Faculty Bibliography

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

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

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

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

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

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

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