tbuckley/cabot-search huggingface dataset:
In situ analysis of alpha-adrenoceptors on arteriolar and venular smooth muscle in rat skeletal muscle microcirculation.
Authors: J E Faber
Journal: Circulation Research (1988)

The purpose of this study was to determine whether both alpha 1- and alpha 2-adrenergic receptors exist on vascular smooth muscle of microvessels and whether adrenergic constriction of anatomically distinct microvascular segments is differentially subserved by either receptor subtype. The cremaster skeletal muscle of anesthetized rats was acutely denervated and suspended in a Krebs bath containing cocaine, normetanephrine, and propranolol to block uptake1, uptake2, and beta-receptors, respectively. Intravital microscopy was used to study large distributing arterioles (mean diameter, 100 microns), small precapillary arterioles (25 microns), and capacitance venules (140 microns). Concentration-response (diameter change) curves were obtained for bath-added agonists norepinephrine (mixed alpha 1/alpha 2), phenylephrine (alpha 1), and B-HT 933 (alpha 2) in the absence or presence of antagonists prazosin (alpha 1) and yohimbine (alpha 2). Apparent pD2(-log ED50) values for large arterioles and venules were, respectively, as follows: norepinephrine (7.41 and 7.15), phenylephrine (5.95 and 5.41), and B-HT 933 (5.05 and 5.06). Low concentrations of prazosin (10(-8) M) and yohimbine (10(-7) M) produced receptor subtype-selective antagonism and parallel, dextral displacement of norepinephrine curves for large arterioles and venules. The large arteriole pKB (-log KB) was 7.83 +/- 0.65 for prazosin and 7.36 +/- 0.46 for yohimbine. Higher concentrations of prazosin (10(-7) and 3 X 10(-7) M) and yohimbine (10(-6) M) produced further dextral but nonparallel displacement of norepinephrine curves. In contrast, receptor subtype-selective concentrations of only yohimbine inhibited adrenergic constriction of small, precapillary arterioles; but prazosin had no effect at receptor subtype-selective concentrations. These data suggest that adrenergic regulation of large arterioles and venules in skeletal muscle uses both alpha 1- and alpha 2-adrenoceptors. Precapillary arterioles, however, may be subserved predominantly by alpha 2-receptors.
Cardiac hypertrophy associated with myeloproliferative neoplasms in JAK2V617F transgenic mice
Authors: Kaiyao Shi, Wanke Zhao, Yun Chen, Wanting Tina Ho, Ping Yang, Zhizhuang Joe Zhao
Journal: Journal of Hematology & Oncology (2014)

Myeloproliferative neoplasms (MPNs) are blood malignancies manifested in increased production of red blood cells, white blood cells, and/or platelets. A major molecular lesion associated with the diseases is JAK2V617F, an activation mutation form of tyrosine kinase JAK2. Cardiovascular events represent the leading cause of morbidity and mortality associated MPNs, but the underlying mechanism is not well understood. Previously, we generated JAK2V617F transgenic mice which displayed MPN-like phenotypes. In the present study, we further characterized these mice by analyzing the time course of MPN phenotype development and associated cardiac abnormalities. We performed detailed histochemical staining of cardiac sections. JAK2V617F transgenic mice developed cardiomegaly as a subsequent event of increased blood cell production during the course of MPN phenotype development. The cardiomegaly is manifested in increased ventricular wall thickness and enlarged cardiomyocytes. Trichrome and reticulin staining revealed extensive collagen fibrosis in the heart of JAK2V617F transgenic mice. Thrombosis in the coronary artery and inflammatory cell infiltration into cardiac muscle were also observed in JAK2V617F transgenic mice, and the latter event was accompanied by fibrosis. JAK2V617F-induced blood disorders have a major impact on heart function and lead to cardiac hypertrophy. JAK2V617F transgenic mice represent an excellent model system to study both hematological malignancies and cardiovascular diseases.
The Hyperglycemia and Adverse Pregnancy Outcome Study
Authors: Patrick M. Catalano, H. David McIntyre, J. Kennedy Cruickshank, David R. McCance, Alan R. Dyer, Boyd E. Metzger, Lynn P. Lowe, Elisabeth R. Trimble, Donald R. Coustan, David R. Hadden, Bengt Persson, Moshe Hod, Jeremy J.N. Oats
Journal: Diabetes Care (2012)

