136 research outputs found

    Regulation of thymocyte positive selection and motility by GIT2

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    Thymocytes are highly motile cells that migrate under the influence of chemokines in distinct thymic compartments as they mature. The motility of thymocytes is tightly regulated; however, the molecular mechanisms that control thymocyte motility are not well understood. Here we report that G protein–coupled receptor kinase-interactor 2 (GIT2) was required for efficient positive selection. Notably, Git2−/− double-positive thymocytes showed greater activation of the small GTPase Rac, actin polymerization and migration toward the chemokines CXCL12 (SDF-1) and CCL25 in vitro. By two-photon laser-scanning microscopy, we found that the scanning activity of Git2−/− thymocytes was compromised in the thymic cortex, which suggests GIT2 has a key role in regulating the chemokine-mediated motility of double-positive thymocytes.National Institutes of Health (U.S.) (R01AI064227)Leukemia & Lymphoma Society of Americ

    Prisoners' attitudes towards cigarette smoking and smoking cessation: a questionnaire study in Poland

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    BACKGROUND: In the last decade Poland has successfully carried out effective anti-tobacco campaigns and introduced tobacco control legislation. This comprehensive strategy has focused on the general population and has led to a considerable decrease in tobacco consumption. Prisoners constitute a relatively small part of the entire Polish population and smoking habits in this group have been given little attention. The aim of the study was to assess the prevalence of cigarette smoking in Polish male prisoners, factors determining smoking in this group, prisoners' attitudes towards smoking cessation, and to evaluate prisoners' perception of different anti-tobacco measures. METHODS: An anonymous questionnaire including personal, demographic and smoking data was distributed among 944 male inmates. Of these, 907 men aged between 17 and 62 years (mean 32.3 years) met the inclusion criteria of the study. For the comparison of proportions, a chi-square test was used with continuity correction whenever appropriate. RESULTS: In the entire group, 81% of the subjects were smokers, 12% – ex-smokers, and 7% – never smokers. Current smokers had significantly lower education level than non-smokers (p < 0.0001) and ever-smokers more frequently abused other psychoactive substances than never smokers (p < 0.0001). Stress was reported as an important factor in prompting smoking (77%). Forty-nine percent of daily smokers were aware of the adverse health consequences of smoking. The majority of smokers (75%) had attempted to quit smoking in the past. Forty percent of smoking prisoners considered an award for abstaining from cigarettes as the best means to limit the prevalence of smoking in prisons. CONCLUSION: The prevalence of cigarette smoking among Polish prisoners is high. However, a majority of smokers attempt to quit, and they should be encouraged and supported. Efforts to reduce cigarette smoking in prisons need to take into consideration the specific factors influencing smoking habits in prisons

    Status of national health research systems in ten countries of the WHO African Region

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    BACKGROUND: The World Health Organization (WHO) Regional Committee for Africa, in 1998, passed a resolution (AFR/RC48/R4) which urged its Member States in the Region to develop national research policies and strategies and to build national health research capacities, particularly through resource allocation, training of senior officials, strengthening of research institutions and establishment of coordination mechanisms. The purpose of this study was to take stock of some aspects of national resources for health research in the countries of the Region; identify current constraints facing national health research systems; and propose the way forward. METHODS: A questionnaire was prepared and sent by pouch to all the 46 Member States in the WHO African Region through the WHO Country Representatives for facilitation and follow up. The health research focal person in each of the countries Ministry of Health (in consultation with other relevant health research bodies in the country) bore the responsibility for completing the questionnaire. The data were entered and analysed in Excel spreadsheet. RESULTS: The key findings were as follows: the response rate was 21.7% (10/46); three countries had a health research policy; one country reported that it had a law relating to health research; two countries had a strategic health research plan; three countries reported that they had a functional national health research system (NHRS); two countries confirmed the existence of a functional national health research management forum (NHRMF); six countries had a functional ethical review committee (ERC); five countries had a scientific review committee (SRC); five countries reported the existence of health institutions with institutional review committees (IRC); two countries had a health research programme; and three countries had a national health research institute (NHRI) and a faculty of health sciences in the national university that conducted health research. Four out of the ten countries reported that they had a budget line for health research in the Ministry of Health budget document. CONCLUSION: Governments of countries of the African Region, with the support of development partners, private sector and civil society, urgently need to improve the research policy environment by developing health research policies, strategic plans, legislations, programmes and rolling plans with the involvement of all stakeholders, e.g., relevant sectors, research organizations, communities, industry and donors. In a nutshell, development of high-performing national health research systems in the countries of the WHO African Region, though optional, is an imperative. It may be the only way of breaking free from the current vicious cycle of ill-health and poverty

