tbuckley/cabot-search huggingface dataset:
Recombination within the HLA-D region. Correlation of molecular genotyping with functional data.
Authors: M A Robinson, E O Long, A H Johnson, R J Hartzman, B Mach, T J Kindt
Journal: The Journal of Experimental Medicine (1984)

Molecular genotyping of the HLA-D/DR region in a family correlated with serologic and cellular typing data. It was further possible to predict a subtle difference in SB region-related functions from such molecular studies. A family that included an individual who inherited an HLA haplotype with a paternal recombination between HLA-B and the HLA-D/DR region was identified by classic HLA typing techniques. Segregation of HLA-D/DR region genes in this family was studied by Southern blot analysis using cDNA probes for DR alpha, DR beta, DC alpha, DC beta, and SB beta. Restriction enzyme fragment polymorphisms observed for every gene tested were in concordance with assigned HLA haplotypes (including the individual known to have inherited a paternal recombinant haplotype) with one exception: two HLA identical siblings were observed to have different SB beta restriction fragment patterns. Further testing revealed that one individual inherited a maternal HLA haplotype recombinant between the HLA-D/DR region and SB beta. Although both maternal SB alleles typed as SB4, allelic differences could be detected cellularly by primed lymphocytes and by the differential expression of a class II cell surface antigen using monoclonal antibody. Therefore, predicted and nonpredicted recombinant haplotypes were detected in a family by molecular genotyping.
Use of ruxolitinib to successfully treat chronic mucocutaneous candidiasis caused by gain-of-function signal transducer and activator of transcription 1 (STAT1) mutation
Authors: Eleanor Higgins, Tariq Al Shehri, Maeve A McAleer, Niall Conlon, Conleth Feighery, Desa Lilic, Alan D Irvine
Journal: Journal of Allergy and Clinical Immunology (2015)
Reliability and Validity of DSM-IV Axis V
Authors: Mark J. Hilsenroth, Steven J. Ackerman, Matthew D. Blagys, Becky D. Baumann, Matthew R. Baity, Steven R. Smith, Jennifer L. Price, Candy L. Smith, Tracy L. Heindselman, Mollie K. Mount, Daniel J. Holdwick
Journal: American Journal of Psychiatry (2000)

The authors investigated the reliability and convergent and discriminant validity of the DSM-IV Global Assessment of Functioning Scale and two experimental DSM-IV axis V global rating scales, the Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale.Forty-four patients admitted to a university-based outpatient community clinic were rated by trained clinicians on the three DSM-IV axis V scales. Patients also completed self-report measures of DSM-IV symptoms as well as measures of relational, social, and occupational functioning.The Global Assessment of Functioning Scale, Global Assessment of Relational Functioning Scale, and Social and Occupational Functioning Assessment Scale all exhibited very high levels of interrater reliability. Factor analysis revealed that the Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale are each more related to the Global Assessment of Functioning Scale individually than they are to each other. The Global Assessment of Functioning Scale was significantly related to concurrent patient responses on the SCL-90-R global severity index. The Social and Occupational Functioning Assessment Scale was significantly related to concurrent patient responses on the SCL-90-R global severity index and to a greater degree with both the Social Adjustment Scale global score and the Inventory of Interpersonal Problems total score. Although the Global Assessment of Relational Functioning Scale was not significantly related to any of the three self-report measures, it was related to the presence of clinician-rated axis II pathology.The three axis V scales can be scored reliably. The Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale evaluate different constructs. These findings support the validity of the Global Assessment of Functioning Scale as a scale of global psychopathology; the Social and Occupational Functioning Assessment Scale as a measure of problems in social, occupational, and interpersonal functioning; and the Global Assessment of Relational Functioning Scale as an index of personality pathology. The authors discuss further refinement and use of the three axis V measures in treatment research.
Bacillary Angiomatosis and Bacillary Splenitis in Immunocompetent Adults
Authors: Jordan W. Tappero
Journal: Annals of Internal Medicine (1993)

