tbuckley/cabot-search huggingface dataset:
Expression of a monoclonal antibody-defined, B-lineage transformation antigen specifically identifies Abelson-diseased animals. Genetically determined resistance to Abelson murine leukemia virus acts before induction of gp160(6C3).
Authors: G F Tidmarsh, M O Dailey, I L Weissman
Journal: The Journal of Experimental Medicine (1986)

Mice genetically susceptible or genetically resistant to the leukemogenic effects of A-MuLV(Mo) were tested for their expression of the B-lineage neoplastic transformation-associated antigen, 6C3Ag. Genetically resistant inbred strains and recombinant inbred lines developed neither cells expressing high levels of 6C3Ag (6C3Aghi) in their hematolymphoid tissues nor Abelson leukemias. Genetically susceptible inbred strains and recombinant inbred lines developed high percentages of 6C3Aghi hematolymphoid cells concomitant with development of Abelson leukemias and lymphomas. Thus the genetically-determined resistance to A-MuLV(Mo) leukemogenesis appears to act at some step(s) after virus infection but before the stage of malignant progression, which is marked by 6C3Ag expression.
Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease
Authors: Johannes Grosse, Violeta Chitu, Andreas Marquardt, Petra Hanke, Carolin Schmittwolf, Lutz Zeitlmann, Patricia Schropp, Bettina Barth, Philipp Yu, Rainer Paffenholz, Gabriele Stumm, Michael Nehls, E. Richard Stanley
Journal: Blood (2006)
Professor Roald Bahr awarded the Prince Philip Medal for outstanding contribution to sports and exercise medicine
Authors: M Turner
Journal: British Journal of Sports Medicine (2008)

At a lunchtime ceremony in Buckingham Palace on 15 October 2008, Professor Roald Bahr was presented with the Prince Philip Medal by His Royal Highness, The Duke of Edinburgh, KG, KT. The medal was awarded to Professor Bahr by the Institute of Sport and Exercise Medicine (ISEM), an organisation founded in 1958 and of which HRH The Duke of Edinburgh is an Honorary Fellow.

The Institute was founded by Peter Sebastian and the first Chairman was Sir Arthur Porritt, President of the Royal College of Surgeons of England and later Governor-General of New Zealand. The ISEM, and its Honorary Fellow, played a significant role in the establishment of Sport and Exercise Medicine as a speciality in the UK. At a dinner hosted by HRH The Duke of Edinburgh, held at St James Palace in 1996, HRH urged the President of the Academy of the Medical Royal Colleges, Dame Fiona Caldicott, to revisit the establishment of sports medicine as a speciality after the Academy had …
The public health implications of AIDS research in Africa
Authors: K. M. De Cock
Journal: JAMA (1994)

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic has led to greatly increased international collaboration for medical research, mainly epidemiologic in nature, in Africa. Greater understanding of HIV/AIDS has resulted, and considerable training and technology transfer have occurred. However, analytic and descriptive research in countries heavily affected by AIDS has been slow to turn to assessment of interventions, and practical benefits to those countries' public health and policies have lagged behind scientific knowledge. This article considers the public health implications of selected HIV/AIDS research in sub-Saharan Africa and discusses opportunities for interventions and more applied research. Topics covered include HIV testing and its role, surveillance, control of sexually transmitted diseases, the vulnerability of youth and women, tuberculosis, HIV/AIDS care, and the inadequacy of resources currently committed to HIV/AIDS prevention and control in resource-poor countries. Research on HIV/AIDS in Africa has yielded crucial information but now should prioritize interventions and their evaluation. Specific goals that might limit the effects of the HIV/AIDS epidemic in resource-poor countries are achievable given vision, commitment, and resources.
No Talking, Just Writing! Efficacy of an Internet-Based Cognitive Behavioral Therapy with Exposure and Response Prevention in Obsessive Compulsive Disorder
Authors: Nirmal Herbst, Ulrich Voderholzer, Nicola Thiel, Ronja Schaub, Christine Knaevelsrud, Silke Stracke, Elisabeth Hertenstein, Christoph Nissen, Anne Katrin Külz
Journal: Psychotherapy and Psychosomatics (2014)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Many patients with obsessive-compulsive disorder (OCD) do not receive first-line treatment according to the current guidelines (cognitive behavioral therapy with exposure and response prevention, CBT with ERP) due to barriers to treatment. Internet-based therapy is designed to overcome these barriers. The present study evaluates the efficacy of an Internet-based writing therapy with therapeutic interaction based on the concept of CBT with ERP for patients with OCD. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Thirty-four volunteers with OCD according to DSM-IV-criteria were included in the trial and randomized according to a waiting-list control design with follow-up measures at 8 weeks and 6 months. The intervention consisted of 14 sessions, either starting directly after randomization or with an 8-week delay. Main outcome measure was the change in the severity of OCD symptoms (Yale-Brown Obsessive Compulsive Scale Self-Rating, Y-BOCS SR, and Obsessive-Compulsive Inventory-Revised, OCI-R). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Obsessive-compulsive symptoms were significantly improved in the treatment group compared to the waiting-list control group with large effect sizes of Cohen's d = 0.82 (Y-BOCS SR) and d = 0.87 (OCI-R), using an intention-to-treat analysis. This effect remained stable at 6-month follow-up. Only 4 participants (12%) dropped out prematurely from the study. Of the 30 completers, 90% rated their condition as improved and would recommend the program to their friends. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Internet-based writing therapy led to a significant improvement of obsessive-compulsive symptoms. Even though replications with larger sample sizes are needed, the results support the notion that Internet-based approaches have the potential for improving the treatment situation for patients with OCD.
Abstract MP24: Comparison of Predictive Ability of Dietary and Lifestyle Scores For 10-Year Risk of Cardiovascular Mortality in a Pan-European Cohort Study
Authors: Camille Lassale, Yvonne Van der Schouw, Joline Beulens, Guy Fagherazzi, Nina Roswall, Brian Buijsse, Antonia Trichopoulou, Elizabete Weiderpass, Heinz Freisling, Dora Romaguera, Petra Wark, Elio Riboli, Ioanna Tzoulaki
Journal: Circulation (2015)

