tbuckley/cabot-search huggingface dataset:
Molecular and mechanical synergy: cross-talk between integrins and growth factor receptors*1
Authors: R ROSS
Journal: Cardiovascular Research (2004)

The full repertoire of molecules and mechanisms which lead to cardiac hypertrophy are poorly understood. Many studies over the last several decades have shown how various growth factors are involved in the hypertrophic response. It has also been intuitively obvious that mechanical mechanisms which impose hemodynamic loads on the working myocardium must also be involved in this process. Integrins are cell adhesion receptors that are potent bi-directional signaling molecules. They are cellular mechanoreceptors in many cells and are clearly one of the molecules which orchestrate mechano-biochemical coupling in the heart. In recent years they too have been shown to be involved in the hypertrophic response pathway. This review will detail background information on integrins in general, discuss integrins in the myocardium and illustrate how integrin and growth factor signaling pathways might combinatorially function in the heart.
Pathway inhibition: emerging molecular targets for treating glioblastoma
Authors: W. Wick, M. Weller, M. Weiler, T. Batchelor, A. W. K. Yung, M. Platten
Journal: Neuro-Oncology (2011)

Insights into the molecular pathogenesis of glioblastoma have not yet resulted in relevant clinical improvement. With standard therapy, which consists of surgical resection with concomitant temozolomide in addition to radiotherapy followed by adjuvant temozolomide, the median duration of survival is 12–14 months. Therefore, the identification of novel molecular targets and inhibitory agents has become a focus of research for glioblastoma treatment. Recent results of bevacizumab may represent a proof of principle that treatment with targeted agents can result in clinical benefits for patients with glioblastoma. This review discusses limitations in the existing therapy for glioblastoma and provides an overview of current efforts to identify molecular targets using large-scale screening of glioblastoma cell lines and tumor samples. We discuss preclinical and clinical data for several novel molecular targets, including growth factor receptors, phosphatidylinositol-3 kinase, SRC-family kinases, integrins, and CD95 ligand and agents that inhibit these targets, including erlotinib, enzastaurin, dasatinib, sorafenib, cilengitide, AMG102, and APG101. By combining advances in tumor screening with novel targeted therapies, it is hoped that new treatment options will emerge for this challenging tumor type.
Aspirin-Triggered, Cyclooxygenase-2–Dependent Lipoxin Synthesis Modulates Vascular Tone
Authors: Pierre-Yves von der Weid, Morley D. Hollenberg, Stefano Fiorucci, John L. Wallace
Journal: Circulation (2004)

Aspirin-triggered production of 15-(R)-epilipoxin A(4) (ATL) has been shown to exert potent antiinflammatory effects and gastric-protective effects, but little is known of its actions on the vasculature. In the present study, we have assessed the contribution of ATL to changes in vascular tone induced by aspirin and have examined the role of nitric oxide (NO) as a mediator of such effects.Intravenous administration of lipoxin A(4) resulted in a short-lived (3 to 4 minutes) reduction in blood pressure (BP; approximately 13 mm Hg at 2.5 microg/kg). Aspirin administered alone resulted in a significant increase in serum ATL and an increase in BP of approximately 10 mm Hg. When ATL synthesis was inhibited by pretreatment with a selective cyclooxygenase-2 inhibitor (celecoxib) or a 5-lipoxygenase inhibitor (zileuton), the aspirin-induced increase in BP was significantly augmented. These agents alone did not affect BP. A lipoxin receptor antagonist, Boc2, also increased the pressor effects of aspirin. Moreover, immunodepletion of neutrophils, a major source of 5-lipoxygenase, resulted in a significant reduction of ATL formation and augmented aspirin's pressor effects. Studies of rat aortic and mesenteric artery ring segments confirmed the vasorelaxant effects of lipoxin A(4) and showed them to be endothelium dependent.Aspirin-triggered lipoxin synthesis can modulate vascular tone, possibly contributing to changes in regional blood flow during inflammatory reactions, and to the modulation of systemic BP.
Epidemiology of Diabetes Among Arab Americans
Authors: Linda A. Jaber, Morton B. Brown, Adnan Hammad, Sandra N. Nowak, Qian Zhu, Anisa Ghafoor, William H. Herman
Journal: Diabetes Care (2003)

