 3 variable region of cagA gene by PCR using two different strategies. Additionally, new primers were designed to identify either Western or Eastern CagAEPIYA motiftype by PCR. To confirm the PCR results, PCR products from 14 representative isolates were purified and sequenced. RESULTS: The distribution of the EPIYA motif found was: 2 AB (2.1 %), 1 AC (1.1 %), 1 BC (1.1 %), 70 ABC (73.6 %), 19 ABCC (20 %), and 2 ABCCC (2.1 %). Sequencing analysis confirmed the PCR classification in the 14 studied strains and showed three strains with unusual nucleotide sequences, not reported before. Distribution of the EPIYA-ABC pattern was equivalent in all pathologies (78.9 % in gastric ulcer, 72.5 % in duodenal ulcer and 72.2 % in non-ulcer dyspepsia). CONCLUSION: The PCR results using the new primers confirmed that all studied strains carried the Western CagA type. No specific EPIYA motif was associated with peptic ulcer. This is the first report that shows EPIYA motif distribution in H. pylori isolates from the Caribbean region.
  28. Agudo, S; Perez-Perez, G; Alarcon, T; Lopez-Brea, M. "Rapid detection of clarithromycin resistant Helicobacter pylori strains in Spanish patients by polymerase chain reaction-restriction fragment length polymorphism". Revista espanola de quimioterapia. 2011 Mar;24(1):32-36 (MEDL:21412667 #134135)    

    INTRODUCTION: The aim of this study was to characterize the mutations types present in the 23S rRNA gene related to H. pylori clarithromycin-resistance strains in Spain and evaluate a novel PCR-RFLP method for detection of the most frequent point mutation in our population. METHODS: Gastric biopsies were obtained by endoscopy from patients with gastric symptoms. H. pylori was cultured according to standard microbiological procedures and clarithromycin resistance was determined by E-test. DNA extraction was performed by NucliSens platform with the NucliSens magnetic extraction reagents (bioMerieux) according to the manufacturer instructions. Analyses for point mutations in 23S rRNA gene strains were performed by sequence analysis of amplified polymerase chain reaction products. Restriction fragment length polymorphism was performed using BsaI enzyme to detect restriction sites that correspond to the mutation (A2143G). RESULTS: We found 42 out of 118 (35.6%) strains resistant to clarithromycin by E-test. E-test results were confirmed for the presence of point mutation in 34 (88.1%) of these strains. Mutation A2143G was found in 85.3% of the strains. Analyses with the restriction enzyme BsaI was able to confirm the presence of A2143G mutation. There were 8 H. pylori strains resistant to clarithromycin by E-test but without any point mutation in the 23 rRNA gene. CONCLUSIONS: We conclude that PCR-RFLP is a reliable method to detect clarithromycin-resistance H. pylori strains in countries with a high prevalence of clarithromycin-resistance as Spain. It may be useful before choosing regimens of H. pylori eradication
  29. Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Gonzalez-Valencia, Gerardo; Mendoza, Irma; Penaloza-Espinosa, Rosenda; Ramos, Irma; Kersulyte, Dangeruta; Reyes-Leon, Adriana; Romo, Carolina; Granados, Julio; Munoz, Leopoldo; Berg, Douglas E; Torres, Javier. "Helicobacter pylori Genotyping from American Indigenous Groups Shows Novel Amerindian vacA and cagA Alleles and Asian, African and European Admixture". PLoS ONE. 2011;6(11):e27212-e27212 (MEDL:22073291 #146164)       

    It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America
  30. Demiray-Gurbuz E.; Perez Perez G.; Olivares A.; Yilmaz O.; Gonen C.; Sariotlu S.; Soyturk M.; Simsek I.; Utur Kantar F.. "Simultaneous detection of helicobacter pylori infection and clarithromycin resistance by fluorescence in situ hybridization (FISH) in Turkish dyspeptic patients [Meeting Abstract]". Helicobacter. 2011;16:112-112 (EMBASE:70590166 #142067)    

    Aim: Clarithromycin resistance in H. pylori is considered a major cause of treatment failure. We aimed to evaluate the efficacy of fluorescence in situ hybridization (FISH) method for the simultaneous detection of H. pylori and to determine clarithromycin resistance due to mutations in the 2143 and 2144 positions of 23SrRNA gene compared with traditional culture and antimicrobial susceptibility technics. We assessed cagA status and correlated cagA positivity and clarithromycin resistance. Methods: We studied 179 patients with dyspepsia (45M, 134F; 43.7 +/- 13.7 years). Antrum and corpus biopsy specimens were obtained for rapid urease test, histopathology and culture. H. pylori status was defined when at least two of three tests were positive. Clarithromycin susceptibility in H. pylori strains was assessed by E-test and H. pylori and clarithromycin susceptibility were determined by FISH (BactFISH H. pylori Combi Kit) using formalin-fixed paraffinembedded antrum and corpus biopsy specimens. cagA status in H. pylori strains was also determined by PCR. Results: A total of 119 (66.5%) were H. pylori positive. Among those, 84 (70.6%) were culture positive and 100 (84.0%) were FISH positive. The sensitivity, specificity, PPV and NPV of FISH was 84.0%, 95.0%; 97.1%, and 75.0%, respectively (Kappa = 0.741). FISH detected clarithromycin resistance in 22.0% and by E-test 27.4% of the strains. The concordance was 74.8%. Of the 84 H. pylori strains, 42 (50.0%) were cagA positive. Conclusion: FISH increases the sensitivity to detect H. pylori when compared with microbiology routine methods. FISH is a reliable and highly sensitive method, especially when a quick decision is necessary for treating dyspeptic patient with previous treatment failures
  31. den Hoed, Caroline M; Vila, Anne J; Holster, Ingrid L; Perez-Perez, Guillermo I; Blaser, Martin J; de Jongste, Johan C; Kuipers, Ernest J. "Helicobacter pylori and the birth cohort effect: evidence for stabilized colonization rates in childhood". Helicobacter. 2011 Oct;16(5):405-409 (MEDL:21923687 #137846)       

    Background: The prevalence of Helicobacter pylori has declined over recent decades in developed countries. The increasing prevalence with age is largely because of a birth cohort effect. We previously observed a decline in H. pylori prevalence in 6- to 8-year-old Dutch children from 19% in 1978 to 9% in 1993. Knowledge about birth-cohort-related H. pylori prevalence is relevant as a predictor for the future incidence of H. pylori-associated conditions. Aim: The aim of this study was to investigate whether the birth cohort effect of H. pylori observed between 1978 and 1993 continued in subsequent years. Methods: Anti-H. pylori IgG antibodies and anti-CagA IgG antibodies were determined in serum samples obtained in 2005/2006 from 545 Dutch children aged 7-9 years who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort. The H. pylori and CagA antibodies were determined by enzyme-linked immunosorbent assays that have been extensively validated in children, with a 94% sensitivity for H. pylori colonization and a 92.5% sensitivity for colonization with a cagA-positive strain. Results: Of the 545 children (M/F 300/245), most (91.5%) were of Dutch descent. The H. pylori positivity rate was 9% (95% CI 6.6-11.4%). The prevalence of CagA antibodies was 0.9% (95% CI 0.1-1.6%). No significant differences were demonstrated in H. pylori and cagA prevalence in relation to gender or ethnicity. Conclusion: The prevalence of H. pylori in childhood has remained stable in the Netherlands from 1993 to 2005, suggesting a stabilization of the previously decreasing trend in subsequent birth cohorts. This finding may reflect stabilization in determinants such as family size, housing, and hygienic conditions (or offset by day care). If confirmed in other populations in developed countries, it implies that colonization with H. pylori will remain common in the coming decades. Remarkably however, the rate of colonization with cagA(+) H. pylori strains has become very low, consistent with prior observations that cagA(+) strains are disappearing in Western countries
  32. Francois, Fritz; Roper, Jatin; Joseph, Neal; Pei, Zhiheng; Chhada, Aditi; Shak, Joshua R; de Perez, Asalia Z Olivares; Perez-Perez, Guillermo I; Blaser, Martin J. "The effect of H. pylori eradication on meal-associated changes in plasma ghrelin and leptin". BMC gastroenterology. 2011;11:37-37 (MEDL:21489301 #132313)       

    ABSTRACT: BACKGROUND: Appetite and energy expenditure are regulated in part by ghrelin and leptin produced in the gastric mucosa, which may be modified by H. pylori colonization. We prospectively evaluated the effect of H. pylori eradication on meal-associated changes in serum ghrelin and leptin levels, and body weight. METHODS: Veterans referred for upper GI endoscopy were evaluated at baseline and >/=8 weeks after endoscopy, and H. pylori status and body weight were ascertained. During the first visit in all subjects, and during subsequent visits in the initially H. pylori-positive subjects and controls, blood was collected after an overnight fast and 1 h after a standard high protein meal, and levels of eight hormones determined. RESULTS: Of 92 enrolled subjects, 38 were H. pylori-negative, 44 H. pylori-positive, and 10 were indeterminate. Among 23 H. pylori-positive subjects who completed evaluation after treatment, 21 were eradicated, and 2 failed eradication. After a median of seven months following eradication, six hormones related to energy homeostasis showed no significant differences, but post-prandial acylated ghrelin levels were nearly six-fold higher than pre-eradication (p = 0.005), and median integrated leptin levels also increased (20%) significantly (p < 0.001). BMI significantly increased (5 +/- 2%; p = 0.008) over 18 months in the initially H. pylori-positive individuals, but was not significantly changed in those who were H. pylori-negative or indeterminant at baseline. CONCLUSIONS: Circulating meal-associated leptin and ghrelin levels and BMI changed significantly after H. pylori eradication, providing direct evidence that H. pylori colonization is involved in ghrelin and leptin regulation, with consequent effects on body morphometry
  33. Goldman, Cinthia G; Matteo, Mario J; Loureiro, Julio D; Almuzara, Marisa; Barberis, Claudia; Vay, Carlos; Catalano, Mariana; Heredia, Sergio Rodriguez; Mantero, Paula; Boccio, Jose R; Zubillaga, Marcela B; Cremaschi, Graciela A; Solnick, Jay V; Perez-Perez, Guillermo I; Blaser, Martin J. "Novel gastric helicobacters and oral campylobacters are present in captive and wild cetaceans". Veterinary microbiology. 2011 Aug 26;152(1-2):138-145 (MEDL:21592686 #136497)       

    The mammalian gastric and oral mucosa may be colonized by mixed Helicobacter and Campylobacter species, respectively, in individual animals. To better characterize the presence and distribution of Helicobacter and Campylobacter among marine mammals, we used PCR and 16S rDNA sequence analysis to examine gastric and oral samples from ten dolphins (Tursiops gephyreus), one killer whale (Orcinus orca), one false killer whale (Pseudorca crassidens), and three wild La Plata river dolphins (Pontoporia blainvillei). Helicobacter spp. DNA was widely distributed in gastric and oral samples from both captive and wild cetaceans. Phylogenetic analysis demonstrated two Helicobacter sequence clusters, one closely related to H. cetorum, a species isolated from dolphins and whales in North America. The second related cluster was to sequences obtained from dolphins in Australia and to gastric non-H. pylori helicobacters, and may represent a novel taxonomic group. Dental plaque sequences from four dolphins formed a third cluster within the Campylobacter genus that likely represents a novel species isolated from marine mammals. Identification of identical Helicobacter spp. DNA sequences from dental plaque, saliva and gastric fluids from the same hosts, suggests that the oral cavity may be involved in transmission. These results demonstrate that Helicobacter and Campylobacter species are commonly distributed in marine mammals, and identify taxonomic clusters that may represent novel species
  34. Nagy, Toni A; Allen, Shannon S; Wroblewski, Lydia E; Flaherty, David K; Slaughter, James C; Perez-Perez, Guillermo; Israel, Dawn A; Peek, Richard M Jr. "Helicobacter pylori induction of eosinophil migration is mediated by the cag pathogenicity island via microbial-epithelial interactions". American journal of pathology. 2011 Apr;178(4):1448-1452 (MEDL:21406172 #133350)       

    The host immune response directed against Helicobacter pylori is ineffective in eliminating the organism and strains harboring the cag pathogenicity island augment disease risk. Because eosinophils are a prominent component of H. pylori-induced gastritis, we investigated microbial and host mechanisms through which H. pylori regulates eosinophil migration. Our results indicate that H. pylori increases production of the chemokines CCL2, CCL5, and granulocyte-macrophage colony-stimulating factor by gastric epithelial cells and that these molecules induce eosinophil migration. These events are mediated by the cag pathogenicity island and by mitogen-activated protein kinases, suggesting that eosinophil migration orchestrated by H. pylori is regulated by a virulence-related locus
  35. Pohl, Mary Ann; Zhang, William; Shah, Sunny N; Sanabria-Valentin, Edgardo L; Perez-Perez, Guillermo I; Blaser, Martin J. "Genotypic and Phenotypic Variation of Lewis Antigen Expression in Geographically Diverse Helicobacter pylori Isolates". Helicobacter. 2011 Dec;16(6):475-481 (MEDL:22059399 #141081)       

    Background: Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. Materials and Methods: From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and beta-(1,3)galT loci in 113 H. pylori strains. Results: Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le(a) and Le(b) ) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). Conclusion: These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression
  36. Agudo, Sonia; Perez-Perez, Guillermo; Alarcon, Teresa; Lopez-Brea, Manuel. "High prevalence of clarithromycin-resistant Helicobacter pylori strains and risk factors associated with resistance in Madrid, Spain". Journal of clinical microbiology. 2010 Oct;48(10):3703-3707 (MEDL:20668128 #746822)       

    Clarithromycin is one of the antibiotics used for the treatment of Helicobacter pylori infections, and clarithromycin resistance is the most important factor when it comes to predicting eradication failure. The present study analyzed H. pylori isolates for the presence of 23S rRNA gene mutations and determined the risk factors associated with resistance among H. pylori isolates collected in Madrid, Spain, in 2008. We studied 118 H. pylori strains isolated from the same number of patients. A total of 76.3% of the patients were born in Spain, 52.7% were children, 20.3% had previously been treated, and 66.1% were female. Clarithromycin resistance was determined by Etest. H. pylori strains were considered resistant if the MIC was >/=1 mg/liter. DNA extraction was carried out by use of the NucliSens easyMAG platform with NucliSens magnetic extraction reagents (bioMerieux). The DNA sequences of the 23S rRNA genes of clarithromycin-resistant and -sensitive strains were determined to identify specific point mutations. The vacA genotype and cagA status were determined by PCR. We found that 42 (35.6%) strains were resistant to clarithromycin by Etest. Etest results were confirmed by detection of the presence of point mutations in 34 (88.1%) of these strains. Eight H. pylori strains were resistant to clarithromycin by Etest but did not have a point mutation in the 23S rRNA gene. Mutation at A2143G was found in 85.3% of the strains, mutation at A2142G in 8.8%, and mutation at T2182C in 5.9%. Dual mutations were found in 8.8% of the strains. H. pylori clarithromycin-resistant strains were strongly associated with pediatric patients, with patients born in Spain, and with patients who had previously been treated (P
  37. Chung, Christine; Olivares, Asalia; Torres, Eugenia; Yilmaz, Ozlem; Cohen, Henry; Perez-Perez, Guillermo. "Diversity of VacA intermediate region among Helicobacter pylori strains from several regions of the world". Journal of clinical microbiology. 2010 Mar;48(3):690-696 (MEDL:20053862 #107926)       

    Helicobacter pylori is known to be a major cause of gastric carcinoma and peptic ulceration. cagA positivity and vacA's signal regions and mid-regions are well-characterized markers of H. pylori's virulence. Recently, an intermediate region has been identified as another strong marker of H. pylori-associated disease, and its i1 allele has been linked with severe diseases in colonized hosts. The goal of this study was to determine the prevalence of the intermediate alleles in H. pylori isolates from China, Turkey, and Uruguay and from U.S. Africans and to compare their distribution with other well-characterized virulence factors. Originally, 123 H. pylori strains were studied, but 3 were excluded due to the failure to amplify the intermediate region in these samples. Therefore, a total of 120 strains were analyzed: 30 Chinese isolates, 35 Turkish isolates, 30 Uruguayan isolates, and 25 U.S. African isolates. The s type and the m type were determined by PCR amplification. The i type was identified by PCR amplification and DNA sequencing. CagA status was determined by PCR methodology. There was a strong correlation among CagA positivity, s1, and i1 in Chinese, U.S. African, and Uruguayan isolates, but less correlation among these markers in Turkish isolates. A new intermediate variant (i3) was identified in 25.7% of Turkish strains and 3.3% of the Chinese strains. In summary, the distribution of CagA positivity and s1 correlated with the i1 in the three populations, except in the Turkish population, which showed a disproportionate representation of the i3 allele. Phylogenetic mapping confirmed the i-typing method previously defined and adopted for this study. The phylogenetic tree showed country-specific correlation with the intermediate region. Our results showed that the i1 allele is strongly associated with CagA positivity and the vacA s1 allele, suggesting its role as a virulence marker and potential predictor for clinical outcome
  38. Cook, Michael B; Dawsey, Sanford M; Diaw, Lena; Blaser, Martin J; Perez-Perez, Guillermo I; Abnet, Christian C; Taylor, Philip R; Albanes, Demetrius; Virtamo, Jarmo; Kamangar, Farin. "Serum pepsinogens and Helicobacter pylori in relation to the risk of esophageal squamous cell carcinoma in the alpha-tocopherol, beta-carotene cancer prevention study". Cancer epidemiology biomarkers & prevention. 2010 Aug;19(8):1966-1975 (MEDL:20647397 #134354)       

    BACKGROUND: Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved. METHODS: We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Gastric atrophy (PGI/PGII <4) was associated with ESCC (OR, 4.58; 95% CI, 2.00-10.48). There was no evidence for an association between H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24). CONCLUSIONS: These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect. IMPACT: Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC
  39. Galvan-Portillo, Marcia V; Onate-Ocana, Luis F; Perez-Perez, Guillermo I; Chen, Jia; Herrera-Goepfert, Roberto; Chihu-Amparan, Lilia; Flores-Luna, Lourdes; Mohar-Betancourt, Alejandro; Lopez-Carrillo, Lizbeth. "Dietary folate and vitamin B12 intake before diagnosis decreases gastric cancer mortality risk among susceptible MTHFR 677TT carriers". Nutrition. 2010 Feb;26(2):201-208 (MEDL:19577428 #133455)       

    OBJECTIVE: To assess gastric cancer survival in relation to dietary intake of methyl donors and the methylenetetrahydrofolate reductase 677C>T (MTHFR 677C>T) polymorphism. METHODS: A prospective cohort of 257 incidental, histologically confirmed gastric cancer cases was assembled in January 2004 and followed until June 2006. Patients were recruited from the main oncology and/or gastroenterology units in Mexico City and were queried regarding their sociodemographic information, clinical history, and dietary habits 3 y before the onset of their symptoms. The intake of methyl donors was estimated with a food-frequency questionnaire and the MTHFR 677C>T polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism analysis. Cox's multivariate regression models were used to estimate the mortality risk of gastric cancer. RESULTS: MTHFR 677TT carriers with low folate and vitamin B12 intakes had the lowest survival rate in cases of gastric cancer. High intakes of folate and vitamin B12 before diagnosis was associated with decreased gastric cancer mortality risk in susceptible MTHFR 677TT carriers (mortality risk for folate 0.14, 95% confidence interval 0.04-0.46, P for trend=0.001; mortality risk for vitamin B12 0.23, 95% confidence interval 0.08-0.66, P for trend=0.008). CONCLUSION: Folate and related B vitamins may be used as an intervention strategy to improve the survival outcome of gastric cancer
  40. Gao, Zhan; Perez-Perez, Guillermo I; Chen, Yu; Blaser, Martin J. "Quantitation of major human cutaneous bacterial and fungal populations". Journal of clinical microbiology. 2010 Oct;48(10):3575-3581 (MEDL:20702672 #114044)       

    Because the human skin microbiota may play roles in the causation or modification of skin diseases, we sought to provide initial quantitative analysis from different cutaneous locations. We developed quantitative PCRs to enumerate the total bacterial and fungal populations, as well as the most common bacterial and fungal genera present in six locales, in eight healthy subjects. We used a set of primers and TaqMan MGB probes based on the bacterial 16S rRNA and fungal internally transcribed spacer region, as well as bacterial genus-specific probes for Propionibacterium, Corynebacterium, Streptococcus, and Staphylococcus and a fungal genus-specific probe for Malassezia. The extent of human DNA contamination of the specimen was determined by quantitating the human housekeeping GAPDH gene. The highest level of 16S rRNA copies of bacteria was present in the axilla (4.44 +/- 0.18 log(10) copies/mul [mean +/- standard error of the mean]), with normalization based on GAPDH levels, but the other five locations were similar to one another (range, 2.48 to 2.89 log(10) copies/mul). There was strong symmetry between the left and right sides. The four bacterial genera accounted for 31% to 59% of total bacteria, with the highest percent composition in the axilla and the lowest in the forearm. Streptococcus was the most common genus present on the forehead and behind the ear. Corynebacterium spp. were predominant in the axilla. Fungal levels were 1 to 2 log(10) lower than for bacteria, with Malassezia spp. accounting for the majority of fungal gene copies. These results provide the first quantitation of the site and host specificities of major bacterial and fungal populations in human skin and present simple methods for their assessment in studies of disease
  41. Garza-Gonzalez, E; Perez-Perez, G I; Mendoza-Ibarra, S I; Flores-Gutierrez, J P; Bosques-Padilla, F J. "Genetic risk factors for inflammatory bowel disease in a North-eastern Mexican population". International journal of immunogenetics. 2010 Oct;37(5):355-359 (MEDL:20518842 #416912)       

    The purpose of this study was to assess the role of Helicobacter pylori and several genetic polymorphisms in relation to inflammatory bowel disease (IBD). We studied 44 unrelated patients with IBD and 75 subjects with no history of IBD as controls. Using pyrosequencing technology, we identified gene polymorphisms in IL-10, TNF-A, ILB-31, and TLR4. H. pylori status was determined by serology. Individuals homozygous for IL10-592 A or IL10-1082 A genotypes show significantly lower occurrence of IBD (P=0.03 and P<0.01, respectively). Individuals heterozygous at IL10-1082 have significantly increased occurrence of IBD, both ulcerative colitis and Crohn's disease (P<0.01). There was no difference in the prevalence of H. pylori infection between cases and controls. This study provides evidence that variation in IL10 is correlated with IBD occurrence in this Mexican population.
  42. Gonzalez, Nicolas; Fernandez, Lucia; Perez Perez, Guillermo; Saona, Gustavo; Raisler, Katherine; Eugenia Torres, Maria; Olivares, Asalia; Stein, Silvana; Cohen, Henry. "[Helicobacter pylori infection in Uruguayan patients of African origin: clinical, endoscopic and genetic characteristics]". Acta gastroenterologica Latinoamericana. 2010 Sep;40(3):206-210 (MEDL:21053478 #746842)    

