長期的な酸化脂質摂取が線虫の生殖能力と寿命に与える影響

Fatty acids, which are biologically and functionally crucial components of triacylglycerol and phospholipid,are very sensitive to oxygen attack, and subsequently produce substances such as hydroperoxides and aliphaticlong-chain aldehydes. Although these compounds, collectively called oxidized lipids, are known to be toxicto organism, long-term effects of the oxidized lipids uptake upon organism have much to be uncovered. Inthis study, the effects of long-term uptake of oxidized lipids upon fecundity and life-span were analyzed usingmodel organism, Caenorhabditis elegans. Although oxidized lipids showed little effect on fecundity, mean lifespanof the worms were shortened when they were fed with oxidized fatty acids. However, maximum life span was not affected by oxidized lipid indicating the toxic effect of the oxidized lipids were not uniform throughoutthe life cycle; relatively strong in the early stage of life and gradually become weak as aging proceeds. The toxiceffects of oxidized lipids were diminished by addition of anti-oxidative vitamin α-tocopherol. The expressionof anti-oxidative stress enzyme gene, such as superoxide dismutases and catalases, were analyzed by RT-PCR.The expression of these genes were increased upon long-term oxidized lipids exposure. This indicates that antioxidantprotection system indeed responded to the oxidative stress caused by the oxidized lipids

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

金沢大学医薬保健研究域医学系The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society

Body Mass Index and Risk of Cancer in Men and Women

We conducted a 14-year follow-up study to analyze the hazard ratio (HR) of cancer incidence in relation to body mass index (body weight (kg) / body height (m)? , BMI) and lifestyle-related factors in Saga Prefecture, Japan. The subjects were 2,170 people, who were randomly selected from men and women aged from 40 to 69 years old, and who had completed a standardized questionnaire on lifestyle in 1983. Information about death and corresponding data in 1997 were obtained either by mail and/or through the city or town offices, and we identified cancer subjects by using the list of the Saga Cancer Registry. A total of 239 subjects (160 males and 79 females) were diagnosed as having cancer, revealing a significantly larger population of male victims compared to females. After adjusting for age, physical activ-ity, alcohol consumption and smoking status, a negative relationship was observed between BMI and the risk of stomach cancer in females, and a positive relationship was observed between BMI and the risk of colon cancer in males. In conclusion, in addition to some lifestyle-related factors, BMI was also show to be associated with the risk of some forms of cancer