tbuckley/cabot-search huggingface dataset:
Adenovirus type 5 exerts genome-wide control over cellular programs governing proliferation, quiescence, and survival
Authors: Daniel L Miller, Chad L Myers, Brenden Rickards, Hilary A Coller, S Jane Flint
Journal: Genome biology (2007)

Abstract Background Human adenoviruses, such as serotype 5 (Ad5), encode several proteins that can perturb cellular mechanisms that regulate cell cycle progression and apoptosis, as well as those that mediate mRNA production and translation. However, a global view of the effects of Ad5 infection on such programs in normal human cells is not available, despite widespread efforts to develop adenoviruses for therapeutic applications. Results We used two-color hybridization and oligonucleotide microarrays to monitor changes in cellular RNA concentrations as a function of time after Ad5 infection of quiescent, normal human fibroblasts. We observed that the expression of some 2,000 genes, about 10% of those examined, increased or decreased by a factor of two or greater following Ad5 infection, but were not altered in mock-infected cells. Consensus k-means clustering established that the temporal patterns of these changes were unexpectedly complex. Gene Ontology terms associated with cell proliferation were significantly over-represented in several clusters. The results of comparative analyses demonstrate that Ad5 infection induces reversal of the quiescence program and recapitulation of the core serum response, and that only a small subset of the observed changes in cellular gene expression can be ascribed to well characterized functions of the viral E1A and E1B proteins. Conclusion These findings establish that the impact of adenovirus infection on host cell programs is far greater than appreciated hitherto. Furthermore, they provide a new framework for investigating the molecular functions of viral early proteins and information relevant to the design of conditionally replicating adenoviral vectors.
Angiotensin II induces fibronectin expression associated with cardiac fibrosis in the rat.
Authors: D C Crawford, A V Chobanian, P Brecher
Journal: Circulation Research (1994)

Fibronectin expression was studied in the heart of rats given a continuous infusion of angiotensin II (Ang II). Northern blot analysis showed that left ventricular fibronectin steady-state mRNA increased fivefold to eightfold in response to pressor doses of Ang II after 24 hours. Accumulation of immunodetectable fibronectin in the ventricles occurred after the mRNA levels increased. The changes in fibronectin expression were reversible when Ang II treatment was withdrawn. The Ang II-induced increase in fibronectin mRNA accompanied similar increases for collagen type I, collagen type IV, and atrial natriuretic factor steady-state mRNA. Interstitial and perivascular fibrosis was identified in both ventricles of angiotensin-treated rats within 3 days. In situ hybridization identified cells associated with areas of fibrosis as the principal site of fibronectin mRNA accumulation in treated animals. By comparison, normal hearts showed fibronectin expression primarily within ventricular vascular tissue and the atrial endocardium. A dose-dependent reduction of fibronectin expression followed treatment with losartan, indicating an Ang II type 1 receptor-mediated effect. Normalization of blood pressure during Ang II infusion by either hydralazine or prazosin had different effects on the level of fibronectin steady-state mRNA, indicating that blood pressure elevation was not the principal factor responsible for fibronectin induction. Concurrent administration of angiotensin-converting enzyme inhibitors with Ang II attenuated the increased fibronectin expression. Our data indicate that Ang II induces an acute fibrotic response within the heart and suggests that Ang II stimulates fibronectin expression within nonmyocytic cardiac cells by a direct action.
Insulin resistance in syndrome X
Authors: A. Chauhan, M.C. Petch, P.M. Schofield, B.S. Raheja, S.M. Sadikot, R.B. Phatak, BasilT. Saeed, WilliamA. Bartlett, R.Gordon Murray, AlanF. Jones, JamesM. Beattie
Journal: The Lancet (1993)
Unusual lung consolidation in SLE
Authors: A Nomura
Journal: Thorax (2003)

Pulmonary manifestations of systemic lupus erythematosus (SLE) include acute lupus pneumonitis, chronic interstitial pneumonitis, diaphragmatic dysfunction, atelectasis, pulmonary vascular disease, upper airway dysfunction, and bronchiolitis obliterans.1 Pneumonia due to infection also develops because infection is a major cause of death of patients with SLE.2,3 Here, we report a patient with SLE who suffered from an ambulatory lung consolidation devoid of pathogens.

