Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population

BACKGROUND: Vitamin D has been shown to exert manifold immunomodulatory effects. Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse. We studied the association between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D receptor gene in a Japanese population. We also investigated associations between the vitamin D receptor polymorphism and GAD65-antibody (Ab) positivity. We carried out polymerase chain reaction-restriction fragment length polymorphism analysis in 110 Japanese T1DM patients and 250 control subjects. GAD65 antibodies were assessed in 78 patients with T1DM. RESULTS: We found a significantly higher prevalence of the F allele / the FF genotype in the patients compared to the controls (P = 0.0069 and P = 0.014, respectively). Genotype and allele frequencies differed significantly between GAD65-Ab-positive patients and controls (P = 0.017 and P = 0.012, respectively), but neither between GAD65-Ab-negative patients and controls (P = 0.68 and P = 0.66, respectively) nor between GAD65-Ab-positive and -negative patients (P = 0.19 and P = 0.16, respectively). CONCLUSIONS: Our findings suggest that the vitamin D receptor initiation codon polymorphism influences genetic susceptibility to T1DM among the Japanese. This polymorphism is also associated with GAD65-Ab-positive T1DM, although the absence of a significant difference between GAD65-Ab-negative patients and controls might be simply due to the small sample size of patients tested for GAD65 antibodies

Intra-arterial gas, a clue for diagnosis of peri-aortic inflammation due to infection

We have presented a case of Salmonella-induced infective aortic aneurysm in which the presence of peri-aortic gas was a clue for diagnosis. The disease is clinically infrequent but potentially has a high mortality rate. Clinicians should consider this fatal disease from any trivial findings

The FTO genotype as a useful predictor of body weight maintenance: Initial data from a 5-year follow-up study

ObjectiveWe examined associations between the fat-mass and obesity-associated (FTO) gene (rs9939609) and any weight change over a 5-year period following a 14-week lifestyle intervention among middle-aged Japanese women.Materials/MethodsOne hundred twenty-eight Japanese women (BMI > 25 kg/m2) participated in a 14-week weight loss intervention between 2004 and 2006. Of the participants, 62 consented to the 5-year follow-up measurement session. Of these women, 47 women who achieved a weight loss of at least 10% from their baseline values during the 14-week intervention were included in the analysis. Body weight, body fat, abdominal fat assessed by CT scans, and metabolic risk factors (i.e., blood pressure, lipids, and glucose) were measured at baseline, post-intervention, and at the 5-year follow-up.ResultsDuring the 5-year non-intervention period, increases in body weight, fat mass, total abdominal fat, and subcutaneous abdominal fat were significantly greater in subjects with the homozygous minor allele (AA genotype, n = 4; 8.5%) than in those with the homozygous major allele (TT genotype, n = 31; 66.0%) or heterozygous allele (TA genotype, n = 12; 25.5%). In multiple regression analyses, the variation in rs9939609 was a significant and independent predictor (P < 0.001) for regaining weight during the 5-year follow-up.ConclusionsOur data suggest that Japanese women with the risk allele (AA) of rs9939609 may have more difficulty preventing fat gain from reoccurring after weight loss intervention than women with the other genotypes

Microscopic characterization of the C–F bonds in fluorine–graphite intercalation compounds

The structures of fluorine–graphite intercalation compounds (F-GICs, C₂.₈F and C₃.₅F) have been analyzed by high-resolution transmission electron microscopy (TEM). Cross-sectional TEM images of the F-GICs indicate that the interlayer distance increases by insertion of fluorine with randomly buckled carbon layers. Such a structure can form by alternation in the bond angle at a carbon atom covalently bonded with fluorine. Electron energy loss spectroscopy combined with TEM indicates that the π-orbital network over the graphitic carbon layer reduces with fluorination. The C–F bond is essentially covalent

Helicobacter pylori from gastric cancer and duodenal ulcer show same phylogeographic origin in the Andean Region in Colombia

