α-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer’s disease

The gene encoding α-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer’s disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that α-T-catenin is expressed in human brain, and like other α-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Aβ deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n>700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.     

Describing community needs: examples from the Circles of Care initiative

The assessment of community needs was one of the key foundations of the Circles of Care planning effort. Grantees identified a range of needs at the child, adolescent, family, programmatic, and community levels. This information, along with an emphasis on the importance of each community's history and culture, served as an important guide for each program as they developed their model systems of care.     

Role of nociceptin in the modulation of nociception in the arcuate nucleus of rats

Neuropeptide nociceptin/orphanin FQ is the endogenous ligand for the opioid-receptor-like receptor 1 (ORL1), mediating essential functions in the central and peripheral nervous systems. The present study was performed to investigate the role of nociceptin and ORL1 receptor in nociception and morphine-induced antinociception in the arcuate nucleus of hypothalamus in rats. Hindpaw withdrawal latencies (HWL) were measured by hot-plate and Randall Selitto tests. The HWL to both thermal and mechanical stimulation decreased significantly after intra-arcuate nucleus injection of nociceptin in a dose-dependent manner. The effect of nociceptin was blocked significantly by subsequent intra-arcuate nucleus administration of [Nphe(1)]nociceptin(1-13)-NH(2), an ORL1 receptor antagonist. Furthermore, an intra-arcuate nucleus injection of nociceptin dramatically attenuated the antinociceptive effect induced by morphine either injected in the same site or applied intraperitoneally. These results suggest that nociceptin in the arcuate nucleus induces a hyperalgesic effect by acting on ORL1 receptors. The present study also demonstrates an interaction between nociceptin and opioids in the arcuate nucleus of the hypothalamus.     

Perineurial cell basement membrane thickening and myelinated nerve fibre loss in diabetic and nondiabetic peripheral nerve

Diabetic neuropathy is associated with changes in the extracellular matrix of the perineurium, including thickening of the basement membrane of the perineurial cells. Peripheral vascular disease (PVD) is a common vascular condition that can occur in the absence or presence of diabetes. Thickening of the vascular basement membrane of the vasa nervorum is associated with both diabetes and nondiabetic peripheral vascular disease. However, perineurial cell basement membrane (PCBM) thickening in the nondiabetic PVD state has not, until now, been investigated. In this study, 36 nerve fascicles were examined from three patient groups: a diabetic group, a nondiabetic PVD group, and a group free of both PVD and diabetes (control group). PCBM thickness, fascicle size, and myelinated nerve fibre (MNF) density were measured in all three groups. Endoneurial blood vessels were also observed for evidence of morphological changes. The results showed that the thickness of the PCBM is significantly greater in the diabetic group in comparison with both the control and the nondiabetic PVD group, and this increase in thickness is linearly related to fascicle size. The thickness of the PCBM was not significantly different between the nondiabetic PVD and control groups. Although both the nondiabetic PVD and diabetic groups showed a loss of myelinated nerve fibres in comparison with the control group, this loss was statistically greater in the diabetic group. The endoneurial blood vessels of both the diabetic and nondiabetic PVD groups showed evidence of endothelial cell hyperplasia, hypertrophy, and basement membrane reduplication.     

Casting health messages in terms of responsibility for dietary change: increasing fruit and vegetable consumption

OBJECTIVE: To compare the effectiveness of messages emphasizing the importance of either personal or social responsibility for dietary behavior change in increasing fruit and vegetable intake. DESIGN/SETTING: Randomly assigned individually or socially oriented messages were delivered at baseline, 1 week, and 2 and 3 months later. Telephone surveys were conducted at baseline and 1 and 4 months later. PARTICIPANTS: 528 callers to a cancer information hotline who were not meeting the "5 A Day" dietary recommendation. INTERVENTIONS: A brief telephone-delivered message and 3 mailings of pamphlets and promotional items encouraging fruit and vegetable intake that emphasized either personal or social responsibility. MAIN OUTCOME MEASURES: Fruit and vegetable intake 1 and 4 months post baseline. ANALYSIS: Chi-square, t tests, and analyses of variance and covariance. RESULTS: Both types of messages increased intake substantially (P =.01). To some extent, the social responsibility message continued to motivate increased intake over time compared with the personal responsibility message. CONCLUSIONS AND IMPLICATIONS: These minimal interventions had a substantial impact on fruit and vegetable intake. Health messages might be more effective over the longer term if they are designed to emphasize the importance of social responsibility, although further study is needed to confirm the robustness of these findings.     

How many problems do family physicians manage at each encounter? A WReN study

PURPOSE: The number of problems managed concurrently by family physicians during patient encounters has not been fully explored despite the implications for quality assessment, guideline implementation, education, research, administration, and funding. Our study objective was to determine the number of problems physicians report managing at each visit and compare that with the number reflected in the chart and the bill. METHODS: Twenty-nine members of the Wisconsin Research Network reported on encounters with 572 patients using a physician problem log. The patient chart notes and the diagnoses submitted for billing from the encounters were compared with the information in these logs. RESULTS: The physicians reported managing an average of 3.05 problems per encounter and recorded 2.82 in the chart and 1.97 on the bill. For all patients, 37% of encounters addressed more than 3 problems, and 18% addressed more than 4. For patients older than 65 years, there was an average of 3.88 problems at each visit, and for diabetic patients there was an average of 4.60. There was evidence for the selective omission of mental health and substance problems from the diagnoses used for billing. CONCLUSIONS: Family medicine involves the concurrent care of multiple problems, which billing data do not adequately reflect. Our findings suggest a mismatch between family medicine and current approaches to quality assessment, guideline implementation, education, research, administration, and funding. Activities in all these areas need to address the physician's task of prioritizing and integrating care for multiple problems concurrently.     

Monoclonal antibody (3G5)-defined ganglioside: cell surface marker of corneal keratocytes

PURPOSE: To evaluate the anti-ganglioside monoclonal antibody 3G5 as a marker of corneal keratocytes. METHODS: 3G5 expression on keratocytes was investigated by immunofluorescence microscopy. Studies were performed on frozen sections of normal human, bovine, porcine, rabbit, rat, and mouse corneas and on repairing rabbit cornea. In vitro studies were performed on tissue-cultured human, bovine, porcine, mouse, and rabbit keratocytes. RESULTS: 3G5 stained frozen sections of human, bovine, porcine, rat, and rabbit cornea but not mouse cornea and the staining pattern followed the distribution of stromal keratocytes but did not stain epithelium or endothelium. Subconfluent human and bovine keratocyte cultures were 3G5 negative. Almost 100% of the human and bovine cells that were maintained at confluence without replacement of serum-containing culture medium for 2 weeks became 3G5 positive. The 3G5 antigen was constitutively expressed on cultured rabbit and porcine keratocytes under all conditions examined. Mouse keratocyte cultures did not express 3G5. The 3G5 antigen was not present on myofibroblastic cells in the repairing area of a full-thickness wound in rabbit cornea that had been healing for 20 days. The area surrounding the healing wound expressed 3G5 antigen in an altered distribution, whereas 3G5 antigen was distributed in the expected pattern in areas that were distant from the wound. When rabbit keratocytes were induced to express the myofibroblast marker alpha-smooth muscle actin by treatment with TGFbeta1 in vitro, the pattern of 3G5 staining was altered. CONCLUSIONS: The 3G5 antigen is a useful marker for the identification of corneal keratocytes and for documenting their response to environmental stimuli associated with wound repair.