tbuckley/cabot-search huggingface dataset:
Suppression of chronic ventricular arrhythmias with propranolol.
Authors: R L Woosley, D Kornhauser, R Smith, S Reele, S B Higgins, A S Nies, D G Shand, J A Oates
Journal: Circulation (1979)

The antiarrhythmic efficacy of propranolol was evaluated in 32 patients with chronic high frequency ventricular arrhythmias in a placebo-controlled protocol. After a placebo control period, propranolol was begun and the dosage increased sequentially until arrhythmia suppression was achieved, side effects appeared, or a maximum dosage of 960 mg/day was reached. Computerized analysis of ambulatory recordings was used to quantify the arrhythmias. Twenty-four patients had 70--100% arrhythmia suppression at plasma levels ranging from 12--1100 ng/ml (end of dosing interval). Eight patients in this group had frequent episodes of ventricular tachycardia that were totally suppressed at or below the dosage that produced greater than or equal to 70% suppression of ventricular ectopic depolarizations (VEDs). A biphasic dose-response curve was seen in five patients who responded with a decrease in arrhythmia frequency in the lower ranges of dosages but had increased frequency of ectopic rhythms as the dosage was increased above the optimal level. Only one-third of patients responded at doses less than or equal to 160 mg/day. However, with dosages of 200--640 mg/day, an additional 40% responded. Propranolol appears to control ventricular arrhythmias safely and effectively in many patients. The finding that the antiarrhythmic effect in many patients required plasma concentrations greater than those that produce substantial beta-adrenergic blockage raises a question whether blockade of cardiac beta receptors can directly account for all of the antiarrhythmic actions of propranolol.
Subcutaneous recombinant interleukin-2 (rIL-2) in out-patients with metastatic renal cell carcinoma
Authors: J.M. Tourani, V. Lucas, D. Mayeur, B. Dufour, M. Di Palma, C. Boaziz, P. Grise, C. Varette, J.M. Pavlovitch, E. Pujade-Lauraine, D. Larregain, E. Ecstein, M. Untereiner, E. Vuillemin, S. Merran, J.M. Andrieu
Journal: Annals of Oncology (1996)
Soccer specific aerobic endurance training
Authors: J Hoff, U Wisløff, L C Engen, O J Kemi, J Helgerud
Journal: British Journal of Sports Medicine (2002)

Background: In professional soccer, a significant amount of training time is used to improve players' aerobic capacity. However, it is not known whether soccer specific training fulfils the criterion of effective endurance training to improve maximal oxygen uptake, namely an exercise intensity of 90–95% of maximal heart rate in periods of three to eight minutes. Objective: To determine whether ball dribbling and small group play are appropriate activities for interval training, and whether heart rate in soccer specific training is a valid measure of actual work intensity. Methods: Six well trained first division soccer players took part in the study. To test whether soccer specific training was effective interval training, players ran in a specially designed dribbling track, as well as participating in small group play (five a side). Laboratory tests were carried out to establish the relation between heart rate and oxygen uptake while running on a treadmill. Corresponding measurements were made on the soccer field using a portable system for measuring oxygen uptake. Results: Exercise intensity during small group play was 91.3% of maximal heart rate or 84.5% of maximal oxygen uptake. Corresponding values using a dribbling track were 93.5% and 91.7%. No higher heart rate was observed during soccer training. Conclusions: Soccer specific exercise using ball dribbling or small group play may be performed as aerobic interval training. Heart rate monitoring during soccer specific exercise is a valid indicator of actual exercise intensity.
Extending the Horizon in Chronic Heart Failure
Authors: Sally C. Inglis, Sue Pearson, Suzette Treen, Tamara Gallasch, John D. Horowitz, Simon Stewart
Journal: Circulation (2006)

