NYU Health Sciences Libraries Faculty Bibliography

Zhiheng Pei

School of Medicine. Pathology; Medicine. Associate Professor of Pathology and Medicine, 2000-
  1. Ligr, Martin; Wu, Xinyu; Daniels, Garrett; Zhang, David; Wang, Huamin; Hajdu, Cristina; Wang, Jinhua; Pan, Ruimin; Pei, Zhiheng; Zhang, Lanjing; Melis, Marcovalerio; Pincus, Matthew R; Saunders, John K; Lee, Peng; Xu, Ruliang. "Imbalanced expression of Tif1gamma inhibits pancreatic ductal epithelial cell growth". American journal of cancer research. 2014;4(3):196-210 (MEDL:24959375 #1051012)    

    Transcriptional intermediary factor 1 gamma (Tif1gamma) (Ectodermin/PTC7/RFG7/TRIM33) is a transcriptional cofactor with an important role in the regulation of the TGFbeta pathway. It has been suggested that it competes with Smad2/Smad3 for binding to Smad4, or alternatively that it may target Smad4 for degradation, although its role in carcinogenesis is unclear. In this study, we showed that Tif1gamma interacts with Smad1/Smad4 complex in vivo, using both yeast two-hybrid and coimmunoprecipitation assays. We demonstrated that Tif1gamma inhibits transcriptional activity of the Smad1/Smad4 complex through its PHD domain or bromo-domainin pancreatic cells by luciferase assay. Additionally, there is a dynamic inverse relationship between the levels of Tif1gamma and Smad4 in benign and malignant pancreatic cell lines. Overexpression of Tif1gamma resulted in decreased level of Smad4. Both overexpression and knockdown of Tif1gamma resulted in growth inhibition in both benign and cancerous pancreatic cell lines, attributable to a G2-phase cell cycle arrest, but only knockdown of Tif1gamma reduces tumor cell invasiveness in vitro. Our study demonstrated that imbalanced expression of Tif1gamma results in inhibition of pancreatic ductal epithelial cell growth. In addition, knockdown of Tif1gamma may inhibit tumor invasion. These data suggest that Tif1gamma might serve as a potential therapeutic target for pancreatic cancer.
  2. Ligr, Martin; Wu, Xinyu; Daniels, Garrett; Zhang, David; Wang, Huamin; Hajdu, Cristina; Wang, Jinhua; Pan, Ruimin; Pei, Zhiheng; Zhang, Lanjing; Melis, Marovalerio; Pinchus, Matthew R; Saunders, John K; Lee, Peng; Xu, Ruliang. "Imbalanced expression of Tif1ã inhibits pancreatic ductal epithelial cell growth". American journal of cancer research. 2014;4(3):196-210 (ORIGINAL:0009001 #1032102)      
  3. Ma, Yingfei; Madupu, Ramana; Karaoz, Ulas; Nossa, Carlos W; Yang, Liying; Yooseph, Shibu; Yachimski, Patrick S; Brodie, Eoin L; Nelson, Karen E; Pei, Zhiheng. "Human papillomavirus community in healthy persons, defined by metagenomics analysis of human microbiome project shotgun sequencing data sets". Journal of virology. 2014 May;88(9):4786-4797 (MEDL:24522917 #884102)       

    Human papillomavirus (HPV) causes a number of neoplastic diseases in humans. Here, we show a complex normal HPV community in a cohort of 103 healthy human subjects, by metagenomics analysis of the shotgun sequencing data generated from the NIH Human Microbiome Project. The overall HPV prevalence was 68.9% and was highest in the skin (61.3%), followed by the vagina (41.5%), mouth (30%), and gut (17.3%). Of the 109 HPV types as well as additional unclassified types detected, most were undetectable by the widely used commercial kits targeting the vaginal/cervical HPV types. These HPVs likely represent true HPV infections rather than transitory exposure because of strong organ tropism and persistence of the same HPV types in repeat samples. Coexistence of multiple HPV types was found in 48.1% of the HPV-positive samples. Networking between HPV types, cooccurrence or exclusion, was detected in vaginal and skin samples. Large contigs assembled from short HPV reads were obtained from several samples, confirming their genuine HPV origin. This first large-scale survey of HPV using a shotgun sequencing approach yielded a comprehensive map of HPV infections among different body sites of healthy human subjects. IMPORTANCE: This nonbiased survey indicates that the HPV community in healthy humans is much more complex than previously defined by widely used kits that are target selective for only a few high- and low-risk HPV types for cervical cancer. The importance of nononcogenic viruses in a mixed HPV infection could be for stimulating or inhibiting a coexisting oncogenic virus via viral interference or immune cross-reaction. Knowledge gained from this study will be helpful to guide the designing of epidemiological and clinical studies in the future to determine the impact of nononcogenic HPV types on the outcome of HPV infections.
  4. Yang, Liying; Chaudhary, Noami; Baghdadi, Jonathan; Pei, Zhiheng. "Microbiome in reflux disorders and esophageal adenocarcinoma". Cancer journal. 2014 May-Jun;20(3):207-210 (MEDL:24855009 #1013072)       

    The incidence of esophageal adenocarcinoma has increased dramatically in the United States and Europe since the 1970s without apparent cause. Although specific host factors can affect risk of disease, such a rapid increase in incidence must be predominantly environmental. In the stomach, infection with Helicobacter pylori has been linked to chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. However, the role of H. pylori in the development of esophageal adenocarcinoma is not well established. Meanwhile, several studies have established that a complex microbiome in the distal esophagus might play a more direct role. Transformation of the microbiome in precursor states to esophageal adenocarcinoma-reflux esophagitis and Barrett metaplasia-from a predominance of gram-positive bacteria to mostly gram-negative bacteria raises the possibility that dysbiosis is contributing to pathogenesis. However, knowledge of the microbiome in esophageal adenocarcinoma itself is lacking. Microbiome studies open a new avenue to the understanding of the etiology and pathogenesis of reflux disorders.
  5. Ahn, Jiyoung; Sinha, Rashmi; Pei, Zhiheng; Dominianni, Christine; Goedert, James J.; Hayes, Richard B.; Yang, Liying. "Human gut microbiome and risk of colorectal cancer, a case-control study [Meeting Abstract]". Cancer research. 2013 APR 15;73(8 1 1):- (ISI:000331220600149 #853262)       
  6. Ahn, Jiyoung; Sinha, Rashmi; Pei, Zhiheng; Dominianni, Christine; Wu, Jing; Shi, Jianxin; Goedert, James J; Hayes, Richard B; Yang, Liying. "Human gut microbiome and risk for colorectal cancer". Journal of the National Cancer Institute. 2013 Dec;105(24):1907-1911 (MEDL:24316595 #737232)       

    We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94 control subjects. 16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME pipeline. Taxonomic differences were confirmed with quantitative polymerase chain reaction and adjusted for false discovery rate. All statistical tests were two-sided. From 794217 16S rRNA gene sequences, we found that CRC case subjects had decreased overall microbial community diversity (P = .02). In taxonomy-based analyses, lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of Fusobacterium (multivariable odds ratio [OR] = 4.11; 95% confidence interval [CI] = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found in case subjects compared with control subjects. Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention.
  7. Daniels, Garrett; Pei, Zhiheng; Logan, Susan K; Lee, Peng. "Mini-review: androgen receptor phosphorylation in prostrate cancer". American journal of clinical & experimental urology. 2013;1:25-29 (ORIGINAL:0008652 #745662)      

