Pathological fractures due to intraosseous fat necrosis associated with pancreatitis

SIR, Necrosis of fatty bone marrow is an unusual complicationof severe pancreatic disorders. We describe a patient presentingwith multiple pathological fractures associated with alcoholicpancreatitis. A 76-yr-old man was admitted to our hospital in May 2000 forpain and swelling of the right hand, both feet and     

Effect of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease

Both postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis, and to be a potent risk factor for cardiovascular event. To examine effects of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease (CAD), a total of 112 consecutive male patients with angiographically confirmed CAD were loaded with a high-fat and high-glucose test meal. CAD patients were divided into three groups as “non-diabetic”, “prediabetic”, and “diabetic” CAD groups. The serum triglyceride (TG) and remnant-like particle cholesterol (RLP-C) levels at the 6th hour in diabetic CAD group showed significantly higher than non-diabetic CAD group, and the incremental area under the curves (iAUCs) of these levels in diabetic CAD group were significantly greater than non-diabetic CAD group (TG, P = 0.0194; RLP-C, P = 0.0219). There were no significant differences in the iAUCs of TG or RLP-C between prediabetic and non-diabetic CAD group. The AUCs of plasma insulin levels or insulin resistance index (IRI): (AUCs of insulin) × (AUCs of glucose) as the insulin resistance marker were greater in diabetic CAD group than non-diabetic CAD group (insulin, P = 0.0373; IRI, P = 0.0228). The AUCs of serum TG or RLP-C levels showed a correlation with the AUCs of plasma insulin (AUC-TG, r = 0.5437, P < 0.0001; AUC-RLP-C, r = 0.6847, P < 0.0001), and they correlated well with the insulin resistance index (AUC-TG, r = 0.7724, P < 0.0001; AUC-RLP-C, r = 0.7645, P < 0.0001). We found that the insulin resistance showed a close relationship with postprandial hyperlipidemia in CAD patients. Diabetic, but not prediabetic state, may be a risk for postprandial impaired lipid metabolism in CAD patients.     

Induction of hepatitis B virus surface antigen‐specific cytotoxic T lymphocytes can be up‐regulated by the inhibition of indoleamine 2, 3‐dioxygenase activity

Cytotoxic T lymphocytes (CTLs) are thought to be major effectors involved in viral clearance during acute infections, including hepatitis B virus (HBV) infection. A persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which may be reflective of tolerance to HBV. Efficient induction of HBV‐specific CTLs leads to the clearance of HBV in patients with a chronic HBV infection. Previously, we reported that α‐galactosylceramide (α‐GalCer), a specific natural killer T (NKT) cell agonist, enhanced the induction of HBV surface antigen (HBsAg)‐specific CTLs. In the present study, we found that inhibition of indoleamine 2,3‐dioxygenase (IDO) activity enhanced the induction of HBsAg‐specific CTLs after immunization with HBsAg and α‐GalCer. The administration of HBsAg and α‐GalCer increased the production of interleukin‐2 and interleukin‐12b, which are crucial for the induction of HBsAg‐specific CTLs. The production of these cytokines was more strongly enhanced in IDO knockout mice compared with wild‐type mice. In addition, α‐GalCer induced the production of IDO in CD11b⁺ cells, and these cells inhibited proliferation of HBsAg‐specific CTLs. Our results lead to strategies for improving the induction of HBsAg‐specific CTLs.     

Role of insulin receptor substrate‐1 for diethylnitrosamine plus high‐fat diet‐induced hepatic tumorigenesis in mice

We investigated the role of insulin receptor substrate (Irs)‐1 for diethylnitrosamine (DEN) plus high‐fat (HF) diet‐induced hepatic tumorigenesis in mice. We gave DEN by intraperitoneal injection at the dose of 80 mg/kg to 18‐week‐old wild‐type (WT) and Irs1‐knockout (Irs1^−/−) mice, which were fed a HF diet from 8 weeks‐of‐age until they were killed (52 weeks). The Irs1^−/− mice showed significantly lower plasma alanine aminotransferase levels, triglyceride contents in the liver and also lower expression levels of the genes encoding inflammatory cytokines than the WT mice. The incidence of DEN plus HF diet‐induced hepatic tumors was 71.4% in the WT mice, whereas it was just 14.3% in the Irs1^−/− mice. The present study showed that Irs1 played an important role in DEN plus HF diet‐induced hepatic tumorigenesis.