tbuckley/cabot-search huggingface dataset:
Heart Failure Affects Mitochondrial but Not Myofibrillar Intrinsic Properties of Skeletal Muscle
Authors: E. De Sousa, V. Veksler, X. Bigard, P. Mateo, R. Ventura-Clapier
Journal: Circulation (2000)

Background —Congestive heart failure (CHF) induces abnormalities in skeletal muscle that are thought to in part explain exercise intolerance. The aim of the present study was to determine whether these changes actually result in contractile or metabolic functional alterations and whether they are muscle type specific. Methods and Results —With a rat model of CHF (induced by aortic banding), we studied mitochondrial function, mechanical properties, and creatine kinase (CK) compartmentation in situ in permeabilized fibers from soleus (SOL), an oxidative slow-twitch muscle, and white gastrocnemius (GAS), a glycolytic fast-twitch muscle. Animals were studied 7 months after surgery, and CHF was documented on the basis of anatomic data. Alterations in skeletal muscle phenotype were documented with an increased proportion of fast-type fiber and fast myosin heavy chain, decreased capillary-to-fiber ratio, and decreased citrate synthase activity. Despite a slow-to-fast phenotype transition in SOL, no change was observed in contractile capacity or calcium sensitivity. However, muscles from CHF rats exhibited a dramatic decrease in oxidative capacities (oxygen consumption per gram of fiber dry weight) of 35% for SOL and 45% for GAS ( P &lt;0.001). Moreover, the regulation of respiration with ADP and mitochondrial CK and adenylate kinase was impaired in CHF SOL. Mitochondrial CK activity and content (Western blots) were dramatically decreased in both muscles. Conclusions —CHF results in alterations in both mitochondrial function and phosphotransfer systems but unchanged myofibrillar function in skeletal muscles, which suggests a myopathy of metabolic origin in CHF.
Correlation between two-dimensional video analysis and subjective assessment in evaluating knee control among elite female team handball players
Authors: Silje Stensrud, Grethe Myklebust, Eirik Kristianslund, Roald Bahr, Tron Krosshaug
Journal: British Journal of Sports Medicine (2010)

Poor frontal plane knee control has been shown to be a risk factor for anterior cruciate ligament injuries in ball/team sports. It is necessary to develop simple tests that can identify players with poor knee control and among other factors be able to optimise preventive training programmes. The present study investigated the correlation between a two-dimensional (2D) video analysis and subjective assessment performed by one physiotherapist in evaluating knee control. We also tested the correlation between three simple clinical tests using both methods. A cohort of 186 female elite team handball players completed three tests: single-leg squat (SLS), single-leg vertical drop jump (SLVDJ) and two-leg vertical drop jump (VDJ). Receiver operating characteristic (ROC) analyses showed good to excellent agreement between 2D video analysis and subjective assessment for SLS and VDJ (area under the ROC curve (AUC) 0.83-0.89), but not for SLVDJ (AUC 0.65-0.76). Poor knee control was detected in 25-40% of the players using SLS and VDJ. In contrast, poor knee control was identified in less than 1% of the subjects based on the SLVDJ test. This indicates that SLVDJ may be inadequate for evaluating poor frontal plane knee control. The correlation between the SLS and VDJ tests was found to be low, suggesting that these tests identified different subjects with poor knee control. These results indicate that subjective assessment can be used to screen for poor knee control and that both SLS and VDJ tests should be used in screening athletes for poor knee control.
Molecular Mechanics and Dynamics of Leukocyte Recruitment During Inflammation
Authors: Scott I. Simon, Chad E. Green
Journal: Annual Review of Biomedical Engineering (2005)

▪ Abstract Discovery of new genes and proteins directly supporting leukocyte adhesion is waning, whereas there is heightened interest in the cell mechanics and receptor dynamics that lead from transient tethering via selectins to affinity shifts and adhesion strengthening through integrins. New optical tools enable real-time imaging of leukocyte rolling and arrest in parallel plate flow channels (PPFCs), and detection of single-molecule force spectroscopy provides an inner view of the intercellular adhesive contact region. Leukocyte recruitment during acute inflammation is triggered by ligation of G protein–coupled chemotactic receptors (GPCRs) and clustering of selectins. This, in turn, activates β 2 -integrin (CD18), which facilitates cell capture and arrest in shear flow. This review provides a conceptual model for the molecular events supporting leukocyte recruitment.
Hierarchy of ventricular pacemakers.
Authors: R R Hope, B J Scherlag, N El-Sherif, R Lazzara
Journal: Circulation Research (1976)

