tbuckley/cabot-search huggingface dataset:
Relation between Influenza Vaccination and Outpatient Visits, Hospitalization, and Mortality in Elderly Persons with Chronic Lung Disease
Authors: Kristin L. Nichol
Journal: Annals of Internal Medicine (1999)

Background: Influenza vaccine is underused in groups targeted for vaccination. Objective: To define the effects of influenza and the benefits of influenza vaccination in elderly persons with chronic lung disease. Design: Retrospective, multiseason cohort study. Setting: Large managed care organization. Patients: All elderly members of a managed care organization who had a previous diagnosis of chronic lung disease. Measurements: Outcomes in vaccinated and unvaccinated persons for the 1993-1994, 1994-1995, and 1995-1996 influenza seasons were compared after adjustment for baseline demographic and health characteristics. All data were obtained from administrative databases. Results: Vaccination rates were greater than 70% for each season. Among unvaccinated persons, hospitalization rates for pneumonia and influenza were twice as high in the influenza seasons as they were in the interim (noninfluenza) periods. Influenza vaccination was associated with fewer hospitalizations for pneumonia and influenza (adjusted risk ratio, 0.48 [95% CI, 0.28 to 0.82]) and with lower risk for death (adjusted odds ratio, 0.30 [CI, 0.21 to 0.43]) during the influenza seasons. It was also associated with fewer outpatient visits for pneumonia and influenza and for all respiratory conditions. Conclusions: For elderly persons with chronic lung disease, influenza is associated with significant adverse health effects and influenza vaccination is associated with substantial health benefits, including fewer outpatient visits, fewer hospitalizations, and fewer deaths. Health care providers should take advantage of all opportunities to immunize these high-risk patients.
Quantitative Appraisal of Treatment Options for IgA Nephropathy
Authors: Francis W. Ballardie
Journal: Journal of the American Society of Nephrology (2007)

IgA nephropathy has an impact on renal health care costs worldwide. The paucity of good clinical trials highlights the uncertainty in determining best treatment and for how long. Ongoing debate still raises questions on why opinions vary but may suggest that current data are not fully understood. The scale of benefit of immunosuppressive drugs in suppressing clinical nephritis or improving outcome is unmatched by use of renin-angiotensin inhibitors alone. By minimizing the use of immunosuppressive drugs, higher risk patients may hazard more ESRD. This review addresses how disparate views have formed, quantifying existing data, to give balance to recommendations.
Effective immunosuppressive therapy in a patient with primary pulmonary hypertension
Authors: F Bellotto, P Chiavacci, F Laveder, A Angelini, G Thiene, R Marcolongo
Journal: Thorax (1999)

The case history is described of a young woman who presented with primary pulmonary hypertension and non-specific inflammatory signs. The patient received prolonged immunosuppressive treatment with low dose methotrexate and prednisone without any vasodilator agent. After one year the pulmonary artery pressure fell from a mean value of 47 mm Hg to 30 mm Hg and there was a corresponding clinical response. This case suggests that, in patients with pulmonary hypertension of unknown origin, immunopathogenetic factors should be sought in order to consider the utility of immunosuppressive therapy.
Hepatic and Intestinal Drug Transporters: Prediction of Pharmacokinetic Effects Caused by Drug-Drug Interactions and Genetic Polymorphisms
Authors: Kenta Yoshida, Kazuya Maeda, Yuichi Sugiyama
Journal: The Annual Review of Pharmacology and Toxicology (2012)

Recent studies of membrane transporters have revealed their importance in determining the pharmacokinetics of transporter substrates. When drug-drug interactions (DDIs) or genetic polymorphisms (i.e., pharmacogenetics) affect the activities of transporters, the pharmacokinetics of transporter substrate drugs is altered; this alteration influences the substrate drugs' subsequent pharmacological or toxicological effects. In predicting these effects quantitatively from in vitro experimental results, we must first determine the contribution of each transporter to the overall elimination process. Furthermore, the accurate estimation of effective inhibitor concentrations at the site of interaction (e.g., intestinal lumen, extracellular and intracellular space of hepatocytes) is challenging. In predicting pharmacogenetic effects, the extrapolation from in vitro observations to in vivo outcomes (e.g., changes in intrinsic activities and/or expression levels) is still evolving. In this review, we describe the current status of, and difficulties inherent in, the accurate prediction of the altered pharmacokinetics caused by transporter-mediated DDIs and pharmacogenetics.
Effect of Cardiac Myosin Binding Protein-C on Mechanoenergetics in Mouse Myocardium
Authors: Bradley M. Palmer, Teruo Noguchi, Yuan Wang, John R. Heim, Norman R. Alpert, Patrick G. Burgon, Christine E. Seidman, J.G. Seidman, David W. Maughan, Martin M. LeWinter
Journal: Circulation Research (2004)