    Androgen receptor (AR) plays an important role in the tumorigenesis and progression of prostate cancer (PCa), and is the primary therapeutic target for PCa treatment. AR activity can be regulated via phosphorylation at multiple phosphorylation sites within the protein. Modifications by phosphorylation alter AR function, including its cellular localization, stability and transcriptional activity, ultimately leading to changes in cancer cell biology and disease progression. Here we present a brief overview of AR phosphorylation sites in PCa, focusing on functional roles of phospho-AR (p-AR) species, relevance in PCa disease progression, and potential as biomarkers and/or therapeutic targets through the use of kinase inhibitors. Additionally, recent evidence has shown the important role of AR activity in the cancer associated stroma on PCa growth and progression. The phosphorylation status of epithelial and stromal AR may be distinct; however, the current data available on stromal AR phosphorylation is limited. Further research will determine global view on the synergistic effects of phosphorylation across multiple AR sites in both epithelial and stromal cells and validate whether together they can be used as prognostic markers and/or effective therapeutic targets for PCa. (AJCEU1311003)
  8. Hale, Christopher S; Huang, Hongying; Melamed, Jonathan; Xu, Ruliang; Roberts, Larry; Wieczorek, Rosemary; Pei, Zhiheng; Lee, Peng. "Urethral adenocarcinoma associated with intestinal-type metaplasia, case report and literature review". International journal of clinical & experimental pathology. 2013;6(8):1665-1670 (MEDL:23923086 #484212)    

    The presence of glandular epithelium in urinary tract biopsies poses a diagnostic challenge. Intestinal metaplasia of the urethra may be seen in many congenital, iatrogenic, and reactive conditions, as well as in association with malignant conditions such as urethral adenocarcinoma. We present a case of a 61 year-old woman presenting with microscopic hematuria. Successive biopsies showed glandular epithelium with focal atypia in close association with inflammation, but no overt malignancy. Only on surgical resection was the associated high grade adenocarcinoma revealed. When intestinal-type mucosa is present within a urinary tract biopsy, associated malignancy may be present only focally. Thorough sampling and consideration of the differential diagnosis is imperative.
  9. Hu, J; Franzen, O; Pei, Z; Itzkowitz, S; Peter, I. "Multiple double-barcoding 16S sequencing on the MiSeq platform to study the gut microbiome in ashkenazi jews with crohn's disease [Meeting Abstract]". Inflammatory bowel diseases. 2013 December 2013;19:S119-S121 (EMBASE:71356040 #838112)    

    BACKGROUND: Crohn's disease (CD) results from defects in the mucosal immune response to luminal factors in genetically susceptible individuals. The role of the gut microbiome in CD pathogenesis has been suggested by several studies. Until recently454-pyrosequencing approach was considered the gold standard for microbiome studies. However, newer, more efficient, and cost-effective technologies are now available(1). Compared to other next-generation platforms, Illumina MiSeq has the advantage of higher throughput, better sequencing accuracy, and a shorter running time (24hrs). In this study, we designed a cost-efficient double-barcoding 16S rRNA sequencing using the MiSeq 2x250 pair-end method to evaluate the performance of MiSeq on 16S rRNA sequencing of the fecal microbiome of Ashkenazi Jews (AJ, a genetically homogeneous high-risk population) with and without Crohn's disease. (Figure presented) METHODS: Stool from 27 AJ-CD patients (in remission) and 16 AJ healthy controls was analyzed. We established a protocol for a multiple double-barcoding 16S rRNA sequencing using the MiSeq system (Fig. 1) and performed a taxon-based and phylogenetic analysis. Total DNA was extracted from the fecal samples and PCRamplified with unique 8-bp barcoded primer sets targeting the 347-803 V3-to-V4 hypervariable regions. The 460bp PCR amplicons were pooled in equal molar amounts and sent for library preparation and sequencing. RESULTS: A single MiSeq run generated a total of ;10 million paired reads. Our quality report revealed more than 95% reads with the average sequencing quality score passing Q30 and more than 50% reads with the quality of any individual base calling passing Q30. After merging, filtering by quality of the individual base calling and read length (>400bp), we obtained, on average, ;10 thousand reads per sample. QIIME pipeline(2) was applied for taxonomy assignment (Fig. 2a) and diversity analysis. Repeated measurements of 8 subjects showed high correlations (r2 > 0.99). We observed a!
  10. Hu, Jianzhong; Nomura, Yoko; Bashir, Ali; Fernandez-Hernandez, Heriberto; Itzkowitz, Steven; Pei, Zhiheng; Stone, Joanne; Loudon, Holly; Peter, Inga. "Diversified microbiota of meconium is affected by maternal diabetes status". PLoS ONE. 2013;8(11):e78257-e78257 (e78257) (MEDL:24223144 #714872)       

    OBJECTIVES: This study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status. METHODS: The first intestinal discharge (meconium) was collected from 23 newborns stratified by maternal diabetes status: 4 mothers had pre-gestational type 2 diabetes mellitus (DM) including one mother with dizygotic twins, 5 developed gestational diabetes mellitus (GDM) and 13 had no diabetes. The meconium microbiome was profiled using multi-barcode 16S rRNA sequencing followed by taxonomic assignment and diversity analysis. RESULTS: All meconium samples were not sterile and contained diversified microbiota. Compared with adult feces, the meconium showed a lower species diversity, higher sample-to-sample variation, and enrichment of Proteobacteria and reduction of Bacteroidetes. Among the meconium samples, the taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the DM group showing higher alpha-diversity than that of no-diabetes or GDM groups. No global difference was found between babies delivered vaginally versus via Cesarean-section. Regression analysis showed that the most robust predictor for the meconium microbiota composition was the maternal diabetes status that preceded pregnancy. Specifically, Bacteroidetes (phyla) and Parabacteriodes (genus) were enriched in the meconium in the DM group compared to the no-diabetes group. CONCLUSIONS: Our study provides evidence that meconium contains diversified microbiota and is not affected by the mode of delivery. It also suggests that the meconium microbiome of infants born to mothers with DM is enriched for the same bacterial taxa as those reported in the fecal microbiome of adult DM patients.
  11. Khan, Abraham; Sam Serouya, Sam; Poles, Michael A; Traube, Morris; Halahalli-Srinivasa, Vani Murthy; Chen, Chien Ting; Yang, Liying; Pei, Zhiheng; Francois, Fritz. "A Burning Issue: Defining GERD in Non-Erosive Disease [Meeting Abstract]". Gastroenterology. 2013;144(5 Suppl 1):S851-S851 (ORIGINAL:0008452 #523002)    
  12. 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.
  13. Statnikov, Alexander; Henaff, Mikael; Narendra, Varun; Konganti, Kranti; Li, Zhiguo; Yang, Liying; Pei, Zhiheng; Blaser, Martin J; Aliferis, Constantin F; Alekseyenko, Alexander V. "A comprehensive evaluation of multicategory classification methods for microbiomic data". Microbiome. 2013;1(1):11-11 (MEDL:24456583 #764032)       