A 61 year old woman with SLE had been …
Scores of asthma and asthma severity reveal new regions of linkage in EGEA study families
Authors: E. Bouzigon, V. Siroux, M-H. Dizier, A. Lemainque, C. Pison, M. Lathrop, F. Kauffmann, F. Demenais, I. Pin
Journal: European Respiratory Journal (2007)

There is ongoing debate as to how asthma should be defined in order to forward understanding of the underlying mechanisms. The aim of the present study was to build quantitative scores of asthma and asthma severity and to assess whether refinement of disease phenotypes can facilitate the identification of chromosomal regions harbouring susceptibility genes. A genome-wide linkage scan was conducted in 110 families with at least two asthmatic siblings (n = 508) from the French Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The phenotypes studied were an asthma severity score (assessed among asthmatics by combining clinical data and treatment), forced expiratory volume in one second (FEV(1)) and an asthma score (including both asthmatics and nonasthmatics and representing the whole disease spectrum). This analysis showed genome-wide suggestive evidence of linkage of the asthma score to 18p11, a novel region undetected in a previous screen of dichotomous asthma. There was potential linkage of 2p23 to asthma severity score and of three regions (1p36, 2q36 and 6q14) to FEV(1). Moreover, FEV(1) appeared to have no genetic determinant in common with asthma severity and asthma scores. Asthma and asthma severity quantitative scores revealed new regions of linkage and thus provide support for considering these phenotypes in future genetic studies.
Plasma Fibrinogen: A New Factor of the Metabolic Syndrome: A population-based study
Authors: Gluseppina Imperatore, Gabriele Riccardi, Ciro Iovine, Angela A Rivellese, Olga Vaccaro
Journal: Diabetes Care (1998)

OBJECTIVE To evaluate whether hyperfibrinogenemia represents a component of the metabolic syndrome. RESEARCH DESIGN AND METHODS A cross-sectional study was conducted on the relation between fibrinogen and the metabolic syndrome in a working population of 1,252 nondiabetic men, aged 35–64 years, randomly selected among all men participating in a health screening. We measured anthropometric characteristics, blood pressure, fasting plasma fibrinogen, cholesterol (total, LDL, and HDL), triglycerides, glucose, and insulin. Individuals with two or more metabolic abnormalities (defined as being in the highest quartile of the distribution of diastolic blood pressure, plasma glucose, or triglycerides or being in the lowest quartile of HDL cholesterol) were considered to have the metabolic syndrome. RESULTS Age-adjusted fibrinogen levels correlated significantly with BMI, waist-to-hip ratio, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, triglycerides, insulin, and HDL cholesterol (inversely). Subjects with the metabolic syndrome had significantly higher plasma fibrinogen levels than those without (285.1 ± 1.9 vs. 300.2 ± 3.0 mg/dl, mean ± SE, P = 0.0001). Plasma fibrinogen concentrations and the prevalence of hyperfibrinogenemia (defined as ≥350 mg/dl) increased progressively from 279 to 307 mg/dl (P = 0.0001) and from 9 to 22% (P = 0.0024), respectively, across categories with an increasing number of metabolic disorders characterizing the syndrome (only one, any two, three or more). In multivariate analyses, both plasma insulin and the metabolic syndrome were significantly and independently associated with plasma fibrinogen. CONCLUSIONS The finding suggests that hyperfibrinogenemia may be considered a component of the metabolic syndrome. This may also explain the increased cardiovascular risk associated with hyperinsulinemia/insulin resistance.
Deficiency of a surface membrane glycoprotein (Mo1) in man.
Authors: N Dana, R F Todd, J Pitt, T A Springer, M A Arnaout
Journal: Journal of Clinical Investigation (1984)

Deficiency of a granulocyte surface glycoprotein of 150,000-D had been associated with defective C3- and IgG-dependent phagocytosis in a patient with recurrent bacterial infections. By using monoclonal antibodies, we found that this patient's granulocytes, monocytes, and null cells were deficient in Mo1 (equivalent to OKM1 and Mac-1), a cell surface molecule consisting of two noncovalently linked glycoproteins of 155,000 and 94,000 D. The 155,000-D subunit is closely associated with the human complement receptor that recognizes C3bi and/or a further degradation product termed C3dg (C3bi receptor); the 94,000-D subunit has been shown to be shared, on normal cells, by two other surface membrane glycoproteins: lymphocyte function-associated antigen-1 (LFA-1) and P-150, 95. Both subunits of Mo1 were deficient on the patient's granulocytes as determined by immunoprecipitation with subunit-specific monoclonal antibodies as well as fluorescence analysis. Mol-deficient monocytes, like granulocytes, had defective C3-and IgG-dependent phagocytosis. Natural killing activity by the patient's peripheral blood leukocytes was normal. Mo1-deficient granulocytes and monocytes rosetted normally with sheep erythrocytes coated with C3bi. This rosetting was totally inhibited by a mixture of anti-Mo1 and anti-C3b (the major fragment of C3) receptor antibodies but not by either antibody alone. Since monoclonal antibodies to the 155,000-D subunit of Mo1 can inhibit C3bi receptor binding, immune phagocytosis, opsonized zymosan-induced degranulation, and superoxide generation by normal phagocytes (functions which are defective in Mo1-deficient cells), it appears likely that Mo1 deficiency may in part underlie the functional aberrations leading to recurrent bacterial infections in man.
Effects of Norepinephrine on the Renal Vasculature in Normal and Endotoxemic Dogs
Authors: RINALDO BELLOMO, JOHN A. KELLUM, STEPHEN R. WISNIEWSKI, MICHAEL R. PINSKY, Brian Ondulik
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Section:ChooseTop of pageAbstract <<CONCEPTUAL FRAMEWORKMETHODSRESULTSDISCUSSIONReferencesCITING ARTICLES
Filling the gap: Micro-C accesses the nucleosomal fiber at 100–1000 bp resolution
Authors: Julien Mozziconacci, Romain Koszul
Journal: Genome biology (2015)

