tbuckley/cabot-search huggingface dataset:
Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive rats. The ventricle is a major site of synthesis and secretion of brain natriuretic peptide.
Authors: Y Ogawa, K Nakao, M Mukoyama, K Hosoda, G Shirakami, H Arai, Y Saito, S Suga, M Jougasaki, H Imura
Journal: Circulation Research (1991)

To study synthesis, storage, and secretion of brain natriuretic peptide (BNP) in the heart, we have measured BNP mRNA and BNP concentrations in the hearts of Wistar-Kyoto rats and also have investigated its secretion from the isolated perfused heart. The atrium expressed the BNP gene at a high level, and a considerable amount of BNP mRNA also was present in the ventricle, which corresponded to approximately 40% of the atrial BNP mRNA concentration. When tissue weight was taken into account, the total content of BNP mRNA in the ventricle was approximately threefold larger than that in the atrium, although the atrial natriuretic peptide (ANP) mRNA content in the ventricle was only 7% of that in the atrium. By contrast, the BNP concentration in the ventricle was 4.07 +/- 0.97 pmol/g, which was less than 1% of that in the atrium (451 +/- 86 pmol/g). The basal secretory rate of BNP from the isolated perfused whole heart was 49.3 +/- 6.1 fmol/min, approximately 60% of which was maintained even after atrial removal, whereas the secretory rate of ANP was reduced to less than 5%. We also studied age-matched spontaneously hypertensive rats-stroke prone. The rank order of the BNP mRNA concentration in the hearts of these rats was left ventricle greater than right ventricle greater than right atrium = left atrium, and the total BNP mRNA content and BNP secretory rate in the ventricle were twice as large as in Wistar-Kyoto rats. These results demonstrate that BNP is a novel cardiac hormone in rats and is predominantly synthesized in and secreted from the ventricle. This is in striking contrast to ANP, which occurs mainly in the atrium. The results also suggest possible pathophysiological roles of BNP in certain cardiovascular disorders.
Does the change in season affect disease activity in patients with psoriatic arthritis?
Authors: Zahi Touma, Arane Thavaneswaran, Vinod Chandran, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2012)

To determine whether there is seasonal variation in disease activity of patients with psoriatic arthritis (PsA).The authors identified the first available set of consecutive summer and winter visits for every patient from the prospective cohort of PsA. Comparison between summer and winter visits, and comparison of the repeated summer/winter visits, from 1978 until 2011 for the same identified patients was conducted for demographics, disease activity outcomes, laboratory results and treatment. The authors categorised disease activity into high, moderate and low states, and improvement versus flare/worsening. Descriptive statistics were computed and multivariate analyses using logistic regression and generalised estimating equations were conducted.The first available summer and winter visit were identified for 253 patients, and 1789 observations were analysed. There was no statistically significant difference in patients' demographics, disease activity outcomes, laboratory results and treatment between summer and winter visits. Bath Ankylosing Spondylitis Disease Activity Index scores were greater for summer visits and patients graded their disease as being worse in winter as compared with summer in the univariate analysis, but this difference did not hold in the multivariate analysis.The change in season does not affect PsA patients' characteristics and disease activity outcomes as determined by the physicians and patients.
Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts
Authors: Moshe Talpaz, Ronald Paquette, Lawrence Afrin, Solomon I Hamburg, Josef T Prchal, Katarzyna Jamieson, Howard R Terebelo, Gregory L Ortega, Roger M Lyons, Ramon V Tiu, Elliott F Winton, Kavita Natrajan, Olatoyosi Odenike, David Claxton, Wei Peng, Peter O’Neill, Susan Erickson-Viitanen, Lance Leopold, Victor Sandor, Richard S Levy, Hagop M Kantarjian, Srdan Verstovsek
Journal: Journal of Hematology & Oncology (2013)

Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts. ClinicalTrials.gov: NCT01348490 .
A mutant, noninhibitory plasminogen activator inhibitor type 1 decreases matrix accumulation in experimental glomerulonephritis
Authors: Yufeng Huang, Masashi Haraguchi, Daniel A. Lawrence, Wayne A. Border, Ling Yu, Nancy A. Noble
Journal: Journal of Clinical Investigation (2003)

In fibrotic renal disease, elevated TGF-β and angiotensin II lead to increased plasminogen activator inhibitor type 1 (PAI-1). PAI-1 appears to reduce glomerular mesangial matrix turnover by inhibiting plasminogen activators, thereby decreasing plasmin generation and plasmin-mediated matrix degradation. We hypothesized that therapy with a mutant human PAI-1 (PAI-1R) that binds to matrix vitronectin but does not inhibit plasminogen activators, would enhance plasmin generation, increase matrix turnover, and decrease matrix accumulation in experimental glomerulonephritis. Three experimental groups included normal, untreated disease control, and PAI-1R–treated nephritic rats. Plasmin generation by isolated day 3 glomeruli was dramatically decreased by 69%, a decrease that was reversed 43% (P < 0.02) by in vivo PAI-1R treatment. At day 6, animals treated with PAI-1R showed significant reductions in proteinuria (48%, P < 0.02), glomerular staining for periodic acid–Schiff positive material (33%, P < 0.02), collagen I (28%, P < 0.01), collagen III (34%, P < 0.01), fibronectin (48%, P < 0.01), and laminin (41%, P < 0.01), and in collagen I (P < 0.01) and fibronectin mRNA levels (P < 0.02). Treatment did not alter overexpression of TGF-β1 and PAI-1 mRNAs, although TGF-β1 protein was significantly reduced. These observations strongly support our hypothesis that PAI-1R reduces glomerulosclerosis by competing with endogenous PAI-1, restoring plasmin generation, inhibiting inflammatory cell infiltration, decreasing local TGF-β1 concentration, and reducing matrix accumulation.
ANTIMICROBIAL AGENTS IN THE PREVENTION OF DIETARY HEPATIC INJURY (NECROSIS, CIRRHOSIS) IN RATS
Authors: Paul György, Joseph Stokes, Harry Goldblatt, Hans Popper
Journal: The Journal of Experimental Medicine (1951)

The effect of various antimicrobial agents, such as aureomycin, terramycin, streptomycin, chloromycetin, penicillin, polymyxin, and sulfaguanidine on the development of massive dietary necrosis of the liver in rats has been studied. Delay in the production of hepatic necrosis was obtained from aureomycin and, to a lesser extent, from terramycin and streptomycin. Indication of temporary protection was shown by sulfaguanidine, whereas chloromycetin, polymyxin, and penicillin were not protective. B12, added alone, or in combination with aureomycin, to the basal experimental diet had no influence on the development of hepatic necrosis. A combination of pectin with streptomycin enhanced the protective effect of the antibiotic. All the antimicrobial agents tested, without relation to their effect on hepatic necrosis, produced temporary stimulation of growth in the experimental animals. The beneficial effect of aureomycin was not limited to the delay of hepatic necrosis but manifested itself also in the prevention of hepatic cirrhosis in rats fed a low protein (casein)-high fat diet. In contrast to control animals showing the usual combination of cirrhosis and renal changes, the rats receiving supplements of aureomycin were free of both cirrhosis and renal changes. The rats receiving aureomycin took more food in and gained weight. No microscopic alterations were seen in the pancreas of the control rats with cirrhosis. In both groups of experiments (necrosis and cirrhosis) the antimicrobial agents, with the exception of penicillin, were given mixed with the food. Their possible effect on the intestinal flora is discussed.
Hyperinsulinemia and blood pressure sensitivity to sodium in young blacks.
Authors: B Falkner, S Hulman, H Kushner
Journal: Journal of the American Society of Nephrology (1992)