    INTRODUCTION: Prevalence of H pylori varies in different regions around the world and its associated clinical manifestations are more severe in certain ethnic groups. Prevalence of H pylori in different groups is scarcely known in Uruguay. OBJECTIVES: To determine the prevalence, clinical and endoscopic characteristics of H pylori infection in Uruguayan patients of African origin. METHODS: Fifty Afro-descendant patients attending the Clinics of Gastroenterology at Hospital de Clinicas in Montevideo, were studied. They were all examined by upper endoscopy and H pylori infection was determined by histology, urease test and culture. Presence of cagA was ascertained by PCR. RESULTS: The prevalence of H pylori infection determined by histology and urease test in Afro-descendants was 70%. No relationship was found between symptoms that led to consultation and the presence of infection. It was not possible either to establish a relationship between H pylori and endoscopic findings. CagA gene was detected in 62% of cases, but there was no relationship between its presence and the endoscopic findings. CONCLUSIONS: The prevalence of H pylori infection in Afro-descendant Uruguayan patients is high, comparable with that found in other developing regions. However, an association of the presence of infection with symptoms or endoscopic findings was not found. CagA did not result in a risk factor for the presence of more severe gastroduodenal lesions in this group of patients.
  43. Guvenir, M.; Yilmaz, O.; Olivares, A.; Gonen, C.; Sarioglu, S.; Ellidokuz, H.; Soyturk, M.; Simsek, I.; Perez, G. I. Perez. "Characterization of H-pylori CagA EPIYA motifs in H-pylori strains of Turkish Origin [Meeting Abstract]". Helicobacter. 2010 AUG;15(4):370-370 (ISI:000279986200164 #114023)    
  44. Perez-Perez, Guillermo I; Maw, Anna M; Feingold-Link, Lani; Gunn, Jennifer; Bowers, Andrea L; Minano, Cecilia; Rautelin, Hilpi; Kosunen, Timo U; Blaser, Martin J. "Longitudinal Analysis of Serological Responses of Adults to Helicobacter pylori Antigens". Journal of infectious diseases. 2010 Sep 15;202(6):916-923 (MEDL:20698790 #111828)       

    Because Helicobacter pylori persist for decades in the human stomach, the aim of this study was to examine the long-term course of H. pylori-specific serum immunoglobulin G (IgG) responses with respect to subclass and antigenic target. We studied paired serum samples obtained in 1973 and in 1994 in Vammala, Finland, from 64 healthy H. pylori-positive adults and from other healthy control subjects. H. pylori serum immunoglobulin A, IgG, and IgG subclass responses were determined by antigen-specific enzyme-linked immunosorbent assays. H. pylori-specific IgG1 and IgG4 subtype responses from 47 subjects were similar in 1973 and 1994, but not when compared with unrelated persons. H. pylori-specific IgG1:IgG4 ratios among the participants varied >1000-fold; however, 57 (89.1%) of 64 subjects had an IgG1:IgG4 ratio >1.0, consistent with a predominant IgG1 (Th1) response. Furthermore, ratios in individual hosts were stable over the 21-year period ([Formula: see text]; [Formula: see text]). The immune response to heat shock protein HspA was unchanged in 49 (77%) of the 64 subjects tested; of the 15 whose serostatus changed, all seroconverted and were significantly younger than those whose status did not change. These findings indicate that H. pylori-specific antibody responses are host-specific with IgG1:IgG4 ratios stable over 21 years, IgG1 responses predominating, and HspA seroconversion with aging
  45. Sabbaghian, M Shirin; Ranaudo, Jeffrey; Zeng, Lin; Alongi, Alexandra P; Perez-Perez, Guillermo; Shamamian, Peter. "Identification of Helicobacter spp. in bile and gallbladder tissue of patients with symptomatic gallbladder disease". HPB : the official journal of the International Hepato Pancreato Biliary Association. 2010 Mar;12(2):129-133 (MEDL:20495657 #109804)       

    BACKGROUND: This experimental study was designed to determine if Helicobacter spp. contribute to benign gallbladder disease using polymerase chain reaction (PCR) methods. METHODS: Patients with benign gallbladder disease scheduled for elective cholecystectomy at New York University Langone Medical Center were recruited from February to May 2008. Bile, gallbladder tissue and gallstones were collected. DNA was isolated from these specimens and amplified via PCR using C97F and C98R primers specific for Helicobacter spp. Appropriate positive and negative controls were used. Products were analysed with agarose gel electrophoresis, sequenced and results aligned using sequencher. Plasma was collected for detection of anti-Helicobacter pylori antibodies via enzyme-linked immunosorbent assay. RESULTS: Of 36 patients, 12 patients' bile and/or tissue were positive for Helicobacter spp. by PCR. Species were most homologous with H. pylori, although other Helicobacter spp. were suggested. Six of 12 patients demonstrated anti-Helicobacter antibodies in plasma, suggesting that the remaining six might have demonstrated other species besides H. pylori. Four of six plasma samples with anti-Helicobacter antibodies were anti-CagA (cytotoxin associated gene) negative. DISCUSSION: Helicobacter spp. can be detected in bile and gallbladder tissue of patients with benign gallbladder disease. The contribution of these bacteria to the pathophysiology of gallbladder disease and gallstone formation requires further study
  46. Valenzuela, Manuel; Perez-Perez, Guillermo; Corvalan, Alejandro H; Carrasco, Gonzalo; Urra, Hery; Bravo, Denisse; Toledo, Hector; Quest, Andrew F G. "Helicobacter pylori-induced loss of the inhibitor-of-apoptosis protein survivin is linked to gastritis and death of human gastric cells". Journal of infectious diseases. 2010 Oct;202(7):1021-1030 (MEDL:20735270 #746832)       

    Helicobacter pylori infects the human stomach and modifies signaling pathways that affect gastric epithelial cell proliferation and viability. Chronic exposure to this pathogen contributes to the onset of gastric atrophy, an early event in the genesis of gastric cancer associated with H. pylori infection. Susceptibility to H. pylori-induced cell death ultimately depends on the presence of protective host cell factors. Although expression of the inhibitor-of-apoptosis protein survivin in adults is frequently linked to the development of cancer, evidence indicating that the protein is present in normal gastric mucosa is also available. Thus, we investigated in human gastric tissue samples and cell lines whether H. pylori infection is linked to loss of survivin and increased cell death. Our results show that infection with H. pylori decreased survivin protein levels in the mucosa of patients with gastritis. Furthermore, survivin down-regulation correlated with apoptosis and loss of cell viability in gastrointestinal cells cocultured with different H. pylori strains. Finally, overexpression of survivin in human gastric cells was sufficient to reduce cell death after infection. Taken together, these findings implicate survivin as an important survival factor in the gastric mucosa of humans.
  47. Hou, Lifang; Savage, Sharon A; Blaser, Martin J; Perez-Perez, Guillermo; Hoxha, Mirjam; Dioni, Laura; Pegoraro, Valeria; Dong, Linda M; Zatonski, Witold; Lissowska, Jolanta; Chow, Wong-Ho; Baccarelli, Andrea. "Telomere length in peripheral leukocyte DNA and gastric cancer risk". Cancer epidemiology biomarkers & prevention. 2009 Nov;18(11):3103-3109 (MEDL:19861514 #165590)       

    Telomere length reflects lifetime cumulative oxidative stress from environmental exposures, such as cigarette smoking and chronic inflammation. Shortened telomere length is thought to cause genomic instability and has been associated with several cancers. We examined the association of telomere length in peripheral leukocyte DNA with gastric cancer risk as well as potential confounding factors and risk modifiers for telomere length-related risk. In a population-based study of gastric cancer conducted in a high-risk population in Warsaw, Poland, between 1994 and 1996, we measured relative telomere length in 300 cases and 416 age- and gender-matched controls using quantitative real-time PCR. Among controls, telomeres were significantly shorter in association with aging (P < 0.001), increasing pack-years of cigarette smoking (P = 0.02), decreasing fruit intake (P = 0.04), and Helicobacter pylori positivity (P = 0.03). Gastric cancer cases had significantly shorter telomere length (mean +/- SD relative telomere length, 1.25 +/- 0.34) than controls (1.34 +/- 0.35; P = 0.0008). Gastric cancer risk doubled [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.33-3.13] among subjects in the shortest compared with the highest quartile of telomere length (P(trend) < 0.001). Telomere length-associated risks were higher among individuals with the lowest risk profile, those H. pylori-negative (OR, 5.45; 95% CI, 2.10-14.1), nonsmokers (OR, 3.07; 95% CI, 1.71-5.51), and individuals with high intake of fruits (OR, 2.43; 95% CI, 1.46-4.05) or vegetables (OR, 2.39; 95% CI, 1.51-3.81). Our results suggest that telomere length in peripheral leukocyte DNA was associated with H. pylori positivity, cigarette smoking, and dietary fruit intake. Shortened telomeres increased gastric cancer risk in this high-risk Polish population.
  48. Shak, Joshua R; Dick, Jonathan J; Meinersmann, Richard J; Perez-Perez, Guillermo I; Blaser, Martin J. "Repeat-associated plasticity in the Helicobacter pylori RD gene family". Journal of bacteriology. 2009 Nov;191(22):6900-6910 (MEDL:19749042 #104893)       

    The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3' region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host
  49. Torres-Debat, M E; Perez-Perez, G; Olivares, A; Fernandez, L; Raisler, K; Gonzalez, N; Stein, S; Bazet, M C; Alallon, W; Cohen, H. "Antimicrobial susceptibility of Helicobacter pylori and mechanisms of clarithromycin resistance in strains isolated from patients in Uruguay". Revista espanola de enfermedades digestivas. 2009 Nov;101(11):757-762 (MEDL:20001152 #133755)    

    The prevalence and mechanisms of antibiotic resistance of Helicobacter pylori have not yet been investigated in Uruguay. The objective of this study was to assess the susceptibility of H. pylori to the most frequently used antibiotics and to determine the mechanism of resistance to clarithromycin. Seventy-nine isolates were obtained from gastric biopsies of 50 adult patients during two periods, 2001 and 2006. The former group enrolled the general population (GP), the latter group Afro-descendant (AD) subjects. The minimum inhibitory concentrations of clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin were determined using the E-test technique. Amplification was achieved through PCR and nucleic acid sequencing to detect mutations in the site of action of clarithromycin in the rRNA gene 23S. No amoxicillin or tetracycline-resistant strains were found. Clarithromycin resistance was found in 12% of the patients overall: 19.4% resistance in AD patients and no resistance in the GP group. This difference was statistically significant. The highest resistance was seen with metronidazole (36%), present in similar proportions in the two groups: 36.8% (GP) and 35.5% (AD). One GP patient and one AD patient had levofloxacin-resistant strains. Sequencing analysis of gene 23S rRNA showed that only mutation in position 2143 was presented in all clarithromycin-resistant strains
  50. Buadze, M; Olivares, A; Kutubidze, T; Labauri, L; Chavchanidze, D; Lobzhanidze, G; Perez-Perez, GI. "Prevalence of H. pylori in Georgian pediatric patients with peptic ulcer diseases [Meeting Abstract]". Helicobacter. 2008 OCT;13(5):447-448 (ISI:000258404600165 #86817)    
  51. Contreras, Monica; Pujol, Flor H; Perez-Perez, Guillermo I; Marini, Elisabetta; Michelangeli, Fabian A; Ponce, Liliana; Dominguez-Bello, Maria G. "Helicobacter pylori seroprevalence in Amerindians from isolated locations". American journal of tropical medicine & hygiene. 2008 Apr;78(4):574-576 (MEDL:18385351 #79186)    

    Helicobacter pylori seems universally distributed in all human populations, with high prevalence in the third world. Because H. pylori is an ancestral indigenous microbe of the human stomach, we hypothesized that its prevalence in isolated Amerindians would be high. A serologic study was performed on 19 Guahibo-Piaroa and 17 Warao in Venezuela, using H. pylori whole cell (WC) and CagA antigens from US strains. For Guahibo-Piaroa Amerindians, CagA seropositivity was 95%, but WC seropositivity was only 74%. For Warao, both CagA and WC seropositive proportions were low (65% and 76%, respectively). Because all CagA-seropositive individuals carry H. pylori, the results suggest that there has been bacterial antigen divergence, probably caused by genetic drift/natural selection, on humans and their microbes in isolated human groups
  52. Epplein, Meira; Nomura, Abraham M Y; Hankin, Jean H; Blaser, Martin J; Perez-Perez, Guillermo; Stemmermann, Grant N; Wilkens, Lynne R; Kolonel, Laurence N. "Association of Helicobacter pylori infection and diet on the risk of gastric cancer: a case-control study in Hawaii". Cancer causes & control. ccc. 2008 Oct;19(8):869-877 (MEDL:18369531 #79187)       

    OBJECTIVE: The risk factors most strongly associated with gastric cancer are the gastric bacteria Helicobacter pylori and diet. Utilizing data from a case-control study among residents in Hawaii, we examined the association of diet, presence of H. pylori, and non-cardia gastric cancer risk. METHODS: Serum taken at diagnosis for cases (n = 212) and at interview for controls (n = 336) was assayed for IgG antibodies to H. pylori group antigens and to a recombinant fragment of the cytotoxin-associated antigen A (CagA) protein, and subjects completed food frequency questionnaires. Risk measures were calculated using logistic regression. The likelihood ratio test was used to assess interactions. RESULTS: Inverse associations were found between gastric cancer risk and increasing intake of several micronutrients and vegetables among all individuals. For H. pylori/CagA-positive subjects, significant trends were present for total, green, and yellow vegetables, while a significant trend was present only for yellow vegetables among H. pylori/CagA-negative individuals. For intestinal gastric cancer, there was a suggestion that intake of vegetables, especially cruciferous vegetables, had a stronger protective effect for the H. pylori/CagA-positive group. CONCLUSIONS: Diet may play a greater role in the etiology of non-cardia gastric cancer among individuals with evidence of H. pylori infection than among those without
  53. Francois, F; Roper, J; Goodman, A J; Pei, Z; Ghumman, M; Mourad, M; de Perez, A Z Olivares; Perez-Perez, G I; Tseng, C-H; Blaser, M J. "The association of gastric leptin with oesophageal inflammation and metaplasia". Gut: journal of the British Society of Gastroenterology. 2008 Jan;57(1):16-24 (MEDL:17761783 #75709)       

    BACKGROUND: Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis. AIMS: To determine whether leptin receptors are present in the oesophagus, and whether serum or gastric leptin levels are associated with oesophageal inflammation and metaplasia. METHODS: From patients referred for upper endoscopy, biopsies were obtained from the stomach and distal oesophagus, and serum samples were collected. Patients were classified as having normal, inflamed or Barrett's oesophagus. Quantitative immunohistochemistry was performed on representative sections, and leptin levels in plasma and gastric biopsy samples were determined by specific immunoassay. RESULTS: Of 269 individuals enrolled, 105 were Helicobacter pylori-negative. Of the 88 patients with complete oesophageal biopsies, 44 were normal, 24 were inflamed and 20 were Barrett's oesophagus. Receptors for leptin were highly expressed on oesophageal epithelial cells, with similar density and staining pattern in all three conditions, and plasma and antral leptin levels did not differ significantly. Patients with Barrett's had significantly (p = 0.01) higher fundic leptin levels (median 202 (interquartile range 123-333) pg/mg) compared with normal (126 (78-221) pg/mg) or inflamed (114 (76-195) pg/mg) oesophagus. In multivariate analysis, for every twofold increase in fundic leptin, the odds of having Barrett's was 3.4 times (95% CI 1.5 to 7.6) higher compared with having a normal oesophagus. CONCLUSIONS: Leptin receptor expression on oesophageal epithelial cells provides a pathway for leptin-mediated signal transduction. Variation in gastric leptin production could contribute to differential oesophageal healing and metaplasia progression
  54. Garza-Gonzalez, Elvira; Bocanegra-Garcia, Virgilio; Bosques-Padilla, Francisco-Javier; Flores-Gutierrez, Juan-Pablo; Moreno, Francisco; Perez-Perez, Guillermo-Ignacio. "mRNA levels of TLR4 and TLR5 are independent of H pylori". World journal of gastroenterology : WJG. 2008 Sep 14;14(34):5306-5310 (MEDL:18785283 #102589)       

    AIM: To determine if the presence H pylori or its virulence affect toll-like receptor 4 (TLR4) and TLR5 mRNA expression levels. METHODS: For the in vivo assays, gastric biopsies were obtained from 40 patients and H pylori status was determined. For the in vitro assays, human gastric adenocarcinoma mucosal cells (AGS) were cultured in the presence or absence of twelve selected H pylori strains. H pylori strains isolated from culture-positive patients and selected strains were genotyped for cagA and vacA. The cDNA was obtained from mRNA extracted from biopsies and from infected AGS cells. TLR4 and TLR5 mRNA levels were examined by real-time PCR. RESULTS: The presence of H pylori did not affect the mRNA levels of TLR4 or TLR5 in gastric biopsies. The mRNA levels of both receptors were not influenced by the vacA status (P > 0.05 for both receptors) and there were no differences in TLR4 or TLR5 mRNA levels among the different clinical presentations/histological findings (P > 0.05). In the in vitro assay, the mRNA levels of TLR4 or TLR5 in AGS cells were not influenced by the vacAs1 status or the clinical condition associated with the strains (P > 0.05 for both TLR4 and TLR5). CONCLUSION: The results of this study show that the mRNA levels of TLR4 and TLR5 in gastric cells, both in vivo and in vitro, are independent of H pylori colonization and suggest that vacA may not be a significant player in the first step of innate immune recognition mediated by TLR4 or TLR5
  55. Reibman, Joan; Marmor, Michael; Filner, Joshua; Fernandez-Beros, Maria-Elena; Rogers, Linda; Perez-Perez, Guillermo I; Blaser, Martin J. "Asthma is inversely associated with Helicobacter pylori status in an urban population". PLoS ONE. 2008;3(12):e4060-e4060 (MEDL:19112508 #91964)       

    BACKGROUND: Microbial exposures have been suggested to confer protection from allergic disorders and reduced exposures to gastrointestinal microbiota have been proposed as an explanation for the increase in asthma prevalence. Since the general prevalence of Helicobacter pylori has been decreasing, we hypothesized that H. pylori serostatus would be inversely related to the presence of asthma. METHODS: Adults were recruited to participate in the New York University (NYU)/Bellevue Asthma Registry in New York City. Adult asthma cases (N = 318) and controls (N = 208) were identified and serum IgG antibodies to H. pylori whole cell antigens or the immunodominant CagA antigen were measured. RESULTS: As expected, the asthma cases and controls differed with respect to atopy and lung function. Seropositivity to H. pylori or CagA antigen was present in 47.1% of the total case and control study population. Asthma was inversely associated with CagA seropositivity (OR = 0.57, 95% CI = 0.36-0.89). Median age of onset of asthma (doctor's diagnosis) was older (21 years) among individuals with CagA+ strains than among H. pylori- individuals (11 years) (p = 0.006). CONCLUSION: These data are consistent with the hypothesis that colonization with CagA+ H. pylori strains is inversely associated with asthma and is associated with an older age of asthma onset in an urban population. The data suggest H. pylori as a marker for protection
  56. Romero-Gallo, Judith; Harris, Elizabeth J; Krishna, Uma; Washington, Mary Kay; Perez-Perez, Guillermo I; Peek, Richard M Jr. "Effect of Helicobacter pylori eradication on gastric carcinogenesis". Laboratory investigation. 2008 Mar;88(3):328-336 (MEDL:18180700 #79188)       

    Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet the effects of bacterial eradication on carcinogenesis remain unclear. Animal models provide important insights into factors that are involved in gastric carcinogenesis, and we previously utilized such a model to demonstrate that an in vivo-adapted H. pylori strain, 7.13, rapidly and reproducibly induces inflammation-mediated gastric carcinoma. In the current study, we used this bacterial strain as a prototype to define the role of targeted antimicrobial therapy in gastric carcinogenesis. Mongolian gerbils were infected with H. pylori for 4 or 8 weeks, treated with antimicrobial agents or vehicle, and then euthanized at 8 weeks after the completion of therapy. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals receiving antimicrobial therapy. Gastric dysplasia or cancer developed in >60% of the gerbils that remained persistently colonized with H. pylori, but in none of the animals treated with antibiotics following 4 weeks of infection. Infection with H. pylori for 8 weeks prior to therapy resulted in an attenuation, but not complete prevention, of pre-malignant and malignant lesions. Similarly, antibiotic therapy initiated at 4, but not 8, weeks after H. pylori challenge significantly reduced expression of the Th1 pro-inflammatory cytokine interferon-gamma within colonized gastric mucosa. These results indicate that treatment of H. pylori in this model decreases the incidence and severity of lesions with carcinogenic potential. The effectiveness of eradication is dependent upon the timing of intervention, providing insights into mechanisms that may regulate the development of malignancies arising within the context of inflammatory states
  57. Roper, Jatin; Francois, Fritz; Shue, Peter L; Mourad, Michelle S; Pei, Zhiheng; Olivares de Perez, Asalia Z; Perez-Perez, Guillermo I; Tseng, Chi-Hong; Blaser, Martin J. "Leptin and ghrelin in relation to Helicobacter pylori status in adult males". Journal of clinical endocrinology & metabolism. 2008 Jun;93(6):2350-2357 (MEDL:18397989 #159212)       

    CONTEXT: Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach. OBJECTIVE: We sought to determine whether the presence of Helicobacter pylori affects gastric and systemic levels of leptin and ghrelin. DESIGN, SETTING, AND PATIENTS: We consecutively enrolled 256 patients referred for upper endoscopy at a Veterans Affairs outpatient endoscopy center. OUTCOMES: We obtained fasting serum, fundic and antral biopsies, and gastric juice. Based on histological, biochemical, and serological assays, patients were categorized as H. pylori+ or H. pylori-. Leptin and total ghrelin levels in serum, gastric biopsies, and gastric juice were determined by specific ELISAs. RESULTS: Of the 256 subjects, 120 were H. pylori+ and 96 were H. pylori-; 40 patients of indeterminate status were excluded. Serum and fundic leptin levels correlated with body mass index in the H. pylori+ (r = 0.35; P < 0.0001 and r = 0.35; P < 0.0001, respectively) and H. pylori- (r = 0.65; P < 0.0001 and r = 0.41; P < 0.0001, respectively) groups, but H. pylori+ subjects had significantly lower serum leptin levels [median 2.2 ng/ml (interquartile range 0.9-4.6) vs. 4.0 ng/ml (1.7-7.2); P = 0.0003]. Serum ghrelin levels were similar in the H. pylori+ and H. pylori- groups [median 1651 pg/ml (interquartile range 845-2247) vs. 1629 pg/ml (992-2886); P = 0.23]. H. pylori status did not significantly affect gastric biopsy leptin and ghrelin levels. Ghrelin levels in gastric juice varied over 4 log(10) (<80-776,000 pg/ml) and correlated with gastric juice pH in the H. pylori+ group (r = 0.68; P < 0.0001). CONCLUSIONS: These findings provide evidence that H. pylori status affects leptin and ghrelin homeostasis, presumably via intragastric interactions.
  58. Shak, Joshua R; Roper, Jatin; Perez-Perez, Guillermo I; Tseng, Chi-hong; Francois, Fritz; Gamagaris, Zoi; Patterson, Carlie; Weinshel, Elizabeth; Fielding, George A; Ren, Christine; Blaser, Martin J. "The Effect of Laparoscopic Gastric Banding Surgery on Plasma Levels of Appetite-Control, Insulinotropic, and Digestive Hormones". Obesity surgery. 2008 Sep;18(9):1089-1096 (MEDL:18408980 #78623)       