    BACKGROUND: Recent advances in next-generation DNA sequencing enable rapid high-throughput quantitation of microbial community composition in human samples, opening up a new field of microbiomics. One of the promises of this field is linking abundances of microbial taxa to phenotypic and physiological states, which can inform development of new diagnostic, personalized medicine, and forensic modalities. Prior research has demonstrated the feasibility of applying machine learning methods to perform body site and subject classification with microbiomic data. However, it is currently unknown which classifiers perform best among the many available alternatives for classification with microbiomic data. RESULTS: In this work, we performed a systematic comparison of 18 major classification methods, 5 feature selection methods, and 2 accuracy metrics using 8 datasets spanning 1,802 human samples and various classification tasks: body site and subject classification and diagnosis. CONCLUSIONS: We found that random forests, support vector machines, kernel ridge regression, and Bayesian logistic regression with Laplace priors are the most effective machine learning techniques for performing accurate classification from these microbiomic data.
  14. Francois, Fritz; Khan, Abraham; Yang, Liying; Serouya, Sam M; Pei, Zhiheng. "Gastroesophageal Reflux Disease: Molecular Predictors in Neoplastic Progression of Barrett's Esophagus" IN: Gastroesophageal reflux disease. [S. l.] : InTech, cop. 2012. . p.21-60.  (OCLC:840098715-01 #519652)      
  15. Hu, Jianzhong; Bashir, Ali; Pendleton, Matthew; Pei, Zhiheng; Itzkowitz, Steven; Peter, Inga. "Multiple Bar-Coding 16S Sequencing by Pacbio RS Platform to Study the Gut Microbiome in Ashkenazi Jews With Crohn's Disease [Meeting Abstract]". Inflammatory bowel diseases. 2012 DEC;18 1 1:S114-S115 (ISI:000311172600294 #203182)    
  16. Pei, Anna; Li, Hongru; Oberdorf, William E.; Alekseyenko, Alexander V.; Parsons, Tamasha; Yang, Liying; Gerz, Erika A.; Lee, Peng; Xiang, Charlie; Nossa, Carlos W.; Pei, Zhiheng. "Diversity of 5S rRNA genes within individual prokaryotic genomes [Letter]". FEMS microbiology letters. 2012 OCT;335(1):11-18 (ISI:000308582400002 #180171)       
  17. Pei, Anna; Li, Hongru; Oberdorf, William E; Alekseyenko, Alexander V; Parsons, Tamasha; Yang, Liying; Gerz, Erika A; Lee, Peng; Xiang, Charlie; Nossa, Carlos W; Pei, Zhiheng. "Diversity of 5S rRNA genes within individual prokaryotic genomes". FEMS microbiology letters. 2012 Jul;:11-18 (MEDL:22765222 #175922)       

    We examined intragenomic variation of paralogous 5S rRNA genes to evaluate the concept of ribosomal constraints. In a dataset containing 1161 genomes from 779 unique species, 96 species exhibited > 3% diversity. Twenty-seven species with > 10% diversity contained a total of 421 mismatches between all pairs of the most dissimilar copies of 5S rRNA genes. The large majority (401 of 421) of the diversified positions were conserved at the secondary structure level. The high diversity was associated with partial rRNA operon, split operon, or spacer length-related divergence. In total, these findings indicated that there are tight ribosomal constraints on paralogous 5S rRNA genes in a genome despite of the high degree of diversity at the primary structure level.
  18. 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.
  19. Saxena, Deepak; Li, Yihong; Yang, Liying; Pei, Zhiheng; Poles, Michael; Abrams, William R; Malamud, Daniel. "Human Microbiome and HIV/AIDS". Current HIV/AIDS reports. 2012 Mar;9(1):44-51 (MEDL:22193889 #156495)       

    Understanding of the human microbiome continues to grow rapidly; however, reports on changes in the microbiome after HIV infection are still limited. This review surveys the progress made in methodology associated with microbiome studies and highlights the remaining challenges to this field. Studies have shown that commensal oral, gut, vaginal, and penile bacteria are vital to the health of the human immune system. Our studies on crosstalk among oral and gastrointestinal soluble innate factors, HIV, and microbes indicated that the oral and gut microbiome was altered in the HIV-positive samples compared to the negative controls. The importance of understanding the bacterial component of HIV/AIDS, and likelihood of "crosstalk" between viral and bacterial pathogens, will help in understanding the role of the microbiome in HIV-infected individuals and facilitate identification of novel antiretroviral factors for use as novel diagnostics, microbicides, or therapeutics against HIV infection.
  20. Tripathi, Prabhanshu; Stefka, Andrew; Feehley, Taylor; Patton, Tiffany; Chang, Eugene; Antonopoulos, Dionysios; Pei, Zhiheng; Nagler, Cathryn. "Antibiotic induced alterations in the commensal microbiome reduce CD4+Foxp3+Tregs in the colonic lamina propria and increase allergic responses to food [Meeting Abstract]". Journal of immunology. 2012 MAY 1;188:- (ISI:000304659702197 #169553)    
  21. Tripathi, Prabhanshu; Stefka, Andrew; Feehley, Taylor; Pei, Zhiheng; Nagler, Cathryn. "Tlr4-/- mice have reduced proportions of CD4+Foxp3+Tregs in the colonic lamina propria and increased susceptibility to allergic responses to food [Meeting Abstract]". Journal of immunology. 2012 MAY 1;188:- (ISI:000304659702193 #169554)    
  22. Yang, Liying; Francois, Fritz; Pei, Zhiheng. "Molecular pathways: pathogenesis and clinical implications of microbiome alteration in esophagitis and barrett esophagus". Clinical cancer research. 2012 Apr;18(8):2138-2144 (MEDL:22344232 #164339)       

    Esophageal adenocarcinoma is preceded by the development of reflux-related intestinal metaplasia or Barrett esophagus, which is a response to inflammation of the esophageal squamous mucosa, reflux esophagitis. Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to the diverse microbial ecosystem or microbiome and inducing chronic inflammation. The esophageal microbiome is altered in both esophagitis and Barrett esophagus, characterized by a significant decrease in gram-positive bacteria and an increase in gram-negative bacteria in esophagitis and Barrett esophagus. Lipopolysaccharides (LPS), a major structure of the outer membrane in gram-negative bacteria, can upregulate gene expression of proinflammatory cytokines via activation of the Toll-like receptor 4 and NF-kappaB pathway. The potential impact of LPS on reflux esophagitis may be through relaxation of the lower esophageal sphincter via inducible nitric oxide synthase and by delaying gastric emptying via cyclooxygenase-2. Chronic inflammation may play a critical role in the progression from benign to malignant esophageal disease. Therefore, analysis of the pathways leading to chronic inflammation in the esophagus may help to identify biomarkers in patients with Barrett esophagus for neoplastic progression and provide insight into molecular events suitable for therapeutic intervention in prevention of esophageal adenocarcinoma development in patients with reflux esophagitis and Barrett esophagus. Clin Cancer Res; 18(8); 2138-44. (c)2012 AACR.
  23. Ahn, Jiyoung; Yang, Liying; Paster, Bruce J; Ganly, Ian; Morris, Luc; Pei, Zhiheng; Hayes, Richard B. "Oral microbiome profiles: 16S rRNA pyrosequencing and microarray assay comparison". PLoS ONE. 2011;6(7):e22788-e22788 (e22788) (MEDL:21829515 #156313)       

    OBJECTIVES: The human oral microbiome is potentially related to diverse health conditions and high-throughput technology provides the possibility of surveying microbial community structure at high resolution. We compared two oral microbiome survey methods: broad-based microbiome identification by 16S rRNA gene sequencing and targeted characterization of microbes by custom DNA microarray. METHODS: Oral wash samples were collected from 20 individuals at Memorial Sloan-Kettering Cancer Center. 16S rRNA gene survey was performed by 454 pyrosequencing of the V3-V5 region (450 bp). Targeted identification by DNA microarray was carried out with the Human Oral Microbe Identification Microarray (HOMIM). Correlations and relative abundance were compared at phylum and genus level, between 16S rRNA sequence read ratio and HOMIM hybridization intensity. RESULTS: The major phyla, Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria were identified with high correlation by the two methods (r = 0.70 approximately 0.86). 16S rRNA gene pyrosequencing identified 77 genera and HOMIM identified 49, with 37 genera detected by both methods; more than 98% of classified bacteria were assigned in these 37 genera. Concordance by the two assays (presence/absence) and correlations were high for common genera (Streptococcus, Veillonella, Leptotrichia, Prevotella, and Haemophilus; Correlation = 0.70-0.84). CONCLUSION: Microbiome community profiles assessed by 16S rRNA pyrosequencing and HOMIM were highly correlated at the phylum level and, when comparing the more commonly detected taxa, also at the genus level. Both methods are currently suitable for high-throughput epidemiologic investigations relating identified and more common oral microbial taxa to disease risk; yet, pyrosequencing may provide a broader spectrum of taxa identification, a distinct sequence-read record, and greater detection sensitivity.
  24. DeSantis, Todd Z; Keller, Keith; Karaoz, Ulas; Alekseyenko, Alexander V; Singh, Navjeet N S; Brodie, Eoin L; Pei, Zhiheng; Andersen, Gary L; Larsen, Niels. "Simrank: Rapid and sensitive general-purpose k-mer search tool". BMC ecology. 2011;11:11-11 (MEDL:21524302 #177250)       

