Vesicle-associated proteins and quantal release at single active zones of amphibian (Bufo marinus) motor-nerve terminals.

A study was made to determine the disposition of vesicle-associated proteins (syntaxin, SV2, SNAP-25) and calcium channels with respect to the spatial extent of spontaneous and evoked quantal release within regions of amphibian motor-nerve terminal branches delineated by FM1-43 stained vesicle clusters (blobs). Discrete concentrations of vesicles revealed approximately 2 microm apart along the length of terminal branches through FM1-43 staining were identical in size and spacing to those identified along terminal branches with SV2 antibody (AbSV2). Fluorescent antibodies to syntaxin 1 (AbS), SNAP-25 (AbS25) and the calcium channel alpha1B subunit (Abalpha1B) were found in relatively high concentrations coincident with the AbSV2 blobs. Three extracellular recording electrodes were placed in the vicinity of individual FM1-43 blobs, and an algorithm was used to determine the spatial origin of miniature endplate potentials (MEPPs) and EPPs together with their relative amplitudes. MEPPs and EPPs originated throughout the region stained by FM1-43 but not elsewhere; amplitude-frequency distributions of MEPPs and EPPs were similar for all FM1-43 blobs with average coefficients of variation of no less than 0.28. A linear relationship existed between the size of an FM1-43 blob, measured as the integrated extent of FM1-43 staining of a blob, and the frequency of MEPPs as well as the probability of EPPs from the blob. There was a proximo-distal gradient in the size of FM1-43 blobs along the length of single terminal branches, suggesting a gradient in release probability along the branches. The frequency distribution of the distances between blobs was approximately Gaussian, whereas the frequency distribution of the size of blobs was highly skewed and was best fitted with a gamma distribution. It is concluded that there are correlations among the extent of labeling of SNAP-25, syntaxin and calcium channels at a release site, the store of vesicles to be found there, and the probability of spontaneous and evoked quantal release.     

Decreased erythrocyte and platelet phospholipids and fatty acids in juvenile neuronal ceroid-lipofuscinosis (Batten disease)

Total cellular and phospholipid fatty acids were analyzed in erythrocytes and platelets from six patients with juvenile neuronal ceroid-lipofuscinosis (Spielmeyer-Vogt, Batten disease, JNCL). The results were compared to those of age-matched controls. The amounts of total fatty acid and the phospholipid classes, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) were significantly decreased in patients when related to cellular protein. The reductions in total fatty acids were 27% in erythrocytes and 50% in platelets. Erythrocyte PC reduction was 36%, PE was 44% and PS 27%. There were no major qualitative differences in the phospholipid fatty acids, suggesting that the fatty acid composition of the reduced phospholipid was normal, and that there is a generalized phospholipid deficiency in these cells in JNCL. This was not related to nutritional status. The pathogenesis of Batten disease may be related to abnormal membrane function resulting from this marked phospholipid deficiency.     

IPEX is a unique X-linked syndrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena.

The rare syndrome known as IPEX (OMIM: 304930) is characterized by immune-dysfunction, polyendocrinopathy, enteropathy, and X-linked inheritance. The gene responsible for IPEX maps to Xp11.23-q13.3, a region of the X chromosome that also harbors the Wiskott-Aldrich syndrome gene ( WASP ). IPEX syndrome results from mutations of a unique DNA binding protein gene, FOXP3. Mutations invariably impair the seemingly essential forkhead domain of the protein, which is uniquely located in the carboxyl terminus, affecting protein function. In this review, we describe the identification of IPEX as a unique X-linked syndrome, the clinical features of IPEX, mutations of the immune-specific FOXP3 DNA binding protein, and bone marrow transplantation as a potential cure for the syndrome, which is usually lethal within the first year of life in affected males.     

Diabetes Care and Outcomes: Disparities Across Rural America

We examined differences in receipt of diabetes care and selected outcomes between rural and urban persons living with diabetes, using nationally representative data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS). “Rural” was defined as living in a non-metropolitan county. Diabetes care variables were physician visit, HbA1c testing, foot examination, and dilated eye examination. Outcome variables were presence of foot sores and diabetic retinopathy. Analysis was limited to persons 18 and older self-reporting a diagnosis of diabetes (n = 29,501). A lower proportion of rural than urban persons with diabetes reported a dilated eye examination (69.1 vs. 72.4%; P = 0.005) or a foot examination in the past year (70.6 vs. 73.7%; P = 0.016). Conversely, a greater proportion of rural than urban persons reported diabetic retinopathy (25.8 vs. 22.0%; P = 0.007) and having a foot sore taking more than four weeks to heal (13.2 vs. 11.2%; P = 0.036). Rural residence was not associated with receipt of services after individual characteristics were taken into account in adjusted analysis, but remained associated with an increased risk for retinopathy (OR = 1.20, 95% CI = 1.02–1.42). Participation in Diabetes Self-Management Education (DSME) was positively associated with all measures of diabetes care included in the study. Availability of specialty services and travel considerations could explain some of these differences.     

The process of evidence-based practice in occupational therapy: Informing clinical decisions

As we move into the 21st century, there are increasing demands placed on occupational therapists to ensure their practice is based on sound evidence. Evidence-based practice is an approach to clinical decision making that has gained considerable interest and influence during the last decade. This article describes and explains the process of evidence-based practice and its application to clinical occupational therapy practice. Directions for resources that may assist therapists' self-directed learning are also provided. As health care becomes more evidence-based, awareness of the principles, skills, and resources for evidence-based practice is of relevance to all occupational therapists.     

Mechanisms of injury in unilateral testis torsion

We investigated the mechanisms of injury involved in unilateral testis torsion as well as the interventional effects of orchiectomy at 48 h and immunosuppression with corticosteroids in rats. Torsion was associated with abnormal contralateral testis histology and raised antilymphocytes and antisperm antibody titers. Both orchiectomy and steroid administration lessened these findings, suggesting that an immunological process underlies the abnormality seen in this experiment model.