    BACKGROUND: We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB. METHODS: Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays. RESULTS: Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p < 0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p < 0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p > 0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months. CONCLUSIONS: LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term
  59. Sierra, Rafaela; Une, Clas; Ramirez, Vanessa; Alpizar-Alpizar, Warner; Gonzalez, Maria-I; Ramirez, Jose-A; De Mascarel, Antoine; Cuenca, Patricia; Perez-Perez, Guillermo; Megraud, Francis. "Relation of atrophic gastritis with Helicobacter pylori-CagA(+) and interleukin-1 gene polymorphisms". World journal of gastroenterology : WJG. 2008 Nov 14;14(42):6481-6487 (MEDL:19030199 #102590)       

    AIM: To determine the association of Helicobacter pylori (H pylori) CagA(+) infection and pro-inflammatory polymorphisms of the genes interleukin (IL)-1RN and IL-1B with the risk of gastric atrophy and peptic ulcers in a dyspeptic population in Costa Rica, a country with high incidence and mortality of gastric cancer. METHODS: Seven biopsy specimens, a fasting blood sample and a questionnaire concerning nutritional and sociodemographic factors were obtained from 501 consecutive patients who had undergone endoscopy for dyspeptic symptoms. A histopathological diagnosis was made. Pepsinogen concentrations were analyzed by enzyme linked immunosorbent assay (ELISA). Infection with H pylori CagA(+) was determined by serology and polymerase chain reaction (PCR). IL-1B and IL-1RN polymorphisms genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP) and PCR respectively. RESULTS: In this dyspeptic population, 86% were H pylori positive and of these, 67.8% were positive for CagA. Atrophic antral gastritis (AAG) was associated with CagA(+) status [odd ratio (OR) = 4.1; P < 0.000] and fruit consumption (OR = 0.3; P < 0.00). Atrophic body gastritis (ABG) was associated with pepsinogen PGI/PGII < 3.4 (OR = 4.9; P < 0.04) and alcohol consumption (OR = 7.3; P < 0.02). Duodenal ulcer was associated with CagA(+) (OR = 2.9; P < 0.04) and smoking (OR = 2.4; P < 0.04). PGI < 60 microg/L as well as PGI/PGII < 3.4 were associated with CagA(+). CONCLUSION: In a dyspeptic population in Costa Rica, H pylori CagA(+) is not associated with ABG, but it is a risk factor for AAG. The pro-inflammatory cytokine polymorphisms IL-1B + 3945 and IL-1RN are not associated with the atrophic lesions of this dyspeptic population
  60. Yilmaz, O; Demiray, E; Soyturk, M; Perez, GIP; Sagol, O; Bekmen, N; Simsek, I; Akpinar, H. "Evaluation of serum pepsinogen I and II levels, gastrin-17 and H. pylori antibodies in patients with dyspepsia [Meeting Abstract]". Helicobacter. 2008 OCT;13(5):454-454 (ISI:000258404600183 #86819)    
  61. Yilmaz, O; Demiray, E; Soyturk, M; Perez, GIP; Sarioglu, S; Bekmen, N; Simsek, I; Akpinar, H. "The effect of H. pylori eradication on serum pepsinogen I and II levels, gastrin-17, and H. pylori antibodies in patients with dyspepsia [Meeting Abstract]". Helicobacter. 2008 OCT;13(5):453-454 (ISI:000258404600181 #86818)    
  62. Blaser, Martin J; Nomura, Abraham; Lee, James; Stemmerman, Grant N; Perez-Perez, Guillermo I. "Early-life family structure and microbially induced cancer risk". PLoS medicine. 2007 Jan;4(1):e7-e7 (MEDL:17227131 #79193)       

    BACKGROUND: Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men. METHODS AND FINDINGS: We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative), belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0) among those in a sibship of seven or more individuals than in a sibship of between one and three persons. CONCLUSIONS: These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions
  63. Demiray, E; Tumer, S; Perez, GIP; Olivares, AZ; Sagol, O; Altungoz, O; Soyturk, M; Yilmaz, O. "A new approach in the determination of clarithromycin resistance in Helicobacter pylori infection [Meeting Abstract]". Helicobacter. 2007 AUG;12(4):389-389 (ISI:000249017800044 #74188)    
  64. Garza-Gonzalez, E; Mendoza-Ibarra, SI; Bosques, F; Perez-Perez, GI. "G796A nucleotide-binding oligomerization domain (NOD) 1 and C-590T interleukin-4 polymorphisms in Helicobacter pylori related diseases [Meeting Abstract]". Zoonoses & public health. 2007 JAN;54(1):151-151 (ISI:000250519200513 #87171)    
  65. Garza-Gonzalez, Elvira; Bosques-Padilla, Francisco J; Mendoza-Ibarra, Sandra I; Flores-Gutierrez, Juan P; Maldonado-Garza, Hector J; Perez-Perez, Guillermo I. "Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer". BMC cancer. 2007;7:70-70 (MEDL:17462092 #73822)       

    BACKGROUND: The intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC). The host response to H. pylori has been related to genetic polymorphisms that influence both innate and adaptive immune responses.Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399Ile and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population. METHODS: We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399Ile by PCR-RFLP and for IL8-251 by the amplification refractory mutation system (ARMS)-PCR. RESULTS: The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square H-W = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399Ile). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for TLR4- Asp299Gly [the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82)] and for TLR4 Thr399Ile [the 1.3% of GC patients and the 5% of the control population (p = 0.2)]. In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1-4.2) (p = 0.023). CONCLUSION: This study showed that the IL8-251*A allele could be related to the development of distal gastric cancer in this Mexican population
  66. Ghose, Chandrabali; Perez-Perez, Guillermo I; Torres, Victor J; Crosatti, Marialuisa; Nomura, Abraham; Peek, Richard M Jr; Cover, Timothy L; Francois, Fritz; Blaser, Martin J. "Serological Assays for Identification of Human Gastric Colonization by Helicobacter pylori Strains Expressing VacA m1 or m2". Clinical & vaccine immunology. 2007 Apr;14(4):442-450 (MEDL:17267587 #71774)       

    The Helicobacter pylori vacA gene encodes a secreted protein (VacA) that alters the function of gastric epithelial cells and T lymphocytes. H. pylori strains containing particular vacA alleles are associated with differential risk of disease. Because the VacA midregion may exist as one of two major types, m1 or m2, serologic responses may potentially be used to differentiate between patients colonized with vacA m1- or vacA m2-positive H. pylori strains. In this study, we examined the utility of specific antigens from the m regions of VacA as allele-specific diagnostic antigens. We report that serological responses to P44M1, an H. pylori m1-specific antigen, are observed predominantly in patients colonized with m1-positive strains, whereas responses to VacA m2 antigens, P48M2 and P55M2, are observed in patients colonized with either m1- or m2-positive strains. In an Asian-American population, serologic responses to VacA m region-specific antigens were not able to predict the risk of development of gastric cancer
  67. Kamangar, F; Qiao, Y-L; Blaser, M J; Sun, X-D; Katki, H; Fan, J-H; Perez-Perez, G I; Abnet, C C; Zhao, P; Mark, S D; Taylor, P R; Dawsey, S M. "Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China". British journal of cancer. 2007 Jan;96(1):172-176 (MEDL:17179990 #416872)       

    In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15-2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies.
  68. Mendoza-Ibarra, Sandra Iveth; Perez-Perez, Guillermo Ignacio; Bosques-Padilla, Francisco Javier; Urquidi-Rivera, Martha; Rodriguez-Esquivel, Zulma; Garza-Gonzalez, Elvira. "Utility of diagnostic tests for detection of Helicobacter pylori in children in northeastern Mexico". Pediatrics International. 2007 Dec;49(6):869-874 (MEDL:18045288 #79189)       

    BACKGROUND: The presence of Helicobacter pylori in pediatric population has been associated with recurrent abdominal pain (RAP), although this association is unclear. One of the major problems in studying the role of H. pylori in RAP is that methods used to detect the bacteria in children have poor sensitivity and specificity. The aims of the present study were to determine the prevalence of H. pylori in pediatric patients with RAP in northeastern Mexico and to assess the diagnostic utility of invasive tests and serology in this population. METHODS: A total of 40 patients (mean age, 7.9 years; range 2-16 years; F: M, 0.81), who underwent an endoscopy procedure for RAP, were studied. The presence of H. pylori was assessed using invasive diagnostic tests (culture, rapid urease test, polymerase chain reaction and histology) and one non-invasive test: determination of IgG antibodies. The prevalence of H. pylori in the present group and the diagnostic utility for each test were evaluated. RESULTS: The prevalence of H. pylori in the present pediatric group with RAP was 12.5-42.5% depending on the criteria of positivity used. The non-invasive methods (serology) had acceptable values in sensitivity and specificity in comparison with invasive tests. CONCLUSIONS: This is the first report on prevalence of H. pylori in pediatric patients with RAP from the northeastern region of Mexico. The prevalence of H. pylori was low compared with the adult population in the same geographic region. Serology had the best diagnostic utility
  69. Perez Perez, GI; Torres, E; Raisler, K; Olivares, AZ; Reynolds, SP; Gonzalez, N; Fernandez, L; Cohen, H. "Analysis of genetic diversity associated with ethnicity in Helicobacter pylori strains isolated in Montevideo, Uruguay [Meeting Abstract]". Zoonoses & public health. 2007 JAN;54(1):112-112 (ISI:000250519200379 #87170)    
  70. Perez, GIP; Olivares, AZ; Yilmaz, O. "Isolation and characterisation of Helicobacter pylori in dyspeptic patients for Izmir, Turkey [Meeting Abstract]". Zoonoses & public health. 2007 JAN;54(1):111-111 (ISI:000250519200378 #87169)    
  71. Perez-Perez, Guillermo Ignacio; Portal-Celhay, Cynthia; Bosques-Padilla, Francisco Javier; Garza-Gonzalez, Elvira. "[Development of a protocol of pyrosequencing for determination of the polymorphism at position -31 of the interleukin-1beta gene in the study of risk of development of stomach cancer]". Revista de gastroenterologia de Mexico. 2007 Jan-Mar;72(1):10-14 (MEDL:17685194 #73954)    

    BACKGROUND: Single nucleotide polymorphism association studies among cases and controls have been widely used for genetic analysis. The pyrosequencing method is based on indirect luminometric quantification of the pyrophosphate that is released as a result of nucleotide incorporation onto an amplified template. It has the advantages of accuracy, flexibility, automatization and speed when compared with PCR-RFLP method. AIM: To develop a protocol for allele frequency determination using pyrosequencing technology in the detection of the polymorphism at position -31 of the interleukin-1beta (IL-1beta) gene. METHODS: 162 patients (F/M = 0.93) who were enrolled at the Hospital Universitario Dr 'Jose Eleuterio Gonzalez' were studied. 123 patients had non-ulcer dyspepsia and 39 had histologically confirmed gastric cancer (GC). The polymorphism of IL-1beta -31 was determined by both RFLP and pyrosequencing methods. PCR-RFLP method used Alul restriction endonuclease. The same specific primers for PCR-RFLP and pyrosequencing were used for initial amplification and an additional biotinylated specific primer was designed for sequencing. RESULTS: 157 (96.9%) samples were clearly typed by the pyrosequencing method and the results were in accordance with the results of the PCR-RFLP method. The results of 5 samples (3.1%) were not in accordance between both methods. Two of them were T/T and 2 were C/T by sequencing method and all four were C/C by RFLP. Another sample was C/ C by sequencing and T/T by RFLP. CONCLUSION: The pyrosequencing method is not only suitable for the IL-1beta -31 genotyping but is a fast and unexpensive way of genotyping since requires smaller amounts of DNA, and required significantly less time in the generation of results than the RFLP technique. The protocol developed is useful for the typing of the IL-1beta -31 polymorphism
  72. Tsukanov, VV; Butorin, NN; Maady, AS; Barkalov, SV; Amelchugova, OS; Perez-Perez, GI. "Correlation between gastric cancer markers and prevalence of Helicobacter pylori CagA in different populations of eastern Siberia [Meeting Abstract]". Helicobacter. 2007 AUG;12(4):453-453 (ISI:000249017800223 #74189)    
  73. Young, B; Roper, H; Mourad, M; Olivares de Perez, AZ; Perez-Perez, GI; Pei, ZH; Blaser, MJ; Francois, F. "Fasting gastric leptin levels are elevated in diabetics independent of BMI [Meeting Abstract]". American journal of gastroenterology. 2007 SEP;102(6):S163-S163 (ISI:000249397800125 #74153)    
  74. Bik, Elisabeth M; Eckburg, Paul B; Gill, Steven R; Nelson, Karen E; Purdom, Elizabeth A; Francois, Fritz; Perez-Perez, Guillermo; Blaser, Martin J; Relman, David A. "Molecular analysis of the bacterial microbiota in the human stomach". Proceedings of the National Academy of Sciences of the United States of America. 2006 Jan 17;103(3):732-737 (MEDL:16407106 #62128)       

    The microbiota of the human stomach and the influence of Helicobacter pylori colonization on its composition remain largely unknown. We characterized bacterial diversity within the human gastric mucosa by using a small subunit 16S rDNA clone library approach and analyzed 1,833 sequences generated by broad-range bacterial PCR from 23 gastric endoscopic biopsy samples. A diverse community of 128 phylotypes was identified, featuring diversity at this site greater than previously described. The majority of sequences were assigned to the Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria phyla. Ten percent of the phylotypes were previously uncharacterized, including a Deinococcus-related organism, relatives of which have been found in extreme environments but not reported before in humans. The gastric clone libraries from 19 subjects contained H. pylori rDNA; however, only 12 of these subjects tested positive for H. pylori by conventional laboratory methods. Statistical analysis revealed a large degree of intersubject variability of the gastric ecosystem. The presence of H. pylori did not affect the composition of the gastric community. This gastric bacterial rDNA data set was significantly different from sequence collections of the human mouth and esophagus described in other studies, indicating that the human stomach may be home to a distinct microbial eco-system. The gastric microbiota may play important, as-yet-undiscovered roles in human health and disease
  75. Cho, Alex; Chaudhry, Amina; Minsky-Primus, Lisa; Tso, Alan; Perez-Perez, Guillermo; Diehl, David L; Marcus, Stuart G; Gany, Francesca M. "Follow-up care after a diagnosis of Helicobacter pylori infection in an Asian immigrant cohort". Journal of clinical gastroenterology. 2006 Jan;40(1):29-32 (MEDL:16340630 #61482)       

    GOAL: To study the rate at which Helicobacter pylori infection is treated in an immigrant cohort after diagnosis by esophagogastroduodenoscopy (EGD). BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide, and is especially prevalent in East Asia; immigrants from this part of the world remain at higher risk. Infection with H. pylori is a known risk factor for gastric cancer. There have been no studies of completion of H. pylori treatment in immigrant populations. STUDY: Prospective cohort study of East Asian immigrants diagnosed with H. pylori infection who underwent EGD in a gastric cancer screening protocol. Our primary outcome was self-report or chart evidence of completion of treatment of H. pylori. RESULTS: Sixty-eight of the 126 participants (54%) tested positive for H. pylori infection on EGD. Forty-nine (72%) were seen for a follow-up visit at one of the clinics involved in the study. According to clinic records, 39 of these 49 participants (57% of all H. pylori-positive participants) were prescribed treatment. Only 31 participants (46%) completed treatment. Of possible explanatory factors, only having a 'regular doctor' was significantly associated with treatment completion (odds ratio=5.6; 95% confidence interval, 1.2-25.0). CONCLUSIONS: In a sample of Asian immigrants, the rate of treatment of H. pylori infection, a potentially modifiable risk factor, was lower than expected. Having a 'regular doctor' appeared to increase the likelihood of receiving appropriate follow-up care
  76. Cho, Alex; Chaudhry, Amina; Minsky-Primus, Lisa; Tso, Alan; Perez-Perez, Guillermo; Diehl, David; Marcus, Stuart G; Gany, Francesca M. "Acceptance of repeat esophagogastroduodenoscopy to detect gastric cancer in a chinese immigrant cohort". Journal of clinical gastroenterology. 2006 Aug;40(7):606-611 (MEDL:16917402 #68529)       

    GOAL: To study the feasibility of using repeat esophagogastroduodenoscopy (EGD) to screen for Helicobacter pylori infection and gastric cancer in an Asian immigrant cohort. BACKGROUND: Immigrants in the United States (US) from countries with high per capita rates of gastric cancer remain at higher risk for gastric cancer. The existence of the possibly modifiable risk factor of H. pylori infection and the poor outcomes associated with late-stage disease make screening higher-risk groups with EGD an appealing possibility. It is unknown whether Asian immigrants in the US would accept an EGD-based strategy for gastric cancer screening. STUDY: Cross-sectional study of adult Chinese immigrants in New York City with dyspepsia who underwent EGD in an earlier gastric cancer detection study, who were offered a second EGD four years later. Our main outcome measure was acceptance or refusal of repeat EGD. RESULTS: Seventy-three of the 115 Chinese participants in the earlier study were successfully contacted for this current study. Twenty-three of 73 (32%) underwent repeat EGD. Leading reasons given for declining were lack of symptoms and lack of time. Significantly associated with acceptance of repeat EGD was the belief that EGD will find stomach cancer 'nearly always' in someone who has it (P=0.0054; odds ratio=14.0, 2.1 to 94.2 95% confidence interval). CONCLUSIONS: Acceptance of repeat EGD for gastric cancer detection in a cohort of Chinese immigrants was relatively low despite the mitigation of cost and language factors, 2 major barriers to healthcare access. Relocation seemed to be a factor as well. In this population, perceptions of the benefits of EGD may influence acceptance of testing for cancer detection purposes
  77. Goldman, Cinthia; Barrado, Andres; Janjetic, Mariana; Balcarce, Norma; Cueto Rua, Eduardo; Oshiro, Masaru; Calcagno, Maria L; Sarrasague, Margarita-Martinez; Fuda, Julian; Weill, Ricardo; Zubillaga, Marcela; Perez-Perez, Guillermo I; Boccio, Jose. "Factors associated with H. pylori epidemiology in symptomatic children in Buenos Aires, Argentina". World journal of gastroenterology : WJG. 2006 Sep 7;12(33):5384-5388 (MEDL:16981273 #79195)    

    AIM: To determine prevalence of H pylori infection in symptomatic children in Buenos Aires, Argentina, and to investigate factors associated with H pylori positivity. METHODS: A total of 395 children with upper gastrointestinal symptoms referred to the Gastroenterology Unit of the Children Hospital 'Sor Maria Ludovica' were evaluated for the presence of H pylori by the (13)C-Urea Breath Test ((13)C-UBT). A questionnaire was applied to the recruited population. RESULTS: Prevalence of H pylori infection was 40.0% in this population (mean age 9.97 +/- 3.1 years). The factors associated with H pylori positivity were number of siblings (P < 0.001), presence of pet cats (P = 0.03) and birds (P = 0.04) in the household, and antecedents of gastritis among family members (P = 0.01). After multivariate analysis, number of siblings [Odds ratio (OR) = 1.39; 95% CI, 1.20-1.61] and contact with pet cats (OR = 1.76; 95% CI, 1.00-3.09) remained as variables associated with H pylori infection. CONCLUSION: The prevalence of H pylori infection in children with upper gastrointestinal symptoms in Argentina was similar to that reported in developed countries. Children from families with a higher crowding index and presence of pet cats have a higher risk of being colonized with H pylori
  78. Gorthi, S P; Kapoor, Lata; Chaudhry, Rama; Sharma, Nidhi; Perez-Perez, Guillermo I; Panigrahi, Pinaki; Behari, Madhuri. "Guillain-Barre syndrome: association with Campylobacter jejuni and Mycoplasma pneumoniae infections in India". National medical journal of India. 2006 May-Jun;19(3):137-139 (MEDL:16836263 #79196)    

    BACKGROUND: Guillain-Barre syndrome is the most common cause of acute neuromuscular paralysis and is considered a post-infectious disease. METHODS: Twenty patients with Guillain-Barre syndrome admitted to the Neurosciences Centre at the All India Institute of Medical Sciences from November 1997 to August 1998 were investigated for evidence of antecedent infections. This case-control study included 2 controls for each patient, one a household control and the other an age- and sex-matched hospital control suffering from a neurological illness other than Guillain-Barre syndrome. Evidence of recent Campylobacter jejuni infection was investigated by culture and serology, and for Mycoplasma pneumoniae by serology. RESULTS: There was evidence of recent C. jejuni infection in 35% of the patients compared with 25% of household controls and none of the hospital controls. M. pneumoniae infection was seen in 50% of patients compared with 25% of household controls and 15% of hospital controls. About one-third of the patients (30%) had evidence of both infections. The association of both infections in patients was found to be statistically significant as compared to hospital controls. CONCLUSION: C. jejuni and M. pneumoniae may be important antecedent illnesses in patients with Guillain-Barre syndrome in India
  79. Kamangar, Farin; Dawsey, Sanford M; Blaser, Martin J; Perez-Perez, Guillermo I; Pietinen, Pirjo; Newschaffer, Craig J; Abnet, Christian C; Albanes, Demetrius; Virtamo, Jarmo; Taylor, Philip R. "Opposing risks of gastric cardia and noncardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity". Journal of the National Cancer Institute. 2006 Oct 18;98(20):1445-1452 (MEDL:17047193 #79194)       

    BACKGROUND: Colonization with Helicobacter pylori is a risk factor for gastric adenocarcinoma, but the magnitude of this association and its relationship to anatomic location of the cancer, duration of follow-up, age at diagnosis, histologic subtype, and H. pylori strain differences are less clear. We conducted a prospective nested case-control study of H. pylori serology to address these questions. METHODS: Case and control subjects were selected from the 29,133 50- to 69-year-old males recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. At baseline, detailed demographic data and a serum sample were collected. From 1985 to 1999, 243 incident cases of gastric adenocarcinoma were diagnosed in cohort members. Serum samples from 234 case subjects (173 with noncardia gastric cancers and 61 with gastric cardia cancers) and 234 age-matched control subjects were assayed for antibodies against H. pylori whole-cell and CagA antigens. We fit conditional logistic regression models to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of H. pylori seropositivity, defined as seropositivity to either whole-cell or CagA antigens, with noncardia gastric and gastric cardia cancers. All statistical tests were two-sided. RESULTS: H. pylori seropositivity was strongly associated with the risk of noncardia gastric cancer (adjusted OR = 7.9, 95% CI = 3.0 to 20.9) but was inversely associated with the risk of gastric cardia cancer (adjusted OR = 0.31, 95% CI = 0.11 to 0.89). H. pylori seropositivity rates did not vary statistically significantly by length of follow-up, age at diagnosis, or histologic subtype. A calculation of rates showed that the absolute risks of noncardia gastric and cardia gastric adenocarcinomas in the H. pylori-positive participants of this cohort would be 63 and 12 per 100,000 person-years, respectively, whereas corresponding rates in H. pylori-negative participants would be 8 and 37 per 100,000 person-years, respectively. CONCLUSION: H. pylori is a strong risk factor for noncardia gastric cancer but is inversely associated with the risk of gastric cardia cancer. These findings bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries
  80. Marcano-Lozada, MJ; Urrestarazu, MI; Serrano, NM; Perez-Perez, GI. "Association of Helicobacter pylori and chronic idiopathic urticaria [Meeting Abstract]". Helicobacter. 2006 AUG;11(4):369-369 (ISI:000239005100152 #68674)    
  81. Moreno-Gutierrez, FJ; Garza-Gonzalez, E; Bosques-Padilla, FJ; Perez-Perez, GI. "In vivo and in vitro expression of the TLR-4 and TLR-5 receptors during Helicobacter pylori infection [Meeting Abstract]". Helicobacter. 2006 AUG;11(4):349-349 (ISI:000239005100096 #68673)    
  82. Olivares, Asalia; Buadze, Merab; Kutubidze, Tina; Lobjanidze, Manana; Labauri, Levani; Kutubidze, Ramaz; Chikviladze, Daredjan; Zhvania, Manana; Kharzeishvili, Omar; Lomidze, Nodar; Perez-Perez, Guillermo I. "Prevalence of Helicobacter pylori in Georgian patients with dyspepsia". Helicobacter. 2006 Apr;11(2):81-85 (MEDL:16579837 #64075)       

