Role of LRP in TGFbeta2-mediated neuronal uptake of Abeta and effects on memory

There is increasing evidence that soluble amyloid-beta peptide (Abeta) uptake into neurons is an early event in the pathogenesis of Alzheimer's disease (AD). Identification of the early events leading to neuronal dysfunction is key to developing therapeutic strategies, but relative roles of receptors and factors modulating uptake are poorly understood. Studies have shown that transforming growth factor beta (TGFbeta), particularly TGFbeta2, can influence the targeting of Abeta to cells in vitro. TGFbeta2 can target Abeta to neurons in organotypic hippocampal slice cultures (OHSC). We examine a specific mechanism for TGFbeta2-mediated targeting of Abeta to neurons. The receptor-associated protein (RAP), a low-density lipoprotein receptor-related protein (LRP) antagonist, can attenuate the cellular targeting of Abeta both in vitro and in vivo and prevent Abeta/TGFbeta2-induced memory retention deficits. Using both in vitro and in vivo methods, we identify LRP as playing a role in TGFbeta2-mediated Abeta uptake, neurodegeneration, and spatial memory impairment.     

Long-term effect of an oral healthcare programme on oral hygiene in a nursing home

This article reports on the long-term effect of an oral healthcare programme aimed at improving and maintaining the oral hygiene of elderly residents in a nursing home. The method was based on (i) motivation and oral-care training of the nursing staff, (ii) production of picture-based oral-care procedure cards, (iii) distribution of adequate oral-care equipment, (iv) practical implementation of new routines, and (v) assessment of results attained. The level of oral hygiene in the nursing home was assessed using the mucosal-plaque score (MPS) index. Overall evaluation was made before the start of the study, after 3 months, and eventually after 6 yr. Before implementation of the oral healthcare programme, 36% of the residents had an acceptable score. Six years later, the proportion was 70%. The evaluation showed that the introduction of such an oral healthcare programme significantly improved the oral hygiene of the residents on a long-term basis. However, 30% of the residents did not achieve an acceptable score because they were very ill or dying, aggressive or wanted to brush their teeth themselves.     

Medicinal herb use in a population-based survey of adults: prevalence and frequency of use, reasons for use, and use among their children

PURPOSE: There is sparse population-based data on health factors related to medicinal herb use and use of medicinal herbs in children. For a sample of American adults, we estimated the prevalence and frequency of medicinal herb use, factors related to use, reasons for use, patient-physician discussion, and the proportion of respondents who gave herbs to their children. METHODS: The data used in this study was from the 2001 North Carolina Behavioral Risk Factor Surveillance System, a population-based telephone survey of English-speaking adults (n = 2982). RESULTS: Approximately 20% of respondents reported using medicinal herbs in the past year. Of these, 34% reported discussion of herb use with a physician; 69% reported taking herbs to maintain health, 20% to prevent illness, and 11% to treat illness. Of the total sample, 7% reported using herbs everyday and 5% of the respondents reported giving their children herbal medicines in the past year. CONCLUSIONS: Medicinal herb use is common in this population sample. The lack of discussion between users and their physicians highlights the importance of patient-physician communication to avoid possible herb-drug interactions and surgical complications. Herb use appears to be a popular strategy for maintaining health. Children may be vulnerable to herbal toxicity and therefore clinicians need to know about their medicinal herb use and counsel appropriately.     

Interferon-γ regulates the interaction of RBL-2H3 cells with fibronectin through production of nitric oxide

Interferon-gamma (IFN-gamma) is an important regulatory cytokine in cell proliferation, differentiation, adhesion, mediator release, and gene induction. This diversity of effector roles is achieved by a variety of incompletely understood mechanisms. In the mast cell (MC), IFN-gamma downregulates mediator synthesis and secretion. The present study demonstrates and characterizes for the first time IFN-gamma inhibition of adhesion of the MC analogue RBL-2H3 to the extracellular matrix protein fibronectin (FN). Inhibition requires preincubation of the cells with IFN-gamma for 20 hr, and is statistically significant at 100 U/ml IFN-gamma. Flow cytometry indicates that cell surface expression of very late antigen-4 (VLA-4), VLA-5, and the vitronectin receptor (VNR) remain constant following IFN-gamma treatment, indicating the inhibitory effect of IFN-gamma on adhesion to FN is not achieved through a reduction in integrin receptors for FN. Fluorescent labelling with Texas red phalloidin demonstrated rearrangement of the actin cytoskeleton in response to IFN-gamma was not significant. The tyrosine phosphatase inhibitor vanadate, and the nitric oxide (NO) synthase inhibitor L-NAME, reduced the IFN-gamma effect on adhesion to FN by 62 and 70%, respectively, demonstrating that the IFN-gamma effect is dependent upon the production of NO, potentially though a tyrosine phosphatase dependent mechanism. The NO donors sodium nitroprusside and S-nitrosoglutathione mimicked the effect of IFN-gamma. Thus, following stimulation with IFN-gamma, NO plays an autocrine role in the MC, and is able to modulate integrin function. This adds to the pathways NO is able to inhibit in the mast cell, shows that endogenous NO is able to inhibit these pathways, and suggests NO is impinging upon an element common to many signalling mechanisms in the MC.     

A NONPARAMETRIC PROCEDURE OF THE SAMPLE SIZE DETERMINATION FOR SURVIVAL RATE TEST

Inthesurvivalstudiesofchronicdiseases,themostfrequentlyusedmethodsofdataanalysisarethenonparametricestimationsandcomparisonsofsurvivalratesatdifferenttimesbuttherehavebeennomatchedmethodsfordeterminingtherequiredsamplesizesofar.Insteadhavebeenoftenusedtheparametricmethodsbasedontheassumptionofexponentialdistributions[1～7]suchthattherelevantsamplesizesmaynotbesatisfiedwiththeprescribedpower.Thispaperreportsanonparametricprocedureofthesamplesizedeterminationforsurvivalratetest.1　SurvivalRateT…     

Characteristics and perspectives of families waiting to adopt a child with Down syndrome.

PURPOSE: The study's purpose was to obtain information on the characteristics and perspectives of families interested in adopting children with Down syndrome. METHODS: A questionnaire-based survey was administered to individuals and families on a waiting list to adopt children with Down syndrome. Information on (1) demographic, (2) family structure, (3) Down syndrome exposure, (4) Down syndrome knowledge, (5) reasons for considering adoption, (6) adoption process, and (7) perspective on raising children with Down syndrome was assessed. RESULTS: From 199 mailed surveys, there were 72 respondents (36.2%) of whom six had previously adopted a child with Down syndrome. Forty-eight percent learned of the possibility of adopting children with Down syndrome through the Internet, whereas only one respondent obtained this information from a medical professional. The primary reasons for considering adoption were that prospective adoptive families were equipped with the necessary resources and had previous positive experiences with individuals who have Down syndrome. CONCLUSIONS: Many families are eager to adopt children with Down syndrome. Interest in this option stems from having resources to care for these children and previous positive experiences with individuals with Down syndrome. Information regarding adoption was rarely obtained from health care providers. When counseling pregnant women diagnosed with a Down syndrome fetus, adoption should be discussed so that all options regarding pregnancy management may be explored.