    BACKGROUND: Terabyte-scale collections of string-encoded data are expected from consortia efforts such as the Human Microbiome Project http://nihroadmap.nih.gov/hmp. Intra- and inter-project data similarity searches are enabled by rapid k-mer matching strategies. Software applications for sequence database partitioning, guide tree estimation, molecular classification and alignment acceleration have benefited from embedded k-mer searches as sub-routines. However, a rapid, general-purpose, open-source, flexible, stand-alone k-mer tool has not been available. RESULTS: Here we present a stand-alone utility, Simrank, which allows users to rapidly identify database strings the most similar to query strings. Performance testing of Simrank and related tools against DNA, RNA, protein and human-languages found Simrank 10X to 928X faster depending on the dataset. CONCLUSIONS: Simrank provides molecular ecologists with a high-throughput, open source choice for comparing large sequence sets to find similarity.
  25. 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
  26. Jain, Shilpa; Singhal, Shashideep; Francis, Franto; Hajdu, Cristina; Wang, Jin-Hua; Suriawinata, Arief; Wang, Yin-Quan; Zhang, Miao; Weinshel, Elizabeth H; Francois, Fritz; Pei, Zhi-Heng; Lee, Peng; Xu, Ru-Liang. "Association of overexpression of TIF1gamma with colorectal carcinogenesis and advanced colorectal adenocarcinoma". World journal of gastroenterology : WJG. 2011 Sep 21;17(35):3994-4000 (MEDL:22046087 #140416)       

    AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1gamma), Smad4 and transforming growth factor-beta (TGFbetaR) across a spectrum representing colorectal cancer (CRC) development. METHODS: Tissue microarrays were prepared from archival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1gamma, Smad4 and TGFbetaRII. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4). RESULTS: Overexpression of TIF1gamma was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P < 0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFbetaRII was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P < 0.05). Furthermore, there was a correlation between TIF1gamma overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P < 0.05). The levels of TIF1gamma overexpression were significantly higher in stage III than in stage I and II CRC (P < 0.05). CONCLUSION: The findings suggest that over-expression of TIF1gamma occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome
  27. Lee, Lili; Zhou, Fang; Simms, Anthony; Wieczorek, Rosemary; Fang, Yanan; Subietas-Mayol, Antonio; Wang, Beverly; Heller, Patricia; Huang, Hongying; Pei, Zhiheng; Osman, Iman; Meehan, Shane; Lee, Peng. "Metastatic balloon cell malignant melanoma: a case report and literature review". International journal of clinical & experimental pathology. 2011 Mar;4(3):315-321 (MEDL:21487528 #133175)    

    A case of metastatic balloon cell malignant melanoma (BCMM) is presented. The balloon melanoma cells (BMC) were absent in the shave biopsy of the primary lesion and present as a minor component in the wide and deep excision. A subsequent right neck lymph node metastasis showed complete replacement of the lymph node by large, foamy cells. Though the tumor was amelanocytic and Fontana-Masson stain failed to reveal melanin, it stained positively for S-100, HMB-45, and Melan-A. Ultrastructurally, the foamy cells were characterized by cytoplasmic vacuolization and a lack of melanosomes. The differential diagnosis of metastatic balloon cell malignant melanoma is broad, and clinicopathologic correlation may play a critical role in achieving the correct diagnosis
  28. Pei, Anna; Oberdorf, William E; Nossa, Carlos W; Chokshi, Pooja; Blaser, Martin J; Yang, Liying; Rosmarin, David M; Pei, Zhiheng. "Diversity of 23S rRNA Genes Within Individual Prokaryotic Genomes" IN: Handbook of molecular microbial ecology. I. Metagenomics and complementary approaches. Hoboken, N.J. : Wiley-Blackwell, 2011. . p.17-28.  (OCLC:729724623-01 #845682)    
  29. Wu, Xinyu; Chen, Fei; Sahin, Aysegul; Albarracin, Constance; Pei, Zhiheng; Zou, Xuanyi; Singh, Baljit; Xu, Ruliang; Daniels, Garrett; Li, Yirong; Wei, Jianjun; Blake, Marvin; Schneider, Robert J; Cowin, Pamela; Lee, Peng. "Distinct function of androgen receptor coactivator ARA70alpha and ARA70beta in mammary gland development, and in breast cancer". Breast cancer research & treatment. 2011 Jul;128(2):391-400 (MEDL:20814820 #138162)       

    Steroid receptor coactivators are important in regulating the function of the receptors in endocrine organ development and in cancers, including breast. Androgen receptor (AR) coactivator ARA70, was first identified as a gene fused to the ret oncogene and later characterized as an AR coactivator. We previously reported that the full length ARA70alpha functions as a tumor suppressor gene and that ARA70beta functions as an oncogene in prostate cancer. Here we show that both ARA70alpha and ARA70beta function as AR and estrogen receptor (ER) coactivators in breast cancer cells. However, ARA70alpha and ARA70beta serve different functions in mammary gland development and breast cancer tumorigenesis. We observed hypoplastic development of mammary glands in MMTV driven ARA70alpha transgenic mice and overgrowth of mammary glands in ARA70beta transgenic mice at virgin and pregnant stages. We determined that ARA70alpha inhibited cell proliferation, and that ARA70beta promotes proliferation in MCF7 breast cancer cells. These effects were observed in hormone-free media, or in media with androgen or estrogen, though to varying degrees. Additionally, we observed that ARA70beta strongly enhanced the invasive ability of MCF7 breast cancer cells in in vitro Matrigel assays. Significantly, decreased ARA70alpha expression is associated with increased tendency of breast cancer metastasis. In summary, ARA70alpha and ARA70beta have distinct effects in mammary gland development and in the progression of breast cancer
  30. Nossa, Carlos W; Oberdorf, William E; Yang, Liying; Aas, Jorn A; Paster, Bruce J; Desantis, Todd Z; Brodie, Eoin L; Malamud, Daniel; Poles, Michael A; Pei, Zhiheng. "Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut microbiome". World journal of gastroenterology : WJG. 2010 Sep;16(33):4135-4144 (MEDL:20806429 #156189)       

    AIM: To design and validate broad-range 16S rRNA primers for use in high throughput sequencing to classify bacteria isolated from the human foregut microbiome. METHODS: A foregut microbiome dataset was constructed using 16S rRNA gene sequences obtained from oral, esophageal, and gastric microbiomes produced by Sanger sequencing in previous studies represented by 219 bacterial species. Candidate primers evaluated were from the European rRNA database. To assess the effect of sequence length on accuracy of classification, 16S rRNA genes of various lengths were created by trimming the full length sequences. Sequences spanning various hypervariable regions were selected to simulate the amplicons that would be obtained using possible primer pairs. The sequences were compared with full length 16S rRNA genes for accuracy in taxonomic classification using online software at the Ribosomal Database Project (RDP). The universality of the primer set was evaluated using the RDP 16S rRNA database which is comprised of 433 306 16S rRNA genes, represented by 36 phyla. RESULTS: Truncation to 100 nucleotides (nt) downstream from the position corresponding to base 28 in the Escherichia coli 16S rRNA gene caused misclassification of 87 (39.7%) of the 219 sequences, compared with misclassification of only 29 (13.2%) sequences with truncation to 350 nt. Among 350-nt sequence reads within various regions of the 16S rRNA gene, the reverse read of an amplicon generated using the 343F/798R primers had the least (8.2%) effect on classification. In comparison, truncation to 900 nt mimicking single pass Sanger reads misclassified 5.0% of the 219 sequences. The 343F/798R amplicon accurately assigned 91.8% of the 219 sequences at the species level. Weighted by abundance of the species in the esophageal dataset, the 343F/798R amplicon yielded similar classification accuracy without a significant loss in species coverage (92%). Modification of the 343F/798R primers to 347F/803R increased their universality among foregut species. Assuming that a typical polymerase chain reaction can tolerate 2 mismatches between a primer and a template, the modified 347F and 803R primers should be able to anneal 98% and 99.6% of all 16S rRNA genes in the RDP database. CONCLUSION: 347F/803R is the most suitable pair of primers for classification of foregut 16S rRNA genes but also possess universality suitable for analyses of other complex microbiomes.
  31. Pei, Anna Y; Oberdorf, William E; Nossa, Carlos W; Agarwal, Ankush; Chokshi, Pooja; Gerz, Erika A; Jin, Zhida; Lee, Peng; Yang, Liying; Poles, Michael; Brown, Stuart M; Sotero, Steven; Desantis, Todd; Brodie, Eoin; Nelson, Karen; Pei, Zhiheng. "Diversity of 16S rRNA genes within individual prokaryotic genomes". Applied & environmental microbiology. 2010 Jun;76(12):3886-3897 (MEDL:20418441 #156291)       