To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.
755 5-YEAR ENTECAVIR TREATMENT IN NUC-NAÏVE, FIELD-PRACTICE PATIENTS WITH CHRONIC HEPATITIS B SHOWED EXCELLENT VIRAL SUPPRESSION AND SAFETY PROFILE BUT NO PREVENTION OF HCC IN CIRRHOTICS
Authors: P. Lampertico, R. Soffredini, M. Viganò, E. Minola, G. Cologni, M. Rizzi, S. Zaltron, A. Vavassori, F. Castelli, E. Angeli, G.A. Gubertini, C. Magni, G. Rizzardini, A. Testa, G. D'Offizi, M. Vinci, G. Pinzello, E. Fatta, S. Fargion, S. Colombo, O. Fracassetti, P. Del Poggio, B. Coco, M.R. Brunetto, M. Andreoletti, A. Colli, M. Fasano, T. Santantonio, G. Colloredo, L. Pasulo, S. Fagiuoli, A.E. Colombo, G. Bellati, M. Milanese, M. Strazzabosco, M. Pozzi, N. Terreni, G. Spinzi, M. Quagliuolo, M. Borzio, G. Lunghi, F. Facchetti, F. Invernizzi, M. Colombo
Journal: Journal of Hepatology (2013)
Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features
Authors: Lori J. Goldstein, Robert Gray, Sunil Badve, Barrett H. Childs, Carl Yoshizawa, Steve Rowley, Steven Shak, Frederick L. Baehner, Peter M. Ravdin, Nancy E. Davidson, George W. Sledge, Edith A. Perez, Lawrence N. Shulman, Silvana Martino, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2008)

Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features.A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory.Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18).The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.
Endogenous oncogenic Nras mutation promotes aberrant GM-CSF signaling in granulocytic/monocytic precursors in a murine model of chronic myelomonocytic leukemia
Authors: Jinyong Wang, Yangang Liu, Zeyang Li, Juan Du, Myung-Jeom Ryu, Philip R. Taylor, Mark D. Fleming, Ken H. Young, Henry Pitot, Jing Zhang
Journal: Blood (2010)
Erythropoiesis-Stimulating Agent Use in Cancer: Preclinical and Clinical Perspectives
Authors: Murat O. Arcasoy
Journal: Clinical Cancer Research (2008)

Abstract Erythropoiesis-stimulating agents (ESA) used for the treatment of chemotherapy-induced anemia in cancer patients have been associated with adverse outcomes of enhanced tumor progression and impaired survival in a series of recent clinical trials. As clinical practice guidelines for ESA administration in cancer patients have evolved to improve safety, the mechanisms underlying the adverse outcomes and whether ESAs exert direct and/or indirect effects in primary tumors to modulate tumor cell growth, survival, and chemoradiotherapy responses remain uncertain. Erythropoietin receptor (EpoR) expression in tumor cells has raised the simplistic possibility that Epo signaling mediated via a functional cellular receptor may contribute to tumor progression in a direct manner. However, Epo biology in cancer is likely to be complex and an interplay of multiple factors is potentially involved in the overall tumor response to exogenous Epo. Optimization of ESA use as an important supportive therapy modality in cancer patients, and further investigation of the role of Epo-EpoR in cancer biology will require a combination of carefully designed preclinical and clinical studies designed to ascertain not only the effect of ESA therapy on clinical outcomes such as tumor response, progression-free, and overall survival but also to investigate the potential effects of Epo on biomarkers of EpoR activation and factors related to tumor biology and chemoradiation responsiveness.
Dexamethasone, Prostaglandin A, and Retinoic Acid Modulation of Murine and Human Melanoma Cells Grown in Soft Agar&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M D Bregman, E Peters, D Sander, F L Meyskens
Journal: JNCI Journal of the National Cancer Institute (1983)

