tbuckley/cabot-search huggingface dataset:
British Thoracic Society survey of knowledge of healthcare professionals managing patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease requiring non-invasive ventilation
Authors: E. Ballard, L. McDonnell, S. Keilty, A. C. Davidson, N. Hart
Journal: Thorax (2010)

The use of non-invasive ventilation (NIV) in acute hypercapnic exacerbations of chronic obstructive pulmonary disease (COPD) is the subject of published guidance from the Royal College of Physicians, the British Thoracic Society (BTS) and the Intensive Care Society, as well as international consensus statements.1–3 Although these guidelines have been updated, data from the UK COPD audit detailing admissions to UK hospitals have shown that …
The Hedgehog Signaling Pathway in Cancer
Authors: Marie Evangelista, Hua Tian, Frederic J. de Sauvage
Journal: Clinical Cancer Research (2006)

Abstract The Hedgehog (Hh) pathway is a signaling cascade that directs patterning in most animals and is crucial for proper development. At the molecular level, Hh ligands drive cell proliferation in some cell types while causing others to undergo differentiation. Hh signaling is most active during embryogenesis, and aberrant reactivation of the pathway in adult tissue can lead to the development of cancer. A comprehensive understanding of Hh signaling during development will undoubtedly shed light into the mechanism of Hh in cancer progression and identify potential targets for therapeutic intervention.
Regulation of Cyclin D1 RNA Stability by SNIP1
Authors: Cameron P. Bracken, Steven J. Wall, Benjamin Barré, Kostya I. Panov, Paul M. Ajuh, Neil D. Perkins
Journal: Cancer Research (2008)

Abstract Cyclin D1 expression represents one of the key mitogen-regulated events during the G1 phase of the cell cycle, whereas Cyclin D1 overexpression is frequently associated with human malignancy. Here, we describe a novel mechanism regulating Cyclin D1 levels. We find that SNIP1, previously identified as a regulator of Cyclin D1 expression, does not, as previously thought, primarily function as a transcriptional coactivator for this gene. Rather, SNIP1 plays a critical role in cotranscriptional or posttranscriptional Cyclin D1 mRNA stability. Moreover, we show that the majority of nucleoplasmic SNIP1 is present within a previously undescribed complex containing SkIP, THRAP3, BCLAF1, and Pinin, all proteins with reported roles in RNA processing and transcriptional regulation. We find that this complex, which we have termed the SNIP1/SkIP–associated RNA-processing complex, is coordinately recruited to both the 3′ end of the Cyclin D1 gene and Cyclin D1 RNA. Significantly, SNIP1 is required for the further recruitment of the RNA processing factor U2AF65 to both the Cyclin D1 gene and RNA. This study shows a novel mechanism regulating Cyclin D1 expression and offers new insight into the role of SNIP1 and associated proteins as regulators of proliferation and cancer. [Cancer Res 2008;68(18):7621–8]
Plasma cyclic nucleotide levels in exercise-induced asthma.
Authors: J P Hartley, C J Davies, T J Charles, R D Monie, S G Nogrady, M D Winson
Journal: Thorax (1981)