The long-term impact of chronic heart failure management programs over the typical life span of affected individuals is unknown.The effects of a nurse-led, multidisciplinary, home-based intervention (HBI) in a typically elderly cohort of patients with chronic heart failure initially randomized to either HBI (n=149) or usual postdischarge care (UC) (n=148) after a short-term hospitalization were studied for up to 10 years of follow-up (minimum 7.5 years of follow-up). Study end points were all-cause mortality, event-free survival (event was defined as death or unplanned hospitalization), recurrent hospital stay, and cost per life-year gained. Median survival in the HBI cohort was almost twice that of UC (40 versus 22 months; P<0.001), with fewer deaths overall (HBI, 77% versus 89%; adjusted relative risk, 0.74; 95% CI, 0.53 to 0.80; P<0.001). HBI was associated with prolonged event-free survival (median, 7 versus 4 months; P<0.01). HBI patients had more unplanned readmissions (560 versus 550) but took 7 years to overtake UC; the rates of readmission (2.04+/-3.23 versus 3.66+/-7.62 admissions; P<0.05) and related hospital stay (14.8+/-23.0 versus 28.4+/-53.4 days per patient per year; P<0.05) were significantly lower in the HBI group. HBI was associated with 120 more life-years per 100 patients treated compared with UC (405 versus 285 years) at a cost of 1729 dollars per additional life-year gained when we accounted for healthcare costs including the HBI.In altering the natural history of chronic heart failure relative to UC (via prolonged survival and reduced frequency of recurrent hospitalization), HBI is a remarkably cost- and time-effective strategy over the longer term.
Genetically determined, interferon-dependent resistance to influenza virus in mice.
Authors: O Haller, H Arnheiter, I Gresser, J Lindenmann
Journal: The Journal of Experimental Medicine (1979)

The genetically determined resistance towards orthomyxoviruses exhibited by mice homozygous (A2G) or heterozygous (A2G X A/J) for the gene Mx was abolished or greatly diminished by treatment with anti-interferon globulin (AIF). AIF induced increased susceptibility to challenge with hepatotropic, neurotropic, and pneumotropic strains of influenza A virus. Hepatotropic virus titers in blood and livers of AIF-treated, Mx-bearing mice were higher by a factor of 10(3)--10(6) than those in untreated mice of the same genotype, and were comparable to those in genetically susceptible (untreated or AIF-treated) mice. Peritoneal macrophages from Mx-bearing untreated mice were resistant to challenge with a macrophage-adapted strain of influenza A virus even in the presence of AIF. However, when macrophages were taken from resistant mice injected with AIF and also cultivated in the presence of AIF, they were as susceptible to the virus as macrophages taken from susceptible mice. We conclude that interferons is an important factor in resistance to orthomyxoviruses governed by the gene Mx.
Distinct epithelial gene expression phenotypes in childhood respiratory allergy
Authors: Lisa Giovannini-Chami, Brice Marcet, Chimène Moreilhon, Benoît Chevalier, Marius I. Illie, Kévin Lebrigand, Karine Robbe-Sermesant, Thierry Bourrier, Jean-François Michiels, Bernard Mari, Dominique Crénesse, Paul Hofman, Jacques de Blic, Laurent Castillo, Marc Albertini, Pascal Barbry
Journal: European Respiratory Journal (2011)

Epithelial cell contribution to the natural history of childhood allergic respiratory disease remains poorly understood. Our aims were to identify epithelial pathways that are dysregulated in different phenotypes of respiratory allergy. We established gene expression signatures of nasal brushings from children with dust mite-allergic rhinitis, associated or not associated with controlled or uncontrolled asthma. Supervised learning and unsupervised clustering were used to predict the different subgroups of patients and define altered signalling pathways. These profiles were compared with those of primary cultures of human nasal epithelial cells stimulated with either interleukin (IL)-4, IL-13, interferon (IFN)-α, IFN-β or IFN-γ, or during in vitro differentiation. A supervised method discriminated children with allergic rhinitis from healthy controls (prediction accuracy 91%), based on 61 transcripts, including 21 T-helper cell (Th) type 2-responsive genes. This method was then applied to predict children with controlled or uncontrolled asthma (prediction accuracy 75%), based on 41 transcripts: nine of them, which were down-regulated in uncontrolled asthma, are directly linked to IFN. This group also included GSDML , which is genetically associated with asthma. Our data revealed a Th2-driven epithelial phenotype common to all children with dust mite allergic rhinitis. It highlights the influence of epithelially expressed molecules on the control of asthma, in association with atopy and impaired viral response.
High-Density Lipoprotein and the Dynamics of Atherosclerotic Lesions
Authors: Mohamad Navab, Brian J. Van Lenten, Srinivasa T. Reddy, Alan M. Fogelman
Journal: Circulation (2001)