To characterize the pattern of pacemaker dominance in the ventricular specialized conduction system (VSCS), escape ventricular pacemakers were localized and quantified in vivo and in virto, in normal hearts and in hearts 24 hours after myocardial infarction. Excape pacemaker foci were localized in vivo during vagally induced atrial arrest by means of electrograms recorded from the His bundle and proximal bundle branches and standard electrocardiographic limb leads. The VSCS was isolated using a modified Elizari preparation or preparations of each bundle branch. Peacemakers were located by extra- and intracellular recordings. Escape pacemaker foci in vivo were always in the proximal conduction system, usually the left bundle branch. The rate was 43+/-11 (mean+/-SD) beats/min. After beta-adrenergic blockade, the mean rate fell to 31+/-10 beats/min, but there were no shifts in pacemaker location. In the infarcted hearts, pacemakers were located in the peripheral left bundle branch. The mean rate was 146+/-20 beats/min. In isolated normal preparations, the dominant pacemakers usually were in the His bundle, firing at a mean rate of 43+/-10 beats/min. The rates of pacemakers diminished with distal progression. In infarcted hearts, the pacemakers invariably were in the infarct zone. The mean firing rates were not influenced by beta-adrenergic blockade. The results indicate that the dominant pacemakers are normally in the very proximal VSCS, but after myocardial infarction pacemaker dominance is shifted into the infarct. Distribution of pacemaker dominance is independent of sympathetic influence.
Respiratory muscle and pulmonary function in polymyositis and other proximal myopathies.
Authors: N M Braun, N S Arora, D F Rochester
Journal: Thorax (1983)

We studied 53 patients with proximal myopathy to determine at what level of muscle weakness hypercapnic respiratory failure is likely, and which tests of pulmonary function or respiratory muscle strength would best suggest this development. Respiratory muscle strength was determined from maximal static efforts and in half the patients, both inspiratory and expiratory muscle strengths were less than 50% of normal. In the 37 patients without lung disease respiratory muscle weakness was accompanied by significant decreases in vital capacity, total lung capacity, and maximum voluntary ventilation; by significant increases in residual volume and arterial carbon dioxide tension (PaCO2); and greater likelihood of dependence on ventilators, atelectasis, and pneumonia. Hypercapnia was particularly likely when respiratory muscle strength was less than 30% of normal in uncomplicated myopathy, and when vital capacity was less than 55% of the predicted value in any patient.
Pin1 regulates TGF-β1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis
Authors: Zhong-Jian Shen, Stephane Esnault, Louis A. Rosenthal, Renee J. Szakaly, Ronald L. Sorkness, Pamela R. Westmark, Matyas Sandor, James S. Malter
Journal: Journal of Clinical Investigation (2008)

Eosinophilic inflammation is a cornerstone of chronic asthma that often culminates in subepithelial fibrosis with variable airway obstruction. Pulmonary eosinophils (Eos) are a predominant source of TGF-β1, which drives fibroblast proliferation and extracellular matrix deposition. We investigated the regulation of TGF-β1 and show here that the peptidyl-prolyl isomerase (PPIase) Pin1 promoted the stability of TGF-β1 mRNA in human Eos. In addition, Pin1 regulated cytokine production by both in vitro and in vivo activated human Eos. We found that Pin1 interacted with both PKC-α and protein phosphatase 2A, which together control Pin1 isomerase activity. Pharmacologic blockade of Pin1 in a rat asthma model selectively reduced eosinophilic pulmonary inflammation, TGF-β1 and collagen expression, and airway remodeling. Furthermore, chronically challenged Pin1–/– mice showed reduced peribronchiolar collagen deposition compared with wild-type controls. These data suggest that pharmacologic suppression of Pin1 may be a novel therapeutic option to prevent airway fibrosis in individuals with chronic asthma.
Commentaries on the end of year editorial on the definition of ischaemia in last December's issue
Authors: A de Hemptinne
Journal: Cardiovascular Research (1995)

