Dimerization of Receptor Protein-Tyrosine Phosphatase alpha in living cells

BACKGROUND: Dimerization is an important regulatory mechanism of single membrane-spanning receptors. For instance, activation of receptor protein-tyrosine kinases (RPTKs) involves dimerization. Structural, functional and biochemical studies suggested that the enzymatic counterparts of RPTKs, the receptor protein-tyrosine phosphatases (RPTPs), are inhibited by dimerization, but whether RPTPs actually dimerize in living cells remained to be determined. RESULTS: In order to assess RPTP dimerization, we have assayed Fluorescence Resonance Energy Transfer (FRET) between chimeric proteins of cyan- and yellow-emitting derivatives of green fluorescent protein, fused to RPTPα, using three different techniques: dual wavelength excitation, spectral imaging and fluorescence lifetime imaging. All three techniques suggested that FRET occurred between RPTPα -CFP and -YFP fusion proteins, and thus that RPTPα dimerized in living cells. RPTPα dimerization was constitutive, extensive and specific. RPTPα dimerization was consistent with cross-linking experiments, using a non-cell-permeable chemical cross-linker. Using a panel of deletion mutants, we found that the transmembrane domain was required and sufficient for dimerization. CONCLUSIONS: We demonstrate here that RPTPα dimerized constitutively in living cells, which may be mediated by the transmembrane domain, providing strong support for the model that dimerization is involved in regulation of RPTPs

Cost-effectiveness of nurse-led self-help for recurrent depression in the primary care setting: design of a pragmatic randomized trial

<p>Abstract</p> <p>Background</p> <p>Major Depressive Disorder is a leading cause of disability, tends to run a recurrent course and is associated with substantial economic costs due to increased healthcare utilization and productivity losses. Interventions aimed at the prevention of recurrences may reduce patients' suffering and costs. Besides antidepressants, several psychological treatments such as preventive cognitive therapy (PCT) are effective in the prevention of recurrences of depression. Yet, many patients find long-term use of antidepressants unattractive, do not want to engage in therapy sessions and in the primary care setting psychologists are often not available. Therefore, it is important to study whether PCT can be used in a nurse-led self-help format in primary care. This study sets out to test the hypothesis that usual care plus nurse-led self-help for recurrent depression in primary care is feasible, acceptable and cost-effective compared to usual care only.</p> <p>Design</p> <p>Patients are randomly assigned to ‘nurse-led self-help treatment plus usual care’ (134 participants) or ‘usual care’ (134 participants). Randomisation is stratified according to the number of previous episodes (2 or 3 previous episodes versus 4 or more). The primary clinical outcome is the cumulative recurrence rate of depression meeting DSM-IV criteria as assessed by the Structured-Clinical-Interview-for-DSM-IV- disorders at one year after completion of the intervention. Secondary clinical outcomes are quality of life, severity of depressive symptoms, co-morbid psychopathology and self-efficacy. As putative effect-moderators, demographic characteristics, number of previous episodes, type of treatment during previous episodes, age of onset, self-efficacy and symptoms of pain and fatigue are assessed. Cumulative recurrence rate ratios are obtained under a Poisson regression model. Number-needed-to-be-treated is calculated as the inverse of the risk-difference. The economic evaluation is conducted from a societal perspective, both as a cost-effectiveness analysis (costs per depression free survival year) and as a cost-utility analysis (costs per quality adjusted life-year).</p> <p>Discussion</p> <p>The purpose of this paper is to outline the rationale and design of a nurse-led, cognitive therapy based self-help aimed at preventing recurrence of depression in a primary care setting. Only few studies have focused on psychological self-help interventions aimed at the prevention of recurrences in primary care patients.</p> <p>Trial registration</p> <p>NTR3001 (<url>http://www.trialregister.nl</url>)</p

Survival of atraumatic restorative treatment (ART) sealants and restorations: a meta-analysis

The purpose of this study is to perform a systematic investigation plus meta-analysis into survival of atraumatic restorative treatment (ART) sealants and restorations using high-viscosity glass ionomers and to compare the results with those from the 2005 ART meta-analysis. Until February 2010, four databases were searched. Two hundred four publications were found, and 66 reported on ART restorations or sealant survival. Based on five exclusion criteria, two independent reviewers selected the 29 publications that accounted for the meta-analysis. Confidence intervals (CI) and or standard errors were calculated and the heterogeneity variance of the survival rates was estimated. Location (school/clinic) was an independent variable. The survival rates of single-surface and multiple-surface ART restorations in primary teeth over the first 2 years were 93% (CI, 91–94%) and 62% (CI, 51–73%), respectively; for single-surface ART restorations in permanent teeth over the first 3 and 5 years it was 85% (CI, 77–91%) and 80% (CI, 76–83%), respectively and for multiple-surface ART restorations in permanent teeth over 1 year it was 86% (CI, 59–98%). The mean annual dentine lesion incidence rate, in pits and fissures previously sealed using ART, over the first 3 years was 1%. No location effect and no differences between the 2005 and 2010 survival rates of ART restorations and sealants were observed. The short-term survival rates of single-surface ART restorations in primary and permanent teeth, and the caries-preventive effect of ART sealants were high. Clinical relevance: ART can safely be used in single-surface cavities in both primary and permanent teeth. ART sealants have a high caries preventive effect

Sero-epidemiology of mumps in western Europe.