lump et al 1 reported in 1994 that the expression of a human transgene for apoA-I, the major apolipoprotein of HDL, in apoE knockout mice dramatically reduced lesion formation.In the present issue of Circulation, Rong et al 2 demonstrate that the composition and structure of advanced atherosclerotic plaques can be significantly altered by the expression of this same transgene.Rong and colleagues 2 used a novel transplant model.They fed apoE knockout mice a Western diet for 6 months to generate advanced lesions.Subsequently, they surgically removed portions of the aorta from these mice and transplanted them into the aortas of syngeneic mice on a chow diet, some of which also expressed the transgene for human apoA-I.The recipient mice expressing the human transgene had Ϸ2.5-fold higher HDL cholesterol levels and expressed 130Ϯ15 mg/dL of human apoA-I.The non-HDL cholesterol levels were approximately half of those that had been present in the donor mice and were similar, regardless of whether the transgene was expressed or not.Five months later, despite non-HDL cholesterol levels that were half those of the donor mice, there was progression in the transplanted lesions, although there was less progression in the mice expressing the human apoA-I transgene.However, the characteristics of the lesions were dramatically different.The recipients expressing the transgene had a Ͼ80% decrease in lesion macrophage area and a Ͼ300% increase in smooth muscle cell content, with most of the changes occurring in the superficial subendothelial layer.
A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome
Authors: C.M. Boomsma, M.J.C. Eijkemans, E.G. Hughes, G.H.A. Visser, B.C.J.M. Fauser, N.S. Macklon
Journal: Human Reproduction Update (2006)

Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70–5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98–6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95–6.17) and preterm birth (OR 1.75; 95% CI: 1.16–2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25–4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03–9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.
Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone
Authors: Daniel G. Branstetter, Scott D. Nelson, J. Carlos Manivel, Jean-Yves Blay, Sant Chawla, David M. Thomas, Susie Jun, Ira Jacobs
Journal: Clinical Cancer Research (2012)

Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB.Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL.Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells.Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.
Association of variants in <i>MMEL1</i> and <i>CTLA4</i> with rheumatoid arthritis in the Han Chinese population
Authors: Patrick Danoy, Meng Wei, Hadler Johanna, Lei Jiang, Dongyi He, Linyun Sun, Xiaofeng Zeng, Peter M Visscher, Matthew A Brown, Huji Xu
Journal: Annals of the Rheumatic Diseases (2011)

Background The genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations. Objective To investigate these associations in the Han Chinese population. Methods Haplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r 2 =0.8) across 19 distinct RA genomic regions. A two phase case–control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p&lt;0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied. Results Robust association was detected for MMEL1 and CTLA4 , and modest association was identified for another six loci: PADI4 , STAT4 , PRDM1 , CDK6 , TRAF1-C5 and KIF5A-PIP4K2C . All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6×10 −5 unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4 , significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3×10 −5 unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed. Conclusion This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.
INFLUENCE OF GLANDS WITH INTERNAL SECRETION ON THE RESPIRATORY EXCHANGE
Authors: W. J. M. Scott
Journal: The Journal of Experimental Medicine (1922)

1. Severe and sufficient non-fatal injury to the suprarenal cortex by freezing or by ligation in cats causes a significant and prolonged increase in heat production. 2. Lethal injury to the suprarenals by freezing, ligation, or partial excision in cats causes a fall in heat production. 3. Insufficient injury to the suprarenals by freezing, ligation, or partial excision in cats produces no significant alteration in heat production. 4. Further evidence of a dose thyroid-suprarenal cortex interrelationship is indicated by the rapidity of thyroid hyperplasia and by the effects of KI after suprarenal crippling.
Soluble Domain 1 of Platelet–Endothelial Cell Adhesion Molecule (PECAM) Is Sufficient to Block Transendothelial Migration In Vitro and In Vivo
Authors: Fang Liao, Jahanara Ali, Tricia Greene, William A. Muller
Journal: The Journal of Experimental Medicine (1997)

