tbuckley/cabot-search huggingface dataset:
Similar rates of production of T and B lymphocytes in the bone marrow.
Authors: S Dejbakhsh-Jones, H Okazaki, S Strober
Journal: The Journal of Experimental Medicine (1995)

The rate of renewal of T lymphocytes in the bone marrow of euthymic C57BL/Ka and athymic nu/nu BALB/c mice was estimated by in vivo labeling with bromodeoxyuridine. T lymphocytes accounted for 16-18% of marrow cells in euthymic mice as judged by immunofluorescent staining with monoclonal antibodies for Thy-1, CD3, and alpha/beta T cell antigen receptor markers. About 70% of marrow cells expressed receptors (Mac-1, Gr-1, B220) for myeloid, macrophage, and B lineage cells. Approximately 13% of cells in the athymic bone marrow expressed alpha/beta T cell receptors. Sorted marrow T cells proliferated in response to stimulation with anti-alpha/beta antibodies in vitro and showed functional rearrangements of V beta and J beta genes. Sorted non-T cells did not respond to stimulation in vitro, and all V beta and J beta gene rearrangements identified were nonfunctional. In vivo labeling studies indicated that approximately 17 x 10(6) bone marrow T cells are renewed daily in euthymic mice and approximately 14 x 10(6) are renewed in athymic mice. Approximately 11 x 10(6) mature B cells (immunoglobulin M+) are renewed daily in the bone marrow of the latter mice. To determine whether marrow precursors can give rise to T cells directly, marrow cells from euthymic and athymic mice were depleted of T cells by cell sorting and incubated in vitro for 48 h in the absence of exogenous growth factors or thymic stromal cells. Examination of the cells after culture showed that 10-12% stained brightly for alpha/beta T cell receptors. Although functional rearrangements of V beta and J beta genes were not detected before culture, the majority of rearrangements were functional after culture. The emergence of the bright alpha/beta T cells in culture was dependent on depletion T cells from the marrow cells before culture. The results suggest that most marrow T cells are generated in the marrow itself.
THE STRUCTURAL BASIS FOR BINDING OF COMPLEMENT BY IMMUNOGLOBULIN M
Authors: Mary M. Hurst, John E. Volanakis, Raymond B. Hester, Robert M. Stroud, J. Claude Bennett
Journal: The Journal of Experimental Medicine (1974)

An insight into the structural features of human IgM that are responsible for its capacity to bind the first component of complement (C) has been obtained by examining the ability of IgM subfragments to bind active C1 (C1). The smallest two fragments found to bind C1 were the major CNBr fragment of the Fc portion of IgM and the C(H)4 fragment of the carboxy-terminal domain. The smallest fragment which fixes C1 has a disaggregated mol wt of 6,800, consists of 60 residues, and contains no carbohydrate. Structural considerations and sequence overlaps suggest that the amino-terminal side of the C(H)4 domain (24 amino acid residues) might be responsible for fixing C1.
Career choices for generation X
Authors: C. Vaughan
Journal: BMJ (1995)

Young doctors want flexible career paths, not long term commitments

Young doctors are not choosing to train or settle in general practice as they did a decade ago, which has serious implications for training schemes and practices recruiting new partners. Changes in the NHS may partly explain this. Baker et al found that the four commonest reasons given by qualified general practitioners for not practising as principals were the commitment out of hours, difficulty combining work with family commitments, requirements of the general practice contract, and increasing demands from patients.1

A broader shift in values and expectations of work may also be occurring, and we need to understand the social context in which young graduates have grown up. The old certainties of work and family life have …
Autocrine Motility Factor Modulates EGF-Mediated Invasion Signaling
Authors: Dhong Hyo Kho, Tianpeng Zhang, Vitaly Balan, Yi Wang, Seung-Wook Ha, Youming Xie, Avraham Raz
Journal: Cancer Research (2014)