    Analysis of intragenomic variation of 16S rRNA genes is a unique approach to examining the concept of ribosomal constraints on rRNA genes; the degree of variation is an important parameter to consider for estimation of the diversity of a complex microbiome in the recently initiated Human Microbiome Project (http://nihroadmap.nih.gov/hmp). The current GenBank database has a collection of 883 prokaryotic genomes representing 568 unique species, of which 425 species contained 2 to 15 copies of 16S rRNA genes per genome (2.22 +/- 0.81). Sequence diversity among the 16S rRNA genes in a genome was found in 235 species (from 0.06% to 20.38%; 0.55% +/- 1.46%). Compared with the 16S rRNA-based threshold for operational definition of species (1 to 1.3% diversity), the diversity was borderline (between 1% and 1.3%) in 10 species and >1.3% in 14 species. The diversified 16S rRNA genes in Haloarcula marismortui (diversity, 5.63%) and Thermoanaerobacter tengcongensis (6.70%) were highly conserved at the 2 degrees structure level, while the diversified gene in B. afzelii (20.38%) appears to be a pseudogene. The diversified genes in the remaining 21 species were also conserved, except for a truncated 16S rRNA gene in "Candidatus Protochlamydia amoebophila." Thus, this survey of intragenomic diversity of 16S rRNA genes provides strong evidence supporting the theory of ribosomal constraint. Taxonomic classification using the 16S rRNA-based operational threshold could misclassify a number of species into more than one species, leading to an overestimation of the diversity of a complex microbiome. This phenomenon is especially seen in 7 bacterial species associated with the human microbiome or diseases.
  32. Sturt, Amy S; Yang, Liying; Sandhu, Kuldip; Pei, Zhiheng; Cassai, Nicholas; Blaser, Martin J. "Streptococcus gallolyticus subspecies pasteurianus (biotype II/2), a newly reported cause of adult meningitis". Journal of clinical microbiology. 2010 Jun;48(6):2247-2249 (MEDL:20357211 #133500)       

    We report the first case of adult meningitis confirmed to be due to Streptococcus gallolyticus subsp. pasteurianus. Phenotypically reported as Streptococcus bovis biotype II/2, 16S rRNA sequencing revealed S. gallolyticus subsp. pasteurianus. Because of taxonomic uncertainties, S. gallolyticus subsp. pasteurianus may be an underrecognized agent of systemic infections
  33. Chaudhry, S; Lubitz, S; Newman, K; Pei, ZH; Shepard, T; Danoff, A. "Adenomatoid Tumor of the Adrenal Gland Case Report of a Rare Adrenal Lesion". Endocrinologist. 2009 SEP-OCT;19(5):233-236 (ISI:000270014300012 #102951)    

    Objective: To report a rare case of an adenomatoid tumor (AT) of the adrenal gland. Methods: We present a case report, including clinical, radiologic, and pathologic findings, and review the relevant literature. Results: We describe a 60-year-old man in whom an AT of the adrenal gland was discovered incidentally, and review the literature. Fewer than 20 cases of these tumors are reported. The tumors range in size from 0.5 to 11 cm, are more common in men, and are more frequently located in the left adrenal gland. A specific imaging phenotype has not been characterized. Histologic features, including infiltration into the surrounding tissue, and presence of signet ring cells, may raise concern of a more aggressive neoplasm. Immunologic staining for mesothelial and endothelial markers may be necessary to establish a definitive diagnosis. Conclusion: ATs of the adrenal gland are rare benign lesions. They are difficult to differentiate from more common adrenal tumors by computerized tamography (CT) or magnetic resonance imaging (MRI). Pathologic findings also can present challenges in distinguishing these lesions from more aggressive neoplasms. ATs should be considered in the differential diagnosis of adrenal masses, whether discovered as incidental radiologic, surgical, or pathologic findings, or at autopsy, so that the potential consequences of misdiagnosis may be avoided
  34. Newman, Kia; Stahl-Herz, Jay; Kabiawu, Oluyomi; Newman, Elliot; Wieczorek, Rosemary; Wang, Beverly; Pei, Zhiheng; Bannan, Michael; Lee, Peng; Xu, Ruliang. "Pancreatic carcinoma with multilineage (acinar, neuroendocrine, and ductal) differentiation". International journal of clinical & experimental pathology. 2009;2(6):602-607 (MEDL:19636408 #101289)    

    The preponderance of pancreatic tumors is adenocarcinoma of the ductal type; carcinomas with multiple lineage differentiation are extremely rare. We report an unusual case of pancreatic carcinoma with combined acinar and neuroendocrine differentiation and minor ductal component with concurrent acinar-ductal metaplasia (ADM), an early lesion implicated in ductal carcinogenesis. The patient is a 56-year-old man with vague complaints of dull left upper quadrant pain with radiation across the mid-portion of his abdomen. A computer tomography scan revealed an irregular enlargement of the distal 3.2 cm of the pancreatic body. A distal pancreatectomy was then performed. Histologic examination revealed a pancreatic carcinoma with cellular features of eosinophilic granular cytoplasm and salt-pepper nuclei. The acinar differentiation of the carcinoma was confirmed by positivity on periodic acid-Schiff stain resistant to diastase digestion (dPAS), positivity for antitrypsin on immunohistochemistry (IHC), and presence of zymogen granules on electron microscopy (EM). The neuroendocrine differentiation was evident by positive synaptophysin and chromogranin stain on IHC and neuroendocrine granules on EM. The ductal component was only visible by PAS stain and immunostains for CEA and CK19A and accompanied by a number of the acinar-ductal metaplasia lesions adjacent to the main tumor. Thus, the histological, histochemical, immunohistochemical and electron-microscopic evidence all suggested that the pancreatic carcinoma underwent trilineage differentiation
  35. Pei, Anna; Nossa, Carlos W; Chokshi, Pooja; Blaser, Martin J; Yang, Liying; Rosmarin, David M; Pei, Zhiheng. "Diversity of 23S rRNA genes within individual prokaryotic genomes". PLoS ONE. 2009;4(5):e5437-e5437 (MEDL:19415112 #106442)       