The cloning efficiencies of a murine melanoma cell line (S91 CCL 53.1) and a human melanoma cell strain (C8146c) were inhibited by dexamethasone (DEX), prostaglandin A1 (PGA1), and beta-all-trans-retinoic acid (RA) in a dose-dependent manner. Murine melanoma tumor colony-forming units (MTCFU) were inhibited more than 99% by DEX (1 X 10(-7) M) and RA (1 X 10(-7) M) with a concentration needed to produce a 50% reduction in colony formation for both hormones of 5 X 10(-9) M. Combinations of DEX and RA effected a synergistic inhibition on colony formation, which was reflected by a 11/2 log reduction in the hormone concentration needed to produce a greater than 99% inhibition of colony formation. When PGA1 was added to DEX and RA, a greater than additive reduction in colony formation was observed. Human MTCFU from cell strain C8146c were inhibited more than 85% at an RA concentration of 1 X 10(-7) M, but they were reduced only to 40% of control at a DEX concentration of 1 X 10(-6) M. DEX-RA produced an additive inhibition of colony formation. Addition of submaximal amounts of PGA1 to DEX-RA combinations or to either hormone alone resulted in synergistic reduction of human MTCFU. These results demonstrated that the proliferative potential of human and murine melanomas can be simultaneously regulated by DEX, PGA1, and RA.
The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men
Authors: Tomoko Kuroda-Kawaguchi, Helen Skaletsky, Laura G. Brown, Patrick J. Minx, Holland S. Cordum, Robert H. Waterston, Richard K. Wilson, Sherman Silber, Robert Oates, Steve Rozen, David C. Page
Journal: Nature Genetics (2001)
Human health and nature conservation
Authors: Ambra Burls, Woody Caan
Journal: BMJ (2005)

genome sequences between dogs, horses, cats, and humans is well advanced, 6 7 with progress also in pigs, cattle, and sheep.Dogs combine exceptional phenotypic diversity, exemplified by breed differences in size and lifespan, with a relatively uniform genotype.Among some 370 canine genetic disorders, about half have exact human analogues. 8They generally resemble the human disease more closely than do rodent models, reflecting closer evolutionary kinship and DNA sequence identity. 9 The National Human Genome Research Institute regards the canine genome as a key research priority.Molecular genetics adds new dimensions to comparative studiesidentification of novel disease genes, new disease models, new molecular targets for drugs, evaluation of gene therapy, and elucidation of genotypic variation in therapeutic responses.Comparative medicine emerged from the realisation that humans and animals shared similar cellular structures and mechanisms and faced challenges from similar microorganisms.But disease models were just that; resemblances between diseases.Now molecular science can show identical receptors, mediators, and genes.This should not surprise us, unless we are creationists; we share a rich evolutionary legacy of genes, many involved in diseases.Comparative medicine is no longer the study of mere similarities but of the same disease in different species.We need parallel development of comparative clinical studies and research in molecular genetics.The Comparative Clinical Science Panel should provide the necessary strategic coherence to yield knowledge and reduce suffering, unfettered by species. 10 In 1988 Stewart Cameron wrote: "Too little attention has been paid to comparison of human and spontaneous animal disease, either by veterinarians or physicians, and it is to be hoped that greater exchange of information can be organised in future." 11With the development of the Comparative Clinical Science Panel, this hope may now be fulfilled.
Denervation suppresses gastric tumorigenesis
Authors: Chun-Mei Zhao, Yoku Hayakawa, Yosuke Kodama, Sureshkumar Muthupalani, Christoph B. Westphalen, Gøran T. Andersen, Arnar Flatberg, Helene Johannessen, Richard A. Friedman, Bernhard W. Renz, Arne K. Sandvik, Vidar Beisvag, Hiroyuki Tomita, Akira Hara, Michael Quante, Zhishan Li, Michael D. Gershon, Kazuhiro Kaneko, James G. Fox, Timothy C. Wang, Duan Chen
Journal: Science Translational Medicine (2014)

Surgical or pharmacologic interruption of muscarinic innervation to the stomach suppresses gastric tumor growth in mice and humans.
Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention
Authors: R. Benamouzig, B. Uzzan, A. Martin, J. Deyra, J. Little, B. Girard, S. Chaussade
Journal: Gut (2010)