Autocrine motility factor (AMF) enhances invasion by breast cancer cells, but how its secretion and effector signaling are controlled in the tumor microenvironment is not fully understood. In this study, we investigated these issues with a chimeric AMF that is secreted at high levels through a canonical endoplasmic reticulum (ER)/Golgi pathway. Using this tool, we found that AMF enhances tumor cell motility by activating AKT/ERK, altering actin organization, and stimulating β-catenin/TCF and activating protein 1 transcription. EGF enhanced secretion of AMF through its casein kinase II-mediated phosphorylation. RNA interference-mediated attenuation of AMF expression inhibited EGF-induced invasion by suppressing extracellular signal-regulated kinase signaling. Conversely, exogenous AMF overcame the inhibitory effect of EGF receptor inhibitor gefitinib on invasive motility by activating HER2 signaling. Taken together, our findings show how AMF modulates EGF-induced invasion while affecting acquired resistance to cytotoxic drugs in the tumor microenvironment.
Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease
Authors: James D. Lewis, Eric Z. Chen, Robert N. Baldassano, Anthony R. Otley, Anne M. Griffiths, Dale Lee, Kyle Bittinger, Aubrey Bailey, Elliot S. Friedman, Christian Hoffmann, Lindsey Albenberg, Rohini Sinha, Charlene Compher, Erin Gilroy, Lisa Nessel, Amy Grant, Christel Chehoud, Hongzhe Li, Gary D. Wu, Frederic D. Bushman
Journal: Cell Host & Microbe (2015)
Genome-wide analysis of mRNA lengths in Saccharomyces cerevisiae
Authors: Evan H Hurowitz, Patrick O Brown
Journal: Genome biology (2003)

Although the protein-coding sequences in the Saccharomyces cerevisiae genome have been studied and annotated extensively, much less is known about the extent and characteristics of the untranslated regions of yeast mRNAs.We developed a 'Virtual Northern' method, using DNA microarrays for genome-wide systematic analysis of mRNA lengths. We used this method to measure mRNAs corresponding to 84% of the annotated open reading frames (ORFs) in the S. cerevisiae genome, with high precision and accuracy (measurement errors +/- 6-7%). We found a close linear relationship between mRNA lengths and the lengths of known or predicted translated sequences; mRNAs were typically around 300 nucleotides longer than the translated sequences. Analysis of genes deviating from that relationship identified ORFs with annotation errors, ORFs that appear not to be bona fide genes, and potentially novel genes. Interestingly, we found that systematic differences in the total length of the untranslated sequences in mRNAs were related to the functions of the encoded proteins.The Virtual Northern method provides a practical and efficient method for genome-scale analysis of transcript lengths. Approximately 12-15% of the yeast genome is represented in untranslated sequences of mRNAs. A systematic relationship between the lengths of the untranslated regions in yeast mRNAs and the functions of the proteins they encode may point to an important regulatory role for these sequences.
An animal model for evaluating the local and systemic effects of topically applied corticosteroids on epidermal DNA synthesis
Authors: ANTHONY VIVIER, R. C. MARSHALL, L. G. BROOKES
Journal: British Journal of Dermatology (1978)

A simple animal model for studying topically applied glucocorticosteroids for their effect on epidermal DNA synthesis is described. It is designed so that their potential for systemic side effects may be predicted and its usefulness in this respect is illustrated by the results obtained with two of the steroids investigated. One, a new formulation Temetex, is predicted to have considerable systemic potential. The other, Molivate, is remarkable for having moderate local, without demonstrable systemic activity.
The epidemiology of glioma in adults: a "state of the science" review
Authors: L. L. Morgan
Journal: Neuro-Oncology (2015)

This is a wide-ranging and comprehensive study.1 However, the section “Nonionizing Radiation: Cellular Phones” has serious deficiencies. It cites 3 incidence time trend studies,2–4 2 cohort studies,5,6 and 1 case control study.7
Hospital at Home: Feasibility and Outcomes of a Program To Provide Hospital-Level Care at Home for Acutely Ill Older Patients
Authors: Bruce Leff
Journal: Annals of Internal Medicine (2005)