We examined the effect of cardiac myosin binding protein-C (cMyBP-C) on contractile efficiency in isovolumically contracting left ventricle (LV) and on internal viscosity and oscillatory work production in skinned myocardial strips. A 6-week diet of 0.15% 6- n -propyl-2-thiouracil (PTU) was fed to wild-type (+/+ PTU ) and homozygous-truncated cMyBP-C (t/t PTU ) mice starting at age ≈8 weeks and leading to a myosin heavy chain (MHC) isoform profile of 10% α-MHC and 90% β-MHC in both groups. Western blot analysis confirmed that cMyBP-C was present in the +/+ PTU and effectively absent in the t/t PTU . Total LV mechanical energy per beat was quantified as pressure-volume area (PVA). O 2 consumption (Vo 2 ) per beat was plotted against PVA at varying LV volumes. The reciprocal of the slope of the linear Vo 2 -PVA relation represents the contractile efficiency of converting O 2 to mechanical energy. Contractile efficiency was significantly enhanced in t/t PTU (26.1±2.6%) compared with +/+ PTU (17.1±1.6%). In skinned myocardial strips, maximum isometric tension was similar in t/t PTU (18.7±2.1 mN · mm −2 ) and +/+ PTU (21.9±4.0 mN · mm −2 ), but maximum oscillatory work induced by sinusoidal length perturbations occurred at higher frequencies in t/t PTU (7.31±1.17 Hz) compared with +/+ PTU (4.48±0.60 Hz) and was significantly more sensitive to phosphate concentration in the t/t PTU . Under rigor conditions, the internal viscous load was significantly lower in the t/t PTU compared with +/+ PTU , ie, ≈40% lower at 1 Hz. These results collectively suggest that contractile efficiency is enhanced in the t/t PTU , probably through a reduced loss of mechanical energy by a viscous load normally provided by cMyBP-C and through a gain of phosphate-dependent oscillatory work normally inhibited by cMyBP-C.
Activation and Signaling by the AMP-Activated Protein Kinase in Endothelial Cells
Authors: Beate Fisslthaler, Ingrid Fleming
Journal: Circulation Research (2009)

The AMP-activated protein kinase (AMPK) was initially identified as the kinase that phosphorylates the 3-hydroxy 3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme for cholesterol biosynthesis. As the name suggests, the AMPK is activated by increased intracellular concentrations of AMP, and is generally described as a “metabolite-sensing kinase” and when activated initiates steps to conserve cellular energy. Although there is a strong link between the activity of the AMPK and metabolic control in muscle cells, the activity of the AMPK in endothelial cells can be regulated by stimuli that affect cellular ATP levels, such as hypoxia as well as by fluid shear stress, Ca 2+ -elevating agonists, and hormones such as adiponectin. To date the AMPK in endothelial cells has been implicated in the regulation of fatty acid oxidation, small G protein activity and nitric oxide production as well as inflammation and angiogenesis. Moreover, there is evidence indicating that the activation of the AMPK may help to prevent the vascular complications associated with the metabolic syndrome.
The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.
Authors: P H Brodeur, G E Osman, J J Mackle, T M Lalor
Journal: The Journal of Experimental Medicine (1988)

We have constructed a panel of Abelson murine leukemia virus-transformed pre-B cells to study the organization of the mouse VH gene families. Based on the analyses of VH gene deletions on 51 chromosomes with VH gene rearrangements, we have inferred a map order of the Igh locus that holds for both the Igha and Ighb haplotypes. We show that members of each VH gene family are generally clustered, although three family clusters (VHS107, VH36-60, VGAM3.8) are dispersed in two or three subregions of the locus. Members of two VH gene families, VHQ52 and VH7183, are extensively interspersed and map within the same subregion. An examination of the distribution of VH group members (VH II, I, and III) within the locus suggests that two major duplications may, in part, explain the dispersed pattern of VH family clusters. The relationship of VH organization and functional expression is discussed in terms of position-dependent and complexity-driven models.
Breast Cancer Migration and Invasion Depend on Proteasome Degradation of Regulator of G-Protein Signaling 4
Authors: Yan Xie, Dennis W. Wolff, Taotao Wei, Bo Wang, Caishu Deng, Joseph K. Kirui, Haihong Jiang, Jianbing Qin, Peter W. Abel, Yaping Tu
Journal: Cancer Research (2009)