It is known that sympatho-adrenal control of airways is increased in asthma since beta blockade can cause severe bronchoconstriction in asthmatic individuals. It has not been established whether an altered catecholamine response to exercise plays any part in the production of the common symptom of exercise-induced asthma (EIA). We have investigated this indirectly by measuring arterial plasma cyclic nucleotide levels in 10 subjects with EIA and five normal subjects. Cyclic AMP, which in this context reflects beta stimulation, rose significantly by 25.4% in the normal subjects during exercise, while there was no significant change during or after exercise (less than 5%) in the asthmatic subjects. Cyclic GMP rose significantly after exercise in the asthmatic subjects. Six normal subjects repeated the protocol before and after inhalation of salbutamol aerosol, 1600 microgram daily for 18 days. This did not reduce the cAMP response to exercise, and we conclude that the diminished cAMP response of the asthmatic subjects was not caused by their medication. The results may indicate either impaired catecholamine production or endogenous beta receptor hyporesponsiveness in some asthmatic subjects and this may contribute to the development of EIA.
Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma
Authors: Thorsten Stühmer, Manik Chatterjee, Martin Hildebrandt, Pia Herrmann, Hella Gollasch, Christian Gerecke, Sebastian Theurich, Luisa Cigliano, Rudolf A. Manz, Peter T. Daniel, Kurt Bommert, Lyubomir T. Vassilev, Ralf C. Bargou
Journal: Blood (2005)
Hemispheric Specialization in Human Dorsal Frontal Cortex and Medial Temporal Lobe for Verbal and Nonverbal Memory Encoding
Authors: William M Kelley, Francis M Miezin, Kathleen B McDermott, Randy L Buckner, Marcus E Raichle, Neal J Cohen, John M Ollinger, Erbil Akbudak, Thomas E Conturo, Abraham Z Snyder, Steven E Petersen
Journal: Neuron (1998)
Hypertrophic Cardiomyopathy
Authors: Pascale Richard, Philippe Charron, Lucie Carrier, Céline Ledeuil, Theary Cheav, Claire Pichereau, Abdelaziz Benaiche, Richard Isnard, Olivier Dubourg, Marc Burban, Jean-Pierre Gueffet, Alain Millaire, Michel Desnos, Ketty Schwartz, Bernard Hainque, Michel Komajda
Journal: Circulation (2003)

Hypertrophic cardiomyopathy is an autosomal-dominant disorder in which 10 genes and numerous mutations have been reported. The aim of the present study was to perform a systematic screening of these genes in a large population, to evaluate the distribution of the disease genes, and to determine the best molecular strategy in clinical practice.The entire coding sequences of 9 genes (MYH7, MYBPC3, TNNI3, TNNT2, MYL2, MYL3, TPM1, ACTC, andTNNC1) were analyzed in 197 unrelated index cases with familial or sporadic hypertrophic cardiomyopathy. Disease-causing mutations were identified in 124 index patients ( approximately 63%), and 97 different mutations, including 60 novel ones, were identified. The cardiac myosin-binding protein C (MYBPC3) and beta-myosin heavy chain (MYH7) genes accounted for 82% of families with identified mutations (42% and 40%, respectively). Distribution of the genes varied according to the prognosis (P=0.036). Moreover, a mutation was found in 15 of 25 index cases with "sporadic" hypertrophic cardiomyopathy (60%). Finally, 6 families had patients with more than one mutation, and phenotype analyses suggested a gene dose effect in these compound-heterozygous, double-heterozygous, or homozygous patients.These results might have implications for genetic diagnosis strategy and, subsequently, for genetic counseling. First, on the basis of this experience, the screening of already known mutations is not helpful. The analysis should start by testing MYBPC3 and MYH7 and then focus on TNNI3, TNNT2, and MYL2. Second, in particularly severe phenotypes, several mutations should be searched. Finally, sporadic cases can be successfully screened.
Functional Anatomy of Auditory Verbal Imagery in Schizophrenic Patients With Auditory Hallucinations
Authors: Sukhwinder S. Shergill, Ed Bullmore, Andrew Simmons, Robin Murray, Philip McGuire
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This study investigated the functional neuroanatomy of inner speech and auditory verbal imagery in schizophrenic patients predisposed to auditory hallucinations. METHOD: Eight patients with schizophrenia with a history of prominent auditory hallucinations and six comparison subjects underwent functional magnetic resonance imaging while generating inner speech or imagining external speech. RESULTS: Patients showed no differences while generating inner speech but experienced a relatively attenuated response in the posterior cerebellar cortex, hippocampi, and lenticular nuclei bilaterally and the right thalamus, middle and superior temporal cortex, and left nucleus accumbens during auditory verbal imagery. CONCLUSIONS: Patients with schizophrenia who were prone to auditory hallucinations show attenuated activation when processing inner speech in areas implicated in verbal self-monitoring.
Host and Pathogen Factors for<i>Clostridium difficile</i>Infection and Colonization
Authors: Vivian G. Loo, Anne-Marie Bourgault, Louise Poirier, François Lamothe, Sophie Michaud, Nathalie Turgeon, Baldwin Toye, Axelle Beaudoin, Eric H. Frost, Rodica Gilca, Paul Brassard, Nandini Dendukuri, Claire Béliveau, Matthew Oughton, Ivan Brukner, Andre Dascal
Journal: New England Journal of Medicine (2011)

Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization.We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured.A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain.In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.).
American Medical Society for Sports Medicine recommended sports ultrasound curriculum for sports medicine fellowships
Authors: Jonathan T Finnoff, David Berkoff, Fred Brennan, John DiFiori, Mederic M Hall, Kimberly Harmon, Mark Lavallee, Sean Martin, Jay Smith, Mark Stovak
Journal: British Journal of Sports Medicine (2014)

The American Medical Society for Sports Medicine (AMSSM) developed a musculoskeletal ultrasound curriculum for sports medicine fellowships in 2010. As the use of diagnostic and interventional ultrasound in sports medicine has evolved, it became clear that the curriculum needed to be updated. Furthermore, the name 'musculoskeletal ultrasound' was changed to 'sports ultrasound' (SPORTS US) to reflect the broad range of diagnostic and interventional applications of ultrasound in sports medicine. This document was created to outline the core competencies of SPORTS US and to provide sports medicine fellowship directors and others interested in SPORTS US education with a guide to create a SPORTS US curriculum. By completing this SPORTS US curriculum, sports medicine fellows and physicians can attain proficiency in the core competencies of SPORTS US required for the practice of sports medicine.
Functional Anatomy of T Cell Activation and Synapse Formation
Authors: David R. Fooksman, Santosh Vardhana, Gaia Vasiliver-Shamis, Jan Liese, David A. Blair, Janelle Waite, Catarina Sacristán, Gabriel D. Victora, Alexandra Zanin-Zhorov, Michael L. Dustin
Journal: Annual Review of Immunology (2009)

T cell activation and function require a structured engagement of antigen-presenting cells. These cell contacts are characterized by two distinct dynamics in vivo: transient contacts resulting from promigratory junctions called immunological kinapses or prolonged contacts from stable junctions called immunological synapses. Kinapses operate in the steady state to allow referencing to self-peptide-MHC (pMHC) and searching for pathogen-derived pMHC. Synapses are induced by T cell receptor (TCR) interactions with agonist pMHC under specific conditions and correlate with robust immune responses that generate effector and memory T cells. High-resolution imaging has revealed that the synapse is highly coordinated, integrating cell adhesion, TCR recognition of pMHC complexes, and an array of activating and inhibitory ligands to promote or prevent T cell signaling. In this review, we examine the molecular components, geometry, and timing underlying kinapses and synapses. We integrate recent molecular and physiological data to provide a synthesis and suggest ways forward.
Phosphatidylinositol 3-kinase signaling determines kidney size
Authors: Jian-Kang Chen, Kojiro Nagai, Jianchun Chen, David Plieth, Masayo Hino, Jinxian Xu, Feng Sha, T. Alp Ikizler, C. Chad Quarles, David W. Threadgill, Eric G. Neilson, Raymond C. Harris
Journal: Journal of Clinical Investigation (2015)

Kidney size adaptively increases as mammals grow and in response to the loss of 1 kidney. It is not clear how kidneys size themselves or if the processes that adapt kidney mass to lean body mass also mediate renal hypertrophy following unilateral nephrectomy (UNX). Here, we demonstrated that mice harboring a proximal tubule-specific deletion of Pten (Pten(ptKO)) have greatly enlarged kidneys as the result of persistent activation of the class I PI3K/mTORC2/AKT pathway and an increase of the antiproliferative signals p21(Cip1/WAF) and p27(Kip1). Administration of rapamycin to Pten(ptKO) mice diminished hypertrophy. Proximal tubule-specific deletion of Egfr in Pten(ptKO) mice also attenuated class I PI3K/mTORC2/AKT signaling and reduced the size of enlarged kidneys. In Pten(ptKO) mice, UNX further increased mTORC1 activation and hypertrophy in the remaining kidney; however, mTORC2-dependent AKT phosphorylation did not increase further in the remaining kidney of Pten(ptKO) mice, nor was it induced in the remaining kidney of WT mice. After UNX, renal blood flow and amino acid delivery to the remaining kidney rose abruptly, followed by increased amino acid content and activation of a class III PI3K/mTORC1/S6K1 pathway. Thus, our findings demonstrate context-dependent roles for EGFR-modulated class I PI3K/mTORC2/AKT signaling in the normal adaptation of kidney size and PTEN-independent, nutrient-dependent class III PI3K/mTORC1/S6K1 signaling in the compensatory enlargement of the remaining kidney following UNX.
Severe Hyperhomocysteinemia Promotes Bone Marrow–Derived and Resident Inflammatory Monocyte Differentiation and Atherosclerosis in LDLr/CBS-Deficient Mice
Authors: Daqing Zhang, Pu Fang, Xiaohua Jiang, Jun Nelson, Jodene K. Moore, Warren D. Kruger, Remus M. Berretta, Steven R. Houser, Xiaofeng Yang, Hong Wang
Journal: Circulation Research (2012)