The relationship of blood pressure sensitivity to sodium with plasma insulin concentration was examined in young adult (22 to 28 yr) blacks (N = 45). The study included normotensive and borderline hypertensive subjects. Blood pressure sensitivity to sodium was determined by the change in mean blood pressure after 14 days of sodium loading (10 g of NaCl daily plus usual diet). Plasma insulin concentration was determined during an oral glucose tolerance test (OGTT). The correlation of fasting plasma insulin concentration with blood pressure or blood pressure sensitivity to sodium was not statistically significant. There was a significant correlation (after adjustment for adiposity) of blood pressure sensitivity to sodium with both the sum of insulin (r = 0.41; P < 0.01) and the 60-min plasma insulin concentration during the OGTT. The plasma insulin concentration at 60 min during the OGTT correlated significantly with the change in mean arterial pressure over a 5-yr interval (r = 0.36; P < 0.02). There was a similar significant correlation of blood pressure sensitivity to sodium with change in mean arterial pressure over 5 yr (r = 0.48; P < 0.001). These data demonstrate an association of hyperinsulinemia and blood pressure sensitivity to sodium in the young. The data also suggest that insulin may contribute to the pathogenesis of hypertension in the black population.
C-Reactive Protein Levels and Outcomes after Statin Therapy
Authors: Paul M Ridker, Christopher P. Cannon, David Morrow, Nader Rifai, Lynda M. Rose, Carolyn H. McCabe, Marc A. Pfeffer, Eugene Braunwald
Journal: New England Journal of Medicine (2005)

Statins lower the levels of low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP). Whether this latter property affects clinical outcomes is unknown.
Advances in Diagnostic Bronchoscopy
Authors: Andrew R. Haas, Anil Vachani, Daniel H. Sterman
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Diagnostic bronchoscopy has undergone two major paradigm shifts in the last 40 years. First, the advent of flexible bronchoscopy gave chest physicians improved access to the tracheobronchial tree with a rapid learning curve and greater patient comfort compared with rigid bronchoscopy. The second paradigm shift has evolved over the last 5 years with the proliferation of new technologies that have significantly enhanced the diagnostic capabilities of flexible bronchoscopy compared with traditional methods. At the forefront of these new technologies is endobronchial ultrasound. In its various forms, endobronchial ultrasound has improved diagnostic yield for pulmonary masses, nodules, intrathoracic adenopathy, and disease extent, thereby reducing the need for more invasive surgical interventions. Various navigational bronchoscopy systems have become available to increase flexible bronchoscope access to small peripheral pulmonary lesions. Furthermore, various modalities of airway assessment, including optical microscopic imaging technologies, may play significant roles in the diagnosis of a variety of pulmonary diseases in the future. Finally, the combination of new diagnostic bronchoscopy technologies and novel approaches in molecular analysis and biomarker assessment hold promise for enhanced diagnosis and personalized management of many pulmonary disorders. In this review, we provide a contemporary review of diagnostic bronchoscopy developments over the past decade.
STUDIES IN PORPHYRIA
Authors: H. Leon Bradlow, Peter N. Gillette, T. F. Gallagher, Attallah Kappas
Journal: The Journal of Experimental Medicine (1973)