Abstract Aberrant signaling through G-protein coupled receptors promotes metastasis, the major cause of breast cancer death. We identified regulator of G-protein signaling 4 (RGS4) as a novel suppressor of breast cancer migration and invasion, important steps of metastatic cascades. By blocking signals initiated through Gi-coupled receptors, such as protease-activated receptor 1 and CXC chemokine receptor 4, RGS4 disrupted Rac1-dependent lamellipodia formation, a key step involved in cancer migration and invasion. RGS4 has GTPase-activating protein (GAP) activity, which inhibits G-protein coupled receptor signaling by deactivating G-proteins. An RGS4 GAP-deficient mutant failed to inhibit migration and invasion of breast cancer cells in both in vitro assays and a mouse xenograft model. Interestingly, both established breast cancer cell lines and human breast cancer specimens showed that the highest levels of RGS4 protein were expressed in normal breast epithelia and that RGS4 down-regulation by proteasome degradation is an index of breast cancer invasiveness. Proteasome blockade increased endogenous RGS4 protein to levels that markedly inhibit breast cancer cell migration and invasion, which was reversed by an RGS4-targeted short hairpin RNA. Our findings point to the existence of a mechanism for posttranslational regulation of RGS4 function, which may have important implications for the acquisition of a metastatic phenotype by breast cancer cells. Preventing degradation of RGS4 protein should attenuate aberrant signal inputs from multiple Gi-coupled receptors, thereby retarding the spread of breast cancer cells and making them targets for surgery, radiation, and immune treatment. [Cancer Res 2009;69(14):5743–51]
Gemcitabine(G)-Erlotinib(E) Versus Gemcitabine-Erlotinib-Capecitabine(C) in the First Line Treatment of Patients with Metastatic Pancreatic Cancer (MPC): Efficacy and Safety Results of a Phase IIB Randomized Study from Spanish TTD Collaborative Group
Authors: Benavides Manuel, Gallego Javier, Guillén-Ponce Carmen, Vera Ruth, Iranzo Vega, Alés Inmaculada, Arévalo Sara, Pisa Aleydis, Martin Marta, Salud Antonieta, Falcó Esther, Sáenz Alberto, Manzano Jose Luis, Pulido Gema, Martinez-Galán Joaquina, Pazo Roberto, López-López Carlos, García Teresa, Serra Olbia, M. Fernández-Parra Eva, Irigoyen Antonio, Aranda Enrique
Journal: Annals of Oncology (2014)
Membrane interactions influence the peptide binding behavior of DR1.
Authors: M A Sherman, H A Runnels, J C Moore, L J Stern, P E Jensen
Journal: The Journal of Experimental Medicine (1994)

We analyzed the binding of an influenza matrix protein-derived peptide, MAT(17-31), to cell surface and purified DR1. The pH dependence of peptide binding was dramatically influenced by the membrane environment. Cell surface binding was enhanced at low pH, with little or no binding detected at neutral pH and optimal binding at pH 4. By contrast, hydrogen ion concentration had minimal effect on peptide binding to purified DR1. Exposure to low pH in the absence of peptide did not affect the peptide binding capacity of cell-associated DR1. Purified DR1 was stable at low pH, excluding the possibility that enhanced binding was offset by a competing denaturation event at low pH. The striking effect of pH on peptide binding characteristic of cell surface DR1 was recovered after reconstitution of purified DR1 in B cell membranes by detergent dialysis. This behavior was partially recovered by reconstitution of full-length, but not truncated DR1 in vesicles containing purified lipid. Our results demonstrate that interactions involving membrane components influence the peptide-binding behavior of DR1.
ECONOMIC CAUSES AND CONSEQUENCES OF OBESITY
Authors: Eric A. Finkelstein, Christopher J. Ruhm, Katherine M. Kosa
Journal: Annual Review of Public Health (2004)