The fine three-dimensional structure of the nucleosomal fiber has remained elusive to genome-wide chromosome conformation capture (3C) approaches. A new study mapping contacts at the single nucleosome level (Micro-C) reveals topological interacting domains along budding yeast chromosomes. These domains encompass one to five consecutive genes and are delimited by highly active promoters.
Early and short-term acenocumarine or dalteparin for the prevention of central vein catheter-related thrombosis in cancer patients: a randomized controlled study based on serial venographies
Authors: M. De Cicco, M. Matovic, L. Balestreri, A. Steffan, R. Pacenzia, M. Malafronte, D. Fantin, C.A. Bertuzzi, F. Fabiani, S. Morassut, E. Bidoli, A. Veronesi
Journal: Annals of Oncology (2009)
Pharmacogenetic Screening of CYP3A and ABCB1 in Relation to Population Pharmacokinetics of Docetaxel
Authors: Tessa M. Bosch, Alwin D.R. Huitema, Valerie D. Doodeman, Robert Jansen, Els Witteveen, Wim M. Smit, Rob L. Jansen, Carla M. van Herpen, Marcel Soesan, Jos H. Beijnen, Jan H.M. Schellens
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Despite the extensive clinical experience with docetaxel, unpredictable interindividual variability in efficacy and toxicity remain important limitations associated with the use of this anticancer drug. Large interindividual pharmacokinetic variability has been associated with variation in toxicity profiles. Genetic polymorphisms in drug-metabolizing enzymes and drug transporters could possibly explain the observed pharmacokinetic variability. The aim of this study was therefore to investigate the influence of polymorphisms in the CYP3A and ABCB1 genes on the population pharmacokinetics of docetaxel. Experimental Design: Whole blood samples were obtained from patients with solid tumors and treated with docetaxel to quantify the exposure to docetaxel. DNA was collected to determine polymorphisms in the CYP3A and ABCB1 genes with DNA sequencing. A population pharmacokinetic analysis of docetaxel was done using nonlinear mixed-effect modeling. Results: In total, 92 patients were assessable for pharmacokinetic analysis of docetaxel. A three-compartmental model adequately described the pharmacokinetics of docetaxel. Several polymorphisms in the CYP3A and ABCB1 genes were found, with allele frequencies of 0.54% to 48.4%. The homozygous C1236T polymorphism in the ABCB1 gene (ABCB1*8) was significantly correlated with a decreased docetaxel clearance (−25%; P = 0.0039). No other relationships between polymorphisms and pharmacokinetic variables reached statistical significance. Furthermore, no relationship between haplotypes of CYP3A and ABCB1 and the pharmacokinetics could be identified. Conclusions: The polymorphism C1236T in the ABCB1 gene was significantly related to docetaxel clearance. Our current finding may provide a meaningful tool to explain interindividual differences in docetaxel treatment in daily practice.
Assessment of the Tissue Distribution of Transplanted Human Endothelial Progenitor Cells by Radioactive Labeling
Authors: Alexandra Aicher, Winfried Brenner, Maaz Zuhayra, Cornel Badorff, Schirin Massoudi, Birgit Assmus, Thomas Eckey, Eberhard Henze, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2003)

Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular function after experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs.Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [111In]indium oxine. EPCs (106) were injected in athymic nude rats 24 hours after myocardial infarction (n=8) or sham operation (n=8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, approximately 70% of the radioactivity was localized in the spleen and liver, with only approximately 1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02+/-0.19 in sham-operated animals to 2.03+/-0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69+/-1.54 in sham-operated animals to 4.70+/-1.55 (P<0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone.Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy.
Expandable Wallstent for the treatment of obstruction of the superior vena cava.
Authors: A F Watkinson, D M Hansell
Journal: Thorax (1993)