    BACKGROUND: The concept of ribosomal constraints on rRNA genes is deduced primarily based on the comparison of consensus rRNA sequences between closely related species, but recent advances in whole-genome sequencing allow evaluation of this concept within organisms with multiple rRNA operons. METHODOLOGY/PRINCIPAL FINDINGS: Using the 23S rRNA gene as an example, we analyzed the diversity among individual rRNA genes within a genome. Of 184 prokaryotic species containing multiple 23S rRNA genes, diversity was observed in 113 (61.4%) genomes (mean 0.40%, range 0.01%-4.04%). Significant (1.17%-4.04%) intragenomic variation was found in 8 species. In 5 of the 8 species, the diversity in the primary structure had only minimal effect on the secondary structure (stem versus loop transition). In the remaining 3 species, the diversity significantly altered local secondary structure, but the alteration appears minimized through complex rearrangement. Intervening sequences (IVS), ranging between 9 and 1471 nt in size, were found in 7 species. IVS in Deinococcus radiodurans and Nostoc sp. encode transposases. T. tengcongensis was the only species in which intragenomic diversity >3% was observed among 4 paralogous 23S rRNA genes. CONCLUSIONS/SIGNIFICANCE: These findings indicate tight ribosomal constraints on individual 23S rRNA genes within a genome. Although classification using primary 23S rRNA sequences could be erroneous, significant diversity among paralogous 23S rRNA genes was observed only once in the 184 species analyzed, indicating little overall impact on the mainstream of 23S rRNA gene-based prokaryotic taxonomy
  36. Yang, Liying; Lu, Xiaohua; Nossa, Carlos W; Francois, Fritz; Peek, Richard M; Pei, Zhiheng. "Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome". Gastroenterology. 2009 Aug;137(2):588-597 (MEDL:19394334 #101280)       

    BACKGROUND & AIMS: Gastroesophageal reflux causes inflammation and intestinal metaplasia and its downstream sequelum adenocarcinoma in the distal esophagus. The incidence of esophageal adenocarcinoma has increased approximately 6-fold in the United States since the 1970s, accompanied with a significant increase in the prevalence of gastroesophageal reflux disease (GERD). Despite extensive epidemiologic study, the cause for GERD and the unexpected increases remain unexplainable. Microbes are among the environmental factors that may contribute to the etiology of GERD, but very little research has been done on the esophageal microbiome, particularly in its relation to GERD. This is the first comprehensive reported correlation between a change in the esophageal microbiome and esophageal diseases. METHODS: Biopsy samples of the distal esophagus were collected from 34 patients. Host phenotypes were histologically defined as normal, esophagitis, or Barrett's esophagus (intestinal metaplasia). Microbiomes from the biopsy samples were analyzed by bacterial 16S ribosomal RNA gene survey and classified into types using unsupervised cluster analysis and phenotype-guided analyses. Independence between host phenotypes and microbiome types were analyzed by Fisher exact test. RESULTS: Esophageal microbiomes can be classified into 2 types. The type I microbiome was dominated by the genus Streptococcus and concentrated in the phenotypically normal esophagus. Conversely, the type II microbiome contained a greater proportion of gram-negative anaerobes/microaerophiles and primarily correlated with esophagitis (odds ratio, 15.4) and Barrett's esophagus (odds ratio, 16.5). CONCLUSIONS: In the human distal esophagus, inflammation and intestinal metaplasia are associated with global alteration of the microbiome. These findings raise the issue of a possible role for dysbiosis in the pathogenesis of reflux-related disorders
  37. Celin, N; Bannan, M; Darvishian, F; Hajdu, C; Nonaka, D; Ye, W; Pei, Z; Melamed, J. "Interobserver variability in differentiation of nodal nevus from melanoma micrometastasis in sentinel lymph adenectomy specimens [Meeting Abstract]". Modern pathology. 2008;21(2):409-409 (ISI:000252180200409 #100682)    
  38. 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
  39. Gao, Zhan; Tseng, Chi-hong; Strober, Bruce E; Pei, Zhiheng; Blaser, Martin J. "Substantial alterations of the cutaneous bacterial biota in psoriatic lesions". PLoS ONE. 2008;3(7):e2719-e2719 (MEDL:18648509 #86553)       

    For psoriasis, an idiopathic inflammatory disorder of the skin, the microbial biota has not been defined using cultivation-independent methods. We used broad-range 16S rDNA PCR for archaea and bacteria to examine the microbiota of normal and psoriatic skin. From 6 patients, 19 cutaneous samples (13 from diseased skin and 6 from normal skin) were obtained. Extracted DNA was subjected to the broad range PCR, and 1,925 cloned products were compared with 2,038 products previously reported from healthy persons. Using 98% sequence identity as a species boundary, 1,841 (95.6%) clones were similar to known bacterial 16S rDNA, representing 6 phyla, 86 genera, or 189 species-level operational taxonomic unit (SLOTU); 84 (4.4%) clones with <98% identity probably represented novel species. The most abundant and diverse phylum populating the psoriatic lesions was Firmicutes (46.2%), significantly (P<0.001) overrepresented, compared to the samples from uninvolved skin of the patients (39.0%) and healthy persons (24.4%). In contrast, Actinobacteria, the most prevalent and diverse phylum in normal skin samples from both healthy persons (47.6%) and the patients (47.8%), was significantly (P<0.01) underrepresented in the psoriatic lesion samples (37.3%). Representation of Propionibacterium species were lower in the psoriatic lesions (2.9+/-5.5%) than from normal persons (21.1+/-18.2%; P<0.001), whereas normal skin from the psoriatic patients showed intermediate levels (12.3+/-21.6%). We conclude that psoriasis is associated with substantial alteration in the composition and representation of the cutaneous bacterial biota
  40. Godoy-Vitorino, Filipa; Ley, Ruth E; Gao, Zhan; Pei, Zhiheng; Ortiz-Zuazaga, Humberto; Pericchi, Luis R; Garcia-Amado, Maria A; Michelangeli, Fabian; Blaser, Martin J; Gordon, Jeffrey I; Dominguez-Bello, Maria G. "Bacterial community in the crop of the hoatzin, a neotropical folivorous flying bird". Applied & environmental microbiology. 2008 Oct;74(19):5905-5912 (MEDL:18689523 #95160)       

    The hoatzin is unique among known avian species because of the fermentative function of its enlarged crop. A small-bodied flying foregut fermenter is a paradox, and this bird provides an interesting model to examine how diet selection and the gut microbiota contribute to maximizing digestive efficiency. Therefore, we characterized the bacterial population in the crop of six adult hoatzins captured from the wild. A total of 1,235 16S rRNA gene sequences were grouped into 580 phylotypes (67% of the pooled species richness sampled, based on Good's coverage estimator, with C(ACE) and Chao1 estimates of 1,709 and 1,795 species-level [99% identity] operational taxonomic units, respectively). Members of 9 of the approximately 75 known phyla in Bacteria were identified in this gut habitat; the Firmicutes were dominant (67% of sequences, belonging to the classes Clostridia, Mollicutes, and Bacilli), followed by the Bacteroidetes (30%, mostly in the order Bacteroidales), Proteobacteria (1.8%), and Lentisphaerae, Verrucomicrobia, TM7, Spirochaetes, Actinobacteria, and Aminanaerobia (all <0.1%). The novelty in this ecosystem is great; 94% of the phylotypes were unclassified at the 'species' level and thus likely include novel cellulolytic lineages
  41. Ouyang, Jie; Pei, Zhiheng; Lutwick, Larry; Dalal, Sharvari; Yang, Liying; Cassai, Nicholas; Sandhu, Kuldip; Hanna, Bruce; Wieczorek, Rosemary L; Bluth, Martin; Pincus, Matthew R. "Case report: Paenibacillus thiaminolyticus: a new cause of human infection, inducing bacteremia in a patient on hemodialysis". Annals of clinical & laboratory science. 2008 Autumn;38(4):393-400 (MEDL:18988935 #140207)    

    Paenibacilli are gram-positive, aerobic bacteria that are related to Bacilli but differ in the DNA encoding their 16S rRNA. Until recently, these organisms were not known to cause human disease. There are now several reports of human infection caused by a few members of this genus, most commonly by P. alvei. We report a human infection in a patient with a permacath for chronic hemodialysis who was found to have bacteremia caused by P. thiaminolyticus, which is an environmental bacterium that has never been found to cause human disease. We identified this bacterium by biochemical tests, cloning, sequencing the genomic DNA encoding its 16S rRNA, growth characteristics, and electron microscopic studies. This constitutes the first report of a human infection caused by this organism
  42. Peng, Yi; Chiriboga, Luis; Yee, Herman; Pei, Zhiheng; Wang, Zhenxing; Lee, Peng. "Androgen receptor coactivator ARA70alpha and ARA70beta isoform-specific antibodies: new tools for studies of expression and immunohistochemical localization". Applied immunohistochemistry & molecular morphology. 2008 Jan;16(1):7-12 (MEDL:18091327 #76112)       

