Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis

Helicobacter pylori is a Gram-negative spiral bacterium that causes gastritis and peptic ulcer and has been implicated in the pathogenesis of gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Although Th1 immunity is involved in gastritis and the accumulation of H. pylori-specific CD4(+) T cells in the H. pylori-infected gastric mucosa in human patients, how T cells are primed with H. pylori antigens is unknown because no apparent lymphoid tissues are present in the stomach. We demonstrate here that Peyer's patches (PPs) in the small intestine play critical roles in H. pylori-induced gastritis; no gastritis is induced in H. pylori-infected mice lacking PPs. We also observed that the coccoid form of H. pylori is phagocytosed by dendritic cells in PPs. We propose that H. pylori converts to the coccoid form in the anaerobic small intestine and stimulates the host immune system through PPs.     

Antipneumococcal Activity of BMS 284756 Compared to Those of Six Other Agents

Antipneumococcal activity of BMS 284756 was compared to those of six agents by MIC and time-kill methodologies. BMS 284756 had the lowest MICs compared to those of ciprofloxacin, levofloxacin, and moxifloxacin against quinolone-susceptible (< or =0.016 to 0.06 microg/ml) and quinolone-resistant (0.03 to 1 microg/ml) pneumococci. BMS 284756 was bactericidal against 11 of 12 strains at two times the MIC after 24 h.     

MRSA respiratory tract infection]

Sputum isolates of MRSA have been on the increase, recently. Preventive measures against MRSA nosocomial infections have become important in Japanese hospitals. Clinical study was performed on 29 patients from whom MRSA was isolated more than 10(7) cfu/ml using the quantitative sputum culture method. All had a history of admission, therefore nosocomial infections caused by MRSA could very often occur. MRSA was determined as a causative organism in 3 on the basis of symptoms, laboratory data, chest X-rays, and effect of antimicrobial agents. These three patients improved by a single or combined administration of minocycline, arbekacin and/or fosfomycin. In 15 patients, MRSA was frequently isolated, but was thought to be colonized. In 3 patients, MRSA was not isolated without administration of antimicrobial agents thereafter. It was supposed that most of MRSA isolates from sputum were not the causative organism of the respiratory tract infection.     

Bronchiolitis obliterans organizing pneumonia

A clinicopathological disease entity of bronchiolitis obliterans organizing pneumonia (BOOP) is reviewed. Various clinical backgrounds can be found in patients who were histopathologically diagnosed as BOOP. Historically, the idiopathic BOOP has been identified as a clinicopathological disease entity in 1985. BOOP shows clinically interstitial processes, however some confusion is still present in the aspect of differentiation with bronchiolitis obliterans (BO). Histopathologically, BOOP shows organizing reaction to subacute lung injuries, and absence of remodeling separates BOOP from other chronic fibrosing processes such as UIP. Clinically, there is differences in clinical outcomes between idiopathic, and secondary BOOP. We reviewed whether BOOP can be classified as interstitial pneumonia.     

Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross‐sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ²‐test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low‐grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3–4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low‐grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302‐positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.     

Nectin-4 expression contributes to tumor proliferation,angiogenesis and patient prognosis in human pancreatic cancer

Background

Nectin-4 belongs to the nectin family that has diverse physiological and pathological functions in humans. Recent studies have also suggested some roles for Nectin-4 in several human cancers. However, the precise roles and clinical relevance of Nectin-4 in tumors are largely unknown.

Methods

Nectin-4 expression was investigated in 123 patients with pancreatic cancer by immunohistochemistry. Furthermore, we investigated the association of Nectin-4 in pancreatic cancer with tumor proliferation, angiogenesis and immunity by using immunohistochemistry and siRNA interference method.

Results

Patients with high Nectin-4 expression had poorer postoperative prognosis than those with low expression. Importantly, multivariate analysis indicated that Nectin-4 expression had a significant independent prognostic value in pancreatic cancer (HR = 1.721, 1.085-2.730; P = 0.021). Tumor Nectin-4 expression was significantly correlated with Ki67 expression. In addition, siRNA-mediated gene silencing of Nectin-4 significantly inhibited the cell proliferation in human pancreatic cancer cells, Capan-2 and BxPC-3. Furthermore, Nectin-4 expression was also positively correlated with VEGF expression and intratumoral microvessel density. However, there were no significant correlations of tumor Nectin-4 expression with tumor-infiltrating T cells.

Conclusion

Nectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer.     

Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells

The molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell proliferation are poorly understood, and whether a soluble factor plays a major role remains controversial. Here we demonstrate that the T-cell-receptor complex is not a target for the suppression, suggesting that downstream signals mediate the suppression. We found that Stat5 phosphorylation in T cells is suppressed in the presence of MSCs and that nitric oxide (NO) is involved in the suppression of Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO synthase (NOS) was readily detected in MSCs but not T cells, and a specific inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell proliferation. This production of NO in the presence of MSCs was mediated by CD4 or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin synthase or NOS restored the proliferation of T cells, whereas an inhibitor of indoleamine 2,3-dioxygenase and a transforming growth factor-beta-neutralizing antibody had no effect. Finally, MSCs from inducible NOS-/- mice had a reduced ability to suppress T-cell proliferation. Taken together, these results suggest that NO produced by MSCs is one of the major mediators of T-cell suppression by MSCs.