To examine the prevalence of diabetes and glucose intolerance by age and sex in the Arab-American community of Dearborn, Michigan.Participants were randomly selected adult Arab Americans, 20-75 years of age, from randomly selected households in Dearborn, Michigan. Demographic and anthropometric data were recorded. Glucose tolerance was assessed with 2-h 75-g oral glucose tolerance tests and classified according to 1997 American Diabetes Association and 1998 World Health Organization criteria.A total of 626 eligible adults were selected, and 542 participated (87% response rate). Because prevalence increases with age and the overall response rate for women (328/352; 93%) was higher than that for men (214/274; 78%), prevalence rates were adjusted for age and sex. The overall prevalence of diabetes was 15.5% (95% CI 12.2-18.7%) in women and 20.1% (15.0-25.2%) in men (P = 0.13). The prevalence of previously diagnosed diabetes was similar to that of undiagnosed diabetes. Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) were present in 16.8% (12.8-20.8%) of women and 29.7% (23.4-35.9%) of men (P = 0.0007). The combined rates of glucose intolerance (diabetes, IGT, and IFG) were 32.3% (27.8-36.7%) for women and 49.8% (43.1-56.4%) for men (P < 0.0001). Among younger adults, the prevalence in men was higher than that in women. As expected, subjects with diabetes or IGT/IFG were older and had greater BMI and waist-to-hip ratios than subjects with normal glucose tolerance.The prevalence of diabetes and glucose intolerance is extremely high among adult Arab Americans in Michigan and represents a major clinical and public health problem. Community-based intervention programs to prevent and treat diabetes are urgently needed.
Urokinase in the treatment of childhood empyema
Authors: S C Sit
Journal: Thorax (2003)

Thomson et al reported the first double blind placebo controlled study of intrapleural urokinase for the treatment of childhood empyema.1 They found a statistically significant reduction in hospital stay in the treatment group and concluded that “urokinase is a successful adjunct to the management of parapneumonic empyema”.

The primary management of childhood empyema is controversial with some groups advocating open decortication.2 However, because of reports of wound infection, air leaks and bleeding in open decortication, there has been an increase in the potential for video assisted thorascopic surgery (VATS) as primary treatment for childhood empyema.3 We have recently reported our experience in 21 …
Endomyocardial fibrosis in Behcet's disease
Authors: D. L. T. Huong, B. Wechsler, T. Papo, D. de Zuttere, O. Bletry, A. Hernigou, A. Delcourt, P. Godeau, J.-C. Piette
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To report on four patients with Behçet's disease associated with endomyocardial fibrosis involving the right or the left ventricle. <h3>METHODS</h3> Charts of more than 350 patients with Behçet's disease were reviewed. Endomyocardial fibrosis was confirmed because of cardiac failure in three patients and incidentally discovered by histological examination of an operative specimen in one patient. Echocardiography displayed bright echogen endocardium. Angiocardiography showed a reduced ventricular size. Electron beam computed tomography demonstrated a lowdense area involving the endocardium. Magnetic resonance imaging showed a mass of intermediate intensity on T1 weighted images. Diagnosis of endomyocardial fibrosis was based on histological study of a biopsy specimen in one patient and of an operative specimen in three. <h3>RESULTS</h3> Six other similar cases of endomyocardial fibrosis complicating Behçet's disease were previously reported in the medical literature. Endomyocardial fibrosis predominantly involved the right ventricle. It can be considered a feature of Behçet's disease because: (a) no other cause was discovered; (b) arteritis, valvulopathy, and intraventricular thrombus were closely linked, and (c) all patients with endomyocardial fibrosis had vasculo-Behçet pattern. <h3>CONCLUSION</h3> Endomyocardial fibrosis may be the sequelae of vasculitis involving endocardium or myocardium, or both and complicated with intraventricular thrombosis. Behçet's disease should be added to the list of causes of endomyocardial fibrosis.
Clinical effect of Diskus dry-powder inhaler at low and high inspiratory flow-rates in asthmatic children
Authors: KG Nielsen, IL Auk, K Bojsen, M Ifversen, B Klug, H Bisgaard
Journal: European Respiratory Journal (1998)