The inflammatory response involves sequential adhesive interactions between cell adhesion molecules of leukocytes and the endothelium. Unlike the several adhesive steps that precede it, transendothelial migration (diapedesis), the step in which leukocytes migrate between apposed endothelial cells, appears to involve primarily one adhesion molecule, platelet-endothelial cell adhesion molecule (PECAM, CD31). Therefore, we have focused on PECAM as a target for antiinflammatory therapy. We demonstrate that soluble chimeras made of the entire extracellular portion of PECAM, or of only the first immunoglobulin domain of PECAM, fused to the Fc portion of IgG, block diapedesis in vitro and in vivo. Furthermore, the truncated form of the PECAM-IgG chimera does not bind stably to its cellular ligand. This raises the possibility of selective anti-PECAM therapies that would not have the untoward opsonic or cell-activating properties of antibodies directed against PECAM.
Nuclear Imaging of Met-Expressing Human and Canine Cancer Xenografts with Radiolabeled Monoclonal Antibodies (MetSeekTM)
Authors: Rick V. Hay, Brian Cao, R. Scot Skinner, Yanli Su, Ping Zhao, Margaret F. Gustafson, Chao-Nan Qian, Bin T. Teh, Beatrice S. Knudsen, James H. Resau, Shuren Shen, David J. Waters, Milton D. Gross, George F. Vande Woude
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Met, an oncogene product and receptor tyrosine kinase, is a keystone molecule for malignant progression in solid human tumors. We are developing Met-directed imaging and therapeutic agents, including anti-Met monoclonal antibodies (MetSeekTM). In this study, we compared two antibodies, Met5 and Met3, for nuclear imaging of human and canine Met-expressing tumor xenografts in nude mice. Experimental Design: Xenografts representing cancers of three different human tissue origins and metastatic canine prostate cancer were raised s.c. in host athymic nude mice. Animals were injected i.v. with I-125-Met5 or I-125-Met3, posterior total body gamma camera images were acquired for several days postinjection, and quantitative region-of-interest activity analysis was done. Results: PC-3, SK-LMS-1/HGF, and CNE-2 xenografts imaged with I-125-Met5 were compared with PC-3, SK-LMS-1/HGF, and DU145 xenografts imaged with I-125-Met3. Nuclear imaging contrast was qualitatively similar for I-125-Met5 and I-125-Met3 in PC-3 and SK-LMS-1/HGF host mice. However, by region-of-interest analysis, the set of human tumors imaged with I-125-Met3 exhibited a pattern of rapid initial tumor uptake followed by a continuous decline in activity, whereas the set of human tumors imaged with I-125-Met5 showed slow initial uptake, peak tumor-associated activity at 1 day postinjection, and persistence of activity in xenografts for at least 5 days. GN4 canine prostate cancer xenografts were readily imaged with I-125-Met5. Conclusions: We conclude that radioiodinated Met3 and Met5 offer qualitatively similar nuclear images in xenograft-bearing mice, but quantitative considerations indicate that Met5 might be more useful for radioimmunotherapy. Moreover, canine prostate cancer seems to be a suitable model for second-stage preclinical evaluation of Met5.
Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9
Authors: David Chau, Karen Ng, Thomas Sau-Yan Chan, Yuen-Yee Cheng, Bonnie Fong, Sidney Tam, Yok-Lam Kwong, Eric Tse
Journal: Journal of Hematology & Oncology (2015)

The therapeutic efficacy of arsenic trioxide (As2O3) in acute myeloid leukemia (AML) is modest, which is partly related to its limited intracellular uptake into the leukemic cells. As2O3 enters cells via the transmembrane protein aquaglyceroporin 9 (AQP9). Azacytidine, a demethylating agent that is approved for the treatment of AML, has been shown to have synergistic effect with As2O3. We tested the hypothesis that azacytidine might up-regulate AQP9 and enhances As2O3-mediated cytotoxicity in AML. Arsenic-induced cytotoxicity, the expression of AQP9, and the intracellular uptake of As2O3 were determined in AML cell lines and primary AML cells with or without azacytidine pre-treatment. The mechanism of AQP9 up-regulation was then investigated by examining the expression of transcription factors for AQP9 gene and the methylation status of their gene promoters. As2O3-induced cytotoxicity in AML cell lines was significantly enhanced after azacytidine pre-treatment as a result of AQP9 up-regulation, leading to increased arsenic uptake and hence intracellular concentration. Blocking AQP9-mediated As2O3 uptake with mercury chloride abrogated the sensitization effect of azacytidine. AQP9 promoter does not contain CpG islands. Instead, azacytidine pre-treatment led to increased expression of HNF1A, a transcription activator of AQP9, through demethylation of HNF1A promoter. HNF1 knockdown abrogated azacytidine-induced AQP9 up-regulation and almost completely blocked intracellular As2O3 entry, confirming that azacytidine enhanced As2O3-mediated cell death via up-regulation of HNF1A and hence increased AQP9 and As2O3 intracellular concentration. Azacytidine sensitization to As2O3 treatment was re-capitulated also in primary AML samples. Finally, azacytidine did not enhance arsenic toxicity in a liver cell line, where HNF1A was largely unmethylated. Azacytidine sensitizes AML cells to As2O3 treatment, and our results provide proof-of-principle evidence that pharmacological up-regulation of AQP9 potentially expands the therapeutic spectrum of As2O3. Further clinical trial should evaluate the efficacy of azacytidine in combination with As2O3 in the treatment of AML.