No abstract

Background-Human glutamate-cysteine ligase (GCL) is a rate-limiting enzyme for the synthesis of glutathione that plays a crucial role in antioxidant defense mechanisms in most mammalian cells, including vascular cells. Oxidants transcriptionally upregulate GCL genes for glutathione synthesis, providing a protective mechanism against oxidative stress-induced cellular dysfunction. This study examined the hypothesis that variation in the GCL genes may be associated with coronary artery disease in which oxidative stress plays a pathogenetic role. Methods and Results-We searched for the common variants in the 5Ј-flanking region of the GCL modifier subunit (GCLM) gene in patients with myocardial infarction (MI). We found a polymorphism (Ϫ588C/T) in which the T allele showed lower promoter activity (40% to 50% of C allele) in response to oxidants in the luciferase reporter gene assay. Allele frequencies were determined by polymerase chain reaction-based analysis of restriction fragment length polymorphism in 429 patients with MI and 428 control subjects (as defined by angiography) in Kumamoto Prefecture, Japan. The frequency of the T polymorphism was significantly higher in the MI group than in the control group (CT and TT genotypes: 31.5% in MI group versus 19.2% in control group; PϽ0.001). In multiple logistic regression analysis, the T polymorphism was a risk factor for MI independent of traditional coronary artery disease risk factors (odds ratio, 1.98; 95% confidence interval, 1.38 to 2.83; PϽ0.001). Conclusions-These findings suggest that the Ϫ588T polymorphism of the GCLM gene may suppress GCLM gene induction in response to oxidants and that it is a genetic risk factor for MI.

These findings suggest that long-term lymphatic volume overload can induce chronic tissue inflammation, progressive fibrosis, impaired homeostasis, altered remodelling of adipose tissue, impaired regenerative capacity and immunological dysfunction. Further elucidation of the pathophysiological mechanisms underlying lymphoedema will lead to more reliable therapeutic strategies.

Reports of spontaneous dissection of the superior mesenteric artery are rare. Diagnosis in the acute stage has been considered difficult, but we encountered four cases from November 1998 to November 2001. All four cases were diagnosed using abdominal CT scanning in the acute stage and could be treated conservatively. All patients were provided anticoagulation therapy upon fasting. The mean period of continuous abdominal pain was 10.2 days, the mean period of fasting was 27.2 days, and the mean number of in-hospital days was 44.

The safety and effectiveness of this investigational device was verified over a period up to 36 months after operation. A long-term follow-up would be necessary to further verify the effectiveness of the device in the future.