Commentaries on the end of year editorial on the definition of ischaemia in last December's issue Get access A de Hemptinne, Professor A de Hemptinne, Professor Laboratory of Normal and Pathological Physiology, University of Gent, Gent, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 2, February 1995, Pages 282–283, https://doi.org/10.1016/S0008-6363(95)90002-0 Published: 01 February 1995
The role of transforming growth factor beta in the generation of suppression: an interaction between CD8+ T and NK cells.
Authors: J D Gray, M Hirokawa, D A Horwitz
Journal: The Journal of Experimental Medicine (1994)

CD8+ T cells have suppressor effector functions, but the mechanisms involved in the generation of this activity are poorly understood. We report that natural killer (NK) cells have an important role in the acquisition of this function. CD8+ cells induce NK cells to produce transforming growth factor-beta (TGF-beta) which, in turn, stimulates CD8+ T cells to become suppressors of antibody production. Using a monocyte-dependent and -independent method to induce antibody production, we first observed that the addition of NK cells to CD8+ cells was required for optimal suppression. Next, we determined that the interaction of CD8+ T cells with NK cells resulted in a striking increase NK cell TGF-beta mRNA and its production. This cytokine appeared to be involved in the induction of T suppressor cell activity since: (a) anti-TGF-beta 1 completely abrogated the suppression of immunoglobulin G synthesis; (b) TGF-beta 1 could substitute for NK cells in inducing CD8+ T cells to develop suppressor activity; and (c) a short exposure of T cells to TGF-beta 1 in the absence of B cells was sufficient for the generation of suppressor activity by CD8+ T cells. Interferon gamma did not have this property. These studies provide strong evidence that in addition to its suppressive properties, TGF-beta is involved in the generation of CD8+ T suppressor effector cells. Because NK cell function is decreased in many autoimmune diseases, these cells may fail to interact properly with these individuals' CD8+ cells in generating suppressors of aggressive anti-self responses.
Definition, Prognostic Factors, Treatment, and Response Criteria of Adult T-Cell Leukemia-Lymphoma: A Proposal From an International Consensus Meeting
Authors: Kunihiro Tsukasaki, Olivier Hermine, Ali Bazarbachi, Lee Ratner, Juan Carlos Ramos, William Harrington, Deirdre O’Mahony, John E. Janik, Achiléa L. Bittencourt, Graham P. Taylor, Kazunari Yamaguchi, Atae Utsunomiya, Kensei Tobinai, Toshiki Watanabe
Journal: Journal of Clinical Oncology (2008)

Adult T-cell leukemia-lymphoma (ATL) is a distinct peripheral T-lymphocytic malignancy associated with a retrovirus designated human T-cell lymphotropic virus type I (HTLV-1). The diversity in clinical features and prognosis of patients with this disease has led to its subclassification into the following four categories: acute, lymphoma, chronic, and smoldering types. The chronic and smoldering subtypes are considered indolent and are usually managed with watchful waiting until disease progression, analogous to the management of some patients with chronic lymphoid leukemia (CLL) or other indolent histology lymphomas. Patients with aggressive ATL generally have a poor prognosis because of multidrug resistance of malignant cells, a large tumor burden with multiorgan failure, hypercalcemia, and/or frequent infectious complications as a result of a profound T-cell immunodeficiency. Under the sponsorship of the 13th International Conference on Human Retrovirology: HTLV, a group of ATL researchers joined to form a consensus statement based on established data to define prognostic factors, clinical subclassifications, and treatment strategies. A set of response criteria specific for ATL reflecting a combination of those for lymphoma and CLL was proposed. Clinical subclassification is useful but is limited because of the diverse prognosis among each subtype. Molecular abnormalities within the host genome, such as tumor suppressor genes, may account for these diversities. A treatment strategy based on the clinical subclassification and prognostic factors is suggested, including watchful waiting approach, chemotherapy, antiviral therapy, allogeneic hematopoietic stem-cell transplantation (alloHSCT), and targeted therapies.
Implementing a successful data-management framework: the UK10K managed access model
Authors: Dawn Muddyman, Carol Smee, Heather Griffin, Jane Kaye
Journal: Genome Medicine (2013)