Background: Acutely ill older persons often experience adverse events when cared for in the acute care hospital. Objective: To assess the clinical feasibility and efficacy of providing acute hospital-level care in a patient's home in a hospital at home. Design: Prospective quasi-experiment. Setting: 3 Medicare-managed care (Medicare + Choice) health systems at 2 sites and a Veterans Administration medical center. Participants: 455 community-dwelling elderly patients who required admission to an acute care hospital for community-acquired pneumonia, exacerbation of chronic heart failure, exacerbation of chronic obstructive pulmonary disease, or cellulitis. Intervention: Treatment in a hospital-at-home model of care that substitutes for treatment in an acute care hospital. Measurements: Clinical process measures, standards of care, clinical complications, satisfaction with care, functional status, and costs of care. Results: Hospital-at-home care was feasible and efficacious in delivering hospital-level care to patients at home. In 2 of 3 sites studied, 69% of patients who were offered hospital-at-home care chose it over acute hospital care; in the third site, 29% of patients chose hospital-at-home care. Although less procedurally oriented than acute hospital care, hospital-at-home care met quality standards at rates similar to those of acute hospital care. On an intention-to-treat basis, patients treated in hospital-at-home had a shorter length of stay (3.2 vs. 4.9 days) (P = 0.004), and there was some evidence that they also had fewer complications. The mean cost was lower for hospital-at-home care than for acute hospital care ($5081 vs. $7480) (P < 0.001). Limitations: Possible selection bias because of the quasi-experimental design and missing data, modest sample size, and study site differences. Conclusions: The hospital-at-home care model is feasible, safe, and efficacious for certain older patients with selected acute medical illnesses who require acute hospital-level care.
CELLULAR AND MOLECULAR CHANGES ASSOCIATED WITH INHIBITORY EFFECT OF PIOGLITAZONE ON NEOINTIMAL GROWTH IN PATIENTS WITH TYPE 2 DIABETES AFTER ZOTAROLIMUS-ELUTING STENT IMPLANTATION
Authors: Chul Min Ahn, Soon Jun Hong, Ju Hwan Kim, Kyoung-Mi Lee, Je Sang Kim, Jae Hyoung Park, Do-Sun Lim
Journal: Journal of the American College of Cardiology (2011)
Diminished Basal Phosphorylation Level of Phospholamban in the Postinfarction Remodeled Rat Ventricle
Authors: Boyu Huang, Su Wang, Dayi Qin, Mohamed Boutjdir, Nabil El-Sherif
Journal: Circulation Research (1999)

Three weeks after myocardial infarction (MI) in the rat, remodeled hypertrophy of noninfarcted myocardium is at its maximum and the heart is in a compensated stage with no evidence of heart failure. Our hemodynamic measurements at this stage showed a slight but insignificant decrease of +dP/dt but a significantly higher left ventricular end-diastolic pressure. To investigate the basis of the diastolic dysfunction, we explored possible defects in the beta-adrenergic receptor-G(s/i) protein-adenylyl cyclase-cAMP-protein kinase A-phosphatase pathway, as well as molecular or functional alterations of sarcoplasmic reticulum Ca(2+)-ATPase and phospholamban (PLB). We found no significant difference in both mRNA and protein levels of sarcoplasmic reticulum Ca(2+)-ATPase and PLB in post-MI left ventricle compared with control. However, the basal levels of both the protein kinase A-phosphorylated site (Ser16) of PLB (p16-PLB) and the calcium/calmodulin-dependent protein kinase-phosphorylated site (Thr17) of PLB (p17-PLB) were decreased by 76% and 51% in post-MI myocytes (P<0.05), respectively. No change was found in the beta-adrenoceptor density, G(salpha) protein level, or adenylyl cyclase activity. Inhibition of phosphodiesterase and G(i) protein by Ro-20-1724 and pertussis toxin, respectively, did not correct the decreased p16-PLB or p17-PLB levels. Stimulation of beta-adrenoceptor or adenylyl cyclase increased both p16-PLB and p17-PLB in post-MI myocytes to the same levels as in sham myocytes, suggesting that decreased p16-PLB and p17-PLB in post-MI myocytes is not due to a decrease in the generation of p16-PLB or p17-PLB. We found that type 1 phosphatase activity was increased by 32% (P<0.05) with no change in phosphatase 2A activity. Okadaic acid, a protein phosphatase inhibitor, significantly increased p16-PLB and p17-PLB levels in post-MI myocytes and partially corrected the prolonged relaxation of the [Ca(2+)](i) transient. In summary, prolonged relaxation of post-MI remodeled myocardium could be explained, in part, by altered basal levels of p16-PLB and p17-PLB caused by increased protein phosphatase 1 activity.
Use of QSARs in international decision-making frameworks to predict health effects of chemical substances.
Authors: Mark T D Cronin, Joanna S Jaworska, John D Walker, Michael H I Comber, Christopher D Watts, Andrew P Worth
Journal: Environmental Health Perspectives (2003)