    ARA70 is a coactivator of androgen receptor (AR), a ligand-dependent transcription factor that plays an important role in prostate cancer. There are 2 variants of ARA70, the full length 70 kd ARA70alpha isoform and the internally spliced 35 kd ARA70beta isoform. Recent studies have suggested different expression and roles of the 2 isoforms in several endocrine malignancies, including prostate, breast, and ovarian cancers. To study the roles of these isoforms in cancers, we produced isoform-specific polyclonal antibodies. The anti-ARA70alpha antibody was raised in rabbits against 326 amino acid peptide corresponding to the internal deletion missing from ARA70beta (ARA70id), whereas the anti-ARA70beta antibody was raised against 18 amino acid polypeptide spanning the splice junction, with Gln-Gln motif unique to ARA70beta. The antisera were affinity purified on CNBr-activated sepharose 4B, and their specificity tested against bacterially expressed, Ni-column-purified ARA70alpha, ARA70beta, and ARA70id. The anti-ARA70alpha antibody recognized ARA70alpha and ARA70id, but not ARA70beta. The anti-ARA70beta antibody was specific to ARA70beta and did not cross-react with ARA70alpha or ARA70id. We then used these antibodies to detect ARA70 isoforms in crude extracts made of prostate cancer cell lines and performed immunohistochemical localization of these proteins in prostate tissues. ARA70beta localized to the cytosol, whereas ARA70alpha was found in the nucleus, supporting the notion of their dissimilar functions
  43. 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.
  44. Gao, Zhan; Tseng, Chi-hong; Pei, Zhiheng; Blaser, Martin J. "Molecular analysis of human forearm superficial skin bacterial biota". Proceedings of the National Academy of Sciences of the United States of America. 2007 Feb 20;104(8):2927-2932 (MEDL:17293459 #71419)       

    The microbial ecology of human skin is complex, but little is known about its species composition. We examined the diversity of the skin biota from the superficial volar left and right forearms in six healthy subjects using broad-range small subunit rRNA genes (16S rDNA) PCR-based sequencing of randomly selected clones. For the initial 1,221 clones analyzed, 182 species-level operational taxonomic units (SLOTUs) belonging to eight phyla were identified, estimated as 74.0% [95% confidence interval (C.I.), approximately 64.8-77.9%] of the SLOTUs in this ecosystem; 48.0 +/- 12.2 SLOTUs were found in each subject. Three phyla (Actinobacteria, Firmicutes, and Proteobacteria) accounted for 94.6% of the clones. Most (85.3%) of the bacterial sequences corresponded to known and cultivated species, but 98 (8.0%) clones, comprising 30 phylotypes, had <97% similarity to prior database sequences. Only 6 (6.6%) of the 91 genera and 4 (2.2%) of the 182 SLOTUs, respectively, were found in all six subjects. Analysis of 817 clones obtained 8-10 months later from four subjects showed additional phyla (numbering 2), genera (numbering 28), and SLOTUs (numbering 65). Only four (3.4%) of the 119 genera (Propionibacteria, Corynebacteria, Staphylococcus, and Streptococcus) were observed in each subject tested twice, but these genera represented 54.4% of all clones. These results show that the bacterial biota in normal superficial skin is highly diverse, with few well conserved and well represented genera, but otherwise low-level interpersonal consensus
  45. Kong, Xiangtian; Zhao, Yan; Ksionsk, Marti; Zhou, Meisheng; Walden, Paul; Bosland, Maarten; Pei, Zhiheng; Lee, Peng; Melamed, Jonathan. "Radiographic determination of tissue thickness in paraffin blocks: application to the construction of tissue microarrays". Applied immunohistochemistry & molecular morphology. 2007 Mar;15(1):108-112 (MEDL:17536317 #73238)       

    The determination of tissue thickness in paraffin blocks in the histology laboratory has been largely based on visual estimates. More accurate methods are required for the construction of tissue microarrays (TMAs) to assure a greater yield of cores in sections through the TMA block. We describe an accurate radiographic method to determine tissue thickness in donor paraffin blocks and have validated its application to TMA construction. Individual radiographic analysis was performed on paraffin donor blocks used for the construction of TMAs for determination of donor block tissue thickness. Consecutive numbered slide sections through the TMA block were then examined for the presence or loss of cores in the 150th TMA slide (from the final third of the TMA block) and correlated with the thickness of the individual donor blocks determined radiographically. At the 150th TMA slide, 202 of 1340 cores (15.1%) were depleted. Radiographic measurement showed a greater thickness of the donor paraffin block tissue (2.02 mm) corresponding to the retained cores as compared with the donor tissue (1.54 mm) of the depleted cores (P < 0.001). With progressive slide sections through a TMA block, the retention of tissue cores shows a significant correlation with donor block tissue thickness. Radiographic determination of tissue thickness in donor paraffin blocks can be used in TMA construction. Prior knowledge of tissue thickness in TMA construction can prompt compensatory steps that can enhance the yield of valuable samples and assure sufficient numbers of adequate cores for statistical analysis in biomarker evaluations
  46. 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)    
  47. Fischer, Ingeborg; Wieczorek, Rosemary; Sidhu, Gurdip S; Pei, Zhiheng; West, Brian; Lee, Peng. "Myxoid lipoadenoma of parathyroid gland: a case report and literature review". Annals of diagnostic pathology. 2006 Oct;10(5):294-296 (MEDL:16979523 #68682)       

    Myxoid lipoadenoma of the parathyroid gland is a rare variant of parathyroid adenoma. We present the case of a 40-year-old man with asymptomatic hypercalcemia who underwent surgical removal of a parathyroid adenoma. Histologically, the tumor consisted of monomorphous round-to-oval chief cells arranged in several architectural patterns including solid sheet-like, trabecular, and follicular. The tumor stroma was prominently myxoid with interspersed mature adipose tissue. Immunohistochemistry confirmed expression of thyroid transcription factor and parathyroid hormone by all tumor cells and a low proliferation rate with a Ki-67 labeling index of at most 5%. Although the lesion exhibited characteristics that have been previously associated with 'atypical parathyroid adenoma,' such as dense fibrous bands within the tumor and a trabecular growth pattern, there was no further evidence, neither histologically nor clinically, for malignant behavior of the tumor
  48. Lu, X; Yang, L; Pei, Z. "Bacterium-macrophage interaction in gastroesophageal reflux disease [Meeting Abstract]". Modern pathology. 2006 JAN;19(4):113A-113A (ISI:000234094500511 #61436)    
  49. Lu, X; Yang, L; Pei, Z. "Bacterium-macrophage interaction in gastroesophageal reflux disease [Meeting Abstract]". Laboratory investigation. 2006 JAN;86(4):113A-113A (ISI:000234207600511 #62617)    
  50. Yang, Liying; Pei, Zhiheng. "Bacteria, inflammation, and colon cancer [Editorial]". World journal of gastroenterology : WJG. 2006 Nov 14;12(42):6741-6746 (MEDL:17106919 #79201)    

    Our relationship with the colonic bacterial flora has long been viewed as benign, but recent studies suggest that this symbiosis has risks as well as benefits. This relationship requires that the host not only provide a supportive environment for the symbiotic bacteria, but also actively maintain intact mechanisms for properly managing the physiologic stresses that are closely associated with the symbiont's essential survival functions. Failure to do so breaches the host-symbiont contract, and can result in serious effects on the health of the host. Recent investigations that employ several knockout mouse models reveal the consequences of genetic deficiency in the host regarding these mechanisms, and the latent, pro-inflammatory, tumorigenic nature of normal bacterial flora. Further study of the interactions between normal bacterial flora and hosts could shed light on the etiologies and pathogenesis of inflammatory diseases and related cancers, with implications for human health
  51. Levine, SA; Tang, YW; Pei, ZH. "Recent advances in the rapid detection of Bacillus anthracis". Reviews in medical microbiology. 2005 OCT;16(4):125-133 (ISI:000235223900001 #62536)    