Low-dose aspirin reduces the incidence of colorectal cancer and recurrence of adenomas. Cyclooxygenase-2 (COX-2), one of its main target enzymes, is reportedly over-expressed in colorectal adenomas.To assess COX-2 expression, in relation to adenoma recurrence and the protective effect of aspirin, in a large series of colorectal adenomas, recruited from a double-blind randomised controlled trial comparing recurrences after low-dose aspirin or placebo.Follow-up colonoscopies were performed after 1 and 4 years to assess adenoma recurrence. COX-2 expression was assessed by immunohistochemistry for each adenoma obtained at baseline colonoscopy, separately for epithelium, deep stroma and overall. Architecture, grade of dysplasia, K-ras mutation, p53 and cyclin D1 expression were studied.COX-2 expression could be assessed in 219 adenomas from 136128 adenomas (58%) from 59 patients strongly expressed COX-2. Strong COX-2 expression predominated in adenomas larger than 10 mm (84/129 vs 44/90; p=0.02) and in adenomas showing high-grade dysplasia (22/29 vs 104/188; p=0.04). Deep stromal but not epithelial initial expression of COX-2 predicted adenoma recurrence in the whole population (30/72 patients or 42% strongly expressed deep stromal COX-2 compared with 16/64 or 25% without recurrent adenoma; p=0.04). The protective effect of aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR for recurrence in patients taking aspirin with low COX-2 expression: 0.59; 95% CI 0.39 to 0.90; p=0.02). There was no significant effect of aspirin at the end of the trial.Over-expression of COX-2 was frequent and predominated in large and high-grade dysplasia adenomas. Deep stromal but not epithelial initial expression of COX-2 predicted recurrence of adenomas. Aspirin did not act preferentially on patients whose initial adenomas strongly expressed COX-2.
Identification of a T cell hybridoma that produces large quantities of macrophage-activating factor.
Authors: R D Schreiber, A Altman, D H Katz
Journal: The Journal of Experimental Medicine (1982)

A murine T cell hybridoma, constructed by fusion of alloantigen-activated T cells with the BW5147 T cell lymphoma, which produces a lymphokine capable of inducing tumoricidal activity in macrophages, has been identified. Lymphokine release could be detected only after mitogen stimulation of the T cell hybridoma culture. Upon cloning of the parental hybridoma, 24 out of 27 clones produced tumoricidal-inducing activity. Seven clones produced more cytocidal-inducing activity than did conventional supernatants, generated by concanavalin A stimulation of normal murine spleen cell cultures, which contained macrophage-activating factor (MAF). The supernatant of hybridoma clone 24/G1 was 25 times more active than conventional MAF preparations. Using supernatants from a variety of clones, the levels of macrophage-activating activity and interleukin 2 were found to vary independently of one another. The lymphokine produced by hybridoma clone 24/G1 appeared to be identical to conventional MAF by a variety of criteria including: (a) a requirement for a second signal for induction of tumoricidal activity in macrophages, (b) inactivation after incubation for 1 h at 65 degrees C, and (c) loss of activity after treatment at pH 4.0 but not at pH 5.0. Like conventional MAF, the hybridoma MAF eluted as a single peak after molecular sieve chromatography on Sephadex G100 and exhibited an apparent molecular weight of 55,000. Although somewhat heterogeneous, the majority of hybridoma 24/G1 MAF displayed an isoelectric point of 5.4 as determined using the chromatofocusing technique. These results thus illustrate the usefulness of T cell hybridomas in distinguishing between various lymphokine activities and indicate that the T cell hybridoma clone 24/G1 will be of particular usefulness in achieving the biochemical purification of substantial quantities of murine MAF.
Pharmacokinetics of Rifapentine at 600, 900, and 1,200 mg during Once-Weekly Tuberculosis Therapy
Authors: Marc Weiner, Naomi Bock, Charles A. Peloquin, William J. Burman, Awal Khan, Andrew Vernon, Zhen Zhao, Stephen Weis, Timothy R. Sterling, Katherine Hayden, Stefan Goldberg
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly continuation phase therapy in 35 patients with tuberculosis. Mean area under the plasma concentration–time curve (AUC0–∞) increased significantly with dose (rifapentine AUC0–∞: 296, 410, and 477 μg · hour/ml at 600, 900, and 1,200 mg, respectively; p = 0.02 by linear regression). In multivariate stepwise regression analyses, AUC0–∞ values for rifapentine and the active 25-desacetyl metabolite were associated with drug dose and plasma albumin concentration, and were lower among men and among white individuals. Fifty-four percent of patients had total (free and protein-bound) plasma concentrations of rifapentine and of desacetyl rifapentine detected for more than 36 hours after clearance of concurrently administered isoniazid. Serious adverse effects of therapy in these study patients were infrequent (1 of 35 cases; 3%) and not linked with higher rifapentine AUC0–∞ or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis.
Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity
Authors: Vincent Cottin, H. Nunes, P.Y. Brillet, Pierre-Edouard Delaval, G. Devouassoux, I. Tillie-Leblond, D. Israel-Biet, I. Court-Fortune, D. Valeyre, Jean-François Cordier, . Hôpital Louis Pradel - Groupe D’etudes Et de Recherche Sur Les Maladies "orphelines" Pulmonaires (germ"o"p)
Journal: European Respiratory Journal (2005)