Introduction: Diet quality indexes and lifestyle indexes (which also include other lifestyle characteristics such as smoking and obesity) have recently received increased attention in disease prevention. Hypothesis: We aimed to investigate the comparative predictive performance of a comprehensive list of dietary and lifestyle indexes in relation to cardiovascular (CVD) mortality. Methods: We applied these indexes to men and women from 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study and examined their association with 10-year CVD mortality risk. We computed 10 dietary indexes and 2 diet and lifestyle indexes and calculated quartiles. Cox proportional hazard models stratified by age and study centre, adjusted for age, BMI, energy intake, smoking status, physical activity and educational level were fit to estimate Hazard Ratios (HR) and 95% CI. Harrell’s C-statistic, a discrimination measure of predictive performance, was calculated for each model. Results: After 10 years of follow up, 3761 CVD deaths were observed among 451 256 participants. All dietary indexes, except one, were significantly associated with CVD mortality with HR ranging from 0.75 to 0.84 for the fully adjusted model when comparing top vs bottom quartile (Table 1). Stronger effect size was observed for the diet and lifestyle indexes, particularly the Healthy Lifestyle Index (HLI). Discrimination of the full models was high and did not vary between scores. We found no heterogeneity in HRs across countries for most scores, except a modest heterogeneity for Mediterranean diet scores (I 2 =48%) and HLI (75%); however, heterogeneity across countries of the C-statistics was high for all scores (I 2 = 87%). Conclusion: Our results show that diet quality as a whole, or a cluster of lifestyle behaviours including diet, are consistently associated with a reduction of 10-year CVD mortality risk and that models comprising only age, sex and lifestyle risk factors could serve as predictors of CVD mortality.
Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression
Authors: Tobias Bopp, Christian Becker, Matthias Klein, Stefan Klein-Heßling, Alois Palmetshofer, Edgar Serfling, Valeska Heib, Marc Becker, Jan Kubach, Steffen Schmitt, Sabine Stoll, Hansjörg Schild, Martin S. Staege, Michael Stassen, Helmut Jonuleit, Edgar Schmitt
Journal: The Journal of Experimental Medicine (2007)

Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact–dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon coactivation with naturally occurring T reg cells the cAMP content of responder T cells is also strongly increased. Furthermore, we demonstrate that naturally occurring T reg cells and conventional T cells communicate via cell contact–dependent gap junction formation. The suppressive activity of naturally occurring T reg cells is abolished by a cAMP antagonist as well as by a gap junction inhibitor, which blocks the cell contact–dependent transfer of cAMP to responder T cells. Accordingly, our results suggest that cAMP is crucial for naturally occurring T reg cell–mediated suppression and traverses membranes via gap junctions. Hence, naturally occurring T reg cells unexpectedly may control the immune regulatory network by a well-known mechanism based on the intercellular transport of cAMP via gap junctions.
Methylation of p15 and p16 Genes in Acute Promyelocytic Leukemia: Potential Diagnostic and Prognostic Significance
Authors: C.S. Chim, R. Liang, C.Y.Y. Tam, Y.L. Kwong
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate the frequency of p15 and p16 gene promoter methylation in acute promyelocytic leukemia (APL), and to define its value in the detection of minimal residual disease (MRD) and treatment prognostication. PATIENTS AND METHODS: Bone marrow DNA obtained from 26 patients with APL at diagnosis and during follow-up was studied with the methylation-specific polymerase chain reaction (MS-PCR). Serial marrow DNA was studied by MS-PCR for MRD, and disease-free and overall survival were correlated with p15 methylation status at diagnosis. RESULTS: MS-PCR for p16 and p15 gene methylation has a maximum sensitivity of 10 -4 and 10 -5 . At diagnosis, 19 patients (73.1%) exhibited p15 methylation, whereas only three patients (11.5%) exhibited p16 methylation, all of whom had concomitant p15 methylation. During follow-up, p16 methylation was acquired in two patients, one during the third hematologic relapse, and the other during transformation into therapy-related myelodysplastic syndrome. Six patients were evaluated serially with MS-PCR for p15 methylation at diagnosis and at follow-up examinations. Persistent p15 methylation preceded subsequent hematologic relapses in two patients, and conversion to negative MS-PCR for p15 methylation correlated with prolonged survival in another four patients. The 5-year disease-free survival of patients with p15 methylation was significantly inferior to that of patients without p15 methylation (15% v 62.5%; P = .02), and this remained significant in multivariate analysis. CONCLUSION: In APL, p15 but not p16 gene methylation is frequent. It is possible that p16 methylation is acquired during clonal evolution. p15 methylation is a potential marker of MRD and might be of prognostic significance.
Changes in transcutaneous oxygen tension during exercise in pulmonary emphysema.
Authors: J A Hughes, B J Gray, D C Hutchison
Journal: Thorax (1984)

Continuous measurements of transcutaneous oxygen tension (tcPO2) were made in 23 patients with radiological evidence of emphysema, at rest and during a maximal progressive exercise test. tcPO2 during the final phase of exercise was compared with tcPO2 at rest; the mean change (exercising minus resting value) in tcPO2 (delta tcPO2) was -0.8 mm Hg (SD 10.5, range -18 to +25) (-0.1 kPa (SD 1.4, range -2.4 to +3.3]. delta tcPO2 was correlated with: resting arterial oxygen tension (PaO2) (r = 0.606, p less than 0.005); resting arterial carbon dioxide tension (PaCO2) (r = -0.691, p less than 0.001); FEV1 % predicted (r = 0.688, p less than 0.001); vital capacity % predicted (r = 0.543, p less than 0.01); and transfer factor (TLCO) % predicted (r = 0.604, p less than 0.005). There was no significant difference between the delta tcPO2 of 10 patients who regularly produced sputum and of 13 patients with no sputum. delta tcPO2 appears to be more closely related to the severity of emphysema than to the presence or absence of chronic bronchitis. Pretreatment with fenoterol aerosol resulted in an increased work load in three out of 10 patients. Overall there was no change in delta tcPO2. In all except one patient there was a rise in tcPO2 after the end of exercise. In the 11 patients whose tcPO2 fell during exercise, tcPO2 returned to the resting value within two minutes of the cessation of exercise; this was followed by a further rise beyond the resting value, and a single postexercise arterial sample is therefore a poor indicator of the response of PaO2 to exercise. Measurement of TcPO2 is of value in following rapid changes in PaO2 during and after exercise and avoids the necessity for an indwelling arterial cannula.
Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability
Authors: Prakash Khadka, Jieun Ro, Hyeongmin Kim, Iksoo Kim, Jeong Tae Kim, Hyunil Kim, Jae Min Cho, Gyiae Yun, Jaehwi Lee
Journal: Asian Journal of Pharmaceutical Sciences (2014)

Pharmaceutical particle technology is employed to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids following oral administration. The particle technology involves several approaches from the conventional size reduction processes to the newer, novel particle technologies that modify the solubility properties of the drugs and produce solid, powdered form of the drugs that are readily soluble in water and can be easily formulated into various dosage forms. This review highlights the solid particle technologies available for improving solubility, dissolution and bioavailability of drugs with poor aqueous solubility.
ETIOLOGY OF OROYA FEVER
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1928)