This article is a review of the use of quantitative (and qualitative) structure-activity relationships (QSARs and SARs) by regulatory agencies and authorities to predict acute toxicity, mutagenicity, carcinogenicity, and other health effects. A number of SAR and QSAR applications, by regulatory agencies and authorities, are reviewed. These include the use of simple QSAR analyses, as well as the use of multivariate QSARs, and a number of different expert system approaches.
Phase I/II investigation of paclitaxel, ifosfamide and carboplatin for advanced non-small-cell lung cancer
Authors: A.M. Mauer, R.H. Ansari, P.C. Hoffman, S.A. Krauss, D. Taber, S.A. Tembe, G.T. Gabrys, T. Cotter, L.P. Schumm, L. Szeto, E.E. Vokes
Journal: Annals of Oncology (2003)
Bronchogenic cyst presenting as mediastinal mass with pleural effusion
Authors: A Khalil, MF Carette, B Milleron, M Grivaux, JM Bigot
Journal: European Respiratory Journal (1995)

Mediastinal bronchogenic cysts are usually identified on computed tomography (CT) as well-defined masses of variable density that may contain rim calcifications. Pleural effusion has never been described in association with these cysts. We report two cases of bronchogenic cysts with unusual presentation because of an association with a pleural effusion not explained by pulmonary infection. The patients were studied with CT scan (n = 2) and magnetic resonance imaging (MRI) of the chest (n = 1). In the first case, the pleural effusion directed diagnosis towards lung tumour; and the diagnosis of bronchogenic cyst was made on thoracotomy. In the second case, bronchogenic cyst was suspected on MRI findings. Inflammatory reaction was also suspected on the CT scan, which showed enhancement of the cyst edge. In both cases, surgical excision of the cyst was difficult because of pericystic adhesions to adjacent organs. Therefore, solely on the finding of a pleural effusion, pericystic inflammation had to be suspected.
GENERALIZED LIGAMENTOUS LAXITY MAY BE A PREDISPOSING FACTOR FOR MUSCULOSKELETAL INJURIES
Authors: H Rahmatullah Bin Abd Razak, N Bin Ali, T Sen Howe
Journal: British Journal of Sports Medicine (2014)

Background Generalized ligamentous laxity has been implicated with musculoskeletal injuries. Little evidence has emerged from the Asia-Pacific regarding the epidemiology of generalized ligamentous laxity. Objective The aim of this study is to determine if generalized ligamentous laxity may be a predisposing factor for musculoskeletal injuries in young males. We hypothesized that generalized ligamentous laxity would be more common in individuals with musculoskeletal injuries compared with controls. Design Prospective case-control study. Setting Military. Participants All participants were male Singaporeans who were serving their National Service in the same military institute. The cases comprised of 100 consecutive individuals who presented to the primary healthcare centre in the institute with musculoskeletal injuries involving the upper or lower extremities that occurred as a result of physical activity. Our control group comprised of 100 age- and gender-matched individuals but did not have any musculoskeletal symptoms or injury for a period of 3 months or more from the time of recruitment. Assessment of risk factors Demographic data were gathered using a questionnaire. The surveyed factors include personal history, smoking history and sporting activity as well as the baseline demographic and anthropometric data. Main outcome measurements The Beighton score was used to measure laxity, which was determined to be present by overall scores equal to or exceeding 4. Results Generalized ligamentous laxity was present in 12% of the cases compared with 4% of controls (P=.043). Individuals who presented with musculoskeletal injuries were 3.35 times more likely to have generalized ligamentous laxity as compared to controls. Lower limb injuries were more common than upper limb injuries amongst the cases. Conclusions Generalized ligamentous laxity was more common in individuals who presented with a musculoskeletal injury. It may be a predisposing factor for musculoskeletal injuries. Prehabilitation may be an important aspect of training that should be emphasized to individuals identified to have generalized ligamentous laxity.
The amyloid precursor protein: beyond amyloid.
Authors: Hui Zheng, Edward H Koo
Journal: Molecular Neurodegeneration (2006)