    BACKGROUND: Georgia has showed a high prevalence of peptic ulcer disease (PUD), but the prevalence of Helicobacter pylori in this country is practically unknown. The purpose of this study was to determine the prevalence of H. pylori and specific genotypes in different populations in Georgia. MATERIALS AND METHODS: We studied 62 patients from several hospitals in Tbilisi, Georgia. More than 55% of patients had PUD. We determined H. pylori presence as well as specific genotypes cagA and vacA by polymerase chain reaction. In addition, we studied serum samples from 94 healthy persons to determine H. pylori and CagA prevalence by ELISA. RESULTS: We found a high prevalence of H. pylori and CagA in the healthy population (70.2 and 57.4%, respectively) and a high prevalence of CagA among the H. pylori-positive persons (71.2%). Prevalence increased with age as reported in other countries (p = .05). Among symptomatic persons, we found nearly the same high prevalence of H. pylori (64.5%) as in the asymptomatic population. Furthermore, in symptomatic H. pylori patients, we found 65.0 and 67.5% prevalence of cagA and vacA, respectively. For 33 patients with PUD, 24 patients (72.7%) were H. pylori positive and 66.7% of them were cagA positive. In contrast, among the patients with non-ulcer dyspepsia (NUD), 16 (55.2%) were H. pylori positive and 62.5% of them were colonized with cagA-positive strains. H. pylori and cagA prevalence were not significantly different between PUD and patients with NUD. CONCLUSIONS: We confirmed that among individuals in Georgia, the prevalence of H. pylori is high and cagA-positive strains were equally present among H. pylori-positive patients with PUD and NUD and asymptomatic persons
  83. Perez-Perez, GI; Andersson, M; Olivares, AZ; Gonzalez, EG; Padilla, FB; Torres, J; Blaser, MJ. "Specific geographic genotypes among Helicobacter pylori strains [Meeting Abstract]". Helicobacter. 2006 AUG;11(4):342-342 (ISI:000239005100075 #68671)    
  84. Perez-Perez, GI; Chao, L; Minhong, C; Andersson, M; Olivares, AZ. "Differences in the 3 ' cagA region between Helicobacter pylori strains of East Asian and African origin [Meeting Abstract]". Helicobacter. 2006 AUG;11(4):343-344 (ISI:000239005100080 #68672)    
  85. Perez-Perez, GI; Wong, C; Olivares, AZ; Gonzalez, EG; Padilla, FB; Blaser, MJ. "Stability and variability of cagA and its correlation with disease outcome [Meeting Abstract]". Helicobacter. 2006 AUG;11(4):333-333 (ISI:000239005100052 #68670)    
  86. Perry, Sharon; de la Luz Sanchez, Maria; Yang, Shufang; Haggerty, Thomas D; Hurst, Philip; Perez-Perez, Guillermo; Parsonnet, Julie. "Gastroenteritis and transmission of Helicobacter pylori infection in households". Emerging infectious diseases. 2006 Nov;12(11):1701-1708 (MEDL:17283620 #79192)    

    The mode of transmission of Helicobacter pylori infection is poorly characterized. In northern California, 2,752 household members were tested for H. pylori infection in serum or stool at a baseline visit and 3 months later. Among 1,752 person considered uninfected at baseline, 30 new infections (7 definite, 7 probable, and 16 possible) occurred, for an annual incidence of 7% overall and 21% in children <2 years of age. Exposure to an infected household member with gastroenteritis was associated with a 4.8-fold (95% confidence interval [CI] 1.4-17.1) increased risk for definite or probable new infection, with vomiting a greater risk factor (adjusted odds ratio [AOR] 6.3, CI 1.6-24.5) than diarrhea only (AOR 3.0, p = 0.65). Of probable or definite new infections, 75% were attributable to exposure to an infected person with gastroenteritis. Exposure to an H. pylori-infected person with gastroenteritis, particularly vomiting, markedly increased risk for new infection
  87. Portal-Celhay, Cynthia; Perez-Perez, Guillermo I. "Immune responses to Helicobacter pylori colonization: mechanisms and clinical outcomes". Clinical science (London, 1979). 2006 Mar;110(3):305-314 (MEDL:16464172 #64076)       

    Helicobacter pylori colonizes the stomachs of half of the world's population and usually persists in the gastric mucosa of human hosts for decades or life. Although most H. pylori-positive people are asymptomatic, the presence of H. pylori is associated with increased risk for the development of peptic ulcer disease, gastric adenocarcinoma and gastric lymphoma. The development of a sustained gastric inflammatory and immune response to infection appears to be pivotal for the development of disease. During its long co-existence with humans, H. pylori has evolved complex strategies to maintain a mild inflammation of the gastric epithelium while limiting the extent of immune effector activity. In this review, the nature of the host immune response to H. pylori infection and the mechanism employed by the bacterium to evade them is considered. Understanding the mechanisms of colonization, persistence and virulence factors of the bacterium as well as the innate and adaptive immune responses of the host are critically important for the development of new strategies to prevent the development of H. pylori-induced gastroduodenal disease
  88. Vidal, T; Gutierrez, B; Valmana, CE; Ochoa, R; Megraud, F; Perez-Perez, GI; Paniagua, M; Mendz, GL. "Helicobacter pylori infection diagnosis in gastroduodenal disease in La Habana, Cuba [Meeting Abstract]". Helicobacter. 2006 AUG;11(4):384-385 (ISI:000239005100196 #68675)    
  89. Zuniga-Noriega, Jaime Raul; Bosques-Padilla, Francisco Javier; Perez-Perez, Guillermo Ignacio; Tijerina-Menchaca, Rolando; Flores-Gutierrez, Juan Pablo; Maldonado Garza, Hector Jesus; Garza-Gonzalez, Elvira. "Diagnostic utility of invasive tests and serology for the diagnosis of Helicobacter pylori infection in different clinical presentations". Archives of medical research (Mexico). 2006 Jan;37(1):123-128 (MEDL:16314197 #64078)       

    BACKGROUND: Invasive and noninvasive tests are used for the diagnosis of Helicobacter pylori infection. The aim of this study was to determine the diagnostic utility of rapid urease test (RUT), culture, histology and serology for the diagnosis of H. pylori in patients with different clinical presentations. METHODS: We studied 527 consecutive patients (mean age, 52.5 years; F:M, 1.3; age range 15-89 years) enrolled at the Hospital Universitario, Universidad Autonoma de Nuevo Leon. Patients had gastric cancer (GC, 9.1%), non-ulcer dyspepsia (NUD, 81.4%), or peptic ulcer disease (PUD, 9.1%). The infection by H. pylori was determined by histology, rapid urease test, culture, and serology. Patients were determined as infected with H. pylori if at least a) two invasive tests were positive and b) two tests were positive (invasive or non-invasive). Diagnostic utility was calculated for each assay. RESULTS: Prevalence of infection in the whole studied population was 50.9%. In NUD patients the prevalence was 51.3%, in PUD patients 58.3%, and in GC patients 39.6%. When we used the first diagnostic criteria, for the whole studied population, the RUT was the most reliable test, followed by the culture. Histology had the best sensitivity for the whole studied population and NUD patients and RUT had the best sensitivity value for the GC patients. In the whole studied population, NUD and GC patients, RUT and culture had the best specificity, accuracy and PPV. For PUD patients, serology had the best performance. When we used the second diagnostic criteria, histology and serology had a better performance compared with the results obtained with the first diagnostic criteria. CONCLUSIONS: Diagnostic utility of the tests varies according to the clinical presentations, which should be considered in the selection of the diagnostic test for the detection of H. pylori
  90. Alpizar-Alpizar, W; Perez-Perez, G I; Une, C; Cuenca, P; Sierra, R. "Association of interleukin-1B and interleukin-1RN polymorphisms with gastric cancer in a high-risk population of Costa Rica". Clinical & experimental medicine. 2005 Dec;5(4):169-176 (MEDL:16362796 #64077)       

    Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1beta (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/- had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34-10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09-7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed
  91. Alpizar-Alpizar, Warner; Sierra, Rafaela; Cuenca, Patricia; Une, Clas; Mena, Fernando; Perez-Perez, Guillenno Ignacio. "[Association of the p53 codon 72 polymorphism to gastric cancer risk in a hight risk population of Costa Rica]". Revista de biologia tropical. 2005 Sep-Dec;53(3-4):317-324 (MEDL:17354442 #416932)    

    Gastric cancer is the second most common cancer associated death cause worldwide. Several factors have been associated with higher risk to develop gastric cancer, among them genetic predisposition. The p53 gene has a polymorphism located at codon 72. which has been associated with higher risk of several types of cancer, including gastric cancer. The aim of this study was to determine the association of p53, codon 72 polymorphism. with the risk of gastric cancer and pre-malignant lesions in a high-risk population from Costa Rica. The genotyping was carried out by PCR-RFLP in 58 gastric cancer patients, 99 controls and 41 individuals classified as group I or II. according to the Japanese histological classification. No association was found for p53. codon 72 polymorphism with neither the risk of gastric cancer nor the risk of less severe gastric lesions in the studied population. Based on this study and taking into account other studies carried out with p53, codon 72 polymorphism. the role of this polymorphismn in the development of gastric cancer remains unclear. De novo mutations on p53 gene produced during neoplasic development of this disease might play a greater role than germinal polymorphisms of the gene. Other polymorphic genes have been associated with higher risk to develop gastric cancer.
  92. Bhat, Niranjan; Gaensbauer, James; Peek, Richard M; Bloch, Karen; Tham, Kyi-Toe; Blaser, Martin J; Perez-Perez, Guillermo. "Local and systemic immune and inflammatory responses to Helicobacter pylori strains". Clinical & diagnostic laboratory immunology. 2005 Dec;12(12):1393-1400 (MEDL:16339062 #79197)       

    Colonization with Helicobacter pylori eventuates in varied clinical outcomes, which relate to both bacterial and host factors. Here we examine the relationships between cagA status, serum and gastric juice antibody responses, and gastric inflammation in dyspeptic patients. Serum, gastric juice, and gastric biopsy specimens were obtained from 89 patients undergoing endoscopy. H. pylori colonization and cagA status were determined by histology, culture, and PCR methods, and acute inflammation and chronic inflammation in the gastric mucosa were scored by a single pathologist. Serum and gastric juice antibodies to H. pylori whole-cell and CagA antigens were determined by enzyme-linked immunosorbent assay. Relationships between variables were sequentially analyzed using univariate and multivariate statistical methods. Of the 89 subjects, 62 were colonized by H. pylori. By univariate analyses, levels of serum immunoglobulin G (IgG) and IgA and gastric juice IgA antibodies against whole-cell and CagA antigens each were significantly higher in the H. pylori-positive group than in the H. pylori-negative group (P<0.001). H. pylori and CagA sero-positivities were both significantly associated with enhanced inflammation in gastric antrum and body (P<0.02). The presence of gastric juice antibodies to H. pylori antigens was associated with more severe gastric inflammation. However, in multivariate analyses, only the presence of serum antibodies against CagA and, to a lesser extent, whole-cell antigens remained significantly associated with acute and chronic inflammation in antrum and body (P<0.05). Thus, serum antibody response to CagA correlates with severity of gastric inflammation. Furthermore, given the relationships demonstrated by multivariate analysis, determination of gastric juice antibodies may provide a better representation of serum, rather than secretory, immune response
  93. Cooperberg BA; Bini EJ; Cohen H; Olivares AZ; Dacoll C; Perez-Perez GI. "Preliminary report of the prevalence of Helicobacter pylori and distribution of vacA genotypes in Montevideo, Uruguay". Revista Brasileira de Medicina. 2005;62(7):290-294 (EMBASE:2005399673 #57965)    

    Background: Little is known about the prevalence of Helicobacter pylori and the presence of specific genotypes in Uruguay. Aims: To determine the prevalence of H. pylori in symptomatic individuals in Uruguay, to assess the prevalence of bacterial genotypes, and evaluate the association between specific genotypes and endoscopic findings. Patients: 32 patients presenting to the Hospital de Clinicas in Montevideo for upper endoscopy were enrolled. Methods: H. pylori status was determined by rapid urease test and by culture of gastric biopsy specimens from the antrum and body. H. pylori vacA genotypes were determined by PCR. Results: The prevalence of H. pylori was 66% based on culture and rapid urease test. Analysis of the vacA gene by PCR, we found a high proportion of multiple infections (42.9%). The s1a allele was found in 47.6% of patients and s1b was found in 33.3%. We could not demonstrate a significant association between infection with H. pylori, nor specific bacterial genotypes, and endoscopic findings. Conclusions: The prevalence of H. pylori in symptomatic patients in Montevideo is lower than typically found in developing countries probably as result of the low sensitivity of the two invasive tests used. The vacA genotypes of H. pylori found in Uruguay differs from the rest of Latin America with 47.6% bearing the s1a vacA allele. These results confirmed that European descendents different from Spain and Portugal are important part of the Uruguayan population. copyright Copyright Moreira Jr. Editora. Todos os direitos reservados
  94. Franco, Aime T; Israel, Dawn A; Washington, Mary K; Krishna, Uma; Fox, James G; Rogers, Arlin B; Neish, Andrew S; Collier-Hyams, Lauren; Perez-Perez, Guillermo I; Hatakeyama, Masanori; Whitehead, Robert; Gaus, Kristin; O'Brien, Daniel P; Romero-Gallo, Judith; Peek, Richard M Jr. "Activation of beta-catenin by carcinogenic Helicobacter pylori". Proceedings of the National Academy of Sciences of the United States of America. 2005 Jul 26;102(30):10646-10651 (MEDL:16027366 #64079)       

    Persistent gastritis induced by Helicobacter pylori is the strongest known risk factor for adenocarcinoma of the distal stomach, yet only a fraction of colonized persons ever develop gastric cancer. The H. pylori cytotoxin-associated gene (cag) pathogenicity island encodes a type IV secretion system that delivers the bacterial effector CagA into host cells after bacterial attachment, and cag+ strains augment gastric cancer risk. A host effector that is aberrantly activated in gastric cancer precursor lesions is beta-catenin, and activation of beta-catenin leads to targeted transcriptional up-regulation of genes implicated in carcinogenesis. We report that in vivo adaptation endowed an H. pylori strain with the ability to rapidly and reproducibly induce gastric dysplasia and adenocarcinoma in a rodent model of gastritis. Compared with its parental noncarcinogenic isolate, the oncogenic H. pylori strain selectively activates beta-catenin in model gastric epithelia, which is dependent on translocation of CagA into host epithelial cells. Beta-catenin nuclear accumulation is increased in gastric epithelium harvested from gerbils infected with the H. pylori carcinogenic strain as well as from persons carrying cag+ vs. cag- strains or uninfected persons. These results indicate that H. pylori-induced dysregulation of beta-catenin-dependent pathways may explain in part the augmentation in the risk of gastric cancer conferred by this pathogen
  95. Garza-Gonzalez, Elvira; Bosques-Padilla, Francisco Javier; El-Omar, Emad; Hold, Georgina; Tijerina-Menchaca, Rolando; Maldonado-Garza, Hector Jesus; Perez-Perez, Guillermo Ignacio. "Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico". International journal of cancer. 2005 Mar 20;114(2):237-241 (MEDL:15540224 #79200)       

    Several cytokine gene polymorphisms have been associated with increased risk of distal gastric cancer (GC) and its precursor histological markers in Caucasian, Asian and Portuguese populations although little is known about their role in other ethnic groups. Our study investigates the role of the IL-1B-31, IL-1RN and TNF-A-308 gene polymorphisms as risk factors for the development of GC in a Mexican population. We studied 278 patients who were enrolled at the Hospital Universitario Dr. Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon. The subjects were divided into 2 groups. Sixty-three patients with histologically confirmed distal GC (mean age = 58.8 years, range = 22-84, F:M = 0.56), and 215 patients with no evidence of distal or proximal GC (mean age = 56.1 years, range = 18-92, F:M = 1.17). The IL-1B-31 and the TNF-A-308 polymorphisms were determined by PCR-RFLP and pyrosequencing, respectively, in all cases and controls. The VNTR polymorphism in intron 2 of the 1L-1RN gene was typed by PCR in 25 cases and 201 controls. The H. pylori status was determined by histology, rapid urease test, culture and serology for non-cancer controls and by histology for the GC cases. The carriage of the proinflammatory IL-1B-31*C allele was associated with increased risk of distal GC (odds ratio [OR] = 7.63, 95% confidence interval [CI] = 1.73-46.94, p = 0.003). When cases and controls were matched by age and gender, the OR value was higher (OR = 8.05, 95% CI = 1.8-50.22, p = 0.001). When only H. pylori GC cases and controls were compared, the OR value was 7.8 (95% CI = 1.05-161.8, p = 0.04). No association was found between any of the other polymorphisms studied and distal GC. In this Mexican population, the IL-1B proinflammatory genotype increases the risk of distal GC. These findings are similar to previous reports in Caucasian populations and underscore the importance of cytokine gene polymorphisms in the development of distal GC
  96. Ghose, C; Perez-Perez, G I; van Doorn, L J; Dominguez-Bello, M G; Blaser, M J. "High Frequency of Gastric Colonization with Multiple Helicobacter pylori Strains in Venezuelan Subjects". Journal of clinical microbiology. 2005 Jun;43(6):2635-2641 (MEDL:15956377 #55866)       

    Multiple Helicobacter pylori strains may colonize an individual host. Using enzyme-linked immunosorbent assay and line probe assay (LiPA) techniques, we analyzed the prevalence of mixed H. pylori colonization in 127 subjects from Venezuela, a country of high H. pylori prevalence, from three regions representing different population groups: the Andes (Merida), where Caucasian mestizos predominate, a major city near the coast (Caracas), where Amerindian-Caucasian-African mestizos predominate, and an Amazonian community (Puerto Ayacucho), where Amerindians predominate and mestizos reflect Amerindian and Caucasian ancestry. Among 121 H. pylori-positive persons, the prevalence of cagA-positive strains varied from 50% (Merida) to 86% (Puerto Ayacucho) by LiPA. Rates of mixed colonization also varied, as assessed by LiPA of the vacA s (mean, 49%) and m (mean, 26%) regions. In total, 55% of the individuals had genotypic evidence of mixed colonization. vacA s1c, a marker of Amerindian (East Asian) origin, was present in all three populations, especially from Puerto Ayacucho (86%). These results demonstrate the high prevalence of mixed colonization and indicate that the H. pylori East Asian vacA genotype has survived in all three populations tested
  97. Gorthi, SP; Kapoor, L; Chaudhry, R; Sharma, N; Perez-Perez, GI; Panigrahi, P; Behari, M. "Guillain-Barre syndrome: association with Campylobacter jejuni and Mycoplasma pneumoniae infections in India [Meeting Abstract]". Journal of the neurological sciences. 2005 NOV 15;238(4):S186-S187 (ISI:000235088001361 #98078)    
  98. Haggerty, Thomas D; Perry, Sharon; Sanchez, Luz; Perez-Perez, Guillermo; Parsonnet, Julie. "Significance of transiently positive enzyme-linked immunosorbent assay results in detection of Helicobacter pylori in stool samples from children". Journal of clinical microbiology. 2005 May;43(5):2220-2223 (MEDL:15872245 #79199)       

    In young children, the significance of stool samples transiently positive for Helicobacter pylori antigen is unknown. As part of a larger prospective study on enteric infections, stool samples were obtained from 323 children at two time points 3 months apart and tested for H. pylori antigen using a commercially available enzyme-linked immunosorbent assay (ELISA) test. Seminested PCR for a Helicobacter-specific 16S rRNA gene was performed on all 26 pairs reverting from positive to negative (transient positives), all 4 persistent antigen-positive pairs, and 10 randomly selected persistent antigen-negative pairs. Helicobacter species were amplified from the first stool samples of 15/26 (58%) of the transient positives and 1 (25%) of 4 persistent positives. No Helicobacter species were amplified from the 10 persistent negatives. Among the 15 amplicons from transient-positive stool, H. pylori was sequenced and identified from 12 (80%; 95% confidence interval, 52% to 96%) and other Helicobacter spp. were identified from three (Helicobacter canis, Helicobacter winghamensis, and MIT 99-5504). Four of the 15 remained positive by PCR for the second (antigen-negative) stool sample, including all 3 initially identified as non-H. pylori. Helicobacter bilis was amplified from the second sample of a persistent positive. Two of eight transient positives from whom serum was available had accompanying transient elevations in anti-H. pylori antibodies. Transiently positive stool ELISAs for H. pylori are common and represent H. pylori in the majority of cases where sequences can be obtained. A not-insignificant percentage of antigen-positive stools, however, may represent other Helicobacter species
  99. Harris, Paul; Perez-Perez, Guillermo; Zylberberg, Alejandro; Rollan, Antonio; Serrano, Carolina; Riera, Francisca; Einisman, Helly; Garcia, Daniela; Viviani, Paola. "Relevance of adjusted cut-off values in commercial serological immunoassays for Helicobacter pylori infection in children". Digestive diseases & sciences. 2005 Nov;50(11):2103-2109 (MEDL:16240223 #79198)       

    We assessed the sensitivity and specificity of H. pylori IgG and IgA with a commercial immunoassay performed in Chile and a second non-commercial immunoassay performed in a reference laboratory in the United States, in serum of 80 children and adults referred for gastrointestinal endoscopies in a developing country. Overall, 56% of the patients were infected with H. pylori based on rapid urease test and staining techniques on gastric biopsies. When Receiver Operator Curves (ROC) were developed, the sensitivity and specificity were similar for IgG and IgA. Both immunoassays exhibited better specificity, positive and negative predictive value (NPV) in children than in adults when cut-off values were corrected according to the local population than when they were assessed using the cut-off values pre-defined in other populations. These results underline the need to establish more precise cut-off values corrected in the local populations where assessments of antibodies as diagnostic markers of H. pylori infection are planning
  100. Lin, RM; Francois, F; Olivares, A; Williams, R; Huang, GJ; Poles, MA; Perez-Perez, G. "II-lbeta-511 polymorphism is associated with increased risk of colonic adenomas in an ethnically diverse population". Gastroenterology. 2005 APR;128(4):A9-A9 (ISI:000228619300043 #519622)    
  101. Nomura, Abraham M Y; Kolonel, Laurence N; Miki, Kazumasa; Stemmermann, Grant N; Wilkens, Lynne R; Goodman, Marc T; Perez-Perez, Guillermo I; Blaser, Martin J. "Helicobacter pylori, pepsinogen, and gastric adenocarcinoma in Hawaii". Journal of infectious diseases. 2005 Jun 15;191(12):2075-2081 (MEDL:15897993 #64080)       

