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Periodontitis is an inflammatory disease caused by subgingival microorganisms and their components, such as lipopolysaccharide (LPS). Responses of the host to LPS are mediated by CD14 and LPS-binding protein (LBP). In this study, it was determined that proteases from a periodontal pathogen, Prevotella intermedia, cleave CD14 and LBP, and thereby modulate the virulence of LPS. Culture supernatants from two strains of P. intermedia (ATCC 25611 and 25261) cleaved CD14 and LBP in a concentration-dependent manner. Zymographic and molecular mass analysis revealed the presence of a membrane-associated, 170-kDa, monomeric protease. Class-specific inhibitors and stimulators demonstrated that this enzyme is a metal-requiring, thiol-activated, cysteine protease. The protease was stable over a wide range of temperatures (4-56 degrees C) and pH values (4.5-8.5). This enzyme also decreased the expression of interleukin-1beta (IL-1beta)-specific mRNA in the LPS-activated macrophage-like cell lines U937 and THP-1 in a concentration-dependent manner, indicating that it also cleaves membrane-associated CD14. Furthermore, addition of soluble CD14 abrogated protease-mediated inhibition of IL-1 mRNA expression induced by LPS. The observations suggest that proteolysis of CD14 and LBP by P. intermedia protease might modulate the virulence of LPS at sites of periodontal infections.

Summary Eosinophilic esophagitis, gastritis, duodenitis, and colitis are rare diseases. Few studies have been able to accumulate sufficiently large number of patients to analyze their clinical epidemiology. The aim of the present epidemiologic study was to examine the prevalence and concordant occurrence of gastrointestinal (GI) eosinophilia. Using a database of histopathologic records, a cross-sectional study among 302,061 patients undergoing bidirectional endoscopy evaluated the concordant occurrence of esophageal, gastric, duodenal, and colonic eosinophilia. The prevalence rates (PRs) of GI eosinophilia were expressed per 1,000 study subjects with their 95% Poisson confidence intervals (CIs). The concordant occurrence of various forms of GI eosinophilia was compared to their overall occurrence in the study population by calculating odds ratios (ORs) and their 95% CI. The database contained 3,008 patients with esophageal eosinophilia (PR = 9.96, 9.61–10.32), 366 patients with gastric eosinophilia (1.21, 1.09–1.34), 10 patients with duodenal eosinophilia (0.03, 0.02–0.06), and 124 patients with colonic eosinophilia (0.41, 0.34–0.49). The occurrence of esophageal eosinophilia was associated with an increased occurrence of gastric eosinophilia (OR = 3.58, 2.06–6.23), duodenal (40.22, 12.61–128.31), and colonic eosinophilia (8.12, 4.26–15.49). Similarly, we also found statistically significant associations between gastric eosinophilia and duodenal or colonic eosinophilia, and between duodenal and colonic eosinophilia. In the adult, as in the pediatric population, patients with any type of GI eosinophilia are at an increased risk for simultaneously harboring eosinophilia at multiple sites of their GI tract. With the exception of esophageal eosinophilia, however, other forms of GI eosinophilia are rarely diagnosed.

Background: Lymphocytic gastritis (LyG) is a histopathologic finding of unknown clinical relevance.Aims: To explore the clinical epidemiology of LyG and its associations with Helicobacter pylori (Hp) infection, coeliac disease (CD) and microscopic colitis (MC) Methods: In a cross-sectional study, the demographic, clinical, and histopathologic data of patients with and without LyG were compared. Between 2008 and 2020, 1.5 million patients with endoscopic biopsies of the gastroduodenal mucosa were extracted from a database. LyG diagnoses were reviewed to collect detailed information regarding its topographic distribution within the stomach.In a large subgroup of 400 000 patients, tissue samples from the colon were also available.Results: Of 1 481 336 patients, 341 had LyG with Hp and 2697 had Hp-negative LyG (with an overall prevalence of 0.21%). In patients with Hp-negative LyG, 450 (17%) had corpus-predominant LyG, 1068 antrum-predominant LyG (40%), and 1179 pangastric LyG (44%). LyG was more common in males and in subjects aged 50-70 years.There was no significant ethnic variation. Anaemia, diarrhoea, and weight loss were more common in patients with than without LyG. In 35% and 19% of patients, LyG was associated with CD and MC, respectively. All 72 patients with Hp-positive LyG and 280 of 310 patients with Hp-negative LyG with follow-up biopsies became free of LyG within a year.Conclusions: Most cases of LyG may represent a self-limited expression, frequently associated with other GI conditions, such as Hp infection, CD, and MC. In most patients, LyG is likely to resolve within a year after its initial diagnosis.

H. heilmannii belongs to the Helicobacter family and is found in a small number of gastric biopsies. This bacterium is generally found in primates, cats, pigs, and carnivorous mammals. About 0.5% to 6% of human gastric infections have been attributed to H. heilmannii. The bacterium usually induces mild chronic gastritis but may be associated with peptic ulceration, and rare cases were reported in association with gastric carcinoma and mucosa-associated lymphoid tissue lymphoma. We report a case of H. heilmannii chronic gastritis in a 44-year-old man with a history of chronic heartburn, found to have erythema and granularity in the antrum. Antral biopsy showed mild chronic gastritis with prominent lymphoid aggregates, and rare long, thin, spiral bacilli were present adjacent to the surface epithelium. The long tightly coiled morphology suggestive of H. heilmannii was obvious at 1000 x magnification. The lack of information in the literature regarding cross-reactivity of H. heilmannii to commercially available antibodies used for immunohistochemical detection of H. pylori prompted us to evaluate whether commercially available polyclonal anti-H. pylori antibodies show cross-reactivity between the two organisms. The H. pylori immunostain highlighted H. heilmannii organisms and their characteristic morphology, confirming cross-reactivity with the anti-H. pylori polyclonal antibody. This case illustrates the potential contribution of commercially available polyclonal antibodies against H. pylori to help confirm a diagnosis of H. heilmannii gastritis. The use of immunohistochemical stain to identify H. heilmannii may be useful in cases with a paucity of organisms, with suggestive but not diagnostic forms on routine hematoxylin and eosin stain.

Background: Incomplete intestinal metaplasia (IM) is reportedly associated with higher gastric cancer (GC) risk than its complete variant. AGA Guidelines recommend including IM subtyping in routine pathology reports. This study assesses the prevalence of complete versus incomplete IM in gastric conditions with different GC risks. Methods: IM-subtyping (complete versus incomplete) and grading (IM extension: G1: ≤30%; G2: >30%) were assessed in 386 patients with IM+ve gastric biopsy sets that included both antral and oxyntic samples. Cases were categorized as: a) IM foci in otherwise normal mucosa (n = 59); b) H. pylori gastritis (n = 138); c) reactive gastropathy (141); d) Autoimmune atrophic gastritis ([AIG] n = 48). Odds ratios (OR) and their 95%CI were used in comparing the prevalence of incomplete-IM and the correlation between subtype and IM extension. Results: Incomplete-IM was presents in 37.7% of patients with H. pylori gastritis; 8.3% of those with AIG; 5.0% of those with reactive gastropathy, and none of those with otherwise normal mucosa. Incomplete-IM was strongly associated with more extensive (G2-IM) mucosal intestinalization (OR=6.69; CI95%: 2.77 – 9.40). Conclusion: Incomplete-IM is significantly more prevalent in conditions (H. pylori gastritis) known to carry a higher risk of GC, and is strongly associated with its extension. The low prevalence of incomplete IM in AIG (8.3%), and reactive gastropathy (5.2%) is in keeping with the low GC risk associated with these conditions.

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