Serum lipid survey and its recent trend in the general Japanese population in 2000

To determine the recent serum lipid levels and other serum variables in the general Japanese population and trends in their changes over the past 40 years, a nationwide survey of serum lipid levels was conducted in 36 institutes from various districts around Japan in 2000. The total number of subjects was 12,839, aged 4 through 99 years. The mean total cholesterol level was 201 mg/dl; 202 mg/dl in men and 200 mg/dl in women. The mean HDL-cholesterol level was 59 mg/dl; 55 mg/dl in men and 65 mg/dl in women. The mean LDL-cholesterol level was 118 mg/dl; 121 mg/dl in men and 115 mg/dl in women. The mean triglyceride level was 118 mg/dl; 136 mg/dl in men and 92 mg/dl in women. The total cholesterol level slightly increased by 5 mg/dl in 10 years. Although the triglyceride level in women did not change, the triglyceride level in men increased over 10 years, especially in the 30s through 70s age bracket, indicating a possible increase in metabolic syndromes in the future. The present results will become the standard serum lipid level data for the Japanese people, and succeeding 10-year surveys will clarify the trends of lipid levels in this country.     

Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma

Gentisic acid, an aspirin metabolite, has an antioxidant effect, although its detailed mechanism remains elusive. The present study was designed to determine whether it inhibits low-density lipoprotein (LDL) oxidation and the formation of lipid hydroperoxides in human plasma. The susceptibility of LDL oxidative modification was investigated by a method using 2,2'-azobis or Cu2+. To study the effect of gentisic acid on free radical-induced damage to plasma lipids, cholesterol ester hydroperoxides generated by incubating human fresh plasma with Cu2+ and gentisic acid was analyzed. Gentisic acid inhibited LDL oxidation in a concentration-dependent manner. It significantly inhibited the formation of cholesterol ester hydroperoxides in plasma, and was consumed after the depletion of ascorbic acid and reduced form of coenzyme Q-10 (CoQH2-10), whereas concentrations of other antioxidants remained unchanged. Gentisic acid had a potent free radical scavenging activity with a minimal chelating effect. The potent antioxidant property of gentisic acid may partly account for the anti-atherogenic effects of aspirin.     

Characterization of the human RAB38 and RAB7 genes: exclusion of new major pathological loci for Japanese OCA

BACKGROUND: Oculocutaneous albinisms (OCAs) are due to various gene mutations that cause a disruption of melanogenesis in the melanocyte. Four different genes associated with human OCA have been reported, however, not all of OCA patients can be classified according to these four genes. We have sought to find a new major locus for Japanese OCA. Recently two genes, RAB38 and RAB7, were reported to play an important role in melanogenesis in the melanocyte, suggesting that these two genes could be good candidates for new OCA loci. OBJECTIVE: To determine the structures of the human RAB38 and RAB7 genes, and examine if the two genes are new major loci for Japanese OCA. METHODS: We screened mutations in these genes of 25 Japanese OCA patients who lacked mutations in the OCA1 and OCA2 genes with SSCP/heteroduplexes method. RESULTS: We determined the both genes, and their genomic organizations to design the primers for SSCP/heteroduplexes method. And then we screened mutations, but no mutation was detected. CONCLUSION: Neither of the genes is a new major locus for Japanese OCA.     

Characterization of the normal and hyperplastic thymus on chemical-shift MR imaging

OBJECTIVE: We designed our study to prospectively assess a potential role for chemical-shift MR imaging in identifying a thymus that has not been completely replaced by fat tissue. CONCLUSION: The thymic tissue revealed homogeneous decrease in intensity on opposed-phase MR images relative to that seen on in-phase images in 15 healthy volunteers and two patients with hyperplastic thymus. Chemical-shift MR imaging may be useful in identifying normal thymic tissue and the hyperplastic thymus in early adulthood.     

Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by<Superscript>123</Superscript>I-BMIPP SPECT and<Superscript>99m</Superscript>Tc-tetrofosmin electrocardiographically gated SPECT

OBJECTIVE: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-nine patients with cardiomyopathies (58 +/- 14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis. RESULTS: BMIPP uptake was decreased (p < 0.05), and its washout was increased (p < 0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p > 0.05), but showed a significant correlation with H/M-TF (p < 0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p < 0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p > 0.05) but had a significant correlation with regional perfusion (p < 0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p < 0.005) and perfusion (p < 0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively. CONCLUSION: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.     

Combinations of nondiabetic parental genomes elicit impaired glucose tolerance in mouse SMXA recombinant inbred strains

Type 2 diabetes in humans is not a single gene disorder but a multifactorial disease caused by the interaction of multiple genes and environmental factors. Recombinant inbred (RI) strains are a powerful tool for analyzing not only single genetic traits but also multifactorial genetic traits. By using the SMXA RI mice, we genetically dissected diabetes-related traits (BMI, nonfasting blood glucose concentration, and blood glucose concentration during intraperitoneal glucose tolerance tests). For minimizing the variation of glucose tolerance in each strain, all mice were fed the high-carbohydrate diet and subjected to phenotypic and genetic analyses. The parental strains, SM/J and A/J, were nondiabetic, and the differences of the mean values of diabetes-related traits were small. In contrast, an impaired glucose tolerance was observed in (SM x A)F1 mice, and marked differences in diabetes-related traits were observed in 19 SMXA RI strains. In particular, several SMXA RI strains showed markedly impaired glucose tolerance and hyperglycemia. Quantitative trait locus (QTL) analysis revealed a locus on chromosome (Chr) 10 contributing significant effect on nonfasting blood glucose concentration, as well as six diabetes-related loci on four chromosomes with suggestive evidence of linkage with diabetes-related phenotypes. The A/J-derived QTLs on Chr 2 and 18 and an SM/J-derived QTL on Chr 10 contributed to the impairment of glucose tolerance and/or the increase of blood glucose concentration. The present study indicates that QTLs derived from parental SM/J and A/J genomes, both of which are nondiabetic, interact in the RI genomes, leading to the development of hyperglycemia and diabetic phenotypes. Genetic dissection of this kind of diabetogenesis will increase our understanding of the complex gene-gene interaction and mode of inheritance in human type 2 diabetes.