Six countries (Denmark, England and Wales, France, Germany, Italy and The Netherlands) conducted large serological surveys for mumps, in the mid-1990s, as part of the European Sero-Epidemiology Network (ESEN). The assay results were standardized and related to the schedules and coverage of the immunization programmes and the reported incidence of mumps. Low incidence of disease and few susceptibles amongst adolescents and young adults was observed in countries with high mumps vaccine coverage (e.g. The Netherlands). High disease incidence and large proportions of mumps virus antibody negative samples in adolescent and young adult age groups was noted in countries with poor vaccine coverage (e.g. Italy). The build-up of susceptibles in older children and adolescents in England and Wales, France, the former West Germany and Italy indicate the possibility of further mumps outbreaks in secondary school environments. To control mumps in western Europe, current MMR immunization programmes will need to be strengthened in a number of countries. Sero-surveillance of mumps is an important component of disease control and its usefulness will be enhanced by the development of an international mumps standard

Risk Factors and Health in the Netherlands, a Survey by Municipal Public; annual report 2001

Risk Factors and Health in the Netherlands, a survey on Municipal Health Services. The main aim of the project was to monitor risk factors or determinants of chronic and infectious disease in the general population. Also studied were the differences with respect to many background- and health- related variables between participants interviewed at home and those taking the physical examination. Random sampling by the CBS led to home interviews by trained interviewers of individuals from the age of 0 who were willing to cooperate in the survey. The interview consisted of items related to aspects of health status and use of medicines/medical devices. Questions on lifestyle factors (smoking, drinking and vaccination) were included. At the end of the interview, participants were asked for permission to be approached for an additional health examination. Participants older than 12 years were asked to visit the nearest community or municipal health service (GGD). Of the participant, 56.7% agreed to participate in the additional health examination. A short physical examination was performed at the health centre. Blood samples were taken and blood pressure measured, as well as height, weight, and waist and hip circumferences. In addition, the 'joint-function test' was performed and an additional questionnaire was distributed. Of the people interviewed, 25,7% had visited the community or municipal health centre. The participants undergoing the physical examination were representative of the Dutch population, in that there were no major differences with respect to most of the background- and health-related variables between participants interviewed at home and those taking the physical examination.Het Regenboog-project is een samenwerkingsverband tussen het RIVM, CBS en GGD Nederland en GGD'en. Het doel van het Regenboogproject is een beeld te krijgen van de gezondheidssituatie van de Nederlandse bevolking op het gebied van chronische en infectieziekten. Een aselecte steekproef wordt getrokken door het CBS. Bij deze personen wordt thuis de gezondheidsenquete afgenomen. Vervolgens wordt gevraagd om deel te nemen aan een aanvullend lichamelijk onderzoek op de GGD. Hierop reageert 56,7% positief. Het onderzoek op de GGD bestaat uit het invullen van een vragenlijst over infectieziekten, meting van bloeddruk, lengte, gewicht en middel-heupomtrek. Tot slot wordt er een gewrichtsfunctietest en 4 buisjes bloed afgenomen. Van de geinterviewde personen komt uiteindelijk 25,7 % op de GGD voor het lichamelijk onderzoek. De prevalentie van hypertensie is voor mannen 34% en vrouwen 30%. De prevalentie van overgewicht neemt toe met de leeftijd. De schatting van overgewicht blijkt sterk te verschillen tussen gerapporteerde en gemeten lengte en gewicht. Met name bij vrouwen is dit verschil duidelijk aanwezig. De onderzochte groep blijkt een bruikbare afspiegeling van de Nederlandse bevolking

Risk Factors and Health in the Netherlands, a Survey by Municipal Public; annual report 2001

Het Regenboog-project is een samenwerkingsverband tussen het RIVM, CBS en GGD Nederland en GGD'en. Het doel van het Regenboogproject is een beeld te krijgen van de gezondheidssituatie van de Nederlandse bevolking op het gebied van chronische en infectieziekten. Een aselecte steekproef wordt getrokken door het CBS. Bij deze personen wordt thuis de gezondheidsenquete afgenomen. Vervolgens wordt gevraagd om deel te nemen aan een aanvullend lichamelijk onderzoek op de GGD. Hierop reageert 56,7% positief. Het onderzoek op de GGD bestaat uit het invullen van een vragenlijst over infectieziekten, meting van bloeddruk, lengte, gewicht en middel-heupomtrek. Tot slot wordt er een gewrichtsfunctietest en 4 buisjes bloed afgenomen. Van de geinterviewde personen komt uiteindelijk 25,7 % op de GGD voor het lichamelijk onderzoek. De prevalentie van hypertensie is voor mannen 34% en vrouwen 30%. De prevalentie van overgewicht neemt toe met de leeftijd. De schatting van overgewicht blijkt sterk te verschillen tussen gerapporteerde en gemeten lengte en gewicht. Met name bij vrouwen is dit verschil duidelijk aanwezig. De onderzochte groep blijkt een bruikbare afspiegeling van de Nederlandse bevolking.Risk Factors and Health in the Netherlands, a survey on Municipal Health Services. The main aim of the project was to monitor risk factors or determinants of chronic and infectious disease in the general population. Also studied were the differences with respect to many background- and health- related variables between participants interviewed at home and those taking the physical examination. Random sampling by the CBS led to home interviews by trained interviewers of individuals from the age of 0 who were willing to cooperate in the survey. The interview consisted of items related to aspects of health status and use of medicines/medical devices. Questions on lifestyle factors (smoking, drinking and vaccination) were included. At the end of the interview, participants were asked for permission to be approached for an additional health examination. Participants older than 12 years were asked to visit the nearest community or municipal health service (GGD). Of the participant, 56.7% agreed to participate in the additional health examination. A short physical examination was performed at the health centre. Blood samples were taken and blood pressure measured, as well as height, weight, and waist and hip circumferences. In addition, the 'joint-function test' was performed and an additional questionnaire was distributed. Of the people interviewed, 25,7% had visited the community or municipal health centre. The participants undergoing the physical examination were representative of the Dutch population, in that there were no major differences with respect to most of the background- and health-related variables between participants interviewed at home and those taking the physical examination.VW