tbuckley/cabot-search huggingface dataset:
β3-adrenoceptor deficiency blocks nitric oxide–dependent inhibition of myocardial contractility
Authors: Paul Varghese, Robert W. Harrison, Robert A. Lofthouse, Dimitrios Georgakopoulos, Dan E. Berkowitz, Joshua M. Hare
Journal: Journal of Clinical Investigation (2000)

The cardiac β-adrenergic pathway potently stimulates myocardial performance, thereby providing a mechanism for myocardial contractile reserve. β-Adrenergic activation also increases cardiac nitric oxide (NO) production, which attenuates positive inotropy, suggesting a possible negative feedback mechanism. Recently, in vitro studies suggest that stimulation of the β3-adrenoceptor results in a negative inotropic effect through NO signaling. In this study, using mice with homozygous β3-adrenoceptor deletion mutations, we tested the hypothesis that the β3-adrenoceptor is responsible for β-adrenergic activation of NO. Although resting indices of myocardial contraction were similar, β-adrenergic–stimulated inotropy was increased in β3–/– mice, and similar hyper-responsiveness was seen in mice lacking endothelial NO synthase (NOS3). NOS inhibition augmented isoproterenol-stimulated inotropy in wild-type (WT), but not in β3–/– mice. Moreover, isoproterenol increased myocardial cGMP in WT, but not β3–/–, mice. NOS3 protein abundance was not changed in β3–/– mice, and cardiac β3-adrenoceptor mRNA was detected in both NOS3–/– and WT mice. These findings indicate that the β3-adrenergic subtype participates in NO-mediated negative feedback over β-adrenergic stimulation.
Isolation of a lipid a bound polypeptide responsible for LPS- initiated mitogenesis of C3H/HeJ spleen cells
Authors: DC Morrison, SJ Betz, DM Jacobs
Journal: The Journal of Experimental Medicine (1976)

The experiments by Sultzer and Nilsson (1), and later by Watson and Riblet (2), established that spleen cells from the C3H/HeJ strain of mouse were refractory to the mitogenic effects of bacterial lipopolysaccharides (LPS). More recently, however, experiments from our laboratory (3) demonstrated that spleen cells from C3H/HeJ mice were in fact responsive to some preparations of LPS but not to others, and that the method of extraction played a critical role in determining activity. In particular, preparations of LPS prepared by extraction with aqueous butanol had potent mitogenic activity. Our data showed that the mitogenic activity of such positive preparations of LPS coisolated with the LPS during gel filtration chromatography and subsequent equilibrium banding on CsCl. In addition, lipid A isolated from positive preparations of LPS was also capable of stimulating C3H/HeJ spleen cells. Taken together, these experiments provided rather convincing data that it was the LPS (in particular the lipid A) itself, or some contaminant very tightly bound to the lipid A, which was responsible for its biological activity. We further demonstrated that treatment of positive preparations of LPS with hot phenol rendered such preparations nonmitogenic for C3H/HeJ spleens, yet activity for other strains was only moderately decreased. These experiments would suggest either that the phenol treatment chemically alters the lipid A region of the LPS molecule or that such treatment removes the putative tightly bound contaminant responsible for C3H/HeJ mitogenesis. In the experiments reported here, we have explored in greater detail the role of lipid A in the stimulation of C3H/HeJ spleen cells. For these experiments we have utilized our earlier observations that the antibiotic polymyxin B forms a highly stable molecular complex with the lipid A region of LPS (4), and that such polymyxin B-LPS complexes are unable to mitogenically stimulate B lymphocytes (5). In addition, we have attempted to distinguish between the two potential modes of action of phenol on LPS, namely, the chemical alteration of the lipid A or the removal of a tightly bound contaminant by phenol treatment. The results of the experiments we report here support the interpretation that mitogenic activity of positive preparations of LPS is associated with a low mol wt phenol soluble polypeptide of approximately 10,000 mol wt. After partial purification, this polypeptide intitiates a significant mitogenic response at concentrations as low as 10 μg/ml. We conclude that the C3H/HeJ strain of mouse is a true nonresponder to the stimulatory effects of the lipid A region of LPS.
A combination of phototherapy and cholestyramine for the relief of pruritus in primary biliary cirrhosis
Authors: R. CERIO, G.M. MURPHY, G.E. SLADEN, D.M. MACDONALD
Journal: British Journal of Dermatology (1987)