Bacillary angiomatosis and bacillary peliosis have been described in patients with human immunodeficiency virus (HIV) infection and drug-induced immunosuppression. Patients with these vascular lesions in the absence of profound immunodeficiency have not been well characterized. We studied five patients with histologically confirmed bacillary angiomatosis or bacillary splenitis without clinical immunodeficiency. Studies to detect HIV infection, immunologic defects, and presence of Rochalimaea species DNA in infected tissues were done. Cell cultures were negative for HIV-1 replication, and HIV-1 DNA was not detected. Results of lymphocyte subsets and activation, neutrophil oxidative burst, skin testing to mumps antigen, and assays for quantitative immunoglobulins and complement were normal. DNA amplification and sequencing confirmed infection by Rochalimaea henselae, even in tissue showing bacillary splenitis without peliosis. Bacillary angiomatosis and bacillary splenitis may occur in the absence of demonstrable immunodeficiency. On the basis of the therapeutic response of these five patients, we recommend treatment with erythromycin or doxycycline for a minimum of 6 weeks.
Pelagic protected areas: the missing dimension in ocean conservation
Authors: Edward T. Game, Hedley S. Grantham, Alistair J. Hobday, Robert L. Pressey, Amanda T. Lombard, Lynnath E. Beckley, Kristina Gjerde, Rodrigo Bustamante, Hugh P. Possingham, Anthony J. Richardson
Journal: Trends in Ecology & Evolution (2009)
Granulomatous Diseases of the Gastrointestinal Tract
Authors: D H Present, A E Lindner, H D Janowitz
Journal: Annual Review of Medicine (1966)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Endothelial CD81 is a marker of early human atherosclerotic plaques and facilitates monocyte adhesion
Authors: Jakub Rohlena, Oscar L. Volger, Jaap D. van Buul, Liesbeth H.P. Hekking, Janine M. van Gils, Peter I. Bonta, Ruud D. Fontijn, Jan Andries Post, Peter L. Hordijk, Anton J.G. Horrevoets
Journal: Cardiovascular Research (2008)

In a recent report, we established at the genome-wide level those genes that are specifically upregulated in the endothelium of atherosclerotic plaques in human arteries. As the transcriptome data revealed that mRNA for the tetraspanin family member CD81 is significantly and specifically upregulated in the endothelium overlying early atheroma, we set out to validate these results on the protein level, and investigate the functional consequences of CD81 upregulation. Immunohistochemical analysis in an independent set of donor arteries verified in the endothelium of early human atherosclerotic lesions the enhanced expression of CD81, which appears oxidative stress-dependent. Using lentiviral overexpression and silencing in human umbilical endothelial cells, we established in an in vitro flow adhesion assay that elevated endothelial CD81 is associated with increased monocyte adhesion to non-activated CD81-transduced endothelial cells, approaching the levels normally only attained after tumour necrosis factor α stimulation. The CD81 effect was dependent on both intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as it was abolished in the presence of a mixture of anti-ICAM-1 and anti-VCAM-1 antibodies. Flow cytometry revealed that increased CD81 levels did not increase total ICAM-1 and VCAM-1 surface expression. Instead, it concentrated the available adhesion molecules into membrane clusters, as indicated by confocal and electron microscopy. CD81 also colocalized with ICAM-1 and VCAM-1 in the adhesion rings around bound monocytes. Endothelial CD81 upregulated in early human atheroma has the potential to play a crucial role in the initial stages of atherosclerotic plaque formation by increasing monocyte adhesion prior to the full-blown inflammatory response.
Platelet-Activating Factor–induced Pulmonary Edema Is Partly Mediated by Prostaglandin E<sub>2</sub>, E-Prostanoid 3-Receptors, and Potassium Channels
Authors: Rolf Göggel, Sven Hoffman, Rolf Nüsing, Suh Narumiya, Stefan Uhlig
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Platelet-activating factor (PAF) is an important endogenous mediator of pulmonary edema in many models of acute lung injury. PAF triggers edema formation by simultaneous activation of two independent pathways; one is mediated by a cyclooxygenase metabolite, and the other is blocked by quinine. We examined the hypothesis that the cyclooxygenase-dependent part of PAF-induced edema is mediated by prostaglandin E2 (PGE2). In isolated rat lungs, PAF administration stimulated release of PGE2 into the venous effluate and increased lung weight as a measure of edema formation. Perfusion with a neutralizing PGE2 antibody attenuated the PAF-induced edema formation. In vivo, E-prostanoid 3-receptor–deficient mice showed less pulmonary Evans blue extravasation in response to PAF injection than did mice deficient in EP1, EP2, or EP4 receptors. Perfusion of rat lungs with PGE2 caused pulmonary edema, which was largely prevented by inhibition of voltage-gated potassium channels (25 nM β-dendrotoxin), but not by blocking calcium-dependent potassium currents (100 μM paxilline). In line with its effects on PGE2-induced edema formation, β-dendrotoxin attenuated PAF-induced edema partly if given alone, and completely in combination with quinine. Our findings suggest that PAF-triggered edema is partly mediated by the release of PGE2, activation of EP3 receptors, and activation of voltage-gated potassium channels.
Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib
Authors: Nikhil Wagle, Brian C. Grabiner, Eliezer M. Van Allen, Eran Hodis, Susanna Jacobus, Jeffrey G. Supko, Michelle Stewart, Toni K. Choueiri, Leena Gandhi, James M. Cleary, Aymen A. Elfiky, Mary Ellen Taplin, Edward C. Stack, Sabina Signoretti, Massimo Loda, Geoffrey I. Shapiro, David M. Sabatini, Eric S. Lander, Stacey B. Gabriel, Philip W. Kantoff, Levi A. Garraway, Jonathan E. Rosenberg
Journal: Cancer Discovery (2014)