The amyloid precursor protein (APP) takes a central position in Alzheimer's disease (AD) pathogenesis: APP processing generates the beta-amyloid (Abeta) peptides, which are deposited as the amyloid plaques in brains of AD individuals; Point mutations and duplications of APP are causal for a subset of early onset of familial Alzheimer's disease (FAD). Not surprisingly, the production and pathogenic effect of Abeta has been the central focus in AD field. Nevertheless, the biological properties of APP have also been the subject of intense investigation since its identification nearly 20 years ago as it demonstrates a number of interesting putative physiological roles. Several attractive models of APP function have been put forward recently based on in vitro biochemical studies. Genetic analyses of gain- and loss-of-function mutants in Drosophila and mouse have also revealed important insights into its biological activities in vivo. This article will review the current understanding of APP physiological functions.
Do stigma and other perceived barriers to mental health care differ across Armed Forces?
Authors: Matthew Gould, Amy Adler, Mark Zamorski, Carl Castro, Natalie Hanily, Nicole Steele, Steve Kearney, Neil Greenberg
Journal: Journal of the Royal Society of Medicine (2010)

Summary Objectives Military organizations are keen to address barriers to mental health care yet stigma and barriers to care remain little understood, especially potential cultural differences between Armed Forces. The aim of this study was to compare data collected by the US, UK, Australian, New Zealand and Canadian militaries using Hoge et al.'s perceived stigma and barriers to care measure (Combat duty in Iraq and Afghanistan, mental health problems and barriers to care. New Engl J Med 2004;351:13–22). Design Each member country identified data sources that had enquired about Hoge et al.'s perceived stigma and perceived barriers to care items in the re-deployment or immediate post-deployment period. Five relevant statements were included in the study. Setting US, UK Australian, New Zealand and Canadian Armed Forces. Results Concerns about stigma and barriers to care tended to be more prominent among personnel who met criteria for a mental health problem. The pattern of reported stigma and barriers to care was similar across the Armed Forces of all five nations. Conclusions Barriers to care continue to be a major issue for service personnel within Western military forces. Although there are policy, procedural and cultural differences between Armed Forces, the nations studied appear to share some similarities in terms of perceived stigma and barriers to psychological care. Further research to understand patterns of reporting and subgroup differences is required.
Mimicry and simulation in gesture comprehension
Authors: Martha W. Alibali, Autumn B. Hostetter
Journal: Behavioral and Brain Sciences (2010)

Abstract According to the SIMS model, mimicry and simulation contribute to perceivers' understanding of smiles. We argue that similar mechanisms are involved in comprehending the hand gestures that people produce when speaking. Viewing gestures may elicit overt mimicry, or may evoke corresponding simulations in the minds of addressees. These real or simulated actions contribute to addressees' comprehension of speakers' gestures.
Metastatic Crohn's disease
Authors: D.I. McCALLUM, W.M. GRAY
Journal: British Journal of Dermatology (1976)

Metastatic Crohn's disease is a term used to describe a granulomatous reaction occurring in flexures, and separated from the affected areas of the gastro-intestinal tract by normal skin. Previous reports refer to such lesions affecting the groins, the male genitalia, a flexure on the anterior abdominal wall of an obese patient, and submammary regions. A further case, in which the retro-auricular areas are involved, is presented.
Sleep disordered breathing and the outcome of stroke
Authors: G J Gibson
Journal: Thorax (2004)

Patients with OSA not only have an increased risk of stroke, but also a higher mortality and greater disability after stroke

Interest in abnormal breathing after stroke has a long history dating back at least to the observations of John Cheyne in 1818.1 In recent years this interest has been reawakened by a number of publications on the relations between sleep disordered breathing (SDB) and stroke. These studies have been of two main types—those investigating the possible increased risk of stroke in individuals with obstructive sleep apnoea (OSA) and those reporting a high prevalence of SDB after stroke and its possible effects on residual disability and mortality. Unravelling the direction of causality—that is, whether OSA causes stroke or stroke causes OSA—has proved challenging.2–5

Most of the evidence on the risk of stroke associated with OSA is circumstantial and is based on case-control studies in which a history of snoring, with or without other features suggestive of OSA, is compared in patients with stroke and matched controls.6–11 Such studies lack objective confirmation of pre-stroke OSA, are critically dependent on the validity of the control population, and are subject to recall bias. Moreover, most studies have included subjects who had previously had a stroke where, inevitably, the direction of causality is uncertain. In studies where account has been taken of potential confounding factors such as obesity, smoking and hypertension, the estimated risk of stroke is reduced. Of the possible “confounders”, hypertension is of particular relevance as the contribution of OSA to systemic hypertension has been demonstrated beyond reasonable doubt and clearly it offers a potential causal link with stroke. Even after statistical adjustment for hypertension, however, several studies still support an association between OSA and stroke. Various alternative mechanisms related to demonstrated abnormalities in patients with OSA …