Journal Article A combination of phototherapy and cholestyramine for the relief of pruritus in primary biliary cirrhosis R. CERIO, R. CERIO Department of Dermatology, Guy's Hospital, London SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.M. MURPHY, G.M. MURPHY Department of Gastroenterology, Guy's Hospital, London SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.E. SLADEN, G.E. SLADEN Department of Gastroenterology, Guy's Hospital, London SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.M. MACDONALD D.M. MACDONALD Department of Dermatology, Guy's Hospital, London SE1 9RT, U.K. Dr D.M.MacDonald, Department of Dermatology, Guy's Hospital, St Thomas' Street, London, SEI 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 116, Issue 2, 1 February 1987, Pages 265–267, https://doi.org/10.1111/j.1365-2133.1987.tb05825.x Published: 01 February 1987
Transcoronary Transplantation of Progenitor Cells after Myocardial Infarction
Authors: Birgit Assmus, Jörg Honold, Volker Schächinger, Martina B. Britten, Ulrich Fischer-Rasokat, Ralf Lehmann, Claudius Teupe, Katrin Pistorius, Hans Martin, Nasreddin D. Abolmaali, Torsten Tonn, Stefanie Dimmeler, Andreas M. Zeiher
Journal: New England Journal of Medicine (2006)

Pilot studies suggest that intracoronary transplantation of progenitor cells derived from bone marrow (BMC) or circulating blood (CPC) may improve left ventricular function after acute myocardial infarction. The effects of cell transplantation in patients with healed myocardial infarction are unknown.
Bathing suit ichthyosis with summer exacerbation: a temperature-sensitive case
Authors: M. Yamamoto, Y. Sakaguchi, M. Itoh, N. Nakagawa, A. Fukunaga, K. Hitomi, K. Yamanishi
Journal: British Journal of Dermatology (2011)

Journal Article Bathing suit ichthyosis with summer exacerbation: a temperature‐sensitive case Get access M. Yamamoto, M. Yamamoto Department of Dermatology, Hyogo College of Medicine, 1‐1, Mukogawa‐cho, Nishinomiya, Hyogo 663‐8501, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Sakaguchi, Y. Sakaguchi Department of Dermatology, Hyogo College of Medicine, 1‐1, Mukogawa‐cho, Nishinomiya, Hyogo 663‐8501, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Itoh, M. Itoh Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan Search for other works by this author on: Oxford Academic Google Scholar N. Nakagawa, N. Nakagawa Department of Dermatology, Hyogo College of Medicine, 1‐1, Mukogawa‐cho, Nishinomiya, Hyogo 663‐8501, Japan Search for other works by this author on: Oxford Academic Google Scholar A. Fukunaga, A. Fukunaga Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Hitomi, K. Hitomi Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Yamanishi K. Yamanishi Department of Dermatology, Hyogo College of Medicine, 1‐1, Mukogawa‐cho, Nishinomiya, Hyogo 663‐8501, Japan Kiyofumi Yamanishi. E‐mail: kyamanis@hyo‐med.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 3, 1 March 2012, Pages 672–674, https://doi.org/10.1111/j.1365-2133.2011.10594.x Published: 01 March 2012
Making the diagnosis of asthma
Authors: D R. Taylor
Journal: BMJ (1997)

Asthma is becoming more common in all parts of the world, and establishing the diagnosis is as important to clinical practitioners as it is to epidemiologists. For both the “gold standard” is still a clinical diagnosis based on a characteristic pattern of symptoms: episodes of cough, of dyspnoea, and of chest tightness or wheeze. The epidemiologist, however, wants further objective diagnostic tests to distinguish affected from unaffected people and then to compare populations and monitor trends. Most recent prevalence studies have relied on measurements of bronchial hyperresponsiveness to histamine or methacholine or to an exercise challenge as well as on tests of lung function. Toelle et al have proposed that for epidemiological purposes current asthma should be defined as appropriate symptoms in the previous 12 months together with evidence of increased airway responsiveness.1

The need for a clinician to use more specialised diagnostic testing is less clearly defined, but it may be summarised as the need to establish the diagnosis and assess the severity. International guidelines broadly agree on the management of established asthma, but they differ in their emphasis on confirmatory diagnostic testing. The British guidelines do not mention …
Myocardial capillary permeability after regional ischemia and reperfusion in the in vivo canine heart. Effect of superoxide dismutase.
Authors: J H Svendsen, P J Bjerrum, S Haunsø
Journal: Circulation Research (1991)

This study assesses the effect of the superoxide anion scavenger superoxide dismutase on myocardial capillary permeability-surface area (PS) products for small hydrophilic molecules after ischemia and reperfusion. Open-chest dogs underwent a 20-minute occlusion of the left anterior descending coronary artery followed by 1 hour of reperfusion. Myocardial plasma flow rate and capillary extraction of chromium 51-labeled EDTA or technetium 99m-labeled diethylenetriaminepentaacetic acid were measured by the single-injection, residue-detection method before ischemia and 5 and 60 minutes after the start of reperfusion. In 13 dogs, no scavenger treatment was given (nonprotected control group), whereas eight dogs were treated systemically with 15,000 units/kg superoxide dismutase during 1 hour, starting 20 minutes before ischemia. In the control group, three dogs developed reperfusion ventricular fibrillation in contrast to none in the superoxide dismutase group. Before ischemia, plasma flow rate, myocardial capillary extraction fraction, and PS values were similar in the two groups. Five minutes after the start of reperfusion, plasma flow rate increased significantly (p less than 0.01) in both groups. In the control group, capillary extraction fraction increased by 12% (p = NS) in spite of the higher plasma flow; these increases in capillary extraction fraction and plasma flow induced a 69% increase in PS (p less than 0.01). In the superoxide dismutase-treated group, capillary extraction fraction decreased by 32% (p less than 0.05) in accordance with the increased plasma flow rate, resulting in an unchanged PS (p = NS). Sixty minutes after reperfusion, plasma flow rate, capillary extraction fraction, and PS returned to preocclusion values in both groups (p = NS). The increased capillary extraction fraction and PS values seen in the control group suggest an increased capillary permeability after ischemia and reperfusion. Superoxide anions seem to participate, directly or indirectly, in this response.
Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD
Authors: Rahul Katyal
Journal: European Respiratory Journal (2015)

