Faculty Bibliography

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.

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.

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.

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.

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.