銅合金の溶解・鋳造プロセスにおける溶湯清浄化および凝固割れに関する研究 [論文要旨及び審査の要旨]

関西大

銅合金の溶解・鋳造プロセスにおける溶湯清浄化および凝固割れに関する研究

関西大

Cilostazol Attenuates AngII-Induced Cardiac Fibrosis in apoE Deficient Mice

Cardiac fibrosis is characterized by the net accumulation of extracellular matrix in the myocardium and is an integral component of most pathological cardiac conditions. Cilostazol, a selective inhibitor of phosphodiesterase type III with anti-platelet, anti-mitogenic, and vasodilating properties, is widely used to treat the ischemic symptoms of peripheral vascular disease. Here, we investigated whether cilostazol has a protective effect against Angiotensin II (AngII)-induced cardiac fibrosis. Male apolipoprotein E-deficient mice were fed either a normal diet or a diet containing cilostazol (0.1% wt/wt). After 1 week of diet consumption, the mice were infused with saline or AngII (1000 ng kg(-1) min(-1)) for 28 days. AngII infusion increased heart/body weight ratio (p < 0.05), perivascular fibrosis (p < 0.05), and interstitial cardiac fibrosis (p < 0.0001), but were significantly attenuated by cilostazol treatment (p < 0.05, respectively). Cilostazol also reduced AngII-induced increases in fibrotic and inflammatory gene expression (p < 0.05, respectively). Furthermore, cilostazol attenuated both protein and mRNA abundance of osteopontin induced by AngII in vivo. In cultured human cardiac myocytes, cilostazol reduced mRNA expression of AngII-induced osteopontin in dose-dependent manner. This reduction was mimicked by forskolin treatment but was cancelled by co-treatment of H-89. Cilostazol attenuates AngII-induced cardiac fibrosis in mice through activation of the cAMP-PKA pathway

The Modulation of CD40 Ligand Signaling by Transmembrane CD28 Splice Variant in Human T Cells

The role of CD40 ligand (CD40L)/CD40 signaling in T cell–dependent B cell differentiation and maturation has been amply documented. The mechanism of CD40 signaling in B cells has been well established, whereas the signaling mechanism of CD40L in T cell costimulation remains unknown. In this study we show that CD28i, a transmembrane splice variant of CD28 costimulatory receptor, complexes with CD40L in human T cells. The cross-linking of CD40L resulted in the coendocytosis of CD28i with CD40L. The tyrosine phosphorylation of CD28i followed the cross-linking of CD40L, and the overexpression of CD28i augmented the c-Jun NH2-terminal kinase, p21-activated kinase 2, and nuclear factor κB activation. These data indicate that CD28i, by functioning as a signaling adaptor, transduces CD40L signaling as well as CD28 signaling in human T cells

Rectovaginal Fistula after Low Anterior Resection for Rectal Cancer Using a Double Stapling Technique

A 55-year-old female underwent low anterior resection for rectal cancer using a double stapling technique. She developed a rectovaginal fistula on the 9th postoperative day. She was discharged from hospital after undergoing transverse colostomy, and 5 months later she underwent transvaginal repair of the rectovaginal fistula. She subsequently had an uneventful recovery. The leading cause of this complication is involvement of the posterior wall of the vagina in the staple line when firing the circular stapler. Transvaginal repair with a diverting stoma for rectovaginal fistula is a safe, minimally invasive and effective method

A new therapeutic strategy with istradefylline for postural deformities in Parkinson’s disease

Aim of the study. Postural deformities are common in Parkinson’s disease (PD) patients. Several treatment options have been reported, but responses to these treatments appear unpredictable. Istradefylline is a novel drug for PD. Cases of PD patients whose postural deformities were improved after withdrawal of dopamine agonists and initiation of istradefylline are presented. Materials and Methods. Four consecutive patients with postural deformities including antecollis, Pisa syndrome, and camptocormia were recruited and treated with istradefylline in combination with withdrawal of dopamine agonists, which are possible causes of postural deformities. Results. The dopamine agonists were discontinued an average of 26 months after the development of the postural deformities, and istradefylline was initiated an average of 1.3 months after dopamine agonist withdrawal. Three patients with preserved paraspinal muscle volume showed good responses to the treatment regimen at least two months after dopamine agonist withdrawal. Conclusions and clinical Implications. Postural deformities caused by dopamine agonists generally improve less than two weeks after dopamine agonist withdrawal. Given the response time in the present study, the response was unlikely to be caused solely by dopamine agonist withdrawal. Istradefylline can be a potential therapeutic option; however, appropriate selection of patients for treatment with istradefylline is warranted

Novel human CYP2A6 alleles confound gene deletion analysis

AbstractCytochrome P450 (CYP) 2A6 metabolizes a number of drugs and a variety of procarcinogens. CYP2A6 also catalyzes nicotine C-oxidation leading to cotinine formation, a major metabolic pathway of nicotine in humans. There are genetic polymorphisms in the human CYP2A6 gene and a relationship between the CYP2A6 genotype and smoking habits as well as the incidence of lung cancer has been indicated. CYP2A6*4 alleles are the whole deleted type and are completely deficient in the enzymatic activity. An unequal crossover junction is located in the 3′-flanking region in the CYP2A6*4A allele, whereas the junction is located in either intron 8 or exon 9 in the CYP2A6*4D allele. In the present study, a novel genotyping method to distinguish between two different whole deleted alleles of CYP2A6*4A and CYP2A6*4D was established. In the process, two novel alleles, CYP2A6*1F and CYP2A6*1G, were found. The CYP2A6*1F has a single nucleotide polymorphism (SNP) of C5717T in exon 8, and the CYP2A6*1G has two SNPs, C5717T in exon 8 and A5825G in intron 8. The SNP of C5717T corresponds to C1224T on the cDNA sequence and is a synonymous mutation. Since the CYP2A6*1F produces a recognition site of the restriction enzymes that is the same as CYP2A6*4D, the presence of the CYP2A6*1F allele could cause a mistyping as the CYP2A6*4D allele. According to an improved genotyping method, the allele frequencies of CYP2A6*4A, CYP2A6*4D, CYP2A6*1F, and CYP2A6*1G in 165 Caucasians were 3.0%, 0%, 1.8%, and 1.2%, respectively. The allele frequencies of CYP2A6*4A, CYP2A6*4D, CYP2A6*1F, and CYP2A6*1G in 94 African-Americans were 0%, 0.5%, 0%, and 13.3%, respectively. This is the first report of a method that can distinguish between CYP2A6*4A, CYP2A6*4D, and CYP2A6*1F which could otherwise cause a mistyping as CYP2A6*4D