Understanding the genetic mechanisms of sensitivity to targeted anticancer therapies may improve patient selection, response to therapy, and rational treatment designs. One approach to increase this understanding involves detailed studies of exceptional responders: rare patients with unexpected exquisite sensitivity or durable responses to therapy. We identified an exceptional responder in a phase I study of pazopanib and everolimus in advanced solid tumors. Whole-exome sequencing of a patient with a 14-month complete response on this trial revealed two concurrent mutations in mTOR, the target of everolimus. In vitro experiments demonstrate that both mutations are activating, suggesting a biologic mechanism for exquisite sensitivity to everolimus in this patient. The use of precision (or "personalized") medicine approaches to screen patients with cancer for alterations in the mTOR pathway may help to identify subsets of patients who may benefit from targeted therapies directed against mTOR.
Rapamycin inhibits human in stent restenosis vascular smooth muscle cells independently of pRB phosphorylation and p53
Authors: D ROSNER, N MCCARTHY, M BENNETT
Journal: Cardiovascular Research (2005)

Drug-eluting stents containing the immunosuppressant rapamycin markedly inhibit in stent restenosis (ISR). However, the molecular mechanisms that underlie its effect on ISR-derived vascular smooth muscle cells (VSMCs), as opposed to normal VSMCs, are unknown. Specifically, as ISR-VSMCs have altered cell cycle regulation, rapamycin may arrest these cells via novel molecular pathways.We isolated human VSMCs from sites of ISR, and examined the effect of rapamycin on cell proliferation using MTT assay, time lapse videomicroscopy and flow cytometry. Regulation of G(1)-S transition was examined using Western blotting, and cell size and protein synthesis examined using flow cytometry and collagen assay, respectively. The requirement for pRB and p53 was examined using ISR VSMCs expressing E1A and a dominant negative p53, respectively.ISR-VSMC proliferation was potently inhibited by rapamycin. Arrest was confined to G(1), as cell proliferation (but not cell size) of S/G(2)-arrested cells was unaffected by rapamycin. Moreover, ISR-VSMC lines generated with disrupted p53 or pRB function still arrested in the presence of rapamycin, suggesting that these genes are dispensable for rapamycin-induced arrest. Significantly, rapamycin completely inhibited the phosphorylation of p70(S6K), an mTOR-regulated kinase implicated in the control of proliferation, but had no effect on collagen or total protein synthesis.We demonstrate that rapamycin is a potent inhibitor of ISR VSMC proliferation during G(1). Rapamycin's action does not require p53 or pRB. We show that p70(S6K) is markedly inhibited in rapamycin-arrested ISR cells, suggesting that regulation of its upstream kinase, mTOR, is important for the control of proliferation in ISR cells.
A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial
Authors: Michael P Boyle, Scott C Bell, Michael W Konstan, Susanna A McColley, Steven M Rowe, Ernst Rietschel, Xiaohong Huang, David Waltz, Naimish R Patel, David Rodman
Journal: The Lancet Respiratory Medicine (2014)
1124-191 Predictive risk factors for coronary events in renal transplant patients
Authors: Hallvard Holdaas, Bengt Fellstroem, Alan Jardine, Ed Cole, Gudrun Nyberg, Carola Gronhagen-Riska, Soren Madsen, Hans-Hellmut Neumayer, Bart Maes, Patrice Ambuhl, Anders Olsson, Ingar Holme, Per Fauchald, Terje Pedersen, John Logan
Journal: Journal of the American College of Cardiology (2004)
Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis
Authors: Eoin P. Judge, Aurelie Fabre, Huzaifa I. Adamali, Jim J. Egan
Journal: European Respiratory Journal (2011)