In vitro studies with the Diskus inhaler at low and high flow rates show consistent doses of drug as fine particles &lt;4.7 microm. The present study was designed to ascertain whether this in vitro flow independency translates into flow-independent clinical effect when the device is used by patients at low (30 L x min[-1]) and high (90 L x min[-1]) flow rates. A pilot study in 129 children aged 3-10 yrs demonstrated that 99% of children of 3 yrs and above can generate a flow &gt; or = 30 L x min(-1) through the device, while 26% performed &gt; or = 90 L x min(-1). Eighteen children aged 8-15 yrs with exercise induced asthma inhaled placebo or salmeterol 50 microg at either 30 L x min(-1) or 90 L x min(-1). Exercise challenges were carried out 1 h and 12 h after dosing. The maximum percentage fall in forced expiratory volume in one second (FEVI) after exercise 12 h after treatment was significantly less after salmeterol at either flow rates as compared to placebo. There was no significant difference in the protection from salmeterol on the day of low-flow inhalation versus the day of high-flow inhalation. Consistent in vitro fine particle dosing from the Diskus inhaler translates into a consistent clinical effect at low and high flow rates in children.
Quantitative culture of HIV-1 from bronchoalveolar lavage cells.
Authors: P Pinkston, N Pelletier, C Arena, J Schock, R Garland, R M Rose
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Determination of the infectious virus burden at the organ level is critical for understanding the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection. To evaluate the burden of HIV-1 in the lung, quantitative cultures were performed on bronchoalveolar lavage (BAL) cells from 11 HIV-1 seropositive subjects without respiratory infections and compared with peripheral blood mononuclear cells (PBMC) obtained from the same subjects. Fifty percent (50%) of subjects had positive BAL cell cultures while 82% had positive PBMC cultures. There was much less virus cultured from BAL cells than from PBMCs, whether using phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL) targets (p < 0.05) or adherent monocyte targets (p < 0.02). There was no significant difference between the HIV-1 titers obtained for BAL cells whether using PHA-stimulated PBL or adherent monocyte targets (p = 0.13). These studies demonstrate that BAL cell cultures for HIV-1 in subjects without respiratory infections are less frequently positive than PBMC cultures, that less virus can be recovered from BAL cells than from PBMC, and that HIV-1 isolates from BAL cells replicate in both PHA-stimulated PBL targets and adherent monocyte targets. Quantitative assessment of virus burden in the lung is important for future studies of HIV-1 pathogenesis and for evaluating potential antiretroviral therapies aimed at altering the natural history of organ dysfunction associated with retroviral replication.
Recent development in the design of sialyltransferase inhibitors
Authors: Xiaofang Wang, Li‐He Zhang, Xin‐Shan Ye
Journal: Medicinal Research Reviews (2002)

Abstract Sialylation at the non‐reducing end of glycoconjugates is an important biological process in cellular recognitions, tumor metastases, and immune responses, which are mediated by a family of enzymes known as sialyltransferases. Inhibition of sialyltransferases may prove useful in elucidating the biological functions of sialylation and may have therapeutic applications. This review summarizes the recent development in this field with particular focus on the strategies used for the design of carbohydrate mimetics and the structure‐activity relationships of substrate‐based sialyltransferase inhibitors. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 1, 32–47, 2003; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/med.10030
Indigenous Health and Socioeconomic Status in India
Authors: S. V Subramanian, George Davey Smith, Malavika Subramanyam
Journal: PLoS Medicine (2006)