    BACKGROUND: The objective was to investigate the association of Helicobacter pylori and serum pepsinogen (PG) levels with gastric adenocarcinoma. METHODS: Serum obtained from 299 patients at the time of cancer diagnosis and from 336 population-based control subjects was tested for PG I, PG II, and antibodies to H. pylori and to CagA. RESULTS: Subjects with low PG I levels or low PG I/II ratios were at increased risk for cardia and noncardia gastric cancer, whereas those with H. pylori or CagA seropositivity had an elevated risk for noncardia cancer only. Subjects seropositive for either H. pylori or CagA who had low PG I levels had the highest odds ratio (OR) (9.21 [95% confidence interval {CI}, 4.95-17.13]) for noncardia cancer, compared with subjects with neither factor. Elevated risks were also found among subjects with only 1 factor (OR, 5.40 [95% CI, 2.61-11.20] for low PG I level only; OR, 4.86 [95% CI, 5.90-8.13] for H. pylori or CagA seropositivity only). This pattern persisted when PG I/II ratio replaced PG I level and when CagA seropositivity alone replaced H. pylori immunoglobulin G or CagA seropositivity. CONCLUSIONS: The results suggest that persons with both H. pylori or CagA seropositivity and a low PG I level or PG I/II ratio are highly susceptible to development of noncardia gastric cancer
  102. Perez Perez, Guillermo I. "[New era of Helicobacter pylori]". Revista de gastroenterologia de Mexico. 2005 Nov;70 Suppl 3:31-32 (MEDL:17471853 #79190)    
  103. Perez Perez, Guillermo I. "[When and why should we eradicate the Helicobacter pylori?]". Revista de gastroenterologia de Mexico. 2005 Nov;70 Suppl 3:26-27 (MEDL:17471851 #79191)    
  104. Perez-Perez, Guillermo I; Garza-Gonzalez, Elvira; Portal, Cynthia; Olivares, Asalia Z. "Role of cytokine polymorphisms in the risk of distal gastric cancer development". Cancer epidemiology biomarkers & prevention. 2005 Aug;14(8):1869-1873 (MEDL:16103428 #58894)       

    We review the current information concerning the role of cytokine polymorphisms and the risk of develop distal gastric cancer in different populations. We have included populations colonized with Helicobacter pylori as well as populations without colonization. We found that the study of polymorphisms alone seems insufficient to assess gastric cancer risk and it is necessary to examine environmental factors in different ethnic groups and geographic areas along with the study of H. pylori strains to define better the risk factors associated with distal gastric cancer
  105. Perez-Perez, Guillermo Ignacio; Bosques-Padilla, Francisco Javier; Crosatti, Maria Luisa; Tijerina-Menchaca, Rolando; Garza-Gonzalez, Elvira. "Role of p53 codon 72 polymorphism in the risk of development of distal gastric cancer". Scandinavian journal of gastroenterology. 2005 Jan;40(1):56-60 (MEDL:15841715 #54111)       

    OBJECTIVE: Mutations in the codon 72 of exon 4 in the p53 gene have been associated with higher risk in the development of several types of cancer. This polymorphism occurs with two alleles encoding either arginine (CGC) or proline (CCC). The aim of this study was to assess the role of the codon 72 polymorphism of p53 in the risk for the development of distal gastric cancer (GC) in a Mexican population. MATERIAL AND METHODS: We studied 247 patients who were enrolled at the Servicio de Gastroenterologia, Hospital Universitario 'Dr. Jose Eleuterio Gonzalez' Universidad Autonoma de Nuevo Leon. The study group included 65 distal GC cases [mean age, 58.2 (22-84), median = 60, F:M = 0.6] and 182 patients without evidence of GC [mean age 53.9 (18-89), median = 53, F:M = 1.07) as the control group. The polymorphism in the codon 72 of the p53 gene was determined by PCR-RFLP in all the patients. RESULTS: As expected, the majority of GC patients were old male. We found a previously unknown association of the Arg/Arg genotype and distal GC (OR: 1.96, 95% confidence interval [CI] = 1.06-3.61, p =0.03). Because of age and gender differences, cases and controls were matched in those two variables and the association of Arg/Arg genotype with distal GC persisted (OR: 2.29, 95% CI = 1.22-4.32, p = 0.01). When cases and controls were matched by age, gender, H. pylori positivity and excluding patients with atrophic gastritis and/or intestinal metaplasia (n=97) the association was stronger (OR = 2.37, 95% CI = 1.18-4.77, p = 0.01). CONCLUSIONS: The results of this study suggest that the carriage of the Arg/Arg genotype could be associated with the development of distal GC in this Mexican population
  106. Perez-Perez, Guillermo Ignacio; Olivares, Asalia Zuni; Foo, F Yeong; Foo, Sun; Neusy, Andre J; Ng, Christopher; Holzman, Robert S; Marmor, Michael; Blaser, Martin J. "Seroprevalence of Helicobacter pylori in New York City populations originating in East Asia". Journal of urban health. 2005 Sep;82(3):510-516 (MEDL:16033932 #58190)       

    Helicobacter pylori prevalence is higher in developing countries than in industrialized countries, and within the latter, higher among immigrants than among nativeborn residents. Using a point-prevalence survey, we sought to identify risk factors for H. pylori seropositivity in US urban East Asian-born populations. At a clinic in New York City, we consecutively enrolled 194 East Asian-born adults, who then responded to a survey and provided a blood sample. Assays were performed to detect IgG antibodies against whole cell (WC) and cytotoxin associated gene A (CagA) antigens of H. pylori. For this group (mean age 50.2+/-14.7 years), the mean period of residence in the United States was 11.9+/-7.7 years. The total H. pylori seroprevalence was 70.1%, with highest (81.4%) in Fujianese immigrants. Multiple logistic regression analysis indicated an independent association of H. pylori seropositivity with Fujianese origin [odds ratios (OR) =2.3, 95% confidence interval (95% CI) =1.05-5.0] and inverse associations with period in the United States (OR per year of residency in the United States =0.95, 95% CI =0.91-0.99) and with a history of dyspepsia (OR for a history of stomach pain =0.52, 95% CI =0.3-1.0). We conclude that H. pylori is highly prevalent among recent East Asian immigrants, especially among Fujianese. The protective effects of history of dyspepsia and duration in the United States suggest that these may be markers for antibiotic therapies.
  107. Aspholm-Hurtig, Marina; Dailide, Giedrius; Lahmann, Martina; Kalia, Awdhesh; Ilver, Dag; Roche, Niamh; Vikstrom, Susanne; Sjostrom, Rolf; Linden, Sara; Backstrom, Anna; Lundberg, Carina; Arnqvist, Anna; Mahdavi, Jafar; Nilsson, Ulf J; Velapatino, Billie; Gilman, Robert H; Gerhard, Markus; Alarcon, Teresa; Lopez-Brea, Manuel; Nakazawa, Teruko; Fox, James G; Correa, Pelayo; Dominguez-Bello, Maria Gloria; Perez-Perez, Guillermo I; Blaser, Martin J; Normark, Staffan; Carlstedt, Ingemar; Oscarson, Stefan; Teneberg, Susann; Berg, Douglas E; Boren, Thomas. "Functional Adaptation of BabA, the H. pylori ABO Blood Group Antigen Binding Adhesin". Science. 2004 Jul 23;305(5683):519-522 (MEDL:15273394 #43533)       

    Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations
  108. Duck, William M; Sobel, Jeremy; Pruckler, Janet M; Song, Qunsheng; Swerdlow, David; Friedman, Cindy; Sulka, Alana; Swaminathan, Balasubra; Taylor, Tom; Hoekstra, Mike; Griffin, Patricia; Smoot, Duane; Peek, Rick; Metz, David C; Bloom, Peter B; Goldschmidt, Steven; Parsonnet, Julie; Triadafilopoulos, George; Perez-Perez, Guillermo I; Vakil, Nimish; Ernst, Peter; Czinn, Steve; Dunne, Donald; Gold, Ben D. "Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States". Emerging infectious diseases. 2004 Jun;10(6):1088-1094 (MEDL:15207062 #44762)    

    Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice
  109. Eamranond, Peter P; Torres, Javier; Munoz, Onofre; Perez-Perez, Guillermo I. "Age-Specific Immune Response to HspA in Helicobacter pylori-Positive Persons in Mexico". Clinical & diagnostic laboratory immunology. 2004 Sep;11(5):983-985 (MEDL:15358663 #44760)       

    The immune response to heat shock protein A (HspA) in Helicobacter pylori-positive adults increases with age in developed countries. This response has not been studied with children or in developing countries (G. I. Perez-Perez, J. M. Thiberge, A. Labigne, and M. J. Blaser, J. Infect. Dis. 174:1046-1050, 1996). As determined by using a specific enzyme-linked immunosorbent assay, HspA seropositivity among 592 individuals in Mexico was <10% in children and increased to >40% in adults
  110. Francois, F; Bini, EJ; Perez-Perez, GI; Yee, HT; Blaser, MJ. "A three-component clinical model to predict reflux-related histopathology [Meeting Abstract]". Gastroenterology. 2004;126(4):A324-A324 (ISI:000220890201628 #108227)    
  111. Garza-Gonzalez, E; Bosques-Padilla, F J; Tijerina-Menchaca, R; Perez-Perez, G I. "Characterisation of Helicobacter pylori isolates from the north-eastern region of Mexico". Clinical microbiology & infection. 2004 Jan;10(1):41-45 (MEDL:14706085 #44765)       

    The vacA and cagA genotypes of 50 Helicobacter pylori isolates from patients in the north-eastern region of Mexico were characterised by PCR, and the correlation between genotypes and different clinical outcomes was investigated. Strains of H. pylori that are vacA s1/m1 and cagA positive have previously been associated with more severe clinical outcomes, and some studies have shown differences in the vacA and cagA genotypes in different geographical regions. The six possible combinations of the vacA signal (s) and middle (m) regions were identified in this population, and the most frequent genotype was s2/m2. Thirty-two (64%) isolates were identified as cagA-positive. The s region was not amplified from seven of the cagA-positive isolates, and the m region was not amplified from one cagA-negative isolate, indicating that additional subfamilies of s and m genotypes may exist. The s1/m1 genotype was associated with cagA-positive strains (p < 0.05). No association was found between the vacA and cagA genotypes and clinical outcomes
  112. Garza-Gonzalez, E; Tijerina-Menchaca, R; Perez-Perez, G I; Bosques-Padilla, F J. "Bacteriostatic and bactericidal activity of rabeprazole against Helicobacter pylori [Letter]". Journal of chemotherapy. 2004 Dec;16(6):612-613 (MEDL:15700857 #64081)    
  113. Garza-Gonzalez, Elvira; Bosques-Padilla, Francisco J; Perez-Perez, Guillermo I; Flores-Gutierrez, Juan Pablo; Tijerina-Menchaca, Rolando. "Association of gastric cancer, HLA-DQA1, and infection with Helicobacter pylori CagA+ and VacA+ in a Mexican population". Journal of gastroenterology. 2004 Dec;39(12):1138-1142 (MEDL:15622476 #64082)       

    BACKGROUND: The goal of this study was to determine the importance of Helicobacter pylori CagA+, VacA+, and HLA-DQA1 alleles in a Mexican population with gastric cancer (GC). METHODS: We studied a group of Mexican patients (cases) with distal GC (n=22) or high-grade dysplasia (HGD; n=8) (mean age, 62.7 years, F : M=0.3; age range, 33-84 years) and 77 ethnically matched non-GC controls (mean age, 47.1 years; F : M=1.96; age range, 17-92 years). Both cases and controls were H. pylori-positive by at least two of the following diagnostic tests: rapid urease test, histology, culture, or serology. The presence of antibodies to CagA and VacA proteins was determined by Western blot, and the HLA-DQA1 typing was carried out by a polymerase chain reaction (PCR) sequence-specific primer method. RESULTS: The carriage of H. pylori CagA+, VacA+ strains was associated with GC or HGD (odds ratio [OR], 6.07; 95% confidence interval [CI], 1.56-27.57; P=0.005). The allele frequency of DQA1*0503 was significantly lower in the GC-HGD group than in the non-GC group (OR, 0.13; 95% CI, 0.02-0.59). Logistic regression analysis identified the carriage of HLA-DQA1*0503 as an independent protective factor for GC (OR, 0.19; 95% CI, 0.04-0.94) and colonization with H. pylori CagA+, VacA+ strains as an independent risk factor for GC (OR, 6.15; 95% CI, 1.69-22.37). CONCLUSIONS: Infection with H. pylori CagA+, VacA+ strains represents a significant risk for the development of GC. The absence of HLA-DQA1*0503 could be a host risk factor for the development of GC in Mexican patients
  114. Perez Perez, G; Navarro Merino, M; Romero Perez, Ma M; Saenz Reguera, C; Pons Tubio, A; Polo Padillo, J. "[Respiratory morbidity after hospital discharge in premature infants born at < or = 32 weeks gestation with bronchopulmonary dysplasia]". Anales de pediatria. 2004 Feb;60(2):117-124 (MEDL:14757014 #44764)    

    BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most frequent cause of respiratory morbidity in the first 2 years of life among preterm infants who survive the first 28 days. OBJECTIVES: To evaluate respiratory morbidity in the first 2 years of life in a group of preterm infants born at (32 weeks' gestation with BPD (oxygen requirement at 36 weeks' postconceptional age) by comparing it with that in preterm infants born at (32 weeks without BPD and with a control group of full term infants without neonatal morbidity. To determine whether respiratory morbidity in children with BPD decreases after the age of 2 years. PATIENTS AND METHOD: Group I: preterm children with BPD (n = 29). Group II: preterm children without BPD (n = 29). Group III: children with appropriate gestational age and weight (n = 32). A cross-sectional, descriptive study of the three groups was performed over a 2-year period. In 17 children in group 1, the study was prolonged to the age of 4 years. We analyzed wheezing on at least two occasions, use of inhaled bronchodilators, use of inhaled glucocorticosteroids for more than 6 months, and hospitalization for respiratory illness. The chi-square test and Fischer's exact test were performed. RESULTS: At least one episode of wheezing occurred in 25 children (86.2%) in group I compared with 12 children (41.4%) in group II and 6 (18.8%) in group III. Nineteen children (65.5%) in group I and none in the remaining two groups received treatment with inhaled glucocorticosteroids for more than 6 months (p < 0.001). Inhaled bronchodilators were used by 25 children (86.2%) in group I compared with 12 (41.4%) in group II and 6 (18.8%) in the control group (p < 0.001). Twelve children (41.3%) in group I were hospitalized for respiratory illness compared with 8 (27.6%) in group II. There were no admissions among the control group. None of the children with BPD who received prophylaxis with palivizumab contracted respiratory syncytial virus infection.Seventeen children with BPD were evaluated until the age of 4 years. Episodes of wheezing decreased from 88.2% in the first year to 41 % between the third and fourth years (p < 0.001). Treatment with inhaled glucocorticosteroids for more than 6 months was given to 88.2% in the first year, 41.2 % between the first and second year and to 0 % after the second year (p < 0.001). Hospital admissions for respiratory illness decreased from 52.9% in the first year to 17.6% in the second year. None of the children were hospitalized after the age of 2 years (p < 0.001). CONCLUSIONS: During the first 2 years of life, children with BPD showed a greater number of admissions and episodes of wheezing and a greater need for medical treatment. Respiratory morbidity improved with age, 40% showed recurrent wheezing episodes at the age of 4 years
  115. Perez-Perez, Guillermo I; Rothenbacher, Dietrich; Brenner, Hermann. "Epidemiology of Helicobacter pylori Infection". Helicobacter. 2004;9 Suppl 1(5):1-6 (MEDL:15347299 #44761)       

    ABSTRACT This review summarizes key results of epidemiologic studies published in peer-reviewed journals between April 2003 and March 2004. The prevalence of H. pylori infection continues to vary strongly between developing countries and developed countries, and according to ethnicity, place of birth and socioeconomic factors among people living in the same country. Intrafamilial spread appears to play a central role in transmission of the infection in both developing and developed countries. The role of H. pylori infection in development of noncardia gastric cancer appears to be even much stronger than previously assumed, whereas the lack of an association with cardia cancer and an inverse association with adenocarcinoma of the esophagus could be confirmed. Suggestions for an inverse association of the infection with atopic diseases have recently received further support, whereas evidence concerning the role of the infection (or its eradication) in GERD and a large variety of other extragastric diseases, including cardiovascular disease, remains inconclusive
  116. Aras, Rahul A; Fischer, Wolfgang; Perez-Perez, Guillermo I; Crosatti, MariaLuisa; Ando, Takafumi; Haas, Rainer; Blaser, Martin J. "Plasticity of repetitive DNA sequences within a bacterial (Type IV) secretion system component". Journal of experimental medicine. 2003 Nov 3;198(9):1349-1360 (MEDL:14581606 #42650)       

    DNA rearrangement permits bacteria to regulate gene content and expression. In Helicobacter pylori, cagY, which contains an extraordinary number of direct DNA repeats, encodes a surface-exposed subunit of a (type IV) bacterial secretory system. Examining potential DNA rearrangements involving the cagY repeats indicated that recombination events invariably yield in-frame open reading frames, producing alternatively expressed genes. In individual hosts, H. pylori cell populations include strains that produce CagY proteins that differ in size, due to the predicted in-frame deletions or duplications, and elicit minimal or no host antibody recognition. Using repetitive DNA, H. pylori rearrangements in a host-exposed subunit of a conserved bacterial secretion system may permit a novel form of antigenic evasion
  117. Belongia, Edward A; Chyou, Po-Huang; Greenlee, Robert T; Perez-Perez, Guillermo; Bibb, William F; DeVries, Edna O. "Diarrhea Incidence and Farm-Related Risk Factors for Escherichia coli O157:H7 and Campylobacter jejuni Antibodies among Rural Children". Journal of infectious diseases. 2003 May 1;187(9):1460-1468 (MEDL:12717628 #34616)       

    Serum samples were obtained from 215 farm-resident children and 396 non-farm-resident children living in a defined rural Wisconsin population. Antibodies to Campylobacter jejuni and Escherichia coli O157:H7 lipopolysaccharide (O157 LPS) immunoglobulin G were measured, and the incidence of clinic visits for diarrheal illness was determined. Risk factors were assessed in a telephone interview. There were 363 children (59%) with C. jejuni antibodies (seropositive for >/=2 immunoglobulin classes) and 86 (14%) with O157 LPS antibodies. Increasing age and farm residence were independently associated with C. jejuni seropositivity by multivariate analysis. O157 LPS antibodies were independently associated with increasing age, female sex, manure contact, and sheep contact. The incidence of clinically recognized diarrhea was similar among children with and without antibodies to C. jejuni and O157 LPS, but the clinic visit rate for diarrhea was 46% lower among farm-resident children. These results are consistent with reduced occurrence of clinical illness from repeated antigenic stimulation in a farm environment
  118. Bosques-Padilla, Francisco Javier; Tijerina-Menchaca, Rolando; Perez-Perez, Guillermo Ignacio; Flores-Gutierrez, Juan Pablo; Garza-Gonzalez, Elvira. "Comparison of Helicobacter pylori Prevalence in Symptomatic Patients in Northeastern Mexico with the Rest of the Country. Its Association with Gastrointestinal Disease". Archives of medical research (Mexico). 2003 Jan-Feb;34(1):60-63 (MEDL:12604377 #34619)       

    Prevalence of Helicobacter pylori varies among different geographic regions. The aim of this study was to assess H. pylori prevalence in symptomatic patients in northeastern Mexico and its possible association of H. pylori with disease.We studied 261 symptomatic patients (female/male 1.44, mean age 53 years) who underwent gastrointestinal endoscopy at Hospital Universitario Dr. Jose Eleuterio Gonzalez in Monterrey, Nuevo Leon, Mexico. Among patients included in this study, 209 (80.1%) had nonulcer dyspepsia (NUD), 30 (11.5%) peptic ulcer disease (PUD), and 22 (8.4%) high-grade dysplasia or gastric cancer. H. pylori status was determined by histology, positive rapid urease test, culture, or IgG whole-cell anti-H. pylori. Specific IgG antibodies for CagA status were determined by ELISA as previously described. Patients were defined as infected with H. pylori by positive results of two or more diagnostic tests used.Overall prevalence of H. pylori was 67.8%. According to clinical presentation, gender (male) was related with gastric cancer (p <0.01) and with PUD (p <0.05). Of 177 patients infected with H. pylori, 90 (50.8%) were seropositive for CagA antigen; in addition, H. pylori CagA+ was more common in patients with PUD (77.8%) than with NUD (43.2%) (p <0.05). However, no association was found between gastric cancer patients and presence of CagA+ H. pylori strains.H. pylori prevalence in symptomatic patients in northeastern Mexico is as high as the prevalence reported for the entire country. We confirmed that patients with gastric cancer and PUD are more likely to be male. CagA+ strains were associated with patients who presented PUD but not gastric cancer
  119. Dourado, M E; Duarte, R C; Ferreira, L C; Queiroz, J W; Illa, I; Perez-Perez, G; Guerrant, R L; Jeronimo, S M B. "Anti-ganglioside antibodies and clinical outcome of patients with Guillain-Barre Syndrome in northeast Brazil". Acta neurologica Scandinavica. 2003 Aug;108(2):102-108 (MEDL:12859286 #44767)       

    OBJECTIVES: The goal of this study was to investigate the frequency of GM1 antibodies and to assess whether exposure to Campylobacter jejuni was associated with a distinct clinical variant of Guillain-Barre Syndrome (GBS) or disease outcome in Rio Grande do Norte, Brazil. MATERIAL AND METHODS: Forty-one patients with a presumed diagnosis of GBS were enrolled and prospectively studied between June 1994 and November 1999. RESULTS: Anti-GM1 was present in 51.2% (n = 21) of patients. The presence of anti-GM1 was significantly associated with acute axonal motor neuropathy when compared to acute inflammatory demyelinating polyneuropathy (P = 0.01). Patients with anti-GM1 antibodies presented distal muscle involvement and fewer sensory deficits. Age, time to nadir and ventilatory assistance were not associated with anti-GM1 antibodies. Eight out of 21 patients (32%) presented with anti-C. jejuni antibodies. Clinical features were similar for patients with GBS with positive and negative C. jejuni antibodies. Anti-GM1 antibodies were associated with C. jejuni infection (P = 0.0005). Presence of anti-GM1 and C. jejuni antibodies did not indicate a worse prognosis. CONCLUSION: Patients with GBS and anti-GM1 antibodies had more distal muscle weakness, fewer sensory deficits, more axonal degeneration and C. jejuni infection, but these findings were not associated with a worse prognosis
  120. Falush, Daniel; Wirth, Thierry; Linz, Bodo; Pritchard, Jonathan K; Stephens, Matthew; Kidd, Mark; Blaser, Martin J; Graham, David Y; Vacher, Sylvie; Perez-Perez, Guillermo I; Yamaoka, Yoshio; Megraud, Francis; Otto, Kristina; Reichard, Ulrike; Katzowitsch, Elena; Wang, Xiaoyan; Achtman, Mark; Suerbaum, Sebastian. "Traces of human migrations in Helicobacter pylori populations". Science. 2003 Mar 7;299(5612):1582-1585 (MEDL:12624269 #34570)       

    Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade
  121. Francois, F; Bini, EJ; Perez-Perez, GI; Blaser, MJ. "Do GERD symptoms predict Helicobacter pylori colonization? [Meeting Abstract]". Gastroenterology. 2003;124(4):A624-A624 (ISI:000182675903158 #108237)    
  122. Francois, F; Bini, EJ; Perez-Perez, GI; Yee, HT; Blaser, MJ. "Relationship of Helicobacter pylori and strain characteristics to esophageal pathology [Meeting Abstract]". Gastroenterology. 2003;124(4):A55-A55 (ISI:000182675900269 #108235)    
  123. Francois, F; Weinshel, EH; Perez-Perez, GI; Yee, HT; Blazer, MJ; Bini, EJ. "Endoscopic training: Looking past the surface [Meeting Abstract]". Gastrointestinal endoscopy. 2003;57(5):AB109-AB109 (ISI:000182696600122 #108236)    
  124. Garza-Gonzalez, Elvira; Bosques-Padilla, Francisco J; Tijerina-Menchaca, Rolando; Flores-Gutierrez, Juan P; Maldonado-Garza, Hector J; Perez-Perez, Guillermo I. "Comparision of endoscopy-based and serum-based methods for the diagnosis of Helicobacter pylori". Canadian journal of gastroenterology. 2003 Feb;17(2):101-106 (MEDL:12605246 #34618)    

    Available commercial tests for the diagnosis of Helicobacter pylori infection are based on different types of antigen preparations and hence the diagnostic utility differs substantially. OBJECTIVE: To assess the diagnostic value of the determination of Immunoglobulin (Ig) A and IgG antibodies to H pylori whole cell (WC) and IgG antibodies to cytotoxin associated gene A (CagA) using an in-house ELISA in relation to the results obtained with different invasive methods. METHODS: The study population consisted of 251 Mexican adults, mean age 53 years, age range 15 to 92 years and female to male ratio of 1.5. Peptic ulcer disease was present in 10.8% of these patients, 5.2% had gastric cancer, 11.2% had esophagitis and 72.9% had nonulcer dyspepsia. Biopsy specimens from the body and the antrum of the stomach were obtained for culture, histology and rapid urease test. ELISAs to detect IgA and IgG WC and CagA antibodies were performed using serum. RESULTS: H pylori status was established by the results of the invasive tests. Eighty (31.9%) patients positive to the three tests and 38 (15.1%) negative to all the tests were identified. Based on this result, the sensitivity and specificity of the serology assays were 97.5% and 78.9% for the IgG WC and 70% and 73.7% for the IgA WC, respectively. However, if H pylori status was defined by the positive result of at least one or two invasive diagnostic tests, the sensitivity for the IgG WC decreased to 87.3% and 66.7% respectively, but the specificity was essentially the same. Similar results were obtained for the sensitivity and specificity of IgA using the same criteria. A low CagA prevalence was observed (39%). CONCLUSIONS: Testing for serological IgG antibodies to H pylori WC was the best to assess whether infection by H pylori was present. Neither the IgA WC nor the IgG CagA ELISAs add significant value in the diagnosis of H pylori
  125. Garza-Gonzalez, Elvira; Hold, Georgina; Perez-Perez, Guillermo Ignacio; Bosques-Padilla, Francisco Javier; Tijerina-Menchaca, Rolando; Maldonado-Garza, Hector Jesus; el-Omar, Emad. "[Role of polymorphism of certain cytokines in gastric cancer in Mexico. Preliminary results]". Revista de gastroenterologia de Mexico. 2003 Apr-Jun;68(2):107-112 (MEDL:15127646 #44763)    

    BACKGROUND: Interleukin-10, tumor necrosis factor alpha, Interleukin-1 beta and interleukin-1 receptor antagonist cytokines modulate the inflammatory response in presence of Helicobacter pylori. Pro-inflammatory interleukin 10 (IL-10-592, -1082), TNF alpha (TNF alpha-308), interleukin-1 beta and interleukin-1 receptor antagonist (IL-1B-31*C and IL-1RN*2/*2) genotypes have been associated with higher risk of gastric cancer in Caucasians. The aim of this study was to investigate whether these same genotypes are involved in susceptibility to gastric cancer in Mexican population. MATERIALS AND METHODS: DNA from 33 unrelated Mexican patients with histologically confirmed gastric cancer (n = 25) or high-grade dysplasia (n = 8) (mean age 62.7, F/M = 0.37) and 25 ethnically matched healthy controls (mean age = 39.9, F/M = 3.12) were studied. All cases and controls had evidence of H. pylori infection as shown by at least two positive results from the following diagnostic tests: rapid urease test; culture; histology, or detection of IgG anti-H. pylori antibodies. The -592, -1082 polymorphism in IL-10 gene, the -308 in TNF alpha gene, and the-31 polymorphism in the IL-1B gene were typed by 5' nuclease PCR assays (TaqMan) and the variable number of tandem repeats polymorphism in intron 2 of the 1L-1RN gene was typed by PCR and amplicon sizing as previously described (Nature 2000; 404: 398). RESULTS: Carriage of the pro-inflammatory IL-1B-31*C allele was associated with increased risk of gastric cancer or high-grade dysplasia (OR: 8.7, 95% confidence interval [CI] = 1.5-66.9). No association was found between any IL-IRN, IL-10 or TNF alpha genotypes and gastric cancer or high-grade dysplasia. Logistic regression analysis identified male gender and carriage of IL-1B-31*C as independent risk factors for gastric cancer (OR = 9.2, 95% CI = 2.4-34.5, and OR = 10, 95% CI = 1.6-64, respectively). CONCLUSIONS: The results of this preliminary study confirm that the pro-inflammatory IL-1B genotypes, as well as male gender, are risk factors for development of gastric cancer in Mexican population
  126. Harris, Paul R; Godoy, Alex; Arenillas, Silvana; Riera, Francisca; Garcia, Daniela; Einisman, Helly; Pena, Alfredo; Rollan, Antonio; Duarte, Ignacio; Guiraldes, Ernesto; Perez-Perez, Guillermo. "CagA Antibodies as a Marker of Virulence in Chilean Patients With Helicobacter pylori Infection". Journal of pediatric gastroenterology & nutrition. 2003 Nov;37(5):596-602 (MEDL:14581804 #39016)       

    SUMMARY: BACKGROUND The bacterial and host factors that influence the clinical outcomes of the Helicobacter pylori infection have not been fully identified. Cytotoxin-associated gene product (CagA), one of the virulence factors, has been associated with a more aggressive form of infection. The authors studied the relationship between CagA status and clinical outcome in Chilean children and adults with H. pylori infection.METHODS One hundred eighty consecutive patients undergoing upper gastrointestinal endoscopic analysis were enrolled after informed consent was obtained. Rapid urease test and histologic analysis were used to detect H. pylori infection. IgA and IgG antibodies to H. pylori whole cell antigen preparation and IgG antibodies to CagA were measured by enzyme-linked immunosorbent assay (ELISA).RESULTS H. pylori infection was detected in 42% of the patients by biopsy or urease test and in 38% and 20% of patients by IgG and IgA antibodies, respectively. The prevalence of H. pylori either by the invasive or the serologic tests was directly related to patient age. Among patients with H. pylori, there was no significant association between age and prevalence of CagA. Nearly 70% of the patients with H. pylori and peptic ulcer disease had CagA-positive strains. In contrast, only 49% of the patients with chronic gastritis alone had CagA-positive strains (P < 0.05).CONCLUSIONS In Chile, patients infected with H. pylori have a proportion of CagA-positive strains similar to that reported in developed countries. CagA prevalence was not significantly different in adults and children infected with H. pylori, suggesting that variations in clinical outcome may be related to host immune or environmental factors
  127. Perez-Perez, Guillermo I; Sack, R Bradley; Reid, Raymond; Santosham, Mathuram; Croll, Janne; Blaser, Martin J. "Transient and persistent Helicobacter pylori colonization in Native American children". Journal of clinical microbiology. 2003 Jun;41(6):2401-2407 (MEDL:12791856 #39203)       

    Helicobacter pylori is chiefly acquired in childhood, but the exact timing of acquisition is not well understood. The main goal of this study was to assess H. pylori acquisition in a pediatric population. We studied two cohorts of Native American children: a birth cohort of 50 children and 58 older children (mean age, 53 months). We measured serum immunoglobulin G (IgG), IgM, and IgA antibodies to H. pylori whole-cell antigen and IgG antibodies to CagA. Among 44 birth cohort children monitored for more than 12 months, 24 (54.5%) had seroconversions, 7 (15.9%) were transient, and 17 (38.6%) were persistent. Among the older children, 49 (84.5%) of the 58 children were monitored for 1 year; 34 (69.4%) had H. pylori antibodies at study entry. During the next year, 7 (20.6%) children seroreverted, and of 15 initially negative children, 5 (33.3%) seroconverted. In both groups, evaluation of CagA antibodies increased the sensitivity of H. pylori detection. Serum pepsinogen I (PGI) levels in H. pylori-negative children rose significantly until age 6 months and remained constant for the next 19 months. At the time of H. pylori seroconversion, PGI peaked to levels significantly higher than in the never-seroconverted (P = 0.02) and the pre-seroconverted (P = 0.03) children, but then declined to levels paralleling those of H. pylori-negative children. Thus, H. pylori acquisition, accompanied by a transient PGI increase, was frequent in this population, especially in the second and third years of life, but often was brief
  128. Simon, Joel A; Hudes, Esther S; Perez-Perez, Guillermo I. "Relation of serum ascorbic acid to Helicobacter pylori serology in US adults: the Third National Health and Nutrition Examination Survey". Journal of the American College of Nutrition. 2003 Aug;22(4):283-289 (MEDL:12897042 #44766)       

    PURPOSE: To examine the relation between serum ascorbic acid and Helicobacter pylori serology from a probability sample of US adults. Subjects and Methods: Data from 6,746 adults (ages 20 to 90 years) enrolled in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994 were analyzed. Multiple logistic regression models were examined taking into account sample weights and the complex survey design of NHANES III, and controlling for the effects of potential confounders. Because race appeared to modify the association between serum ascorbic acid and seropositivity to H. pylori, we conducted the analyses stratified by race. RESULTS: A total of 2,189 adults (32%) had a positive serology for H. pylori, and, of these, 1,175 (54%) were positive for the CagA antigen. Among whites, a 0.50 mg/dL increase in serum ascorbic acid level was associated with decreased seroprevalence of H. pylori (Odds Ratio (OR) = 0.89, 95% confidence interval (CI) CI 0.82-0.96, p < 0.01). In analyses that controlled for seroprevalence of H. pylori, a 0.50 mg/dL increase in serum ascorbic acid level among whites was independently associated with a decreased seroprevalence of the pathogenic cagA-positive strain of H. pylori (OR = 0.31, 95% CI 0.12-0.79, p < 0.05). Serum ascorbic acid levels were not significantly associated with H. pylori serology among non-whites (all p > 0.05). CONCLUSIONS: Higher serum levels of ascorbic acid were associated with a decreased seroprevalence of H. pylori and of the pathogenic cagA-positive strain of H. pylori among whites. If these associations are related causally and are not the result of residual confounding by factors such as socioeconomic status, ascorbic acid may affect the risk of H. pylori infection and in turn, the risk for peptic ulcer disease and gastric cancer among white Americans
  129. Torres, Javier; Perez, G Perez; Ximenez, C; Munoz, L; Camorlinga-Ponce, M; Ramos, F; Gomez, A; Munoz, O. "The association of intestinal parasitosis and H. pylori infection in children and adults from a Mexican community with high prevalence of parasitosis". Helicobacter. 2003 Jun;8(3):179-185 (MEDL:12752729 #45297)       

    BACKGROUND: Experimental evidences have suggested that a Th1 response is unable to eliminate H. pylori colonization; whereas a Th2 response, like the one induced by vaccination, reduces H. pylori infection in animal models. Some parasitic infections induce a polarized Th2 response, which theoretically would favor a reduced H. pylori prevalence. The aim of this work was to study the possible association between parasitic infections and H. pylori prevalence. MATERIALS AND METHODS: The study population included 120 children and 188 adults from a low socioeconomic level village. H. pylori prevalence was determined in serum by ELISA; parasitic infections were identified in feces by microscopic examination; and total serum IgE levels, as an indirect indicator of some parasitic infections, were determined by ELISA. RESULTS: In children, H. pylori prevalence was no different between those with and without intestinal parasitic infection. By contrast, adults with intestinal parasitic infection had a significantly lower H. pylori prevalence than adults without parasites (62.6% compared with 80.4%; p = 0.006, OR 2.45). Also in adults, but not in children, total IgE levels were significantly higher in those without H. pylori infection than in those with H. pylori infection (p < 0.001). CONCLUSIONS: Intestinal parasitic infections and serum IgE levels showed an age-dependent association with H. pylori prevalence. In adults, but not in children, intestinal parasitic infections and increased IgE levels where associated with a reduced H. pylori prevalence
  130. Camorlinga, MP; Celis-Cruz, C; Romero, J; Ortiz, M; Lopez-Corella, E; Perez-Perez, G; Coria-Jimenez, R. "Simultaneous experimental colonization of Eriones unguiculatus (Mongolian gerbil) with PAI+ and PAI- Helicobacter pylori strains [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2002 SEP;51(2):A49-A49 (ISI:000178344100175 #55588)    
  131. Cooperberg, BA; Bini, EJ; Perez-Perez, G; Weinshel, EH; Cohen, H; Dacoll, C. "Prevalence of Helicobacter pylori and characterization of genotypes among symptomatic patients from Uruguay [Meeting Abstract]". Gastroenterology. 2002;122(4):T1164-T1164 (ISI:000175366602152 #108248)    
  132. Everhart, James E; Kruszon-Moran, Deanna; Perez-Perez, Guillermo. "Reliability of Helicobacter pylori and CagA serological assays". Clinical & diagnostic laboratory immunology. 2002 Mar;9(2):412-416 (MEDL:11874887 #34621)       

    Background serological assays for Helicobacter pylori are commonly used without knowledge of reliability. This information is needed to define the ability of serological tests to determine either new cases of infection or loss of infection in longitudinal studies. We evaluated the reproducibility and the interrelationships of serological test results for H. pylori and cytotoxin-associated gene product A (CagA) enzyme-linked immunoassays within a subset of participants in a population-based study. Stored samples from 1,229 participants in the third U.S. National Health and Nutrition Examination Survey were replicate serologically tested for H. pylori and CagA. Overall disagreement was 3.4% between duplicate tests for H. pylori (or 2.3% if equivocal results were disregarded). Six percent of samples positive on the first test had an immune serum ratio at least 30% lower on repeat testing. The odds ratio for H. pylori seropositivity on retesting was 2.8 (95% confidence interval [CI] = 1.8 to 4.5) when CagA serology was positive versus when it was negative. CagA antibody was found among 47.8% of H. pylori-equivocal and 7.0% of H. pylori-negative samples. CagA-positive yet H. pylori-negative samples were more likely to occur among Mexican Americans (odds ratio, 5.2; 95% CI = 2.4 to 11.4) and non-Hispanic blacks (odds ratio, 5.5; 95% CI = 2.3 to 13.0) than among non-Hispanic whites. Relying on repeated H. pylori serological tests over time to determine infection rates may result in misinterpretation due to limits in test reproducibility. CagA testing may have a role in verifying infection
  133. Freedman, Abigail; Afonja, Olubunmi; Chang, Mary Wu; Mostashari, Farzad; Blaser, Martin; Perez-Perez, Guillermo; Lazarus, Herb; Schacht, Robert; Guttenberg, Jane; Traister, Michael; Borkowsky, William. "Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month-old infant". JAMA. 2002 Feb 20;287(7):869-874 (MEDL:11851579 #26017)       

    A 7-month-old infant with cutaneous anthrax developed severe systemic illness despite early treatment with antibiotics. The infant displayed severe microangiopathic hemolytic anemia with renal involvement, coagulopathy, and hyponatremia. These findings are unusual with cutaneous anthrax, but have been described in illness resulting from spider toxin and may delay correct diagnosis. The systemic manifestations of the disease persisted for nearly a month despite corticosteroid therapy, but resolved
  134. Garza-Gonzalez, E; Bosques-Padilla, FJ; Perez-Perez, GI; Tijerina-Menchaca, R. "Potential correlation of HLA-DQ alleles and clinical outcomes related to H-pylori CagA plus and VacA [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2002 SEP;51(2):A25-A26 (ISI:000178344100094 #55587)    
  135. Garza-Gonzalez, E; Hold, GL; Perez-Perez, GI; Bosques-Padilla, FJ; Tijerina-Menchaca, R; El-Omar, EM. "Role of the polymorphic cytokines genes in gastric cancer in Mexico [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2002 SEP;51(2):A23-A23 (ISI:000178344100085 #55586)    
  136. Garza-Gonzalez, E; Perez-Perez, G I; Alanis-Aguilar, O; Tijerina-Menchaca, R; Maldonado-Garza, H J; Bosques-Padilla, F J. "Antibiotic susceptibility patterns of Helicobacter pylori strains isolated from northeastern Mexico". Journal of chemotherapy. 2002 Aug;14(4):342-345 (MEDL:12420850 #34620)    

    There are reports of increased antibiotic resistance rates in Helicobacter pylori strains around the world. The aim of this study was to determine the susceptibility patterns in H. pylori strains isolated in Monterrey, Mexico. We studied 62 strains isolated from the same number of symptomatic adult patients. Metronidazole (Mtz), clarithromycin (Cla), amoxicillin (Amx) and tetracycline (Tet) were tested by the E-test method. We observed that 37.1% of the strains were resistant to Mtz (MIC > or = 8 mg/L), and 8.1% to Cla (MIC > or = 8 mg/L), but we did not observe resistance to Amx (MIC > or = 2 mg/L) or Tet (MIC > or = 4 mg/L). In northeastern Mexico, the percentage of resistant strains was similar to that observed in developed countries. These results confirm that it is necessary to evaluate the susceptibility patterns of H. pylori strains by geographic area
  137. Garza-Gonzalez, Elvira; Perez-Perez, Guillermo I; Tijerina-Menchaca, Rolando; Maldonado-Garza, Hector J; Bosques-Padilla, Francisco J. "[Helicobacter pylori genotypes and their association with host's immune response]". Revista de gastroenterologia de Mexico. 2002 Jul-Sep;67(3):155-160 (MEDL:12653051 #34617)    

    BACKGROUND DATA: The study of Helicobacter pylori phenotypes and genotypes is mainly focused on two groups of putative bacterial virulence factors: the cag pathogenicity island (PAI), for which CagA is a marker, and the vacuolating cytotoxin VacA. Several studies have shown the clinical relevance of the determination of IgG anti-CagA antibodies. OBJECTIVE: To assess the prevalence of vacA and cagA genotypes of H. pylori and the association with IgG anti-CagA antibodies in symptomatic patients. METHODS: We studied 50 patients (mean age 53 years, range 15-92). PCR amplification of the vacA s and m regions was performed using the primers described (J Biol Chem 1995; 270: 17771). For cagA PCR, primers described by Rugge et al. were used (Cancer 1999; 85: 2506) and determination of IgG anti-CagA antibodies was done according to the method described by Blaser and Perez (Cancer Res 1995; 55: 2111). RESULTS: All 50 patients studied were positive for H. pylori. Of the 50 H. pylori strains, 7 (14%) were isolated from patients with peptic ulcer disease and 43 (86%) from patients with non-ulcer dyspepsia. The most frequent vacA genotype was s2/m2, associated with cagA-H. pylori strains (p < 0.01). Presence of cagA+ H. pylori strains correlated with the presence of IgG antibodies (Kappa = 0.680). Determination of IgG anti-CagA antibodies showed a sensitivity of 77.4%, specificity of 94.7%, positive value of 96% and negative predictive value of 72%. CONCLUSIONS: The most frequent H. pylori genotype found in northeastern Mexico was vacA s2/m2, cagA-. The presence of this genotype correlated with the clinical presentations observed in these patients. In addition, CagA serology showed a great specificity and good sensitivity that allow us to use this assay to assess the prevalence of CagA+ strains in Mexico
  138. Ghose, Chandrabali; Perez-Perez, Guillermo I; Dominguez-Bello, Maria-Gloria; Pride, David T; Bravi, Claudio M; Blaser, Martin J. "East Asian genotypes of Helicobacter pylori strains in Amerindians provide evidence for its ancient human carriage". Proceedings of the National Academy of Sciences of the United States of America. 2002 Nov 12;99(23):15107-15111 (MEDL:12417749 #34577)       

    Phylogenies of indigenous microbes have been used as surrogates for the origins of the hosts that carry them. Conversely, polymorphisms may be used to date the spread of a microbial species when information about their host populations is available. Therefore, we examined polymorphisms in Helicobacter pylori, which persistently colonize the human stomach, to test the hypothesis that they have been ancient inhabitants of humans. Three H. pylori loci that previously have been shown to have phylogeographic affinity have been analyzed for two populations with different ethnic origins from Venezuela. In a group of Amerindian subjects from Amazonia, East Asian H. pylori genotypes were present for each of the loci examined but were absent in a mestizo population from Caracas. These findings provide evidence that H. pylori has been present in humans at least since ancestors of Amerindians migrated from Asia more than 11,000 years ago
  139. Groves, Frank D; Perez-Perez, Guillermo; Zhang, Lian; You, Wei-cheng; Lipsitz, Stuart R; Gail, Mitchell H; Fraumeni, Joseph F Jr; Blaser, Martin J. "Serum antibodies to Helicobacter pylori and the CagA antigen do not explain differences in the prevalence of precancerous gastric lesions in two Chinese populations with contrasting gastric cancer rates". Cancer epidemiology biomarkers & prevention. 2002 Oct;11(10 Pt 1):1091-1094 (MEDL:12376512 #34582)    

    Incidence and mortality rates for gastric cancer in rural People's Republic of China differ greatly over short distances. In Shandong Province, we studied asymptomatic adult subjects from Bei Duan village (n = 196) in Linqu County (a high-risk area for gastric cancer) and from Shi Huang village (n = 192) in Cangshan County (a low-risk area for gastric cancer). The prevalence of advanced precancerous gastric lesions (APGL) was assessed by microscopic examination of endoscopic stomach biopsies. ELISAs were used to detect serum IgG to Helicobacter pylori whole-cell antigen and to the CagA protein. A logistic regression model was used to quantify the role of the two H. pylori seromarkers in explaining the differences in prevalence of APGL between the two villages after adjusting for age and sex. The prevalence of APGL was much greater in Bei Duan than in Shi Huang. Although H. pylori seroprevalence by the whole-cell ELISA was similar in the two populations, seroprevalence of CagA was significantly greater in Bei Duan. Although age, sex, and both H. pylori seromarkers were associated with APGL in the logistic regression model, the effect of village of residence remained strong after adjustment for all four covariates. Only a relatively small proportion of the difference in prevalence of APGL between these two rural Chinese populations can be explained by differences in H. pylori or CagA seroprevalence
  140. Levine, Steven M; Perez-Perez, Guillermo; Olivares, Asalia; Yee, Herman; Hanna, Bruce A; Blaser, Martin J. "PCR-based detection of Bacillus anthracis in formalin-fixed tissue from a patient receiving ciprofloxacin". Journal of clinical microbiology. 2002 Nov;40(11):4360-4362 (MEDL:12409432 #34579)       