This paper outlines the history behind open access principles and describes the development of a managed access data-sharing process for the UK10K Project, currently Britain's largest genomic sequencing consortium (2010 to 2013). Funded by the Wellcome Trust, the purpose of UK10K was two-fold: to investigate how low-frequency and rare genetic variants contribute to human disease, and to provide an enduring data resource for future research into human genetics. In this paper, we discuss the challenge of reconciling data-sharing principles with the practicalities of delivering a sequencing project of UK10K's scope and magnitude. We describe the development of a sustainable, easy-to-use managed access system that allowed rapid access to UK10K data, while protecting the interests of participants and data generators alike. Specifically, we focus in depth on the three key issues that emerge in the data pipeline: study recruitment, data release and data access.
Combination of three α‐globin gene loci deletions and hemoglobin new york results in a severe hemoglobin H syndrome
Authors: Vivian Chan, T. K. Chan, S. C. Tso, D. Todd
Journal: American Journal of Hematology (1987)

Abstract A Chinese patient with hemoglobin (Hb) H and Hb New York is described. Unlike classical Hb H disease, the additional β New York chain defect resulted in a more marked α β 3‐globin chain imbalance in this patient with only one α‐gene, accounting for her severe anemia (3.4‐6.8 g/dl) during the steady state.
Physical activity interventions for cancer survivors: Figure 1
Authors: M L Irwin
Journal: British Journal of Sports Medicine (2008)

Obesity and a sedentary lifestyle are highly prevalent in cancer survivors, and a growing number of publications have shown statistically and clinically significant associations between low levels of physical activity, obesity and cancer recurrence and death. Adoption and maintenance of physical activity is a difficult challenge for healthy adults, and is likely to be even more difficult after a cancer diagnosis. More effective strategies to increase physical activity in cancer survivors should be explored. The purpose of this paper is to (1) provide a rationale for physical activity interventions and programmes for cancer survivors, and (2) discuss successful approaches to adopting and maintaining physical activity to meet evidence based recommendations and ultimately improve cancer survival and overall survival. Since a majority of cancer survivors are not currently participating in recommended levels of physical activity, resulting in greater disease risk and health care costs, targeted exercise therapy has the potential to benefit a large number of cancer survivors. Cancer survivors should seek out the opportunities that exist towards being physically active, and oncologists should also become aware of the benefits of exercise, assist their patients by endorsing existing physical activity guidelines, and refer their patients to certified cancer exercise trainers.
Lineage and Morphogenetic Analysis of the Cardiac Valves
Authors: Frederik J. de Lange, Antoon F.M. Moorman, Robert H. Anderson, Jörg Männer, Alexandre T. Soufan, Corrie de Gier-de Vries, Michael D. Schneider, Sandra Webb, Maurice J.B. van den Hoff, Vincent M. Christoffels
Journal: Circulation Research (2004)

We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (αMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development.
Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium.
Authors: P Allavena, C Paganin, I Martin-Padura, G Peri, M Gaboli, E Dejana, P C Marchisio, A Mantovani
Journal: The Journal of Experimental Medicine (1991)

