B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase

We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B cell development, signaling, and immunological tolerance. Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically removes acetyl moieties from the 9-OH position of α2–6-linked sialic acid, exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell development, and spontaneously develop antichromatin autoantibodies and glomerular immune complex deposits. The 9-O-acetylation state of sialic acid regulates the function of CD22, a Siglec that functions in vivo as an inhibitor of BCR signaling. These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage.     

Caribbean female patients with type 2 diabetes mellitus have lower serum levels of adiponectin than nondiabetic subjects

BACKGROUND: Previous studies in other populations suggest that low levels of serum adiponectin may be a cardiovascular risk factor. We aimed to determine the baseline concentration of serum adiponectin and its relationship with selected biochemical risk factors for coronary artery disease (CAD) in a cross-section of Caribbean patients with type 2 diabetes. METHODS: Anthropometric indices and fasting plasma concentrations of glucose, insulin, adiponectin, triglyceride, and total and HDL cholesterol were measured in 56 type 2 diabetic patients and 33 nondiabetic subjects. Insulin resistance (IR) was determined using the homeostatic model assessment (HOMA) method. RESULTS: Consistent with previous reports, Caribbean type 2 diabetic patients had significantly lower fasting serum adiponectin levels and higher mean levels of glucose, triglyceride and IR than the nondiabetic subjects (all, p < 0.01). The nondiabetic female subjects had significantly higher serum adiponectin levels than did the female diabetics or nondiabetic males (p < 0.01). Serum adiponectin level was negatively correlated with triglyceride or LDL cholesterol and positively related with HDL cholesterol among nondiabetic subjects, and the latter relationship persisted after adjusting for the effects of age, sex and BMI (r = 0.70, p < 0.01). CONCLUSION: Similar to reports from other populations, Caribbean patients with type 2 diabetes, particularly the females, have lower levels of serum adiponectin than their nondiabetic counterparts and this is an additional CVD risk factor for the patients.     

Glycaemic responses after ingestion of 3 local carbohydrate-based foods in West Indian patients with type-2 diabetes mellitus

BACKGROUND & AIM: Previous studies suggest that inadequate glycaemic control in diabetic patients might be related to the type of carbohydrates the patients consume regularly. Thus, we aimed to assess glucose and insulin responses after diabetic and non-diabetic subjects ingested 3 commonly consumed carbohydrate-based foods. METHODS: Thirty-eight type-2 diabetic and 27 non-diabetic subjects were studied in 3 different occasions of 7 days apart. On each day of the study, anthropometric indices were measured and after collecting fasting blood samples, subjects randomly consumed bread, roti or rice within 10 min. Subsequently 7 ml of venous blood samples were collected at 60, 90, 120 and 150 min for determination of glucose and insulin responses. RESULTS: Although the diabetic patients were older than the healthy subjects (P < 0.05), both subjects had similar weight, body mass index and waist and hip circumferences (P > 0.05). The mean fasting and post meal plasma glucose concentrations for the 3 test foods were higher in diabetic patients than the corresponding values for the healthy subjects (all; P < 0.001). Generally, roti elicited the highest total incremental glucose responses in the diabetic patients irrespective of ethnic group (P < 0.05). CONCLUSION: There were variations in glucose and insulin responses to the 3 test foods. However, roti elicited the highest postprandial hyperglycaemia and should therefore be discouraged in regular dietary plan of diabetic patients.     

Comparative study of endoscopic clips: duration of attachment at the site of clip application

BACKGROUND: Several designs of endoscopic clips are now commercially available, and the indications for endoclip application are rapidly expanding. However, very limited data have been published to aid in choosing between the different types of endoclips. OBJECTIVE: To compare the duration of clip attachment between all commercially available endoclips. SETTING: Long-term experiments on 50-kg pigs under general anesthesia. DESIGN AND INTERVENTIONS: Upper endoscope was inserted into the stomach. One clip of each type (Resolution clip, TriClip, and HX-5L clip) was placed along the same gastric fold at a distance of 0.5 to 1 cm from each other. The animals were recovered. In pig nos. 1 and 2, repeat endoscopy was performed after 2 and 4 weeks. In pig nos. 3 to 5, endoscopy was repeated after 1, 2, and 5 weeks. MAIN OUTCOME MEASUREMENTS: Duration of clip retention at the site of application. RESULTS: In all animals, only the Resolution endoclip remained attached to the site of application for the entire duration of the study (4-5 weeks). No TriClips or HX-5L clips were attached at the 4- to 5-week follow-up endoscopies. Most of the TriClips (67%) detached within the first week after application. Most of the HX-5L clips (80%) dislodged within the first 2 weeks of follow-up. LIMITATIONS: The study was performed in a porcine model with a small number of animals. CONCLUSIONS: The Resolution clip has the longest duration of retention at the site of application (more than 4-5 weeks) and should be preferred when long-term attachment of endoclips is necessary.