    We demonstrate that Bacillus anthracis may be detected from a formalin-fixed, paraffin-embedded biopsy specimen, even after the patient has received antibiotic treatment. Although traditional PCR methods may not be sufficiently sensitive for anthrax detection in such patients, cycle numbers can be increased or PCR can be repeated by using an aliquot from a previous PCR as the template
  141. Limburg, Paul J; Stolzenberg-Solomon, Rachael Z; Colbert, Lisa H; Perez-Perez, Guillermo I; Blaser, Martin J; Taylor, Philip R; Virtamo, Jarmo; Albanes, Demetrius. "Helicobacter pylori seropositivity and colorectal cancer risk: a prospective study of male smokers". Cancer epidemiology biomarkers & prevention. 2002 Oct;11(10 Pt 1):1095-1099 (MEDL:12376513 #34581)    

    Because Helicobacter pylori colonization can produce systemic as well as local effects, it may be associated with carcinogenesis in extra gastric target organs. The currently available data regarding a possible link between H. pylori seropositivity and colorectal cancer risk are limited and inconclusive. In this prospective case-control study nested within the Alpha-Tocopherol, Beta-Carotene Study cohort of Finnish male smokers aged 50-69 years, we examined the association between H. pylori seropositivity and incident colorectal adenocarcinoma. Separate risk estimates were derived by colorectal cancer anatomical subsite and by H. pylori CagA seropositivity status. Demographic, dietary, and lifestyle variables were accounted for in the data analyses using information obtained from a prerandomization questionnaire and physical examination. Baseline serum samples from 118 cases and 236 matched controls were assayed for both H. pylori whole cell and H. pylori CagA antibodies. In total, 258 (73%) and 212 (60%) subjects expressed whole cell and CagA antibodies, respectively. H. pylori seropositivity, defined as one or both antibody assays positive, was present in 273 (77%) subjects. None of the seropositivity results were statistically different between cases and controls. Multivariate odds ratio (95% confidence interval) estimates for whole cell, cagA, and H. pylori seropositivity were 1.05 (0.63-1.74), 1.17 (0.74-1.84), and 0.91 (0.53-1.55), respectively. Stratification by colorectal cancer subsite yielded similarly unremarkable results. On the basis of these data, H. pylori carriage does not appear to be an important risk factor for colorectal adenocarcinoma
  142. Nomura, Abraham M Y; Lee, James; Stemmermann, Grant N; Nomura, Ryan Y; Perez-Perez, Guillermo I; Blaser, Martin J. "Helicobacter pylori CagA seropositivity and gastric carcinoma risk in a Japanese American population". Journal of infectious diseases. 2002 Oct 15;186(8):1138-1144 (MEDL:12355365 #34583)       

    Helicobacter pylori colonization is associated with gastric cancer, but whether and to what extent the risk is greater for strains with the cagA gene than for those without needs to be determined. Between 1967 and 1977, 9963 Japanese American men were recruited and examined. By 1996, incident cases of gastric carcinoma of the distal stomach had been diagnosed in 261 men. Stored serum samples from these case patients and 261 age-matched control subjects were tested for immunoglobulin G antibodies to H. pylori and to the CagA product of H. pylori, using antibody-specific enzyme-linked immunosorbent assays. Compared with H. pylori-negative, CagA-negative men, H. pylori-positive, CagA-negative men had an odds ratio (OR) of 2.7 (95% confidence interval [CI], 1.3-5.6) for intestinal gastric carcinoma. Men seropositive for both H. pylori and CagA had an OR of 4.1 (95% CI, 2.2-7.7). This suggests that colonization by an H. pylori strain with the cagA gene is associated with a greater risk of intestinal gastric carcinoma
  143. Nomura, Abraham M Y; Perez-Perez, Guillermo I; Lee, James; Stemmermann, Grant; Blaser, Martin J. "Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease". American journal of epidemiology. 2002 Jun 1;155(11):1054-1059 (MEDL:12034584 #34587)       

    Although colonization with any Helicobacter pylori strain is associated with peptic ulcer, it is uncertain whether the risk is greater with cagA(+) or cagA(-) strains, which differ in their biology. A nested case-control study was done, based on a cohort of 5,443 Japanese-American men examined on the Hawaiian island of Oahu from 1967 to 1970. A total of 150 men with gastric ulcer, 65 with duodenal ulcer, and 14 with both diseases were identified. The authors matched the 229 cases with 229 population controls and tested their serum for immunoglobulin G antibodies to H. pylori and immunoglobulin G antibodies to the cagA product of H. pylori using enzyme-linked immunosorbent assays. Persons with H. pylori positivity had an odds ratio of 4.0 (95% confidence interval (CI): 1.9, 8.5) for gastric ulcer and 2.5 (95% CI: 0.8, 7.4) for duodenal ulcer. For CagA positivity, the odds ratios were 1.4 (95% CI: 0.9, 2.4) for gastric ulcer and 2.6 (95% CI: 1.1, 5.8) for duodenal ulcer. Subjects who were seropositive for both H. pylori and CagA had an odds ratio of 4.4 (95% CI: 1.8, 10.5) for gastric ulcer and 5.8 (95% CI: 1.1, 30.0) for duodenal ulcer. The results suggest that colonization with a cag(+) H. pylori strain elevates the risk beyond that of a cag(-) H. pylori strain for both gastric and duodenal ulcers
  144. Perez-Perez, G I; Salomaa, A; Kosunen, T U; Daverman, B; Rautelin, H; Aromaa, A; Knekt, P; Blaser, M J. "Evidence that cagA(+) Helicobacter pylori strains are disappearing more rapidly than cagA(-) strains". Gut: journal of the British Society of Gastroenterology. 2002 Mar;50(3):295-298 (MEDL:11839704 #25600)       

    Background and aims: The prevalence of Helicobacter pylori colonisation in populations in developed country has been declining, as shown by community based serological surveys of adults in Vammala, Finland in 1973 and 1994. In this study, we determined whether the proportion of subjects colonised by cagA(+) or cagA(-) H pylori strains has changed as the overall prevalence of H pylori(+) has declined. Methods: We examined 911 sera from Vammala's study for antibodies to the CagA antigen of H pylori using a truncated CagA protein as the antigen in an ELISA and we examined the trend in acquisition and carriage of cagA(+) strains. Results: As expected, the prevalence of carriage of both cagA(+) and cagA(-) strains fell between 1973 and 1994 (p<0.001). However, the prevalence of cagA(+) strains among those <45 years declined (34% to 8%) significantly (p<0.001) more than for cagA(-) strains (12% to 6%). Of 221 subjects with paired serum samples, 12 (5.4%) changed H pylori status; the estimated seroconversion and reversion rates were 0.4% and 0.13% per year, respectively. Except for the few individuals who changed serostatus, absolute antibody levels to H pylori antigens, including CagA, changed little over the 21 year period. Conclusions: The decline in CagA seroprevalence predominantly reflects declining acquisition of cag(+) strains in younger subjects. In addition, these data confirm that H pylori acquisition chiefly occurs during childhood but continues to occur during adulthood, albeit at low rates, in developed countries
  145. Perez-Perez, GI; Olivares, AZ; Peek, RM; Tham, K; Blaser, MJ. "Detection of Helicobacter pylori in gastric juice by PCR [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2002 SEP;51(2):A110-A110 (ISI:000178344100384 #55589)    
  146. Romero-Gallo, Judith; Perez-Perez, Guillermo I; Novick, Richard P; Kamath, Patrick; Norbu, Tsering; Blaser, Martin J. "Responses of endoscopy patients in Ladakh, India, to Helicobacter pylori whole-cell and Cag A antigens". Clinical & diagnostic laboratory immunology. 2002 Nov;9(6):1313-1317 (MEDL:12414766 #34578)       

    Although Helicobacter pylori is a cosmopolitan colonizer of the human stomach, the responses among persons in remote populations from whom H. pylori was cultured have not been studied. We report on studies of 189 persons in the Ladakh region of India in whom serum immunoglobulin G responses to H. pylori whole-cell and Cag A antigens were measured. H. pylori was isolated from 68 of these patients. An H. pylori whole-cell antigen derived from Ladakhi strains outperformed a similar antigen from U.S. strains, as determined by antigen-specific enzyme-linked immunosorbent assays. In total, 95% of the population was seropositive, including individuals responding only to the Cag A antigen. Correlation with culture results showed that these were true positives and, therefore, that the H. pylori whole-cell serology was falsely negative in some cases. In addition to establishing a collection of H. pylori isolates from a remote area in the world, we show that use of H. pylori whole-cell and Cag A serology together increases the sensitivity for the detection of colonization
  147. Tijerina-Menchaca R; Bosques-Padilla FJ; Perez-Perez GI; Maldonado-Garza HJ; Garza-Gonzalez E. "Validacion del Western blot para la deteccion del genotipo de Helicobacter pylori". Medicina universitaria. 2002 Oct-Dec;4(17):212-216 (ORIGINAL:0004619 #38480)    
  148. Torres, Javier; Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Munoz, Leopoldo; Munoz, Onofre. "Specific serum immunoglobulin G response to urease and CagA antigens of Helicobacter pylori in infected children and adults in a country with high prevalence of infection". Clinical & diagnostic laboratory immunology. 2002 Jan;9(1):97-100 (MEDL:11777836 #34622)       

    Few studies have analyzed the immune response to Helicobacter pylori CagA and urease antigens across age groups in the same population. The aim of this study was to analyze the serologic immunoglobulin G (IgG) response to CagA and urease proteins in children and adults with gastrointestinal symptoms and belonging to the same population and similar socioeconomic levels. The serologic response was studied in 352 children and 293 adults with gastrointestinal symptoms. IgG antibodies against CagA and urease were tested by enzyme-linked immunosorbent assay methods using highly purified recombinant antigens. H. pylori infection was defined as a positive result in a serologic assay using whole-cell H. pylori extracts as the antigen. We found, in H. pylori-positive children, a seroprevalence of 46.9% to CagA and 16.2% to urease, whereas in H. pylori-positive adults, a seroprevalence of 78.9% to CagA and 59% to urease was found. In children, the magnitude of the response to CagA was significantly higher and the response to urease was significantly lower than those in adults. The kinetics of serologic response to CagA and to urease across age groups was contrastably different. Whereas CagA is a strong immunogen, urease is a poor immunogen during natural infection. These differences in the humoral response may be important for the short-term or long-term outcome of the infection. These results add to our knowledge of the epidemiology of H. pylori infection
  149. Dominguez-Bello, MG; Godette, G; Sundseth, R; Perez-Perez, GI; Wojciechowski, M; Bonaventura, C; Henkens, R. "Quantitative molecular electrochemical detection of Helicobacter pylori [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2001 SEP;49(4):A99-A99 (ISI:000171232500350 #54874)    
  150. Dominguez-Bello, MG; Perez-Perez, GI; Pacheco, N; Gonzalez, E; Garza-Gonzalez, E; Mora, R; Mago, V; Gomez, I. "Seroprevalence of Helicobacter pylori and CagA in areas of Venezuela with different gastric cancer risks [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2001 SEP;49(4):A36-A36 (ISI:000171232500127 #54873)    
  151. Figueiredo C; Quint W; Nouhan N; van Den Munckhof H; Herbrink P; Scherpenisse J; de Boer W; Schneeberger P; Perez-Perez G; Blaser MJ; van Doorn LJ. "Assessment of Helicobacter pylori vacA and cagA Genotypes and Host Serological Response". Journal of clinical microbiology. 2001 Apr;39(4):1339-1344 (MEDL:11283053 #19027)       

    Helicobacter pylori strains can be distinguished by genotyping of virulence-associated genes, such as vacA and cagA. Because serological discrimination between strain types would reduce the need for endoscopy, 61 patients carrying H. pylori were studied by vacA and cagA genotyping of H. pylori in gastric biopsy specimens and by detection of specific serum antibodies. Serological responses to H. pylori were determined by Helicoblot (versions 2.0 and 2.1). Antibodies to CagA also were determined by a rapid anti-CagA assay (Pyloriset screen CagA) as well as by two noncommercially developed enzyme immunoassays, each using a recombinant CagA protein. Assessment of performance of the Helicoblot assays indicated substantial interobserver variation, with kappa values between 0.20 and 0.93. There was no relationship between the serological profiles on the Helicoblot and the genotypes from the same patients, except for strong associations between the presence of anti-CagA and the cagA-positive and vacA s1 H. pylori genotypes. Detection of anti-CagA by the five different assays varied considerably, with kappa values ranging from 0.21 to 0.78. Using the cagA genotype as the 'gold standard,' the sensitivity and specificity of the anti-CagA assays varied from 71.4 to 85.7% and from 54.2 to 100%, respectively. Thus, serological profiles of antibodies to H. pylori are heterogeneous and, with the exception of anti-CagA antibodies, show no relation to the H. pylori vacA and cagA genotypes. Detection of anti-CagA antibodies is strongly dependent on the test used
  152. Garza-Gonzalez, E; Bosques-Padilla, FJ; Maldonado-Garza, H; Tijerina-Menchaca, R; Perez-Perez, GI. "Characterization of Helicobacter pylori strains isolated from the northeast region of Mexico [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2001 SEP;49(4):A34-A35 (ISI:000171232500121 #54872)    
  153. Ghose, C; Perez-Perez, GI; Dominguez-Bello, MG; Blaser, MJ. "Helicobacter pylori among indigenous peoples of Venezuela: European or Asian origin? [Meeting Abstract]". Clinical infectious diseases. 2001 OCT 1;33(7):1233-1233 (ISI:000171226900871 #54859)    
  154. Limburg P; Qiao Y; Mark S; Wang G; Perez-Perez G; Blaser M; Wu Y; Zou X; Dong Z; Taylor P; Dawsey S. "Helicobacter pylori seropositivity and subsite-specific gastric cancer risks in Linxian, China". Journal of the National Cancer Institute. 2001 Feb 7;93(3):226-233 (MEDL:11158192 #34627)       

    BACKGROUND: Helicobacter pylori carriage (i.e., persistent exposure to the organism without gastric epithelial cell invasion) is an established risk factor for noncardia gastric cancer. However, its association with the risk of cancer of the gastric cardia is controversial. Consequently, we designed this prospective, nested case-control study to further explore the subsite-specific gastric cancer risks associated with H. pylori seropositivity (a surrogate marker for persistent exposure). METHODS: A total of 99 patients with gastric cardia cancer, 82 patients with noncardia gastric cancer, and 192 cancer-free subjects were selected from among the participants (n = 29 584) of a nutrition intervention trial previously conducted in Linxian, China. H. pylori seropositivity was determined by assaying for the presence of H. pylori whole cell and CagA antibodies in baseline serum samples from all subjects. Seropositivity was defined as one or both serum assays being positive. Odds ratios (ORs) for subsite-specific gastric cancer were estimated by multivariate logistic regression analyses. All statistical comparisons were two-sided (alpha =.05). RESULTS: H. pylori seropositivity rates for subjects with gastric cardia cancer, noncardia gastric cancer, and gastric cardia and noncardia cancers combined were 70% (P =.02), 72% (P: =.01), and 71% (P =.003) compared with 56% for cancer-free control subjects. OR estimates for H. pylori seropositivity were 1.87 (95% confidence interval [CI] = 1.10 to 3.17) for gastric cardia cancer, 2.29 (95% CI = 1.26 to 4.14) for noncardia gastric cancer, and 2.04 (95% CI = 1.31 to 3.18) for gastric cardia and noncardia cancers combined. CONCLUSIONS: H. pylori seropositivity was associated with increased risks for both gastric cardia cancer and noncardia gastric cancer in this well-characterized cohort. Thus, H. pylori carriage may increase the risk of cancer throughout the stomach
  155. Moss SF; Sordillo EM; Abdalla AM; Makarov V; Hanzely Z; Perez-Perez GI; Blaser MJ; Holt PR. "Increased gastric epithelial cell apoptosis associated with colonization with cagA + Helicobacter pylori strains". Cancer research. 2001 Feb 15;61(4):1406-1411 (MEDL:11245442 #19030)    

    Gastric colonization by Helicobacter pylori is a risk factor for noncardia gastric cancer. The association between H. pylori and cancer may be attributable to increased epithelial cell turnover, possibly related to antigastric antibodies. Two previous studies reported a disproportionate increase in proliferation relative to apoptosis in patients with H. pylori strains expressing the virulence-related cagA gene. This has led to the hypothesis that an abrogation of apoptosis by cagA-positive strains may promote neoplasia. We, therefore, examined the effect of H. pylori on gastric epithelial proliferation, apoptosis, and the presence of serum antiparietal cell antibodies in a large prospective study. Proliferation and apoptosis were evaluated 'blindly' using validated immunohistochemical methods in two antral and two gastric corpus biopsies from 60 patients with nonulcer dyspepsia, and results were correlated with the presence of serum antiparietal cell antibodies. H. pylori colonization was assessed by histology, biopsy urease test, and serology. Proliferation was increased 2-fold in both antrum and corpus in H. pylori-positive patients, was not related to H. pylori cagA status, and was positively correlated with histological gastritis. Apoptosis was increased in the antrum and body only in patients with cagA-positive H. pylori strains. Antiparietal cell antibodies were not more prevalent in H. pylori colonization, and their presence was inversely related to epithelial apoptosis scores we therefore conclude that in patients with nonulcer dyspepsia, H. pylori carriage is associated with increased proliferation. Futhermore the cag pathogenicity island is associated with increased apoptosis. Our results do not support the hypothesis that there is a relative deficiency of gastric epithelial cell apoptosis associated with the carriage of cagA-positive strains. Host factors may be more important than bacterial products in determining the long-term outcome of H. pylori colonization
  156. Munoz L; Gonzalez-Valencia G; Perez-Perez GI; Giono-Cerezo S; Munoz O; Torres J. "A comparison of Lewis x and Lewis y expression in Helicobacter pylori obtained from children and adults". Journal of infectious diseases. 2001 Apr 1;183(7):1147-1151 (MEDL:11237846 #25603)       

    There are no reports, to our knowledge, on the expression of Lewis (Le) antigens in Helicobacter pylori isolates from children. The aim of this study was to compare the expression of Le antigens by H. pylori isolates from children and from adults. Totals of 278 clones from 22 children with recurrent abdominal pain and 293 clones from 22 adults with (n=10) or without (n=12) duodenal ulcer were studied. Expression of Le(x) and Le(y) antigens was determined by ELISA, using monoclonal anti-Le antibodies. The Le phenotype of the patients was determined in gastric juice with a hemagglutination assay. Clones expressing Le(x) were more common in children than in adults (55.4% vs. 33.4%, respectively; P<.001), and Le(y) was more common in adults than in children (81.6% vs. 66%, respectively; P<.01). A trend analysis showed a significant decline in frequency of clones expressing Le(x) with age (P=.021). In this community, expression of Le antigens differs in H. pylori isolates obtained from children versus adults
  157. Perez-Perez, GI; Dominguez-Bello, MG; Ghose, C; Pacheco, N; Gonzalez, E; Mago, V; de Novoa, PG; Gomez, I; Mora, R; Blaser, MJ. "Presence of specific Asian Helicobacter pylori genotypes in Amerindians in Venezuela [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2001 SEP;49(4):A33-A33 (ISI:000171232500115 #54871)    
  158. Perez-Perez, GI; Garza-Gonzalez, E; Flores-Gutierrez, JP; Maldonado-Garza, HJ; Bosques-Padilla, FJ; Tijerina-Menchaca, R. "Comparison of invasive and serological tests for the diagnostic of Helicobacter pylori [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2001 SEP;49(4):A104-A104 (ISI:000171232500369 #54875)    
  159. Stolzenberg-Solomon RZ; Blaser MJ; Limburg PJ; Perez-Perez G; Taylor PR; Virtamo J; Albanes D. "Helicobacter pylori seropositivity as a risk factor for pancreatic cancer". Journal of the National Cancer Institute. 2001 Jun 20;93(12):937-941 (MEDL:11416115 #34624)       

    BACKGROUND: Pancreatic cancer is among the most fatal cancers worldwide and one for which few preventable risk factors have been established. Gastric carriage of Helicobacter pylori, particularly cytotoxin-associated gene-A-positive (CagA+) strains, is known to be a risk factor for peptic ulcer disease and gastric cancer and may have a similar etiologic relationship with pancreatic cancer. METHODS: We investigated the association of H. pylori carriage and exocrine pancreatic cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years at baseline. Case subjects (n = 121) were matched on date of baseline serum collection, study center, age, trial intervention, and completion of the dietary questionnaire to 226 control subjects who were alive at the time the matching case subject was diagnosed and who remained free of cancer, during up to 10 years of follow-up. Levels of immunoglobulin G antibodies to H. pylori whole-cell and CagA+ antigens from stored baseline serum were measured by enzyme-linked immunosorbent assay. Smoking-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression. Statistical tests were two-sided. RESULTS: Seroprevalence of H. pylori was 82% and 73% among case and control subjects, respectively. Compared with seronegative subjects, those with H. pylori or CagA+ strains were at statistically significantly elevated risk of pancreatic cancer (OR = 1.87 [95% CI = 1.05 to 3.34]; OR = 2.01 [95% CI = 1.09 to 3.70], respectively). CONCLUSIONS: Our findings support a possible role for H. pylori carriage in the development of exocrine pancreatic cancer
  160. Tham KT; Peek RM; Atherton JC; Cover TL; Perez-Perez GI; Shyr Y; Blaser MJ. "Helicobacter pylori genotypes, host factors, and gastric mucosal histopathology in peptic ulcer disease". Human pathology. 2001 Mar;32(3):264-273 (MEDL:11274634 #19028)       

    From 183 patients undergoing upper gastrointestinal endoscopy, we used antral and corpus gastric biopsies for bacterial culture and histopathologic examination, blood samples to detect immunoglobulin G antibodies against Helicobacter pylori, and H pylori genomic DNA to analyze cytotoxin-associated gene A (cagA) and vacuolating cytotoxin (vacA) genotypes. As expected, among H pylori biopsy-positive patients, those with duodenal ulcer (DU) (n = 34) had significantly more severe chronic and acute inflammation (P <.001) and epithelial degeneration (P =.004) in the gastric antrum than in the gastric corpus. Each of those 3 parameters and H pylori density were significantly higher in the antrum of patients with DU than in patients with gastric ulcer (GU) or no ulcer. Colonization with vacA s1/cagA-positive strains of H pylori was associated with inflammation and epithelial degeneration in gastric mucosa and increased risk for peptic ulcer disease (PUD), whereas colonization with vacA s2m2/cagA-negative strains was associated with mild gastric histopathology and was not associated with any significant risk for PUD. The predominant H pylori strains in African Americans were vacA s1bm1/cagA-positive, whereas all genotypes were well represented in non-Hispanic-Caucasians. By multivariate analysis, H pylori colonization was significantly associated with DU (Adjusted odds ratio [AdjOR] = 3.2 [1.4-7.2]) and nonsteroidal anti-inflammatory drugs (NSAID) use was inversely associated (AdjOR = 0.3 [0.2-0.7]). NSAID use (AdjOR = 4.3 [1.02-18.5]) and African-American ethnicity (AdjOR = 10.9 [2.6-50]) were significantly associated with GU. Smoking and age were not significantly associated with either DU or GU. These data indicate that DU is associated with an antral-dominant gastritis, and H pylori genotype and NSAID use independently contribute to the pathogenesis of PUD. HUM PATHOL 32:264-273. This is a US Government work. There are no restrictions on its use
  161. Torres J; Camorlinga M; Perez-Perez G; Gonzalez G; Munoz O. "Validation of the string test for the recovery of Helicobacter pylori from gastric secretions and correlation of its results with urea breath test results, serology, and gastric pH levels". Journal of clinical microbiology. 2001 Apr;39(4):1650-1651 (MEDL:11283108 #34625)       