The experiments reported were designed to determine the influence of malarial infection (Plasmodium inui?), splenectomy, or both combined, upon the course and character of experimental infection with Bartonella bacilliformis in monkeys (Macacus rhesus and M. cynomolgus). Blood withdrawn from a monkey showing spontaneous malarial infection was inoculated intravenously into monkeys (a) 1 month prior to inoculation with virulent verruga material, (b) simultaneously with the verruga material, and (c) during convalescence from verruga infection of moderate severity. All the monkeys contracted the malarial infection and suffered one to three paroxysms during a period of about a month. The verruga lesions appeared in the inoculated animals in due course, were of average size, remained for the usual length of time, and Bartonella bacilliformis was recovered in culture from blood which also contained the plasmodia. The lesions in the convalescent animals continued to heal at the normal rate, and blood cultures were negative for Bartonella bacilliformis, as is usual during convalescence. One of the recovering animals was reinoculated with virulent verruga material a month after the injection of the malarial blood, but neither did new lesions arise nor old ones recur. The malarial infection, therefore, had no effect upon the course of verruga or upon the establishment of immunity to Pattonella bacilliformis, hence it would appear that malaria and verruga may coexist in the same individual without unfavorable effect of one disease upon the course of the other. Similarly, splenectomy led to no appreciable aggravation of Bartonella infection. One monkey subjected to splenectomy and inoculated with verruga material shortly afterwards had an unusually severe reaction, but another, which was infected with material from the first and simultaneously splenectomized, reacted only moderately, while the non-splenectomized control showed a severer type of cutaneous infection. Even the combination of splenectomy and malarial infection did not appreciably aggravate the experimental verruga. Neither relapse of verruga nor reinfection with Bartonella bacilliformis was induced in convalescent or recovered monkeys as a result of splenectomy.
Neurogenesis in the Adult Brain: New Strategies for Central Nervous System Diseases
Authors: D. Chichung Lie, Hongjun Song, Sophia A. Colamarino, Guo-li Ming, Fred H. Gage
Journal: The Annual Review of Pharmacology and Toxicology (2004)

New cells are continuously generated from immature proliferating cells throughout adulthood in many organs, thereby contributing to the integrity of the tissue under physiological conditions and to repair following injury. In contrast, repair mechanisms in the adult central nervous system (CNS) have long been thought to be very limited. However, recent findings have clearly demonstrated that in restricted areas of the mammalian brain, new functional neurons are constantly generated from neural stem cells throughout life. Moreover, stem cells with the potential to give rise to new neurons reside in many different regions of the adult CNS. These findings raise the possibility that endogenous neural stem cells can be mobilized to replace dying neurons in neurodegenerative diseases. Indeed, recent reports have provided evidence that, in some injury models, limited neuronal replacement occurs in the CNS. Here, we summarize our current understanding of the mechanisms controlling adult neurogenesis and discuss their implications for the development of new strategies for the treatment of neurodegenerative diseases.
S14 Time Trends And Risk Factors For Hospitalisation After Community-acquired Pneumonia In Older Adults In England
Authors: E. Millett, B. De Stavola, J. Quint, L. Smeeth, S. Thomas
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Hospitalisation rates for community-acquired pneumonia (CAP) among older individuals have increased in Europe, but the reasons for this remain unclear. It may be due to increasing incidence of CAP in older adults, or an increasing tendency to hospitalise – either due to worsening co-morbidities, and/or changes in service provision. We used English linked electronic health records to investigate trends in hospitalisation after a CAP diagnosis independent of CAP incidence, and determinants of any increasing trend. <h3>Methods</h3> General practice records from the Clinical Practice Research Datalink (1998–2011) were linked to hospital admission records and mortality data, and CAP episodes among patients aged ≥65 years were identified. Episodes resulting in hospitalisation within 28 days of CAP diagnosis were compared to non-hospitalised CAP episodes, and multilevel logistic regression models built to estimate odds ratios for co-morbidities, frailty, and other factors, and to predict the probability of hospitalisation over time. Indicators of CAP severity (including mortality in the 28 days post-CAP) and pathways of care were also examined as explanations for hospitalisation trends. <h3>Results</h3> Hospitalisation after CAP increased markedly over the time period; after controlling for a wide range of comorbidities and other factors, the predicted probability of hospitalisation rose from 57% (1998–2000) to 86% (2009–2010). Factors associated with hospitalisation included 14 co-morbidities, five frailty factors, and four medications/vaccinations. In the fully adjusted model most of these factors were associated with increased odds of hospitalisation, but some (including dementia and terminal illness) lowered the odds of hospitalisation. Over the study period, a growing proportion of CAP patients were admitted to hospital via A and E and the proportion referred by general practitioners decreased. 28-day mortality decreased over time. <h3>Conclusions</h3> Hospitalisation after CAP among those aged ≥65 years has increased in England, independent of co-morbidity and frailty factors, while mortality has decreased. Changes in service provision, patient and physician behaviours may play a role in increasing CAP hospitalisations. If the incidence of CAP in this age group also continues to increase, these combined trends will place an expanding burden on the health service.
Distinct Murine Mucosal Langerhans Cell Subsets Develop from Pre-dendritic Cells and Monocytes
Authors: Tal Capucha, Gabriel Mizraji, Hadas Segev, Ronnie Blecher-Gonen, Deborah Winter, Abed Khalaileh, Yaara Tabib, Tsipora Attal, Maria Nassar, Katya Zelentsova, Hen Kisos, Martin Zenke, Kristin Seré, Thomas Hieronymus, Tal Burstyn-Cohen, Ido Amit, Asaf Wilensky, Avi-Hai Hovav
Journal: Immunity (2015)