Roles of virD4 and cagG genes in the cag pathogenicity island of Helicobacter pylori using a Mongolian gerbil model

BACKGROUND AND AIMS: The roles of the virD4 and the cagG genes in the cag pathogenicity island of Helicobacter pylori for gastroduodenal pathogenesis are unclear and their roles in vivo have not been examined. METHODS: Seven week old male Mongolian gerbils were inoculated with the wild type H pylori TN2GF4, its isogenic virD4, or cagG mutants. Animals were sacrificed at 4, 12, and 24 weeks after inoculation. Gastric inflammation and H pylori density were evaluated by histology, inflammatory response (as measured by interleukin (IL)-1beta mRNA levels), proliferative activity (as assessed by 5'-bromo-2'deoxyuridine labelling indices), and host systemic reaction (as measured by anti-H pylori IgG antibody). RESULTS: Degree of gastric inflammation, proliferative activity, and mucosal IL-1beta mRNA levels remained low throughout the first 12 weeks in gerbils infected with the virD4 mutants. Degree of gastric inflammation and proliferative activity increased at 24 weeks with the virD4 mutants reaching levels comparative with those seen at four weeks with the wild-type strains. Mucosal IL-1beta mRNA levels were also increased at 24 weeks with the virD4 mutants and levels at 24 weeks were similar between the wild-type and virD4 mutants. In contrast, gerbils infected with the cagG mutants had reduced ability to colonise gerbils, and no or little gastric inflammation or proliferative activity was observed. CONCLUSIONS: Loss of the virD4 gene temporally retarded but did not abrogate gastric inflammation. Loss of the cagG gene abolished gastric inflammation partially via reduced ability to colonise gerbils. Unknown factors related to the type IV secretion system other than CagA may influence gastric inflammation.     

Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon

When isolated rat pancreatic islets are treated with 16.7 mM glucose, a time-dependent potentiation (TDP) of insulin release occurs that can be detected by subsequent treatment with 50 mM KCl. It has been thought that TDP by glucose is a Ca2+-dependent phenomenon and only occurs when exposure to glucose is carried out in the presence of Ca2+. In contrast to this, we now demonstrate TDP under stringent Ca2+-free conditions (Ca2+-free buffer containing 1 mM EGTA). In fact, under these Ca2+-free conditions glucose caused an even stronger TDP than in the presence of Ca2+. TDP induced by glucose in the absence of extracellular Ca2+ was unaffected by inhibitors of protein kinase C (PKC). However, cerulenin or tunicamycin, two inhibitors of protein acylation, eradicated TDP without affecting glucose metabolism. The TDP by glucose was not associated with an increase in the cytosolic free Ca2+ concentration ([Ca2+]i) during subsequent treatment with high K+. Exposure of islets to forskolin under Ca(2+)-free conditions did not cause TDP despite a large increase in the cellular cAMP levels. In conclusion, glucose alone induces TDP under stringent Ca2+-free conditions when [Ca2+]i was significantly lowered. Protein acylation is implicated in the underlying mechanism of TDP.     

Six-month multicentric, open-label, randomized trial of twice-daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart in Japanese type 2 diabetic patients (JDDM 11)

To evaluate glycemic control using convenience-oriented biphasic insulin analog compared with intensified insulin therapy, we conducted a 6-month multicentric, open-label, randomized trial in Japanese insulin-naive patients with type 2 diabetes mellitus. A total of 160 adult patients at 19 centers were randomized into two groups: those who received twice-daily injections of biphasic insulin aspart 30 and those on three-times-daily injections of insulin aspart with or without NPH insulin (multiple daily injections). At 6 months, mean HbA(1c) decreased by approximately 2.5% in both groups. Reduction of HbA(1c) on both regimens was better in patients whose prior therapy before starting the study was only diet and exercise (-5.0%) than in patients who were previously taking oral antidiabetic agents (-1.0%). No incidence of major hypoglycemia was observed in either regimen. These results suggest that convenience-oriented insulin therapy using biphasic insulin analog is as useful as intensified insulin therapy with insulin analog for the treatment of type 2 diabetes mellitus over 6 months. Furthermore, early induction of insulin therapy in individuals hitherto using only diet and exercise may provide good glycemic control. This study suggests that convenience-oriented biphasic insulin aspart 30 might be a useful option for the treatment of type 2 diabetes mellitus, especially for insulin-naive patients over 6 months, although it should be changed to another regimen when expected efficacy is not obtained.     