    The efficacy of the string culture test to isolate Helicobacter pylori from gastric secretions of 28 volunteers was studied. With the urea breath test (UBT) as the 'gold standard,' the string culture test showed a sensitivity of 75% and a specificity of 100%. The results of string culture did not correlate with the UBT results, with serum antibody levels, or with the pH levels of gastric secretions
  162. Torres J; Camorlinga-Ponce M; Perez-Perez G; Madrazo-De la Garza A; Dehesa M; Gonzalez-Valencia G; Munoz O. "Increasing multidrug resistance in Helicobacter pylori strains isolated from children and adults in Mexico". Journal of clinical microbiology. 2001 Jul;39(7):2677-2680 (MEDL:11427594 #34623)       

    The susceptibilities to three antimicrobials of 195 Helicobacter pylori strains isolated from Mexican patients is reported; 80% of the strains were resistant to metronidazole, 24% were resistant to clarithromycin, and 18% presented a transient resistance to amoxicillin. Resistance to two or more antimicrobials increased significantly from 1995 to 1997
  163. You WC; Zhang L; Pan KF; Jiang J; Chang YS; Perez-Perez GI; Liu WD; MA JL; Gail MH; Blaser MJ; Fraumeni JF; Xu GW. "Helicobacter pylori prevalence and CagA status among children in two counties of China with high and low risks of gastric cancer". Annals of epidemiology. 2001 Nov;11(8):543-546 (MEDL:11709273 #25601)       

    BACKGROUND: Studies in adult populations in selected countries with widely varying rates of gastric cancer have shown a weak correlation between gastric cancer mortality rates and the prevalence of CagA+ strains of H. pylori. However, only limited data are available in ethnically homogenous populations with varying rates in the same region. METHODS; We compared the prevalence of H. pylori in general and of CagA+ strains in particular among children in Shandong Province, China in areas at high (Linqu County) and low risk (Cangshan County) of gastric cancer. H. pylori status among children aged 3 to 12 years was determined by 13C-UBT, and CagA status was determined by enzyme-linked immunosorbent assay (ELISA). Because of the difficulty in obtaining blood from young children aged 3 to 4 years and from some children aged 5 years, CagA status was determined among part of children 5 years old and children 6 to 12 years old. RESULTS; Among 98 children aged 3 to 12 years in Linqu, 68 (69.4%) was H. pylori-positive, as compared with 29 (28.7%) among 101 children in Cangshan. Among children positive for 13C-UBT, the proportion of the CagA+ strains were identified was 46 (88.5%) of 52 in Linqu and 13 (81.3%) of 16 in Cangshan, respectively. CONCLUSIONS: The prevalence of H. pylori was nearly three times higher among children in Linqu than in Cangshan, which may contribute to the large differential in gastric cancer rates for two neighboring populations in Shandong Province
  164. Ando T; Perez-Perez GI; Kusugami K; Ohsuga M; Bloch KC; Blaser MJ. "Anti-CagA immunoglobulin G responses correlate with interleukin-8 induction in human gastric mucosal biopsy culture". Clinical & diagnostic laboratory immunology. 2000 Sep;7(5):803-809 (MEDL:10973458 #19041)       

    Helicobacter pylori persists in the human stomach despite eliciting both cellular and humoral immune responses and inducing proinflammatory cytokines. To determine whether local humoral and cytokine responses are related to each other and to histologic responses, we studied 66 Japanese patients who underwent gastroscopy. Using specific enzyme-linked immunosorbent assays, we examined gastric antral mucosal-organ biopsy culture supernatants to assess interleukin-6 (IL-6) and interleukin-8 (IL-8) levels and antibody responses to H. pylori whole-cell antigens CagA, HspA, and HspB. Of the patients studied, 11 were H. pylori negative and 55 were H. pylori positive; by PCR, all strains were cagA(+). As expected, compared to H. pylori-negative patients, H. pylori-positive patients had significantly higher humoral responses to all H. pylori antigens and had higher IL-8 (47.8+/-3.5 versus 10.1+/-4.3 ng/mg of biopsy protein; P<0.001) and IL-6 levels (2.8+/-0.3 versus 0.26+/-0.2 ng/mg of protein; P<0.001). Among the H. pylori-positive patients, supernatant anti-CagA immunoglobulin G (IgG) levels were significantly associated with H. pylori density (P<0.005) and neutrophil infiltration (P<0.005) scores. Anti-CagA immunoglobulin A levels were correlated with intestinal metaplasia (P<0.05). Mononuclear cell infiltration scores were significantly associated with supernatant IL-6 levels (P<0.005) and with IgG responses to whole-cell antigens (P<0.05). Supernatant IL-8 levels were significantly associated with anti-CagA IgG (r = 0.75, P<0.001). Anti-CagA responses correlated with neutrophil infiltration, intestinal metaplasia, H. pylori density, and IL-8 levels, suggesting that the absolute levels of these antibodies may be markers for gastric inflammation and premalignant changes in individual hosts
  165. Everhart JE; Kruszon-Moran D; Perez-Perez GI; Tralka TS; McQuillan G. "Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States". Journal of infectious diseases. 2000 Apr;181(4):1359-1363 (MEDL:10762567 #25605)       

    The seroprevalence of Helicobacter pylori infection was examined in the adult US population and among different ethnic groups. Stored sera from 7465 adult participants in the first phase of the third National Health and Nutritional Examination Survey (1988-1991) were tested with a sensitive and specific IgG ELISA, to diagnose infection. Seroprevalence of H. pylori among all participants was 32. 5%. This increased with age, from 16.7% for persons 20-29 years old to 56.9% for those > or =70 years old. Age-adjusted prevalence was substantially higher among non-Hispanic blacks (52.7%) and Mexican Americans (61.6%) than among non-Hispanic whites (26.2%). After controlling for age and other associated factors, the odds ratios relative to non-Hispanic whites decreased for non-Hispanic blacks, from 3.9 (95% confidence interval [CI], 3.1-4.9) to 3.3 (95% CI, 2. 6-4.2), and for Mexican Americans, from 6.3 (95% CI, 4.8-8.3) to 2.3 (95% CI, 1.6-3.5). The high prevalence of H. pylori infection among non-Hispanic blacks and Mexican Americans is partially explained by other factors associated with infection
  166. Haley, CA; D'Agata, EM; Perez-Perez, GI; Blaser, MJ; McGowan, CC. "Association between H-pylori seropositivity and atrophic Gastritis in HIV-infected persons [Meeting Abstract]". Clinical infectious diseases. 2000 JUL;31(1):234-234 (ISI:000088950900170 #54483)    
  167. Harford WV; Barnett C; Lee E; Perez-Perez G; Blaser MJ; Peterson WL. "Acute gastritis with hypochlorhydria: report of 35 cases with long term follow up". Gut: journal of the British Society of Gastroenterology. 2000 Oct;47(4):467-472 (MEDL:10986205 #19040)       

    BACKGROUND: Between 1976 and 1987, 35 cases of acute gastritis with hypochlorhydria (AGH) were seen in our research laboratory. The aims of this study were to determine the natural history of AGH and the role of Helicobacter pylori in its pathogenesis. METHODS: Archived serum and gastric biopsy samples obtained from AGH subjects were examined for evidence of H pylori colonisation. Twenty eight of 33 (85%) surviving AGH subjects returned a mean of 12 years after AGH for follow up studies, including determination of H pylori antibodies, basal and peak acid output, endoscopy, and gastric biopsies. A matched control group underwent the same studies. RESULTS: Archived material provided strong evidence of new H pylori acquisition in a total of 14 subjects within two months, in 18 within four months, and in 22 within 12 months of recognition of AGH. Prevalence of H pylori colonisation at follow up was 82% (23 of 28) in AGH subjects, significantly (p<0.05) higher than in matched controls (29%). Basal and peak acid output returned to pre-AGH levels in all but two subjects. CONCLUSIONS: One of several possible initial manifestations of H pylori acquisition in adults may be AGH. While H pylori colonisation usually persists, hypochlorhydria resolves in most subjects
  168. Keenan J; Day T; Neal S; Cook B; Perez-Perez G; Allardyce R; Bagshaw P. "A role for the bacterial outer membrane in the pathogenesis of Helicobacter pylori infection". FEMS microbiology letters. 2000 Jan 15;182(2):259-264 (MEDL:10620676 #34631)       

    Helicobacter pylori infection in humans is associated with diverse of clinical outcomes which are partly attributed to bacterial strain differences. Secreted bacterial products are thought to be involved in the pathogenesis caused by this non-invasive bacterium. Electron microscopy of gastric biopsies from infected individuals revealed blebbing of the H. pylori outer membrane, similar to the process of outer membrane vesicle shedding which occurs when the bacterium is grown in broth. Porins, a class of proinflammatory proteins, were observed in the outer membrane vesicles. The VacA cytotoxin, which is produced by 50-60% of H. pylori strains and associated with increased pathogenesis of infection, was also found to be vesicle-associated and biologically active. This supports the hypothesis that these vesicles represent a vehicle for the delivery of damaging bacterial products to the gastric mucosa
  169. Legath, AJ; Perez-Perez, GI; Rautelin, H; Kosunen, TU; Blaser, MJ. "Long term stability of serum IgG1/IgG2 antibody ratios to Helicobacter pylori in healthy adults [Meeting Abstract]". Clinical infectious diseases. 2000 JUL;31(1):233-233 (ISI:000088950900169 #54482)    
  170. Legath, AJ; Perez-Perez, GI; Rautelin, H; Kosunen, TU; Peek, RM; Sack, RB; Blaser, MJ. "Serum IgG recognition of Helicobacter pylori antigens after acute acquisition or persistent carriage of the organism [Meeting Abstract]". Clinical infectious diseases. 2000 JUL;31(1):233-233 (ISI:000088950900168 #54481)    
  171. Loffeld RJ; Werdmuller BF; Kuster JG; Perez-Perez GI; Blaser MJ; Kuipers EJ. "Colonization with cagA-positive Helicobacter pylori strains inversely associated with reflux esophagitis and Barrett's esophagus". Digestion. 2000;62(2-3):95-99 (MEDL:11025356 #19035)       

    AIM: The hypothesis that colonization with cagA(+) Helicobacter pylori strains protects against the development of gastroesophageal reflux disease (GERD) and its complications is tested. METHODS: Patients with reflux esophagitis and Barrett's esophagus were studied. Antral biopsy specimens were obtained for detection of H. pylori. A serum sample was obtained for determination of IgG antibodies to H. pylori and to the CagA protein. RESULTS: 736 patients were studied. 118 patients had reflux esophagitis, 36 had Barrett's esophagus, 108 had hiatal hernia without signs of inflammation (the reflux group), and 20 patients had esophageal or stomach cancer. The remaining 454 patients had no signs of GERD. The 262 patients with reflux disease had a significantly lower prevalence of H. pylori (34.9%) than the 454 controls (54.6%; p<0. 001). Among 310 H. pylori-positive patients from whom serum was available, colonization with cagA(+) strains was detected in 59% in the control group versus 35% in the reflux group (p<0.001). Conclusion: Patients with reflux esophagitis and Barrett's esophagus have a significantly lower prevalence of H. pylori colonization than controls, in particular of the cagA(+) type. These data suggest that colonization with cagA(+) H. pylori strains may be protective against the development of GERD
  172. Mao HV; Lak BV; Long T; Chung NQ; Thang DM; Hop TV; Chien NN; Hoan PQ; Henley KS; Perez-Perez GI; Connor BA; Stone CD; Chey WD. "Omeprazole or ranitidine bismuth citrate triple therapy to treat Helicobacter pylori infection: a randomized, controlled trial in Vietnamese patients with duodenal ulcer". Alimentary pharmacology & therapeutics. 2000 Jan;14(1):97-101 (MEDL:10632652 #25607)    

    AIM: To evaluate the effectiveness of triple therapy containing either omeprazole or ranitidine bismuth citrate (RBC) to treat H. pylori infection in Vietnamese duodenal ulcer patients. METHODS: Patients infected with H. pylori were randomized to receive either omeprazole (20 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (OAC), or RBC (400 mg b.d.), clarithromycin (500 mg b.d.) and amoxycillin (1 g b.d.) for 10 days (RAC). H. pylori eradication and ulcer healing was established by a follow-up oesophagogastroduodenoscopy (EGD) at least 4 weeks after therapy. Side-effects and compliance were assessed. RESULTS: One hundred and four out of 108 (96%) patients with a duodenal ulcer were infected with H. pylori. Eighty per cent of infected patients had detectable CagA IgG antibodies. Fifty-seven patients received OAC and 47 received RAC. OAC eradicated H. pylori in 91 and 86% of patients by per protocol (PP) and intention-to-treat (ITT) analysis, respectively. PP and ITT eradication rates for RAC were 96 and 91%. Ulcer healing at the follow-up EGD was 89% with OAC and 100% with RAC. Side-effects were minor. No patient failed to complete the protocol due to side-effects. CONCLUSION: Triple therapy with either omeprazole or RBC is highly effective in eradicating H. pylori and healing duodenal ulcer in Vietnamese patients
  173. Perez-Perez GI. "Accurate diagnosis of Helicobacter pylori. Culture, including transport". Gastroenterology clinics of North America. 2000 Dec;29(4):879-884 (MEDL:11190072 #21247)       

    Bacteriology laboratories are interested in culturing H. pylori for several reasons: (1) to investigate its growth requirements and metabolism; (2) for diagnostic purposes; (3) to establish the antibiotic susceptibility of isolates; (4) to identify potential virulence factors; and (5) to investigate microbial host-cell interactions. Despite the reasons listed, culture of H. pylori from gastric biopsy specimens is becoming less popular among clinical laboratories and physicians. The main reason is that it has become generally accepted that culture techniques are too demanding with many factors that must be controlled, in addition to simple and less expensive methods now available. Some of the disadvantages of culture include (1) special conditions for specimen transportation, (2) speed in processing of the sample to increase the probability of recovering the organism, (3) the use of expensive and complicated media with special conditions for maintenance, (4) the need for special incubation conditions, and (5) the length of time necessary to obtain a result for establishing treatment options in the patient. This article reviews aspects of H. pylori culture that could explain use being relegated to only a few clinical laboratories, some regional laboratories, and reference centers. There are several misconceptions in relation to culture techniques, such as transport and the processing of biopsy specimens. This article has mentioned simple and clear points that optimize the recovery rates of H. pylori by culture
  174. Perez-Perez GI. "[Is the association of Helicobacter pylori with humans a classical example of parasitism?]". Revista de gastroenterologia de Mexico. 2000 Oct-Dec;65(4 Suppl 2):7-12 (MEDL:11464623 #25602)    

    Since the first report of the potential role of Helicobacter pylori as cause of disease of the upper intestinal tract of humans, a major controversial has developed. First, the role of H. pylori as the etiological agent of duodenal and gastric ulcer has been questioned. Second, the possibility of H. pylori as a major risk factor in the development of distal gastric cancer has not been fully accepted. It is interesting that at the time when the etiological role of H. pylori is almost universally accepted, series of publications have suggested that the elimination of H. pylori from asymptomatic individuals might represent a risk for the development of other upper gastrointestinal diseases such as GERD and cancer of the esophagus. The main goal of this revision is to describe the virulence factors associated with H. pylori as well as its interaction with the human host, to establish whether H. pylori should be considered a true pathogen or only a commensal
  175. Perez-Perez GI; Israel DA. "Role of iron in Helicobacter pylori: its influence in outer membrane protein expression and in pathogenicity". European journal of gastroenterology & hepatology. 2000 Dec;12(12):1263-1265 (MEDL:11192313 #25604)       

    The acquisition of iron is a necessity for bacterial growth in Helicobacterpylori, as it is for other organisms. In addition, iron is a critical factor for the virulence of this organism. Therefore, it is not surprising that H. pylori isolates have the potential to express at least three major iron acquisition mechanisms. The association of H. pylori infection with host iron deficiency might indicate that the iron-scavenging systems play a role in the virulence of H. pylori
  176. Perez-Perez, GI; Legath, AJ; Rautelin, H; Kosunen, TU; Blaser, MJ. "Long-term stability of serum IgG1/IgG2 antibody ratios to Helicobacter pylori in healthy adults [Meeting Abstract]". Gut: journal of the British Society of Gastroenterology. 2000 OCT;47(4):A35-A36 (ISI:000090131200138 #54409)    
  177. Riveron AM; Lopez-Canovas L; Baez-Camargo M; Flores E; Perez-Perez G; Luna-Arias JP; Orozco E. "Circular and linear DNA molecules in the Entamoeba histolytica complex molecular karyotype". European biophysics journal. 2000;29(1):48-56 (MEDL:10826778 #34630)       

    Entamoeba histolytica genome was analysed by pulsed field gel electrophoresis under conditions to separate linear chromosomes in the 170-1400 kb range. We identified linear DNA molecules of 227, 366, 631, 850, 1112 and 1361 kb (mean sizes obtained by three different methods) and we estimated their reorientation times and migration velocities at various experimental conditions. DNA shift mobility assays, using ethidium bromide, suggested that bands migrating at 227 and 631 kb contain linear and circular DNA, whereas a band at 436 kb has only circular DNA. We obtained a regression equation relating sizes of supercoiled DNA molecules with their migration velocities during a pulse at constant electric field and temperature. We also developed a computer program (EHPATTERNS) that predicts the migration per pulse and the resolution order of circular and linear E. histolytica DNA at different pulse times and constant driving and frictional forces. The simulation showed that linear DNA molecules frequently co-migrate with circular molecules, but circular molecules change when the pulse time varies. This molecular mixture generates broad bands and difficulties in the interpretation of the molecular karyotype of E. histolytica
  178. Riveron AM; Lopez-Canovas L; Flores E; Perez-Perez G; Luna-Arias JP; Orozco E. "Algorithm to predict MiniCHEF electrophoresis patterns of Entamoeba histolytica DNA". Archives of medical research (Mexico). 2000 Jul-Aug;31(4 Suppl):S279-S281 (MEDL:11070316 #34628)       
  179. Torres J; Perez-Perez G; Goodman KJ; Atherton JC; Gold BD; Harris PR; la Garza AM; Guarner J; Munoz O. "A comprehensive review of the natural history of Helicobacter pylori infection in children". Archives of medical research (Mexico). 2000 Sep-Oct;31(5):431-469 (MEDL:11179581 #34626)       

    Across populations of children, Helicobacter pylori prevalence ranges from under 10% to over 80%. Low prevalence occurs in the U.S., Canada, and northern and western Europe; high prevalence occurs in India, Africa, Latin America, and eastern Europe. Risk factors include socioeconomic status, household crowding, ethnicity, migration from high prevalence regions, and infection status of family members. H. pylori infection is not associated with specific symptoms in children; however, it is consistently associated with antral gastritis, although its clinical significance is unclear. Duodenal ulcers associated with H. pylori are seldom seen in children under 10 years of age. H. pylori-infected children demonstrate a chronic, macrophagic, and monocytic inflammatory cell infiltrate and a lack of neutrophils, as compared with the response observed in adults. The effect of H. pylori infection on acid secretion in children remains poorly defined. The events that occur during H. pylori colonization in children should be studied more thoroughly and should include urease activity, motility, chemotaxis, adherence, and downregulation of the host response. The importance of virulence determinants described as relevant for disease during H. pylori infection has not been extensively studied in children. Highly sensitive and specific methods for the detection of H. pylori in children are needed, especially in younger pediatric populations in which colonization is in its early phases. Criteria for the use of eradication treatment in H. pylori-infected children need to be established. Multicenter pediatric studies should focus on the identification of risk factors, which can be used as prognostic indicators for the development of gastroduodenal disease later in life
  180. Vaezi MF; Falk GW; Peek RM; Vicari JJ; Goldblum JR; Perez-Perez GI; Rice TW; Blaser MJ; Richter JE. "CagA-positive strains of Helicobacter pylori may protect against Barrett's esophagus". American journal of gastroenterology. 2000 Sep;95(9):2206-2211 (MEDL:11007219 #19038)       

    OBJECTIVE: Helicobacter pylori (H. pylori) colonization is associated with chronic gastritis, peptic ulcer disease, and adenocarcinoma of the distal stomach. However, the role of H. pylori strain variation in complicated gastroesophageal reflux disease, especially Barrett's esophagus, is unknown. Therefore, the aim of this study was to evaluate the prevalence of colonization by cagA+ and cagA- H. pylori strains in the spectrum of gastroesophageal reflux disease, including Barrett's esophagus. METHODS: A total of 251 patients undergoing endoscopy were categorized into four groups: controls, patients with gastroesophageal reflux disease alone, and patients with short- and long-segment Barrett's esophagus. All patients underwent upper endoscopies with biopsies and serum collections. H. pylori and degree of mucosal inflammation in gastric biopsies were assessed and serological assessment made for H. pylori and cagA status. RESULTS: The overall prevalence of H. pylori colonization in the study population was 35% (95% confidence interval = 29.5-41.4%) which did not differ significantly among the groups. However, colonization by cagA+ H. pylori strains was significantly more prevalent among controls (11/25; 44%) and patients with gastroesophageal reflux disease (13/36; 36%) than in patients with short-segment (2/10; 20%) or long-segment Barrett's esophagus (0/18; 0%). Patients with Barrett's esophagus were less likely to be colonized by cagA+ H. pylori strains than reflux patients without Barrett's esophagus (odds ratio = 0.27, 95% confidence interval = 0.11-0.67, p = 0.004). CONCLUSIONS: Colonization by cagA+ H. pylori strains may be protective against the formation of short- and long-segment Barrett's esophagus and its malignant complications
  181. Yanez P; la Garza AM; Perez-Perez G; Cabrera L; Munoz O; Torres J. "Comparison of invasive and noninvasive methods for the diagnosis and evaluation of eradication of Helicobacter pylori infection in children". Archives of medical research (Mexico). 2000 Jul-Aug;31(4):415-421 (MEDL:11068086 #34629)       

    BACKGROUND: Acquisition of Helicobacter pylori infection occurs mainly during childhood. To study the events associated with H. pylori colonization in children it is important to have reliable diagnostic methods. Our objective was to validate invasive and noninvasive tests for diagnosis of H. pylori infection in children before and after antimicrobial treatment. METHODS: Before treatment, invasive rapid urease test (RUT) culture and histology, as well as the noninvasive carbon-13 urea breath test (13C-UBT) and serology were validated in 59 children. The gold standard for H. pylori infection was any of three positives of the five tests. After antimicrobial treatment culture, histology, and 13C-UBT were validated in 43 children to determine eradication. The gold standard for eradication was negative in all three tests. RESULTS: For primary diagnosis, RUT was the most sensitive and specific test, followed by 13C-UBT, which performed better than serology, culture, and histology. Concordance tests also showed that RUT and 13C-UBT performed better. For determination of eradication, 13C-UBT and histology were better than culture, which showed poor sensitivity. CONCLUSIONS: RUT performed better for primary diagnosis. However, as endoscopy might not be indicated in most children, 13C-UBT could be the test of choice for diagnosis of H. pylori infection both before and after eradication treatment

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