The aim of this study was to evaluate the risk factors for and outcomes of acute exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and to examine the relationship between disease severity and neovascularisation in explanted IPF lung tissue. 55 IPF patients assessed for lung transplantation were divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic data was collected at baseline, at the time of acute exacerbation and at lung transplantation. Histological analysis and CD31 immunostaining to quantify microvessel density (MVD) was performed on the explanted lung tissue of 13 transplanted patients. Acute exacerbations were associated with increased mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute exacerbations were associated with poor survival (p<0.01). PH at baseline was associated with a significant risk of acute exacerbations (HR 2.217, p=0.041). Neovascularisation (MVD) was significantly increased in areas of cellular fibrosis and significantly decreased in areas of honeycombing. There was a significant inverse correlation between mean pulmonary artery pressure and MVD in areas of honeycombing. Acute exacerbations were associated with significantly increased mortality in patients with advanced IPF. PH was associated with the subsequent development of an acute exacerbation and with poor survival. Neovascularisation was significantly decreased in areas of honeycombing, and was significantly inversely correlated with mean pulmonary arterial pressure in areas of honeycombing.
Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation
Authors: C. Gisselbrecht, H.G. Prentice, A. Bacigalupo, P. Biron, N. Milpied, H. Rubie, D. Cunningham, M. Legros, J.L. Pico, D.C. Linch, A.K. Burnett, J.H. Scarffe, W. Siegert, A. Yver
Journal: The Lancet (1994)
Lung cancer and air pollution.
Authors: A J Cohen, C A Pope
Journal: Environmental Health Perspectives (1995)

Epidemiologic studies over the last 40 years suggest rather consistently that general ambient air pollution, chiefly due to the incomplete combustion of fossil fuels, may be responsible for increased rates of lung cancer. This evidence derives from studies of lung cancer trends, studies of occupational groups, comparisons of urban and rural populations, and case-control and cohort studies using diverse exposure metrics. Recent prospective cohort studies observed 30 to 50% increases in lung cancer rates associated with exposure to respirable particles. While these data reflect the effects of exposures in past decades, and despite some progress in reducing air pollution, large numbers of people in the United States continue to be exposed to pollutant mixtures containing known or suspected carcinogens. It is not known how many people in the United States are exposed to levels of fine respirable particles that have been associated with lung cancer in recent epidemiologic studies. These observations suggest that the most widely cited estimates of the proportional contribution of air pollution to lung cancer occurrence in the United States based largely on the results of animal studies, may be too low. It is important that better epidemiologic research be conducted to allow improved estimates of lung cancer risk from air pollution among the general population. The development and application of new epidemiologic methods, particularly the improved characterization of population-wide exposure to mixtures of air pollutants and the improved design of ecologic studies, could improve our ability to measure accurately the magnitude of excess cancer associated with air pollution.
Presence of Phosphorylated Hepatocyte Growth Factor Receptor/c-Met Is Associated with Tumor Progression and Survival in Patients with Conventional Renal Cell Carcinoma
Authors: Yasuyoshi Miyata, Hiroshi Kanetake, Shigeru Kanda
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Hepatocyte growth factor receptor (HGFR/c-Met) signaling is associated with tumor progression in various cancers. The clinical significance and pathologic roles of phosphorylated HGFR/c-Met in renal cell carcinoma (RCC) are not fully understood; therefore, this study sought to clarify the possible role of two tyrosine residues (pY1234/pY1235 and pY1349) in HGFR/c-Met. Experimental Design: The kinetics of tyrosine phosphorylation at these two residues was examined in a human renal carcinoma cell line, ACHN cells. In addition, phosphorylated HGFR/c-Met expression (using phosphorylation site-specific antibodies for pY1234/pY1235 and pY1349) was examined in 114 tumor sections of conventional RCC patients by immunohistochemistry. The relationships between these expressions and clinicopathologic features and survival were also investigated. Results: Although phosphorylation of Y1349 HGFR/c-Met was observed for 120 minutes after HGF treatment of ACHN cells, maximal phosphorylation of Y1234/Y1235 was observed at 30 minutes followed by a rapid inactivation. Median rates (range) of cancer cells immunopositive for pY1234/pY1235 HGFR/c-Met and pY1349 HGFR/c-Met in the tumor sections were 0% (0-5.2%) and 14.3% (0-64.3%), respectively. Positive expression of pY1349 HGFR/c-Met was significantly associated with high pT stage, presence of metastasis, and high-grade carcinoma. Multivariate Cox analysis revealed that the positive expression of pY1349 HGFR/c-Met was a significant and an independent predictor of cause-specific survival (odds ratio, 2.94; 95% confidence interval, 1.12-7.72; P = 0.028). Conclusions: Phosphorylated HGFR/c-Met may be important in the tumor progression of RCC. Expression of pY1349 HGFR/c-Met is a useful predictor for metastasis and survival of conventional RCC patients.
Angiotensin converting enzyme and angiotensin II type 1-receptor gene polymorphisms and risk of ischaemic heart disease
Authors: G Rice
Journal: Cardiovascular Research (1999)