Obesity is not only a health but also an economic phenomenon. This chapter (a) examines underlying economic causes, such as technological advancements, behind the obesity epidemic; (b) describes economic consequences of obesity, including increasing obesity-related medical expenditures; and (c) discusses the role of government in combating the obesity epidemic. Because of the high costs of obesity, and the fact that the majority of these costs are financed by taxpayers, there is a clear motivation for government to try to reduce these costs. However, because obesity may result from poor information and addictive behavior and/or as a result of living in an increasingly obesogenic environment, interventions will need to be multifaceted to ensure the best chance of success.
Sparing effect of hemiplegia on scleroderma.
Authors: S Sethi, W Sequeira
Journal: Annals of the Rheumatic Diseases (1990)

The paretic limb is spared in patients who develop rheumatic diseases after a hemiplegic stroke. This has been described previously in rheumatoid arthritis, gout, and osteoarthritis. A similar presentation in a case of scleroderma is described in this report. Scleroderma skin changes are absent in the completely paretic limb and were markedly reduced in the weak left leg. Inflammation may be modified either by neuropeptides or by an anatomical neurological lesion and this may explain the phenomenon.
Targeting the c-Met Signaling Pathway in Cancer
Authors: Benedetta Peruzzi, Donald P. Bottaro
Journal: Clinical Cancer Research (2006)

On binding to the cell surface receptor tyrosine kinase (TK) known as c-Met, hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of cellular targets including, epithelial and endothelial cells, hematopoietic cells, neurons, melanocytes, and hepatocytes. These pleiotropic actions are fundamentally important during development, homeostasis, and tissue regeneration. HGF signaling also contributes to oncogenesis and tumor progression in several human cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis. Our present understanding of c-Met oncogenic signaling supports at least three avenues of pathway selective anticancer drug development: antagonism of ligand/receptor interaction, inhibition of TK catalytic activity, and blockade of intracellular receptor/effector interactions. Potent and selective preclinical drug candidates have been developed using all three strategies, and human clinical trials in two of the three areas are now under way.
Mercury-induced autoreactive anti-class II T cell line protects from experimental autoimmune encephalomyelitis by the bias of CD8+ antiergotypic cells in Lewis rats.
Authors: M Castedo, L Pelletier, J Rossert, R Pasquier, H Villarroya, P Druet
Journal: The Journal of Experimental Medicine (1993)

Brown-Norway (BN) rats injected with HgCl2 develop a systemic autoimmune disease associated with a polyclonal B cell activation, due to autoreactive T cells specific for self-class II molecules, while Lewis (LEW) rats injected with HgCl2 do not exhibit autoimmunity and develop a non-antigen-specific, CD8-mediated immunosuppression assessed by a depression of T cell functions, and a protection against experimental autoimmune encephalomyelitis (EAE). Resistance to HgCl2-induced autoimmunity is not due to these suppressor cells since treatment with an anti-CD8 monoclonal antibody (mAb) did not allow autoimmunity to appear. The absence of autoimmunity in this strain could result from the absence of autoreactive T cells, or from quantitative or qualitative differences of these cells between susceptible and resistant strains. In the present study, we show that CD4+ anti-class II T cells are present in HgCl2-injected LEW rats and are as frequent as in BN rats when assessed by limiting dilution analysis. LEW CD4+ autoreactive T cell lines were derived. They proliferated in the presence of normal class II-bearing cells, secreted interleukin 2, and did not induce B cells to produce immunoglobulins. Transfer of one of these lines, LEW Hg A, into normal LEW rats led to the appearance of CD8+ cells responsible for a non-antigen-specific immunosuppression that induced complete protection from EAE. Immunosuppression was abrogated after treatment with an anti-CD8 mAb. In vitro, CD8+ cells from rats injected with the LEW Hg A T cell line proliferated in the presence of activated T cells whatever their origin. We conclude that HgCl2 induces CD4+ autoreactive T cells that proliferate in the presence of class II+ cells in susceptible BN as well as in resistant LEW rats. But while these cells collaborate with B cells to produce autoantibodies in BN rats, they initiate in LEW rats a suppressor circuit involving antiergotypic CD8+ suppressor cells.
Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
Authors: Anna Helgadottir, Solveig Gretarsdottir, Gudmar Thorleifsson, Hilma Holm, Riyaz S. Patel, Thorarinn Gudnason, Gregory T. Jones, Andre M. van Rij, Danny J. Eapen, Annette F. Baas, David-Alexandre Tregouet, Pierre-Emmanuel Morange, Joseph Emmerich, Bengt Lindblad, Anders Gottsäter, Lambertus A. Kiemeny, Jes S. Lindholt, Natzi Sakalihasan, Robert E. Ferrell, David J. Carey, James R. Elmore, Philip S. Tsao, Niels Grarup, Torben Jørgensen, Daniel R. Witte, Torben Hansen, Oluf Pedersen, Roberto Pola, Eleonora Gaetani, Hulda B. Magnadottir, Cisca Wijmenga, Gerard Tromp, Antti Ronkainen, Ynte M. Ruigrok, Jan D. Blankensteijn, Thomas Mueller, Philip S. Wells, Javier Corral, Jose Manuel Soria, Juan Carlos Souto, John F. Peden, Shapour Jalilzadeh, Bongani M. Mayosi, Bernard Keavney, Rona J. Strawbridge, Maria Sabater-Lleal, Karl Gertow, Damiano Baldassarre, Kristiina Nyyssönen, Rainer Rauramaa, Andries J. Smit, Elmo Mannarino, Philippe Giral, Elena Tremoli, Ulf de Faire, Steve E. Humphries, Anders Hamsten, Vilhelmina Haraldsdottir, Isleifur Olafsson, Magnus K. Magnusson, Nilesh J. Samani, Allan I. Levey, Hugh S. Markus, Konstantinos Kostulas, Martin Dichgans, Klaus Berger, Gregor Kuhlenbäumer, E. Bernd Ringelstein, Monika Stoll, Udo Seedorf, Peter M. Rothwell, Janet T. Powell, Helena Kuivaniemi, Pall T. Onundarson, Einar Valdimarsson, Stefan E. Matthiasson, Daniel F. Gudbjartsson, Guðmundur Thorgeirsson, Arshed A. Quyyumi, Hugh Watkins, Martin Farrall, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Journal of the American College of Cardiology (2012)
Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study
Authors: H Cabello, A Torres, R Celis, M El-Ebiary, J Puig de la Bellacasa, A Xaubet, J Gonzalez, C Agusti, N Soler
Journal: European Respiratory Journal (1997)