Rationale: Hyperhomocysteinemia (HHcy) accelerates atherosclerosis and increases inflammatory monocytes (MC) in peripheral tissues. However, its causative role in atherosclerosis is not well established and its effect on vascular inflammation has not been studied. The underlying mechanism is unknown. Objective: This study examined the causative role of HHcy in atherogenesis and its effect on inflammatory MC differentiation. Methods and Results: We generated a novel HHcy and hyperlipidemia mouse model, in which cystathionine β-synthase (CBS) and low-density lipoprotein receptor (LDLr) genes were deficient ( Ldlr −/− Cbs −/+ ). Severe HHcy (plasma homocysteine (Hcy)=275 μmol/L) was induced by a high methionine diet containing sufficient basal levels of B vitamins. Plasma Hcy levels were lowered to 46 μmol/L from 244 μmol/L by vitamin supplementation, which elevated plasma folate levels. Bone marrow (BM)–derived cells were traced by the transplantation of BM cells from enhanced green fluorescent protein (EGFP) transgenic mice after sublethal irradiation of the recipient. HHcy accelerated atherosclerosis and promoted Ly6C high inflammatory MC differentiation of both BM and tissue origins in the aortas and peripheral tissues. It also elevated plasma levels of TNF-α, IL-6, and MCP-1; increased vessel wall MC accumulation; and increased macrophage maturation. Hcy-lowering therapy reversed HHcy-induced lesion formation, plasma cytokine increase, and blood and vessel inflammatory MC (Ly6C high+middle ) accumulation. Plasma Hcy levels were positively correlated with plasma levels of proinflammatory cytokines. In primary mouse splenocytes, L-Hcy promoted rIFNγ-induced inflammatory MC differentiation, as well as increased TNF-α, IL-6, and superoxide anion production in inflammatory MC subsets. Antioxidants and folic acid reversed L-Hcy-induced inflammatory MC differentiation and oxidative stress in inflammatory MC subsets. Conclusions: HHcy causes vessel wall inflammatory MC differentiation and macrophage maturation of both BM and tissue origins, leading to atherosclerosis via an oxidative stress-related mechanism.
Cytolytic T Lymphocytes
Authors: M. Nabholz, H. R. MacDonald
Journal: Annual Review of Immunology (1983)

observations and their interpretation becomes blurred with time. A re-evaluation of the data on CTL may become important at a time when the emphasis of the questions asked about these cells changes. We think the discovery of T-cell growth factor and the design of methods that have allowed the maintenance of CTL clones in permanent culture have ushered in a period in which the established conceptual and experimental framework of cellular immunology is rapidly ceding to a much more cell­ biologically oriented approach to CTL. Therefore, in the second part, we identify some of the questions that arise from the work with CTL clones and that represent this new outlook. Our references are quite eclectic, and for some areas-e.g. lytic mecha­ nisms-we refer mainly to some of the comprehensive reviews that have appeared recently.
Progesterone receptor modulators and the endometrium: changes and consequences†
Authors: Frances McFarland Horne, Diana L. Blithe
Journal: Human Reproduction Update (2007)

