Kanazawa Medical University

About: Kanazawa Medical University is a education organization based out in Kanazawa, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 3103 authors who have published 6322 publications receiving 144592 citations. The organization is also known as: Kanazawa ika daigaku.

Hepatic messenger RNA contents of cytochrome P4502E1 in patients with different P4502E1 genotypes.

Abstract: Since heavy drinkers do not always develop alcoholic liver disease (ALD), genetic factors may be involved. Cytochrome P4502E1 (P4502E1) is the main enzyme that oxidizes ethanol in the non-alcohol dehydrogenase pathway. Recently, the presence of genetic polymorphisms at the 5'-flanking region of this enzyme was confirmed. We recently detected the c2 gene of P4502E1 in most patients with ALD, suggesting that development of ALD may be genetically controlled. Although high transcriptional activity of the c2 gene was confirmed in studies using the Hep G2 cell, little is known about transcriptional activity in humans with the c2 gene. Therefore, messenger RNA (mRNA) contents of P4502E1 in livers of patients with different P4502E1 genotypes were measured. Hepatic mRNA contents in type B were three times higher than in type A, suggesting that transcriptional activity of the c2 gene of P4502E1 is stronger than that of the c1 gene, even in human liver. The results of the present study are compatible with those in the Hep G2 cells. These results suggest that polymorphisms of the P4502E1 gene may be linked to the development of ALD through enhancement of ethanol metabolism in the non-alcohol dehydrogenase pathway.

Alcohol intake and the risk of hyperuricaemia: a 6-year prospective study in Japanese men.

Abstract: Background and aims Since there is little information derived from prospective studies on the amount of alcohol drinking required to induce hyperuricaemia, we attempted to address this issue in a Japanese population. Methods and results A total of 3310 Japanese men aged 20–54 years that were free of hyperuricaemia were classified according to their alcohol intake per week at baseline. Incident hyperuricaemia, defined as >7.0 mg/dl and/or taking medication for hyperuricaemia, was assessed through annual heath examinations for 6 years after the baseline examination. During follow-up, 529 incident cases of hyperuricaemia occurred. There was a positive, dose-response relationship between alcohol intake and the risk of incident hyperuricaemia. The hazard ratio (95% confidence interval) for hyperuricaemia in drinkers compared with non-drinkers was 1.10 (0.85–1.42) for sake , when the consumption of these two beverages was analysed separately. Conclusion Habitual alcohol intake significantly contributed to the development of hyperuricaemia in Japanese men, regardless of type of alcoholic beverage consumed. Therefore, it is essential to reduce excessive alcohol intake to prevent and manage hyperuricaemia.

Fusobacterium detected in colonic biopsy and clinicopathological features of ulcerative colitis in Japan.

Abstract: Fusobacterium species are part of the gut microbiome in humans, but some species have been recognized as opportunistic pathogens implicated in inflammatory diseases including inflammatory bowel diseases. Here, we performed prevalence screening of Fusobacterium in ulcerative colitis (UC) in Japanese patients. We examined Fusobacterium nucleatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) by quantitative real-time PCR in 163 inflamed mucosae from 152 UC patients. Data were correlated with clinical subtypes of UC. In an initial prevalence screen, F. nucleatum and Pan-fusobacterium were detected in 6.3 % (4/64) and 53.1 % (34/64). For all 163 mucosae, the prevalence of Pan-fusobacterium was 54.6 % (89/163). Pan-fusobacterium status was concordant in inflamed and normal adjacent samples, and the matched cases during 1-year follow-up colonoscopy. The higher amount of Pan-fusobacterium was observed in chronic continuous type compared to one attack and relapse/remitting type (p = 0.039). The higher amount of Pan-fusobacterium was also associated with rather mild clinical course of disease, such as non-steroid dependency (p = 0.015), non-refractory phenotype (p = 0.013), and non-severe phenotype (p = 0.04). Based on the distribution of Pan-fusobacterium measurable cases, we identified 10 cases as having a high amount of Pan-fusobacterium (FB-high). The clinicopathological features of FB-high UC cases were also highlighted by chronic continuous type and mild phenotypes of disease. Whole Fusobacterium species, but not F. nucleatum, are common in UC patients and have a role in persistence of colonic inflammation in UC. However, Fusobacterium infection is associated with rather mild clinical phenotypes of UC.

Lipid mediators in diabetic nephropathy

Abstract: The implications of lipid lowering drugs in the treatment of diabetic nephropathy have been considered. At the same time, the clinical efficacy of lipid lowering drugs has resulted in improvement in the cardiovascular functions of chronic kidney disease (CKD) patients with or without diabetes, but no remarkable improvement has been observed in the kidney outcome. Earlier lipid mediators have been shown to cause accumulative effects in diabetic nephropathy (DN). Here, we attempt to analyze the involvement of lipid mediators in DN. The hyperglycemia-induced overproduction of diacyglycerol (DAG) is one of the causes for the activation of protein kinase C (PKCs), which is responsible for the activation of pathways, including the production of VEGF, TGFβ1, PAI-1, NADPH oxidases, and NFҟB signaling, accelerating the development of DN. Additionally, current studies on the role of ceramide are one of the major fields of study in DN. Researchers have reported excessive ceramide formation in the pathobiological conditions of DN. There is less report on the effect of lipid lowering drugs on the reduction of PKC activation and ceramide synthesis. Regulating PKC activation and ceramide biosynthesis could be a protective measure in the therapeutic potential of DN. Lipid lowering drugs also upregulate anti-fibrotic microRNAs, which could hint at the effects of lipid lowering drugs in DN.

Impaired TCR signaling through dysfunction of lipid rafts in sphingomyelin synthase 1 (SMS1)-knockdown T cells.

Abstract: During T cell activation, TCRs cluster at the center of the T cell–antigen-presenting cell interface forming the central supramolecular activation cluster. Although it has been suggested that sphingolipid- and cholesterol-rich microdomains, termed lipid rafts, form platforms for the regulation and transduction of TCR signals, an actual role for membrane sphingomyelin (SM), a key component of lipid rafts, has not been reported. After cloning a gene responsible for SM synthesis, sphingomyelin synthase (SMS) 1, we established a SM-knockdown cell line (Jurkat-SMS1/kd) by transfection of SMS1-short-interfering RNA into Jurkat T cells, which is deficient in membrane expression of SM. Upon CD3 stimulation, expression of CD69 (the earliest leukocyte activation antigen), activation-induced cell adhesion and proliferation as well as TCR clustering was severely impaired in Jurkat-SMS1/kd cells. CD3-induced tyrosine phosphorylation and association of linker for activation of T cell with ZAP-70 and Grb2 and phosphorylation of protein kinase C (PKC) u were also severely impaired in Jurkat-SMS1/kd cells. Finally, translocation of TCR, ZAP-70 and PKCu into lipid rafts was markedly decreased in Jurkat-SMS1/kd cells. These findings indicate that membrane SM is crucial for TCR signal transduction, leading to full T cell activation through lipid raft function.