Background: A recent report has shown that the phylogenetic origin of Helicobacter pylori based on multi-locus sequence typing (MLST) was significantly associated with the severity of gastritis in Colombia. However, the potential relationship between phylogenetic origin and clinical outcomes was not examined in that study. If the phylogenetic origin rather than virulence factors were truly associated with clinical outcomes, identifying a population at high risk for gastric cancer in Colombia would be relatively straightforward. In this study, we examined the phylogenetic origins of strains from gastric cancer and duodenal ulcer patients living in Bogota, Colombia. Methods: We included 35 gastric cancer patients and 31 duodenal ulcer patients, which are considered the variant outcomes. The genotypes of cagA and vacA were determined by polymerase chain reaction. The genealogy of these Colombian strains was analyzed by MLST. Bacterial population structure was analyzed using STRUCTURE software. Results: H. pylori strains from gastric cancer and duodenal ulcer patients were scattered in the phylogenetic tree; thus, we did not detect any difference in phylogenetic distribution between gastric cancer and duodenal ulcer strains in the hpEurope group in Colombia. Sixty-six strains, with one exception, were classified as hpEurope irrespective of the cagA and vacA genotypes, and type of disease. STRUCTURE analysis revealed that Colombian hpEurope strains have a phylogenetic connection to Spanish strains. Conclusions: Our study showed that a phylogeographic origin determined by MLST was insufficient for distinguishing between gastric cancer and duodenal ulcer risk among hpEurope strains in the Andean region in Colombia. Our analysis also suggests that hpEurope strains in Colombia were primarily introduced by Spanish immigrants. © 2014 Shiota et al

Oligomerization of Hepatitis C Virus Core Protein is Crucial for Interaction with the Cytoplasmic Domain of E1 Envelope Protein

Hepatitis C virus (HCV) contains two membrane-associated envelope glycoproteins, E1 and E2, which assemble as a heterodimer in the endoplasmic reticulum (ER). In this study, predictive algorithms and genetic analyses of deletion mutants and glycosylation site variants of the E1 glycoprotein were used to suggest that the glycoprotein can adopt two topologies in the ER membrane: the conventional type I membrane topology and a polytopic topology in which the protein spans the ER membrane twice with an intervening cytoplasmic loop (amino acid residues 288 to 360). We also demonstrate that the E1 glycoprotein is able to associate with the HCV core protein, but only upon oligomerization of the core protein in the presence of tRNA to form capsid-like structures. Yeast two-hybrid and immunoprecipitation analyses reveal that oligomerization of the core protein is promoted by amino acid residues 72 to 91 in the core. Furthermore, the association between the E1 glycoprotein and the assembled core can be recapitulated using a fusion protein containing the putative cytoplasmic loop of the E1 glycoprotein. This fusion protein is also able to compete with the intact E1 glycoprotein for binding to the core. Mutagenesis of the cytoplasmic loop of E1 was used to define a region of four amino acids (residues 312 to 315) that is important for interaction with the assembled HCV core. Taken together, our studies suggest that interaction between the self-oligomerized HCV core and the E1 glycoprotein is mediated through the cytoplasmic loop present in a polytopic form of the E1 glycoprotein

Radiotherapy for choroidal hemangioma

PURPOSE: Circumscribed choroidal hemangioma is an uncommon, benign vascular tumor that typically appears in the posterior pole of the eye. Visual acuity loss typically results from its exudation, followed by serous retinal detachment. The purpose of the study was to evaluate the efficacy and the safety of external beam irradiation in treating circumscribed choroidal hemangioma. METHODS: We treated 4 eyes of 4 patients with circumscribed choroidal hemangioma with external beam irradiation at Okayama University Hospital from 2002 to 2009. A total absorbed dose of 20 Gy (beam energy, 4, 10 MV) was applied to each of the 4 patients. Each patient received a single 2-Gy daily fraction for five consecutive days in a week, for two consecutive weeks. RESULTS: In all cases, the retinal detachment showed complete resolution within 8 to 48 days after treatment. A decrease in tumor thickness was observed in all cases except one in which the follow-up period was rather short (3.7 months). The visual acuity improved in all 4 eyes. No eyes showed deterioration of visual acuity. During follow-up periods of 3.7 months to 58.5 months, there were no signs of radiation-induced cataract, retinopathy or optic neuropathy