Prevalence of diabetes mellitus in individuals with airflow obstruction in a Japanese general population: The Yamagata-Takahata Study

Background

Diabetes has been reported as a comorbidity of chronic obstructive pulmonary disease (COPD) in Western countries, but it has not been demonstrated in epidemiological reports in Japan. The purpose of this study was to clarify whether the relationship between airflow obstruction and diabetes can be confirmed in a Japanese general population.

Detection of fibronectin receptor in sera: its clinical significance as a parameter of hepatic fibrosis.

Pooled sera collected from cirrhotic patients was fractionated by affinity chromatography with a fibronectin receptor monoclonal antibody against the beta-subunit of fibronectin receptor. Eluates were assayed using Western immunoblotting. The relative mobility of the protein reactive with fibronectin receptor antibody was nearly identical to that of the beta-subunit of fibronectin receptor, confirming that fibronectin receptor is present in human serum. Serum levels of the beta-subunit of fibronectin receptor were analyzed by sandwich enzyme-linked immunosorbent assay in patients with various liver diseases. The serum level of fibronectin receptor (micrograms/ml) was significantly higher in patients with chronic hepatitis (inactive, 2.59 +/- 0.04; active, 3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30), alcoholic liver disease (2.96 +/- 0.16) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Strong positive correlation was observed between serum levels of fibronectin receptor and histological findings, particularly in the degree of hepatic fibrosis. Immunohistochemical studies with fibronectin receptor antibody revealed that the beta-subunit of fibronectin receptor was present on the plasma membrane of hepatocytes and sinusoidal lining cells in the normal liver and was increased in fibrotic areas and on the plasma membrane of hepatocytes and sinusoidal lining cells of fibrotic liver. The serum level of fibronectin receptor in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.     

A case of eosinophilic fasciitis without skin manifestations: a case report in a patient with lupus and literature review

Clinical Rheumatology - Eosinophilic fasciitis (EF) is a rare connective tissue disease that causes inflammation and fibrosis of the fascia, inducing pain and motor dysfunction. Characteristic skin...     

Screening for Gaucher Disease Using Dried Blood Spot Tests: A Japanese Multicenter,Cross-sectional Survey

Objective For patients with Gaucher disease (GD), a rare, inherited lysosomal storage disease, obtaining a definitive diagnosis is currently time-consuming and costly. A simplified screening method to measure the glucocerebrosidase (GBA) activity using dried blood spots (DBS) on filter paper has recently been developed. Using this newly developed screening method, we evaluated real-world GD screening in patients suspected of having GD. Methods This multicenter, cross-sectional, observational study with a diagnostic intervention component evaluated real-world screening in patients suspected of having GD based on their clinical symptoms and a platelet count <120,000/μL. The endpoint was the number of patients with low GBA activity determined using DBS. Results In 994 patients who underwent initial DBS screening, 77 had low GBA activity. The assay was not repeated in 1 patient who was diagnosed as having a high possibility of GD due to clinical symptoms, and a further 21 patients completed the study without undergoing the second assay. Of the remaining 55 patients who had 2 DBS assays performed, 11 had a low GBA activity in both assays. Overall, DBS screening identified 12 (1.2%) patients with a low GBA activity, a proportion consistent with prior screening studies. Conclusion These results suggest that the simplified DBS method was less burdensome to patients, was easily utilized by many physicians, and could be a useful first-tier screening assay for GD prior to initiating burdensome genetic testing.     

Streptococcus oralis Meningitis with Gingival Bleeding in a Patient: A Case Report and Review of the Literature

An 81-year-old man with a history of gingival bleeding presented with a fever, headache, and drowsiness. His mouth and full dentures were unsanitary. Laboratory tests revealed Streptococcus oralis meningitis caused by odontogenic bacteremia. We reviewed eight reported cases, including the present case, because S. oralis meningitis is rare. Our review indicated that S. oralis meningitis needs to be considered when encountering cases of a fever, disturbance of consciousness, and headache with episodes of possible odontogenic bacteremia.