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Abstract.To examine the clinical significance of the insulin resistance index as determined by homeostasis model assessment (HOMA-IR), we investigated the relationship between HOMA-IR and the insulin resistance estimated by the euglycemic-hyperinsulinemic clamp method in various subgroups and compared the significance of HOMA-IR with that of fasting plasma insulin levels (FIRI). HOMA-IR was significantly correlated to the inverse of the glucose infusion rate (1/GIR) in both diabetic and non-diabetic subjects (r=0.747, P<0.0001 and r=0.419, P<0.002, respectively).In the diabetic patients, treatment with sulfonylureas did not weaken this correlation (r=0.833, P<0.0001).HOMA-IR was found to be closely related to FIRI (r=0.932, P<0.0001), but HOMA-IR was more closely associated with 1/GIR than FIRI was. HOMA-IR as well as 1/GIR was correlated with the visceral fat area (VFA) more closely than with the subcutaneous fat area (SFA), while FIRI was correlated almost equally with both of them. In conclusion, HOMA-IR is a convenient and beneficial method for evaluating insulin resistance, especially in subjects with visceral fat accumulation, and reflects insulin resistance obtained by euglycemic clamp more accurately than FIRI alone.

Active ulcerative colitis (UC) is associated with elevated granulocytes and monocytes/macrophages (GM) which show activation behavior and increased survival time. Further, fecal calprotectin (a stable neutrophil protein) level parallels intestinal inflammation and can predict UC relapse. Since GM are major sources of inflammatory cytokines and chemokines, they are suspected to have roles in the initiation and perpetuation of UC. Our objective was to investigated relationships between peripheral blood (PB) neutrophils, calprotectin, and UC disease activity. Full PB and calprotectin were determined in 69 healthy controls and 31 patients with UC, then 7 randomly selected patients received GM adsorptive apheresis (GMA) with Adacolumn, 10 sessions of 60-min duration each. Patients with UC had higher neutrophil counts (P < 0.001), but lower lymphocyte counts (P < 0.001) compared with controls. Further, fecal calprotectin levels showed a correlation with UC clinical activity index (CAI; P < 0.001) and mucosal inflammation (P < 0.001). Following GMA, there were falls in neutrophils (P < 0.02), CAI (P < 0.02) and calprotectin (P < 0.02). In conclusion, GM appear to contribute to intestinal inflammation and UC activity and reduction of these cells by GMA should benefit patients with active UC. Further, the correlations among calprotectin, UC activities, and PB neutrophils should serve as the basis for preemptive actions to control this disease.

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Inflammation and immune responses after tissue injury play pivotal roles in the pathology, resolution of inflammation, tissue recovery, fibrosis and remodeling. Regulatory T cells (Tregs) are the cells responsible for suppressing immune responses and can be activated in secondary lymphatic tissues, where they subsequently regulate effector T cell and dendritic cell activation. Recently, Tregs that reside in non-lymphoid tissues, called tissue Tregs, have been shown to exhibit tissue-specific functions that contribute to the maintenance of tissue homeostasis and repair. Unlike other tissue Tregs, the role of Tregs in the brain has not been well elucidated because the number of brain Tregs is very small under normal conditions. However, we found that Tregs accumulate in the brain at the chronic phase of ischemic brain injury and control astrogliosis through secretion of a cytokine, amphiregulin (Areg). Brain Tregs resemble other tissue Tregs in many ways but, unlike the other tissue Tregs, brain Tregs express neural-cell-specific genes such as the serotonin receptor (Htr7) and respond to serotonin. Administering serotonin or selective serotonin reuptake inhibitors (SSRIs) in an experimental mouse model of stroke increases the number of brain Tregs and ameliorates neurological symptoms. Knowledge of brain Tregs will contribute to the understanding of various types of neuroinflammation.

Body fat distribution can be assessed by computed tomography (CT). The ratio of umbilicus was used to classify obese subjects as having visceral fat obesity (VFO) or subcutaneous fat obesity (SFO). Serum triglyceride and total cholesterol levels and plasma glucose area in an oral glucose tolerance test were higher in patients with VFO than in those with SFO. Significant positive correlations were demonstrated between V/S ratio and plasma glucose area, serum triglyceride level, and total cholesterol level as well as systolic or diastolic blood pressure. VFO was more frequently associated with coronary artery disease. Moreover, VFO was more often accompanied by multiple risk factors than was SFO. Steady-state plasma glucose (SSPG) level was significantly higher in patients with VFO than with SFO, suggesting that insulin resistance may be more remarkable in VFO than in SFO. Furthermore, visceral fat accumulation was also associated with these complications even in nonobese subjects. Visceral fat area (VFA) was significantly correlated with fasting plasma glucose, serum triglyceride, and total cholesterol levels. Animal models such as Goto-Kakizaki (GK) rats with ventromedial hypothalamus (VMH) lesions and Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were accompanied by visceral fat accumulation and an early stage of aortic atherosclerosis. Aging, sex hormone, genetic, and dietary factors and physical inactivity may induce visceral fat accumulation. Visceral fat is characterized by its high lipogenic activity as well as its accelerated lipolytic activity. High levels of portal free fatty acids (FFAs) may eventually result in an enhancement of hepatic triglyceride synthesis, causing hyperlipidemia. High portal FFA levels would also induce insulin resistance, thereby causing glucose intolerance, hypertension, and finally atherosclerosis. We propose a term, "visceral fat syndrome," as a highly atherogenic state, which includes visceral fat accumulation, glucose intolerance (insulin resistance), hyperlipidemia, and hypertension.

Variable cDNA regions in the VP2 gene of five highly virulent infectious bursal disease viruses (IBDVs) isolated in Japan were amplified by polymerase chain reaction (PCR) and sequenced. The nucleotide sequences of five highly virulent IBDVs were identical. Comparisons of the nucleotide and the deduced amino acid sequences with those of other strains of IBDV indicated that Japanese highly virulent IBDV is different from all other strains of IBDV that were compared. The number of amino acids that differed between strains (substitution score) showed that highly virulent IBDV is more closely related to European virulent strain 52/70 than to Japanese conventional strains. These results strongly suggest that a single strain of highly virulent IBDV that might have originated from a European strain is prevalent in Japan.