Systematic evidence on the patterns of health deprivation among indigenous peoples remains scant in developing countries. We investigate the inequalities in mortality and substance use between indigenous and non-indigenous, and within indigenous, groups in India, with an aim to establishing the relative contribution of socioeconomic status in generating health inequalities.Cross-sectional population-based data were obtained from the 1998-1999 Indian National Family Health Survey. Mortality, smoking, chewing tobacco use, and alcohol use were four separate binary outcomes in our analysis. Indigenous status in the context of India was operationalized through the Indian government category of scheduled tribes, or Adivasis, which refers to people living in tribal communities characterized by distinctive social, cultural, historical, and geographical circumstances.Indigenous groups experience excess mortality compared to non-indigenous groups, even after adjusting for economic standard of living (odds ratio 1.22; 95% confidence interval 1.13-1.30). They are also more likely to smoke and (especially) drink alcohol, but the prevalence of chewing tobacco is not substantially different between indigenous and non-indigenous groups. There are substantial health variations within indigenous groups, such that indigenous peoples in the bottom quintile of the indigenous-peoples-specific standard of living index have an odds ratio for mortality of 1.61 (95% confidence interval 1.33-1.95) compared to indigenous peoples in the top fifth of the wealth distribution. Smoking, drinking alcohol, and chewing tobacco also show graded associations with socioeconomic status within indigenous groups.Socioeconomic status differentials substantially account for the health inequalities between indigenous and non-indigenous groups in India. However, a strong socioeconomic gradient in health is also evident within indigenous populations, reiterating the overall importance of socioeconomic status for reducing population-level health disparities, regardless of indigeneity.
Selective modification of a private I-A allo-stimulating determinant(s) upon association of antigen with an antigen-presenting cell.
Authors: K L Rock, B Benacerraf
Journal: The Journal of Experimental Medicine (1984)

A large panel of alloreactive, interleukin 2 (IL-2)-producing T cell hybridomas was constructed from B10 alpha BALB/c primary mixed lymphocyte cultures (MLC). Functional hybrids had specificity for either I-Ad or I-Ed. These cells were used to probe determinants on Ia molecules in an attempt to detect molecular association between a nominal antigen and an Ia molecule on an antigen-presenting cell (APC). The response of a small number of these clones was significantly blocked by the addition of the Ir gene-controlled copolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) to culture. A comparison of the inhibited and uninhibited hybrids revealed an identical dose response curve. Further, both types of hybrids were activated by the same stimulator cell and frequently recognized the identical Ia molecule on that cell. Nevertheless, the inhibitory effect of GAT was localized to the stimulator cell and not to the T cell hybrids. All of the hybrids whose stimulation was blocked had specificity for the I-A molecule, which is the gene product known to control and restrict responsiveness to GAT. Further, only GT, but not a number of other related antigens, was also specifically inhibitory, which correlates with the known associational specificity of these antigens on an APC. Finally, the same stimulator cell could be shown to coordinately lose an allostimulatory determinant(s), while it was gaining an I-Ad plus GAT determinant(s). The implications of these findings on the nature of antigen-Ia association and on the role of polymorphic Ia determinants are discussed.
Molecular Analysis of Single Circulating Tumor Cells (CTCS) Isolated from Metastatic Breast Cancer (MBC) Patients (PTS)
Authors: M. Pestrin, F. Galardi, F. Salvianti, F. De Luca, S. Bessi, G. Capaccioli, A. Di Leo, A. Giannini, P. Pinzani, M. Pazzagli
Journal: Annals of Oncology (2013)
The NHS at 60: the next 60 years
Authors: Alan Maynard, Karen Bloor
Journal: Journal of the Royal Society of Medicine (2008)

At its introduction, the National Health Service was described by the Secretary of State for Health, Aneurin Bevan, as ‘the biggest single experiment in social service that the world has ever seen undertaken’.1 The 1946 NHS Act had ambitious objectives: 

‘The Bill imposes no limits on availability – e.g. limitations based on financial means, age, sex, employment or vocation, area of residence or insurance qualification… The Bill places a general duty upon the Minister of Health to promote a comprehensive health service for the improvement of the physical and mental health of the people of England and Wales, and for the prevention, diagnosis and treatment of illness.’2



Through funding largely from taxation, the government sought to provide a secure financial foundation for health services in Britain, avoiding reliance on charity, which Bevan described as ‘repugnant to a civilised community’.3 The service aimed to provide care for the whole population, free at the point of use.