The present study was designed to define molecules and structures involved in the interaction of natural killer (NK) cells with the vascular endothelium in vitro. Resting and interleukin 2 (IL-2)-activated NK cells were studied for their capacity to adhere to resting and IL-1-treated human umbilical vein endothelial cells (EC). In the absence of stimuli, NK cells showed appreciable adhesion to EC, with levels of binding intermediate between polymorphs and monocytes. The binding ability was increased by pretreatment of NK cells with IL-2. Using the appropriate monoclonal antibody, the beta 2 leukocyte integrin CD18/CD11a was identified as the major adhesion pathway of NK cells to unstimulated EC. Activation of EC with IL-1 increased the binding of NK cells. In addition to the CD18-CD11a/intercellular adhesion molecule pathway, the interaction of resting or IL-2-activated NK cells to IL-1-activated EC involved the VLA-4 (alpha 4 beta 1)-vascular cell adhesion molecule 1 receptor/counter-receptor pair. No evidence for appreciable involvement of endothelial-leukocyte adhesion molecule was obtained. Often, NK cells interacted either with the culture substrate or with the EC surface via dot-shaped adhesion structures (podosomes) protruding from the ventral surface and consisting of a core of F-actin surrounded by a ring of vinculin and talin. The identification of molecules and microanatomical structures involved in the interaction of NK cells with EC may provide a better understanding of the regulation of NK cell recruitment from blood, their extravasation, and their migration to tissues.
Association of Smoking Status, Weight Change, and Incident Metabolic Syndrome in Men: A 3-Year Follow-Up Study
Authors: Byung Jin Kim, Bum Soo Kim, Ki Chul Sung, Jin Ho Kang, Man Ho Lee, Jung Ro Park
Journal: Diabetes Care (2009)

We investigated the incidence of the metabolic syndrome and assessed the effect of smoking status and weight change on incident metabolic syndrome.This study included 4,542 men without metabolic syndrome at baseline who were followed for an average of 3 years. Subjects were divided into four categories according to smoking status at baseline and at the 3-year follow-up.The overall incidence of metabolic syndrome was 10.6%: 8.0% in nonsmokers, 7.1% in new smokers, 17.1% in ex-smokers, and 13.9% in sustained smokers (P < 0.001). In a multivariate regression model, ex-smokers had significantly increased odds for incident metabolic syndrome with a mean 1.45 (95% CI 1.06-1.98) compared with sustained smokers. This was no longer significant after including weight change.Smoking cessation within 3 years may be a higher risk factor for incident metabolic syndrome than sustained smoking, indicating that weight control in ex-smokers is critical to attenuate the additional risk for incident metabolic syndrome.
Relationship Between Angiotensin-Converting Enzyme Gene Polymorphism and Body Composition, Functional Performance, and Blood Biomarkers in Advanced Cancer Patients
Authors: Antonio Vigano, Barbara Trutschnigg, Robert D. Kilgour, Nancy Hamel, Laura Hornby, Enriqueta Lucar, William Foulkes, Michel L. Tremblay, José A. Morais
Journal: Clinical Cancer Research (2009)

Nutritional and functional outcome measures have been shown to vary in patients with chronic diseases according to the polymorphic alleles of angiotensin-converting enzyme (ACE), but little is known about the associations between ACE gene polymorphism (ACEGP) and the components of body composition, strength, and selected blood markers in advanced cancer patients (ACP).Data were collected from an inception cohort of 172 newly diagnosed ACP with gastrointestinal and non-small cell lung cancer. ACEGP status was defined by the presence of one of the following three combinations of alleles: insertion/insertion, insertion/deletion, and deletion/deletion. Body composition measurements using Dual-energy X-ray Absorptiometry comprised of the following: total fat mass, percent body fat, lean body mass, and appendicular lean mass. Body mass index; handgrip force by Jamar dynamometry; subjective recording of nutrition and performance status as per patient-generated subjective global assessment; cell blood count and differential, serum albumin, ACE, and C-reactive protein were also recorded.Multiple regression analysis, controlling for gender, age, diagnosis, treatments (radio/chemo), survival, and medication use (ACE inhibitors, anti-inflammatories, statins) revealed the following significant (P </= 0.05) relationships in the insertion/deletion compared with insertion/insertion group: higher hemoglobin (Hb; beta, 6.39 g/dl; 95% confidence interval, 0.01-12.78), lower total fat mass (-5.78 kg; -11.62 to 0.07), percent body fat (-6.04%; -12.20 to 0.12), and lean body mass (-3.26 kg; -6.78 to 0.26). When comparing the DD to the II group, higher serum ACE (9.10; 1.96-16.25), Hb (6.25 g/dl; -0.63 to 13.12), and handgrip force by Jamar (6.85 lbs; 0.78-12.93) were found.Of the variables studied, ACEGP seems to be primarily associated with differences in body composition, Hb, and muscle strength in ACP. Further data are needed to determine the clinical effect of ACEGP in cancer cachexia.