In contrast to the healthy population, distal airway bacterial colonization may occur in patients with chronic lung diseases, who often have altered pulmonary defences. However, the information dealing with this issue is insufficient and is based mainly on nonspecific samples, such as sputum cultures. Using quantitative cultures of bronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples, we studied the bacterial colonization of distal airways in 16 healthy subjects, 33 patients with bronchogenic carcinoma, 18 with chronic obstructive pulmonary disease (COPD), 17 with bronchiectasis, and 32 with a long-term tracheostomy due to laryngeal carcinoma. All patients were without exacerbation, and free from antibiotic treatment at least 1 month before the study protocol. Thresholds for quantitative cultures to define colonization were &gt; or = 10(2) colony-forming units (cfu) x mL(-1) for PSB and &gt; or = 10(3) cfu x mL(-1) for BAL. Only one healthy subject was colonized by a potential pathogenic microorganism (PPM) (Staphylococcus aureus 4x10(2) cfu x mL(-1) in a PSB culture). Colonization was observed in 14 (42%) bronchogenic carcinoma patients (19 non-PPMs, and 10 PPMs); in 15 (83%) COPD patients (22 non-PPMs and 7 PPMs); in 15 (88%) bronchiectasis patients (20 non-PPMs and 13 PPMs); and in 15 (47%) long-term tracheostomy patients (5 non-PPMs and 13 PPMs). The two most frequent non-PPMs isolated in all groups studied were Streptococcus viridans and Neisseria spp. Haemophilus spp., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were the most frequent PPMs isolated in bronchogenic carcinoma, COPD, bronchiectasis and long-term tracheostomized patients, respectively. Pseudomonas aeruginosa colonization was infrequent in all the groups. Our results show that distal airway bacterial colonization is a frequent feature in stable patients with chronic lung diseases and also in patients with long-term tracheostomy. However, the pattern of colonization differs among groups studied. The knowledge of different colonization patterns may be important for future antibiotic prophylactic strategies and for the empirical antibiotic regimens when exacerbations occur in these patients.
Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation
Authors: Joy Kahn, Tamara Byk, Lottie Jansson-Sjostrand, Isabelle Petit, Shoham Shivtiel, Arnon Nagler, Izhar Hardan, Varda Deutsch, Zulma Gazit, Dan Gazit, Stefan Karlsson, Tsvee Lapidot
Journal: Blood (2003)