    Dilated Cardiomyopathy with Increased SR Ca2+ Loading Preceded by a Hypercontractile State and Diastolic Failure in the α1CTG Mouse

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    Mice over-expressing the α1−subunit (pore) of the L-type Ca2+ channel (α1CTG) by 4months (mo) of age exhibit an enlarged heart, hypertrophied myocytes, increased Ca2+ current and Ca2+ transient amplitude, but a normal SR Ca2+ load. With advancing age (8–11 mo), some mice demonstrate advanced hypertrophy but are not in congestive heart failure (NFTG), while others evolve to frank dilated congestive heart failure (FTG). We demonstrate that older NFTG myocytes exhibit a hypercontractile state over a wide range of stimulation frequencies, but maintain a normal SR Ca2+ load compared to age matched non-transgenic (NTG) myocytes. However, at high stimulation rates (2–4 Hz) signs of diastolic contractile failure appear in NFTG cells. The evolution of frank congestive failure in FTG is accompanied by a further increase in heart mass and myocyte size, and phospholamban and ryanodine receptor protein levels and phosphorylation become reduced. In FTG, the SR Ca2+ load increases and Ca2+ release following excitation, increases further. An enhanced NCX function in FTG, as reflected by an accelerated relaxation of the caffeine-induced Ca2+ transient, is insufficient to maintain a normal diastolic Ca2+ during high rates of stimulation. Although a high SR Ca2+ release following excitation is maintained, the hypercontractile state is not maintained at high rates of stimulation, and signs of both systolic and diastolic contractile failure appear. Thus, the dilated cardiomyopathy that evolves in this mouse model exhibits signs of both systolic and diastolic failure, but not a deficient SR Ca2+ loading or release, as occurs in some other cardiomyopathic models

    NT-proBNP and Circulating Inflammation Markers in Prediction of a Normal Myocardial Scintigraphy in Patients with Symptoms of Coronary Artery Disease

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    Myocardial perfusion imaging (MPI) can detect myocardial perfusion abnormalities but many examinations are without pathological findings. This study examines whether circulating biomarkers can be used as screening modality prior to MPI.243 patients with an intermediate risk of CAD or with known CAD with renewed suspicion of ischemia were referred to MPI. Blood samples were analyzed for N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), YKL-40, IL-6, matrix metalloproteinase 9 (MMP-9) and high sensitive C-reactive protein (hsCRP). Patients with myocardial perfusion defects had elevated levels of NT-proBNP (p<0.0001), YKL-40 (p = 0.03) and IL-6 (p = 0.03) but not of hsCRP (p = 0.58) nor of MMP-9 (p = 0.14). The NT-proBNP increase was observed in both genders (p<0.0001), whereas YKL-40 (p = 0.005) and IL-6 (p = 0.02) were elevated only in men. A NT-proBNP cut off-concentration at 25 ng/l predicted a normal MPI with a negative predictive value >95% regardless of existing CAD.20-25% of patients suspected of CAD could have been spared a MPI by using a NT-proBNP cut-off concentration at 25 ng/l with a negative predictive value >95%. NT-proBNP has the potential use of being a screening marker of CAD before referral of the patient to MPI

    High-risk human papillomavirus (HPV) screening and detection in healthy patient saliva samples: a pilot study

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    <p>Abstract</p> <p>Background</p> <p>The human papillomaviruses (HPV) are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco- and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence.</p> <p>Methods</p> <p>Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity.</p> <p>Results</p> <p>Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (<it>p </it>< 0.05). Four patient samples were found to harbor HPV16 DNA, representing 2.6% of the total (n = 151). Three of the four HPV16-positive samples were from patients under 65 years of age and all four were female and Hispanic (non-White). No samples tested positive for HPV18.</p> <p>Conclusions</p> <p>The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short- and long-term consequences of oral HPV infection.</p
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