Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.     

AT-1015, a novel serotonin2A receptor antagonist, improves resaturation of exercised ischemic muscle in hypercholesterolemic rabbits

OBJECTIVE: The effect of AT-1015, a serotonin(2A) receptor antagonist, on the resaturation of ischemic muscle in a hypercholesterolemic rabbit model was examined with near-infrared spectroscopy. METHODS: New Zealand White male rabbits were fed normal chow or cholesterol-rich chow. Ischemia was induced in the right hindlimb by ligation of the femoral artery, accompanied by balloon injury of the iliac artery. At 3 days after induction of ischemia, the bilateral gastrocnemius muscles were subjected to passive contraction for 2 minutes. The oxygen resaturation time of the gastrocnemius muscle after exercise was measured by near-infrared spectroscopy. AT-1015 was orally administered for 3 days after induction of ischemia. Assay of serotonin level in platelet-poor plasma and histologic examination of muscle and artery were performed in another set of rabbits. RESULTS: Oxygen resaturation time of the ischemic gastrocnemius was significantly prolonged in hypercholesterolemic rabbits compared with in normal rabbits without AT-1015, whereas there was no difference between both groups of rabbits that were administered AT-1015. Plasma level of serotonin in hypercholesterolemic rabbits was significantly increased compared with that in normal rabbits. No histologic differences were found in both muscle and artery among all groups. CONCLUSIONS: A serotonin(2A) receptor antagonist improved the oxygen resaturation of ischemic calf muscle after exercise in hypercholesterolemia. The interaction between plasma free serotonin and the serotonin(2A) receptor may play an important role in muscle oxygenation in ischemic limbs.     

Recovery of parathyroid function after total thyroidectomy: long-term follow-up study

BACKGROUND: To prevent postoperative hypoparathyroidism following total thyroidectomy, the parathyroid glands are preserved in situ and/or resected or devascularized parathyroid glands are autotransplanted. A retrospective investigation was conducted utilizing biochemical and specific endocrine assessments to evaluate the difference in recovery of parathyroid function in the long term. METHODS: A total of 103 patients underwent total thyroidectomy at Second Department of Surgery, School of Medicine, Kagawa University between 1990 and 1998. These patients were divided into a preservation group (n = 17), with only preserved glands in situ; a combination group (n = 72), consisting of patients with one or more parathyroid glands preserved in situ and one or more autotransplanted parathyroid glands; and an autotransplantation group (n = 14), with only transplanted glands. RESULTS: The overall incidence of permanent hypoparathyroidism in the preservation group, the combination group, and the autotransplantation group was 0%, 1.4%, and 21.4%, respectively. The mean levels of intact parathyroid hormone in the preservation group, the combination group, and the autotransplantation group recovered to 102%, 107%, and 50% of the preoperative levels at 5-year follow up. CONCLUSION: The results of the present study suggest that parathyroid glands should be preserved in situ whenever possible, to promote better recovery of postoperative function, and that only autotransplantation produces inadequate recovery of long-term function.     

Mitral Regurgitation Associated with Mitral Annular Dilation in Patients with Lone Atrial Fibrillation: An Echocardiographic Study

Background: Whether and how lone atrial fibrillation (AF) is associated with functional mitral regurgitation (MR) remain unclear. Method: We studied 12 lone AF patients without left ventricular (LV) dysfunction and/or dilatation, who underwent mitral valve annuloplasty for functional mitral regurgitation (MR). Ten lone AF patients without MR served as controls. Results: Lone AF Patients with MR had a greater mitral valve annular area and left atrial area than those without MR. There were no differences in LV volumes or LV ejection fraction. Conclusions: Therefore, we concluded that left atrial dilation and corresponding mitral annular dilation may cause MR in lone AF patients without LV dysfunction and/or dilatation.     

Sexual behaviors and their correlates among young people in Mauritius: a cross-sectional study

Background  

Little is known about the HIV/AIDS epidemic in the Indian Ocean region, including Mauritius. National records suggest a prevalence of HIV in Mauritius of < 1% in the general population, which is one of the lowest prevalence rates in southern Africa. However, HIV-positive cases have been increasing recently in Mauritius. We conducted a cross-sectional survey in January 2003 to assess the prevalence of HIVrelated sexual behaviors and their correlates among young people aged 15–24 years in Mauritius.     

Subclassification of non‐solid‐type papillary thyroid carcinoma identification of high‐risk group in common type

Two hundred and sixty‐three cases of primary human papillary thyroid carcinoma (PTC) were analyzed. All cases met the following parameters: tumor size ≥ 10 mm, no distant metastasis at presentation, and no coexistence of other histological type. The histological features of the solid/trabecular component, encapsulation, tall/columnar cell component and loss of polarity/cohesiveness were utilized to subclassify the 263 cases of PTC into five groups: solid type (15.6%), encapsulated group (9.5%), tall/columnar cell group (7.2%), micropapillary/discohesive group (19.8%) and not‐otherwise‐specified group (47.9%). We focused on the latter four non‐solid groups and compared their prognosis with the solid type. The tall/columnar cell group showed the worst disease‐free survival rate (DFS) analyzed by the Kaplan–Meier method, followed by the micropapillary/discohesive group. The not‐otherwise‐specified group and encapsulated group showed a better DFS rate than the solid type. Cancer‐related death was noted in the tall/columnar cell group (21.1%) and micropapillary/discohesive group (3.8%), but not in the other groups. The four non‐solid histological groups were further categorized into two prognostic groups: high‐risk group (including tall/columnar cell group and micropapillary/discohesive group); and low‐risk group (including encapsulated group and not‐otherwise‐specified group). Their 10‐year disease‐free survival rates were 78.7% and 93.1%, respectively. In the present study, histological grouping was significantly correlated with prognosis in the multivariate analysis according to the Cox proportional hazards regression model in addition to clinical parameters of extrathyroid invasion and gross lymph node metastasis, which predicts the patient outcome in terms of tumor recurrence and cancer‐related death more precisely. (Cancer Sci 2008; 99: 1908–1915)     

Generation of human monoclonal antibodies recognising membranous antigens of the lung adenocarcinoma cell line A549 using an AMeX immunohistostaining method.

Four monoclonal antibodies (MAbs) from hybridoma obtained by in vitro stimulation of regional lymph node lymphocytes from lung cancer patients and electrofusion of the stimulated cells with murine or human-mouse myeloma cells were reactive to lung cancer cells in enzyme-linked immunoabsorbent assay, and to lung cancer tissue in immunohistochemical analysis using acetone-methyl benzoate-xylene (AMeX) fixed tissue and in immunofluorescence analysis. Three of the MAbs (designated ZLG40, 27D57 and 28K29) recognised cell-surface antigens of the lung adenocarcinoma cell line A549 and the remaining one (designated 29D38) recognised nuclear membrane antigens of the same cell line. The three surface-binding MAbs showed a significant complement-dependent cytotoxicity (CDC) to the A549 cells, but the membrane-binding 29D38 showed no CDC to the A549 cells. Western blotting of the extracts of the A549 or PC6 (small-cell lung cancer) cell lines by the four MAbs showed a 28K29 antigen band at M(r) of approximately 600,000 (+/- 2-ME), a ZLG40 antigen band at M(r) 50,000 (+/- 2-ME), and one 29D38 antigen band at M(r) of more than 1,000,000 (-2-ME) and M(r) between 20,000 and 80,000 (+2-ME), but no detectable band for 27D57 antigen.