Despite contentious debate around its creation and early concerns, the NHS quickly became embedded in British society. It has amassed a consensus of public and political support that is perhaps unique. Margaret Thatcher stated that she ‘always regarded the NHS and its basic principles as a fixed point in our policies’.4 Successive governments, while reforming structures of delivery, have all retained a system where care is provided ‘based on need, not ability to pay’.5

This apparent political consensus conceals a number of persistent debates, which are likely to continue to dominate NHS policy making over the next sixty years.
<i>O</i> -Linked β- <i>N</i> -Acetylglucosamine Transferase Directs Cell Proliferation in Idiopathic Pulmonary Arterial Hypertension
Authors: Jarrod W. Barnes, Liping Tian, Gustavo A. Heresi, Carol F. Farver, Kewal Asosingh, Suzy A. A. Comhair, Kulwant S. Aulak, Raed A. Dweik
Journal: Circulation (2015)

Idiopathic pulmonary arterial hypertension (IPAH) is a cardiopulmonary disease characterized by cellular proliferation and vascular remodeling. A more recently recognized characteristic of the disease is the dysregulation of glucose metabolism. The primary link between altered glucose metabolism and cell proliferation in IPAH has not been elucidated. We aimed to determine the relationship between glucose metabolism and smooth muscle cell proliferation in IPAH.Human IPAH and control patient lung tissues and pulmonary artery smooth muscle cells (PASMCs) were used to analyze a specific pathway of glucose metabolism, the hexosamine biosynthetic pathway. We measured the levels of O-linked β-N-acetylglucosamine modification, O-linked β-N-acetylglucosamine transferase (OGT), and O-linked β-N-acetylglucosamine hydrolase in control and IPAH cells and tissues. Our data suggest that the activation of the hexosamine biosynthetic pathway directly increased OGT levels and activity, triggering changes in glycosylation and PASMC proliferation. Partial knockdown of OGT in IPAH PASMCs resulted in reduced global O-linked β-N-acetylglucosamine modification levels and abrogated PASMC proliferation. The increased proliferation observed in IPAH PASMCs was directly impacted by proteolytic activation of the cell cycle regulator, host cell factor-1.Our data demonstrate that hexosamine biosynthetic pathway flux is increased in IPAH and drives OGT-facilitated PASMC proliferation through specific proteolysis and direct activation of host cell factor-1. These findings establish a novel regulatory role for OGT in IPAH, shed a new light on our understanding of the disease pathobiology, and provide opportunities to design novel therapeutic strategies for IPAH.
THE PRESERVATION OF LIVING RED BLOOD CELLS IN VITRO
Authors: Peyton Rous, J. R. Turner
Journal: The Journal of Experimental Medicine (1916)

In order to determine the availability for functional uses of red cells kept in vitro by our methods, transfusion experiments have been carried out with rabbits by which a large part of their blood was replaced with kept rabbit cells suspended in Locke's solution. It has been found that erythrocytes preserved in mixtures of blood, sodium citrate, saccharose, and water for 14 days, and used to replace normal blood, will remain in circulation and function so well that the animal shows no disturbance, and the blood count, hemoglobin, and percentage of reticulated red cells remain unvaried. Cells kept for longer periods, though intact and apparently unchanged when transfused, soon leave the circulation. Animals in which this disappearance of cells is taking place on a large scale, remain healthy save for the progressing anemia. The experiments prove that, in the exsanguinated rabbit at least, transfusions of cells kept for a long time in vitro may be used to replace the blood lost, and that when the cells have been kept too long but are still intact they are disposed of without harm. The indications are that kept human cells could be profitably employed in the same way.