BACKGROUND--Palliative treatments for obstruction of the superior vena cava all have disadvantages. The use of a fine braided wire self expanding stent (Wallstent, Schneider (Europe) AG) in patients with malignant and benign causes of superior vena cava obstruction is reported. METHODS--Five patients with obstruction of the superior vena cava were treated with balloon angioplasty of the stricture and the percutaneous insertion of an expandable Wallstent endoprosthesis across the site of the stricture. Four patients had advanced mediastinal malignancy previously treated by radiotherapy and one patient had fibrosing mediastinitis. RESULTS--All patients experienced rapid symptomatic relief and, in three cases, complete palliation was achieved during survival times of seven weeks, nine weeks, and 24 weeks, respectively. Two surviving patients (with a recurrent thymoma and fibrosing mediastinitis) were free of symptoms when followed up at eight and nine months respectively. CONCLUSIONS--Initial experience with the Wallstent endoprosthesis suggests that it is a valuable treatment alternative once conventional therapy has failed and gives rapid relief of symptoms to patients with obstruction of the superior vena cava.
Apo2L/TRAIL Inhibits Tumor Growth and Bone Destruction in a Murine Model of Multiple Myeloma
Authors: Agatha Labrinidis, Peter Diamond, Sally Martin, Shelley Hay, Vasilios Liapis, Irene Zinonos, Natalie A. Sims, Gerald J. Atkins, Cristina Vincent, Vladimir Ponomarev, David M. Findlay, Andrew C.W. Zannettino, Andreas Evdokiou
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Multiple myeloma is an incurable disease, for which the development of new therapeutic approaches is required. Here, we report on the efficacy of recombinant soluble Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to inhibit tumor progression and bone destruction in a xenogeneic model of human multiple myeloma. Experimental Design: We established a mouse model of myeloma, in which Apo2L/TRAIL-sensitive RPMI-8226 or KMS-11 cells, tagged with a triple reporter gene construct (NES-HSV-TK/GFP/Luc), were transplanted directly into the tibial marrow cavity of nude mice. Tumor burden was monitored progressively by bioluminescence imaging and the development of myeloma-induced osteolysis was measured using high resolution in vivo micro-computed tomography. Results: Tumor burden increased progressively in the tibial marrow cavity of mice transplanted with Apo2L/TRAIL-sensitive RPMI-8226 or KMS-11 cells associated with extensive osteolysis directly in the area of cancer cell transplantation. Treatment of mice with recombinant soluble Apo2L/TRAIL reduced myeloma burden in the bone marrow cavity and significantly protected against myeloma-induced osteolysis. The protective effects of Apo2L/TRAIL treatment on bone were mediated by the direct apoptotic actions of Apo2L/TRAIL on myeloma cells within the bone microenvironment. Conclusions: This is the first in vivo study that investigates the efficacy of recombinant Apo2L/TRAIL on myeloma burden within the bone microenvironment and associated myeloma-induced bone destruction. Our findings that recombinant soluble Apo2L/TRAIL reduces myeloma burden within the bone microenvironment and protects the bone from myeloma-induced bone destruction argue against an inhibitory role of osteoprotegerin in Apo2L/TRAIL-induced apoptosis in vivo and highlight the need to clinically evaluate Apo2L/TRAIL in patients with multiple myeloma.
Posttransplantation Diabetes
Authors: Victor M. Montori, Ananda Basu, Patricia J. Erwin, Jorge A. Velosa, Sherine E. Gabriel, Yogish C. Kudva
Journal: Diabetes Care (2002)

OBJECTIVES— To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS— We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS— Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (&amp;lt;10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P = 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS— Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs.
Relapse after discontinuation of infliximab in sarcoidosis patients can be predicted by PET-scan and sIL-2R
Authors: Adriane D.M. Vorselaars, Anouk Verwoerd, Coline H.M. Van Moorsel, Ruth G.M. Keijsers, Ger T. Rijkers, Jan C. Grutters
Journal: European Respiratory Journal (2013)

BACKGROUND:  The biological anti-TNF drug infliximab is used as third-line therapy for severe sarcoidosis. Long-term outcome and relapse rate after discontinuation of infliximab treatment in sarcoidosis patients are unknown.  OBJECTIVES:  To assess the clinical relapse rate after discontinuation of infliximab therapy in sarcoidosis patients and predict relapse by analysis of disease activity markers soluble IL-2 receptor (sIL-2R) and maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET).  METHODS:  In this retrospective cohort study, relapse was defined as the return of symptoms and signs of disease activity with need for retreatment. The proportion of relapse was analyzed using Kaplan-Meier and predicting factors were studied with Cox regression analysis.  RESULTS:  47 sarcoidosis patients who started infliximab therapy could be included in risk analysis. Mean treatment duration was 8.5 months. After treatment discontinuation, 29 patients (62%) relapsed after a mean of 7.8 months. Both mediastinal SUVmax ≥ 6.0 on 18F-FDG PET (HR 3.77, P  CONCLUSIONS:  The majority of patients that discontinued infliximab therapy had relapse of disease and required retreatment. High serum sIL-2R level and high SUVmax on 18F-FDG-PET at initiation of therapy are significant predictors of relapse. Therefore, close monitoring of patients in this category is suggested when they discontinue infliximab treatment.