Fasting plasma glucose cutoff for diagnosis of diabetes in a Japanese population

Objective: We examined the relationship between fasting plasma glucose (FPG) and 2-h post-load glucose (PG) levels, and the optimal FPG cutoff level to correspond to a 2-h PG of 11.1 mmol/liter, the gold standard diagnostic criterion, in a general Japanese population. Design: Cross-sectional study populations of 2421 subjects in 1988 and 2698 subjects in 2002, aged 40-79 yr and without antidiabetic medication, were tested with an oral glucose tolerance test. The relationship between FPG and 2-h PG was investigated by various regression models and a receiver operating characteristic curve. Results: The best-fit model for the relationship between FPG and 2-h PG was a quadratic regression model. The FPG cutoff levels corresponding to the 2-h PG of 11.1 mmol/liter by this model were 6.2 mmol/liter in 1988 and 6.3 mmol/liter in 2002. In the combined populations, the FPG cutoff point was 6.3 mmol/liter; the sensitivity and specificity of this cutoff point for detecting a 2-h PG of 11.1 mmol/liter were 75.2 and 88.6%, respectively. The receiver operating characteristic curve analysis confirmed that the corresponding FPG point was 6.2 mmol/liter in both the 1988 and 2002 populations. In a stratified analysis, the FPG cutoff level increased with increasing body mass index levels; however, even in subjects with body mass index more than or equal to 30 kg/m(2), the FPG cutoff level was lower than 7.0 mmol/liter. Conclusions: Our findings suggest that the FPG cutoff level corresponding to the 2-h PG of 11.1 mmol/liter in the general Japanese population is lower than the current diagnostic criterion.     

Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells

Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1(-/-)) mice, adhesion and spreading to cellular matrix were impaired in mDia1(-/-) bone marrow-derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1(-/-) DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.     

Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells

Mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene are associated with a spectrum of autoinflammatory diseases, including familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurologic, cutaneous, articular syndrome, also known as neonatal-onset multisystem inflammatory disease. CIAS1 encodes cryopyrin, a protein that localizes to the cytosol and functions as pattern recognition receptor. Cryopyrin also participates in nuclear factor-kappaB regulation and caspase-1-mediated maturation of interleukin 10. In this study, we showed that disease-associated mutations in CIAS1 induced rapid cell death of THP-1 monocytic cells. The features of cell death, including 7-AAD staining, the presence of cellular edema, and early membrane damage resulting in lactate dehydrogenase (LDH) release, indicated that it was more likely to be necrosis than apoptosis, and was effectively blocked with the cathepsin B-specific inhibitor CA-074-Me. CA-074-Me also suppressed induced by disease-associated mutation lysosomal leakage and mitochondrial damage. In addition, R837, a recently identified activator of cryopyrin-associated inflammasomes, induced cell death in wild type CIAS1-transfected THP-1 cells. These results indicated that monocytes undergo rapid cell death in a cathepsin B-dependent manner upon activation of cryopyrin, which is also a specific phenomenon induced by disease-associated mutation of CIAS1.     

Bi-focal atrial tachycardia mimicking atrial fibrillation: fusion and interference between two distinct tachycardias

Irregular tachycardias mimicking atrial fibrillation (AF) have previously been described. We report a case of a 60-year-old man with an antiarrhythmic drug-resistant atrial tachycardia (AT) mimicking AF. The tachycardia consisted of two distinct ATs with interference of one repetitive AT with another sustained AT. Radiofrequency (RF) ablation of two distinct right atrial foci eliminated the irregular tachycardia. Although catheter-based pulmonary vein isolation has become a popular therapeutic approach for patients with symptomatic AF, careful evaluation of the intracardiac recordings in the patients undergoing RF ablation for AF is important.     

Seroprevalence of Herpes Simplex Virus 1 and 2 in a Population-Based Cohort in Japan

Background

There have been few population-based studies of the seroprevalence and correlates of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Japan.

Methods

We enrolled a total of 1244 adults, aged 18–59 years, from a population-based cohort in southern Japan, and tested their serum samples using an ELISA kit containing HSV type-specific antigens to glycoproteins G1 and G2.

Results

The seroprevalence of HSV-1 and HSV-2 was 55.4% and 7.4% in men and 63.3% and 9.3% in women, respectively. Overall, 4 percent of the participants (2.3% of men and 5.0% of women) were co-infected with HSV-1 and HSV-2. The seroprevalences of both HSV-1 and HSV-2 increased with age in both sexes, and were always higher among women than among men in each age bracket. The prevalence of HSV-2 infection among HSV-1 infected individuals was lower than that among uninfected individuals, both in men and women. Male current drinkers, and male and female current smokers, were more likely to be infected with HSV-1 and HSV-2, as compared to never drinkers and never smokers, respectively.

Conclusion

It is hoped that the estimates produced in this study will help in understanding the burden of these infections in Japan.Key words: herpes simplex virus types 1 and 2, seroprevalence, risk factors, Japan