    Bacillus anthracis is a Gram-positive, spore-forming rod that causes anthrax. Culture-based methods are the gold standard for the identification of virulent B. anthracis strains but these require days for completion. The experience from the anthrax attacks in September and October of 2001 revealed the urgent need for methods that can rapidly detect this pathogen with high reliability. Because of the extensive homology among non-anthrax Bacillus sp. at the chromosomal level, rapid detection of virulent B. anthracis strains depends oil markers associated with the two plasmids, pXO1 and pXO2, responsible for its virulence. Genes encoding toxins and capsules have been used as markers for pXO1 and pXO2, respectively, in methods that are designed for rapid and sensitive detection of B. anthracis DNA, Such as real-time polymerase chain reaction, direct liquid phase hybridization, and DNA microarrays. A variety of platforms can be modified to suit the needs for rapid detection of B. anthracis antigens, but little is known about plasmid-encoded antigens expressed in spores. Future studies should be aimed at detecting markers for pXO1 and pXO2in viable spores. (c) 2005 Lippincott Williams & Wilkins
  52. Pei, Zhiheng; Yang, Liying; Peek, Richard M; Jr Levine, Steven M; Pride, David T; Blaser, Martin J. "Bacterial biota in reflux esophagitis and Barrettos esophagus". World journal of gastroenterology : WJG. 2005 Dec 14;11(46):7277-7283 (MEDL:16437628 #61597)    

    AIM: To identify the bacterial flora in conditions such as Barrettos esophagus and reflux esophagitis to determine if they are similar to normal esophageal flora. METHODS: Using broad-range 16S rDNA PCR, esophageal biopsies were examined from 24 patients [9 with normal esophageal mucosa, 12 with gastroesophageal reflux disease (GERD), and 3 with Barrettos esophagus]. Two separate broad-range PCR reactions were performed for each patient, and the resulting products were cloned. In one patient with Barrettos esophagus, 99 PCR clones were analyzed. RESULTS: Two separate clones were recovered from each patient (total = 48), representing 24 different species, with 14 species homologous to known bacteria, 5 homologous to unidentified bacteria, and 5 were not homologous (<97% identity) to any known bacterial 16S rDNA sequences. Seventeen species were found in the reflux esophagitis patients, 5 in the Barrettos esophagus patients, and 10 in normal esophagus patients. Further analysis concentrating on a single biopsy from an individual with Barrettos esophagus revealed the presence of 21 distinct bacterial species. Members of four phyla were represented, including Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Microscopic examination of each biopsy demonstrated bacteria in intimate association with the distal esophageal epithelium, suggesting that the presence of these bacteria is not transitory. CONCLUSION: These findings provide evidence for a complex, residential bacterial population in esophageal reflux-related disorders. While much of this biota is present in the normal esophagus, more detailed comparisons may help identify potential disease associations
  53. Sefers, S; Pei, ZH; Tang, YW. "False positives and false negatives encountered in diagnostic molecular microbiology". Reviews in medical microbiology. 2005 APR;16(2):59-67 (ISI:000235223400004 #62535)    

    Nucleic acid-based tests are rapidly expanding in the field of diagnostic microbiology, due to their unique high sensitivity and specificity as well as rapid assay turnaround time. However, the potential of false positives and false negatives can hinder the wide application of these novel techniques. This mini-review article summarizes common causes and potential solutions for false-positives and false-negatives encountered in the field of diagnostic molecular microbiology
  54. Pei, Zhiheng; Bini, Edmund J; Yang, Liying; Zhou, Meisheng; Francois, Fritz; Blaser, Martin J. "Bacterial biota in the human distal esophagus". Proceedings of the National Academy of Sciences of the United States of America. 2004 Mar 23;101(12):4250-4255 (MEDL:15016918 #42671)       

    The esophagus, like other luminal organs of the digestive system, provides a potential environment for bacterial colonization, but little is known about the presence of a bacterial biota or its nature. By using broad-range 16S rDNA PCR, biopsies were examined from the normal esophagus of four human adults. The 900 PCR products cloned represented 833 unique sequences belonging to 41 genera, or 95 species-level operational taxonomic units (SLOTU); 59 SLOTU were homologous with culture-defined bacterial species, 34 with 16S rDNA clones, and two were not homologous with any known bacterial 16S rDNA. Members of six phyla, Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria, and TM7, were represented. A large majority of clones belong to 13 of the 41 genera (783/900, 87%), or 14 SLOTU (574/900, 64%) that were shared by all four persons. Streptococcus (39%), Prevotella (17%), and Veilonella (14%) were most prevalent. The present study identified approximately 56-79% of SLOTU in this bacterial ecosystem. Most SLOTU of esophageal biota are similar or identical to residents of the upstream oral biota, but the major distinction is that a large majority (82%) of the esophageal bacteria are known and cultivable. These findings provide evidence for a complex but conserved bacterial population in the normal distal esophagus
  55. Sidhu, Gurdip S; Cassai, Nicholas D; Pei, Zhiheng. "Pneumocystis carinii: an update". Ultrastructural pathology. 2003 Mar-Apr;27(2):115-122 (MEDL:12746203 #39226)       

    Pneumocystis produces respiratory infection in immunocompromised individuals of several species of mammals, including humans. Each mammalian species has its own specific Pneumocystis species, which does not cross-infect other mammals. The species infecting humans has now been renamed P. jerovici, since P. carinii is reserved for one of two species infecting rats. Long believed to be a protozoan, Pneumocystis is now classified as an Archiascomycetous fungus. This is based on new molecular taxonomic techniques using DNA sequence analysis of srRNA genes. Only two of about 140 copies of the gene that exist in Pneumocystis were used for sequencing, so the evidence is not conclusive; however, it is supported by morphological evidence such as fungus-specific nucleus-associated organelles for cell division. There is also ultrastructural evidence of meiotic division and sexual conjugation. Clinically, several lines of evidence suggest the improbability of latent infection. Adult infections appear to be new infections, a fact that invites a new perspective on prevention
  56. Drake, Wonder Puryear; Pei, Zhiheng; Pride, David T; Collins, Robert D; Cover, Timothy L; Blaser, Martin J. "Molecular analysis of sarcoidosis tissues for mycobacterium species DNA". Emerging infectious diseases. 2002 Nov;8(11):1334-1341 (MEDL:12453366 #34575)    

    We performed polymerase chain reaction analysis, for Mycobacterium species 16S rRNA, rpoB, and IS6110 sequences, on 25 tissue specimens from patients with sarcoidosis and on 25 control tissue specimens consisting of mediastinal or cervical lymph nodes and lung biopsies. Mycobacterium species 16S rRNA sequences were amplified from 12 (48%) rpoB sequences and from 6 (24%) of the sarcoidosis specimens. In total, 16S rRNA or rpoB sequences were amplified from 15 sarcoidosis specimens (60%) but were not detected in any of the control tissues (p=0.00002, chi square). In three specimens, the sequences resembled Mycobacterium species other than M. tuberculosis. All specimens with sequences consistent with M. tuberculosis were negative for IS6110. We provide evidence that one of a variety of Mycobacterium species, especially organisms resembling M. tuberculosis, is found in most patients with sarcoidosis
  57. Yang, GY; Sidhu, GS; Yee, H; Pei, Z; Cassai, N; Wieczorek, R. "Ultrastructural features and TUNEL analysis of glomeruloid adenocarcinoma of the prostate [Meeting Abstract]". American journal of clinical pathology. 2001 OCT;116(4):609-609 (ISI:000171341800082 #54862)    




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