Patients with the genetic liver disease, acute intermittent porphyria (AIP), have a defect in the reductive transformation of steroid hormones that is manifest by the disproportionate generation of 5beta-steroid metabolites from precursor hormones. 5beta-steroid metabolites were earlier shown to be potent inducers experimentally of delta-aminolevulinate synthetase (ALAS), the mitochondrial enzyme that is rate-limiting in porphyrin synthesis, and that is found at high levels of activity in the livers of AIP patients. In this report, the basis for the defective steroid metabolism in AIP has been shown, through studies with the (14)C-labeled adrenal hormone 11beta-hydroxy-Delta(4)-androstenedione, to reside in a substantial deficiency of hepatic steroid Delta(4)-5alpha-reductase activity. This enzymic deficiency was found in all seven AIP patients studied, and ranged from 34% to as much as 70% below the mean enzyme activity characterizing normal subjects. The functional consequence of the low levels of 5alpha-reductase activity in AIP is to divert the reductive transformation of certain natural hormones from the 5alpha- to the 5beta-pathway; the latter is the metabolic route through which endogenous steroids having the potential for inducing hepatic ALAS are generated. It is not presently known whether the 5alpha-reductase deficiency in AIP is acquired in some fashion or whether it has partial genetic determinants. It seems probable, however, that this enzymatic abnormality, coupled with the dramatic increase in hormone synthesis that occurs at puberty, may be of major importance in determining clinical expression of the latent gene defect for AIP in many individuals. The 5alpha-reductases for steroid hormones are known to be localized in the endoplasmic reticulum of hepatic cells and the present findings in AIP thus represent the first demonstration that an enzymic component of these membranous structures is functionally abnormal in this hereditary liver disease.
Direct Serum Bilirubin and the Sulfobromophthalein Test in Occult Liver Disease
Authors: S. Raymond Gambino
Journal: JAMA (1967)

When a sensitive method for measuring direct serum bilirubin (DB) was used, a third of the patients with liver or biliary tract disease had elevated DB levels, but normal levels of total serum bilirubin (TB). The correlation of DB and sulfobromophthalein (BSP) retention was studied because DB and BSP are cleared through the same hepatic pathway. Our findings support the clinical and chemical validity of DB measurements as an index of occult liver disease.
Possible Predictive Tests for Malignant Hyperthermia During Anesthesia
Authors: J. Antonio Aldrete
Journal: JAMA (1971)

A 17-year-old patient survived an episode of fulminant hyperpyrexia during anesthesia with methohexital sodium, nitrous oxide, halothane, and succinylcholine. Five months later, studies performed in his immediate family revealed high creatine phosphokinase (CPK) values in him and slightly elevated values in his mother, brother, sister, and one maternal uncle and grandmother. The patient, his mother, brother, and sister were also found to have elevated serum pyrophosphate (P-P). Upper borderline levels of lactic dehydrogenase occur at expenses of its fraction III. These tests may have possible predictive value in identifying susceptible patients.
Neural Substrates of Language Acquisition
Authors: Patricia Kuhl, Maritza Rivera-Gaxiola
Journal: Annual Review of Neuroscience (2008)

Infants learn language(s) with apparent ease, and the tools of modern neuroscience are providing valuable information about the mechanisms that underlie this capacity. Noninvasive, safe brain technologies have now been proven feasible for use with children starting at birth. The past decade has produced an explosion in neuroscience research examining young children's processing of language at the phonetic, word, and sentence levels. At all levels of language, the neural signatures of learning can be documented at remarkably early points in development. Individual continuity in linguistic development from infants' earliest responses to phonemes is reflected in infants' language abilities in the second and third year of life, a finding with theoretical and clinical implications. Developmental neuroscience studies using language are beginning to answer questions about the origins of humans' language faculty.
Conservative management of early-stage epithelial ovarian cancer: results of a large retrospective series
Authors: R. Fruscio, S. Corso, L. Ceppi, D. Garavaglia, A. Garbi, I. Floriani, D. Franchi, M.G. Cantù, C.M. Bonazzi, R. Milani, C. Mangioni, N. Colombo
Journal: Annals of Oncology (2012)
Ex vivo cytokine release reflects sensitivity to occupational endotoxin exposure
Authors: L. A. M. Smit, D. Heederik, G. Doekes, E. J. M. Krop, G. T. Rijkers, I. M. Wouters
Journal: European Respiratory Journal (2009)