Polymorphisms in several genes of the renin-angiotensin system have been implicated as risk factors for myocardial infarction and ischaemic heart disease. In particular, it has been suggested that the angiotensin converting enzyme insertion/deletion (I/D) polymorphism and the angiotensin II type 1 receptor A1166C polymorphisms might act synergistically to increase the risk of myocardial infarction. The aim of this study was to investigate associations between the angiotensin converting enzyme I/D polymorphism and angiotensin II type 1 receptor polymorphisms and ischaemic heart disease.We screened 331 white European patients who were recruited for routine angiographic investigation of chest pain, and 287 healthy white European controls for the angiotensin converting enzyme I/D and angiotensin II type 1 receptor A1166C polymorphisms, and related the genotype frequencies to angiotensin converting enzyme levels and the clinical phenotypes of atheroma and history of myocardial infarction.Angiotensin converting enzyme levels were related to I/D polymorphism but not to angiotensin II type 1 receptor polymorphism genotypes. I/D polymorphism and angiotensin II type 1 receptor genotypes did not relate individually to risk of myocardial infarction or atheroma in univariate or multivariate analysis. However, evidence of a synergistic relationship between the AC/II and CC/DD genotypes and coronary stenosis in the major arteries was found. No evidence of any relationship between these polymorphisms and history of myocardial infarction by World Health organisation (WHO) criteria was detected.These findings suggest that there is a weak relationship between the angiotensin converting enzyme I/D and angiotensin II type 1 receptor A1166C polymorphisms and coronary atheroma, but no evidence of a relationship with history of myocardial infarction.
Acquired von willebrand disease in multiple myeloma secondary to absorption of von willebrand factor by plasma cells
Authors: C. Richard, M. A. Cuadrado, M. Prieto, J. Batlle, M. Flópez Fernández, M. L. Rodriguez Salazar, C. Bello, M. Recio, T. Santoro, M. T. Gomez Casares, A. Zubizarreta
Journal: American Journal of Hematology (1990)

Abstract A case of acquired von Willebrand disease (AvWD) associated with an IgA lambda multiple myeloma is reported. No form of inhibitor could be detected. SDS‐agarose gel electrophoresis patterns of von Willebrand factor (vWF) both in plasma and platelet lysates were normal but a decrease in all‐sized multimers with a type IA pattern was seen. After 1‐deamino‐8‐D arginine vasopressin (DDAVP) infusion, vWF multimers larger than those seen in the resting state appeared in patient plasma, which were progressively cleared. Indirect immunofluorescence studies with a monoclonal antibody to vWF showed that vWF was selectively absorbed into myelomatous cells. This is the first case of AvWD associated with multiple myeloma resulting from the selective absorption of vWF into abnormal plasma cells. This feature established a new pathophysiological mechanism of AvWD in multiple myeloma and probably in other lymphoproliferative diseases.