Progesterone receptor modulators (PRMs) have been used for contraceptive research, as well as for treatment of fibroids, endometriosis and heavy or irregular menstrual bleeding. Long-term treatment with these compounds results in changes to the endometrium resulting in potential confusion in trying to characterize endometrial biopsies. A meeting was held to discuss the properties of PRMs, the effects of perturbed hormonal control of the endometrium and the need for further understanding of the biology of progesterone receptor action to facilitate the development of new PRMs. A panel of pathologists was convened to evaluate endometrial changes associated with a minimum of three months of chronic treatment with PRMs. Four different agents were used in the treatment regimens but the pathologists were blinded to treatment regimen or agent. The panel agreed that the endometrial biopsies did not fit into a classification of either proliferative or secretory endometrium but exhibited an unusual architecture that could be characterized as glandular dilatation. There was little evidence of mitosis, consistent with a proposed anti-proliferative effect of PRMs. The panel concluded that the biopsies did not reveal evidence of safety concern and that pathologists and investigators familiar with endometrial effects of chronic PRM exposure should consider working with pharmaceutical companies and regulatory agencies to develop standard descriptions of PRM-associated endometrial changes as well as the types of histologic changes that would signal a need for intervention.
Long-Term Primary Culture of Mouse Mammary Tumor Cells: Production of Virus23
Authors: L. J. T. Young, R. D. Cardiff, R. L. Ashley
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Long-Term Primary Culture of Mouse Mammary Tumor Cells: Production of Virus Get access L. J. T. Young, L. J. T. Young Search for other works by this author on: Oxford Academic PubMed Google Scholar R. D. Cardiff, R. D. Cardiff Search for other works by this author on: Oxford Academic PubMed Google Scholar R. L. Ashley R. L. Ashley Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 5, May 1975, Pages 1215–1221, https://doi.org/10.1093/jnci/54.5.1215 Published: 01 May 1975 Article history Received: 11 November 1974 Accepted: 03 January 1975 Published: 01 May 1975
Activation of Microglial Poly(ADP-Ribose)-Polymerase-1 by Cholesterol Breakdown Products during Neuroinflammation
Authors: Antje Diestel, Orhan Aktas, Dagmar Hackel, Ines Häke, Susanne Meier, Cedric S. Raine, Robert Nitsch, Frauke Zipp, Oliver Ullrich
Journal: The Journal of Experimental Medicine (2003)

Multiple sclerosis (MS) is a chronic demyelinating disease in which it has only recently been suggested that damage to neuronal structures plays a key role. Here, we uncovered a link between the release of lipid breakdown products, found in the brain and cerebrospinal fluid (CSF) of MS patients as well as in experimental autoimmune encephalomyelitis, and neuronal damage mediated by microglial activation. The concentrations of the breakdown product 7-ketocholesterol detected in the CSF of MS patients were capable of inducing neuronal damage via the activation and migration of microglial cells in living brain tissue. 7-ketocholesterol rapidly entered the nucleus and activated poly(ADP-ribose)-polymerase (PARP)-1, followed by the expression of migration-regulating integrins CD11a and intercellular adhesion molecule 1. These findings reveal a novel mechanism linking demyelination and progressive neuronal damage, which might represent an underlying insidious process driving disease beyond a primary white matter phenomenon and rendering the microglial PARP-1 a possible antiinflammatory therapeutic target.
THYROID HORMONES RECEPTORS ARE PRESENT AND EFFECTIVE ON HEALTHY AND RUPTURED ROTATOR CUFF TENDONS. A PRELIMINARY REPORT
Authors: Francesco Oliva
Journal: British Journal of Sports Medicine (2013)

Thyroid hormones (THs), T3 and T4, play an essential role in the development and metabolism of many tissues and organs, and have profound metabolic effects in adult life. Thyroid hormone receptors (TRs) seem to be ubiquitous, but, to our knowledge, their presence in tenocytes has not been investigated. We therefore evaluated the expression pattern of TRs isoforms in three groups of patients: one with rotator cuff tendons tears and with thyroid diseases, one with rotator cuff tendons tears without thyroid diseases, and one with healthy rotator cuff tendons and no thyroid disease. In addition, we evaluated the action of THs on growth and apoptosis of primary tenocyte cultures. The α/β nuclear receptor isoforms are present in healthy and pathologic rotator cuff tendons. THs enhance the growth and counteract apoptosis in primary tenocyte cultures in a dose and time dependent manner.