Not everyone exposed to endotoxin develops respiratory symptoms, even at very high exposure levels. The aim was to investigate whether ex vivo lipopolysaccharide (LPS)-induced cytokine release may be predictive of individual sensitivity to occupational endotoxin exposure. In 412 agricultural workers, tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 release was measured in supernatants from LPS-stimulated whole blood, lung function was measured, and respiratory symptoms were assessed by questionnaire. For each cytokine, the population was dichotomised into low and high responders according to median cytokine concentrations. Endotoxin exposure levels were determined based on 249 personal exposure measurements. High IL-10 responders had a higher prevalence of airway symptoms than low IL-10 responders (odds ratios between 2.03 and 5.10; p&lt;0.05). TNF-α response was positively, but not significantly, associated with symptoms, whereas no relationship was found between IL-1β response and symptoms. For all three cytokines, subjects with above-median responses showed significant positive dose–response relationships between endotoxin exposure and asthma symptoms, and significant associations between endotoxin exposure and a lower forced expiratory volume in 1 s (p&lt;0.05). In contrast, exposure–response relationships were weak and statistically nonsignificant for low responders. The ex vivo inflammatory response to LPS reflects, to a large extent, whether individuals are susceptible to adverse respiratory effects induced by high occupational endotoxin exposure.
New echocardiographic predictors of clinical outcome in patients presenting with heart failure and a preserved left ventricular ejection fraction: a subanalysis of the Ka (Karolinska) Ren (Rennes) Study
Authors: Erwan Donal, Lars H. Lund, Emmanuel Oger, Camilla Hage, Hans Persson, Amélie Reynaud, Pierre‐Vladimir Ennezat, Fabrice Bauer, Elodie Drouet, Cecilia Linde, Claude Daubert
Journal: European Journal of Heart Failure (2015)
Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules
Authors: Sunita Patel-Hett, Jennifer L. Richardson, Harald Schulze, Ksenija Drabek, Natasha A. Isaac, Karin Hoffmeister, Ramesh A. Shivdasani, J. Chloë Bulinski, Niels Galjart, John H. Hartwig, Joseph E. Italiano
Journal: Blood (2008)
Gene Therapy Prolongs Survival and Restores Function in Murine and Canine Models of Myotubular Myopathy
Authors: Martin K. Childers, Romain Joubert, Karine Poulard, Christelle Moal, Robert W. Grange, Jonathan A. Doering, Michael W. Lawlor, Branden E. Rider, Thibaud Jamet, Nathalie Danièle, Samia Martin, Christel Rivière, Thomas Soker, Caroline Hammer, Laetitia Van Wittenberghe, Mandy Lockard, Xuan Guan, Melissa Goddard, Erin Mitchell, Jane Barber, J. Koudy Williams, David L. Mack, Mark E. Furth, Alban Vignaud, Carole Masurier, Fulvio Mavilio, Philippe Moullier, Alan H. Beggs, Anna Buj-Bello
Journal: Science Translational Medicine (2014)

Intravenous injection of an adeno-associated viral vector expressing the myotubularin ( MTM1 ) gene improves survival and rescues skeletal muscle function in mice and dogs affected by myotubular myopathy.
Attenuated store-operated Ca2+ entry underpins the dual inhibition of nitric oxide and EDHF-type relaxations by iodinated contrast media
Authors: S. Fernandez-Rodriguez, D. H. Edwards, B. Newton, T. M. Griffith
Journal: Cardiovascular Research (2009)

AimsOur objective was to investigate whether alterations in endothelial Ca2+ homeostasis contribute to the clinical toxicity of iodinated radiographic contrast media (IRCM) by modulating nitric oxide (NO) production and the endothelium-derived hyperpolarizing factor (EDHF) phenomenon.
AN EVALUATION OF N-ETHYL-O-CROTONOTOLUIDE AS AN ANTIPRURITIC
Authors: J. M. HITCH
Journal: British Journal of Dermatology (1952)

Journal Article AN EVALUATION OF N‐ETHYL‐O‐CROTONOTOLUIDE AS AN ANTIPRURITIC Get access J. M. HITCH, M.D. J. M. HITCH, M.D. Raleigh, North Carolina, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 64, Issue 11, 1 November 1952, Pages 408–416, https://doi.org/10.1111/j.1365-2133.1952.tb15876.x Published: 01 November 1952