The syndrome resulting from combined pulmonary fibrosis and emphysema has not been comprehensively described. The current authors conducted a retrospective study of 61 patients with both emphysema of the upper zones and diffuse parenchymal lung disease with fibrosis of the lower zones of the lungs on chest computed tomography. Patients (all smokers) included 60 males and one female, with a mean age of 65 yrs. Dyspnoea on exertion was present in all patients. Basal crackles were found in 87% and finger clubbing in 43%. Pulmonary function tests were as follows (mean+/-sd): total lung capacity 88%+/-17, forced vital capacity (FVC) 88%+/-18, forced expiratory volume in one second (FEV1) 80%+/-21 (% predicted), FEV1/FVC 69%+/-13, carbon monoxide diffusion capacity of the lung 37%+/-16 (% predicted), carbon monoxide transfer coefficient 46%+/-19. Pulmonary hypertension was present in 47% of patients at diagnosis, and 55% during follow-up. Patients were followed for a mean of 2.1+/-2.8 yrs from diagnosis. Survival was 87.5% at 2 yrs and 54.6% at 5 yrs, with a median of 6.1 yrs. The presence of pulmonary hypertension at diagnosis was a critical determinant of prognosis. The authors hereby individualise the computer tomography-defined syndrome of combined pulmonary fibrosis and emphysema characterised by subnormal spirometry, severe impairment of gas exchange, high prevalence of pulmonary hypertension, and poor survival.
Human Rhinovirus Species Induce Differential Antiviral and Inflammatory Responses in Peripheral Blood Mononuclear Cells
Authors: Alalia W. Berry, Megan Yanny, Mark DeVries, Yury Bochkov, Victoria Rajamanickam, James E. Gern, Robert F. Lemanske, Daniel J. Jackson
Journal: Journal of Allergy and Clinical Immunology (2015)
Effect of Catecholamines and Adrenergic Blocking Agents on Oxidative Phosphorylation in Rat Heart Mitochondria
Authors: BURTON SOBEL, ERIC JEQUIER, ALBERT SJOERDSMA, WALTER LOVENBERG
Journal: Circulation Research (1966)

Polarographic methods were used to examine oxidative phosphorylation in mitochondria isolated from hearts of rats treated with 5 mg/kg epinephrine, norepinephrine, or isoproterenol in oil given subcutaneously. Uncoupling of oxidative phosphorylation occurred (P/O ratio 2.1 ± .04 compared to P/O ratio of controls, 2.9 ± .03). Other indices of mitochondrial function, including oxygen consumption, respiratory control, adenosinetriphosphatase activity, and swelling were normal. The time course of depression of P/O ratio was parallel to that of myocardial catecholamine uptake, yet normal mitochondria were not affected by catecholamines in vitro (10 -3 M). Adrenergic blocking agents in vitro did not improve the function of mitochondria from catecholamine-treated animals. No free fatty acids were detectable in extracts of mitochondria from either group by gas liquid chromatography, and the lipid profiles of extracts from each were similar by thin layer chromatography. The data indicate a means by which large quantities of exogenous or endogenous catecholamines could lead to increased oxygen consumption in vivo, or contribute to impairment of myocardial function.