We read with interest the recent article by Vozoris et al. [1], who suggest that benzodiazepine drug use had adverse respiratory outcomes among older adults with chronic obstructive lung disease (COPD). Many studies are in support of this study but we cannot neglect the opposing studies which did not show any adverse effects of benzodiazepines in patients with COPD [2, 3]. American Thoracic Society/European Respiratory Society guidelines [4] state that hypnotics should not be given in patients with "severe" COPD. It would be better if the authors could stage COPD according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Studies of lower dose benzodiazepines and lower dose opioids in patients with COPD were not associated with increased admissions [5]. Short-acting benzodiazepines can be safely used in COPD and might improve quality of life in the elderly <http://ow.ly/DgvXw>
Age–Related Changes in the Endocytic Capacity of Rat Liver Kupffer and Endothelial Cells
Authors: Adriaan Brouwer, Roel J. Barelds, Dick L. Knook
Journal: Hepatology (1985)

There are many indications that the functional capacity of the reticuloendothelial system (RES) declines with age. The aim of this study was to investigate the cellular basis of age-related changes in the clearance function of the RES. The experiments were focused mainly on Kupffer and endothelial cells of the liver which represent a major part of the RES and are primarily responsible for clearance of colloidal material from the circulation. The clearance capacity of the RES was tested clinically and experimentally by intravenous injection of colloids, such as radiolabeled heat-aggregated colloidal albumin. Age-related changes in the endocytosis of 125I-labeled colloidal albumin (CA) in rats were determined by clearance and organ distribution of different doses of intravenously injected CA, uptake of CA by Kupffer and endothelial liver cells in vivo as determined after isolation of the cells from injected rats and kinetic studies on CA uptake by Kupffer cells in culture. The results show that, at a low dose, the clearance of CA is primarily determined by liver blood flow. At a higher saturating dose, plasma clearance and uptake by the liver are not significantly decreased with age. Endocytosis by endothelial cells, which accounts for about 60% of that of the whole liver, is also unchanged with age. In contrast, a significant decrease in endocytic capacity was observed for Kupffer cells in vivo. This age-related functional decline was also observed in Kupffer cells which were isolated from rats of different ages and maintained in culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanism of adenosine-induced inhibition of calcium current in guinea pig ventricular cells.
Authors: M Kato, H Yamaguchi, R Ochi
Journal: Circulation Research (1990)

The mechanism of adenosine-induced inhibition of Ca2+ currents was studied by recording single-channel Ca2+ currents from cell-attached patches on isolated guinea pig ventricular cells with pipettes containing 50 or 100 mM Ba2+. Numerous 100-msec depolarization steps were applied repetitively at 2 Hz from the resting potential of approximately -70 mV. The addition of 0.1 mM adenosine to the superfusate in the presence of 100 nM isoproterenol depressed the isoproterenol-induced increase in ensemble-averaged current: in peak amplitude, from 258 +/- 105% (mean +/- SD) (p less than 0.01) that of control in the presence of isoproterenol to 153 +/- 41% (n = 7) (p less than 0.05) by the addition of adenosine. In these patches, adenosine did not much affect the open probability in nonblank sweeps (control, 0.10 +/- 0.05; isoproterenol, 0.11 +/- 0.08; adenosine and isoproterenol, 0.08 +/- 0.05), but significantly decreased channel availability, defined as the rate of current-containing sweeps in total sweeps (control, 0.36 +/- 0.17; isoproterenol, 0.69 +/- 0.16 [p less than 0.01]; adenosine and isoproterenol, 0.45 +/- 0.20 [p less than 0.01]). The decrease of channel availability by adenosine was due to the shortening of the duration of the available state and the prolongation of that of the unavailable state. The depressive action of adenosine was suppressed by 0.1 mM theophylline. The single-channel conductance in the presence of 100 mM Ba2+ and Bay K 8644 was 26 pS and was not affected by isoproterenol or adenosine. We conclude that adenosine decreases Ca2+ current under beta-adrenergic stimulation mainly by reducing channel availability.
Efficacy, Safety, and Pump Compatibility of Insulin Aspart Used in Continuous Subcutaneous Insulin Infusion Therapy in Patients With Type 1 Diabetes
Authors: Bruce W. Bode, Poul Strange
Journal: Diabetes Care (2001)

The purpose of this study was to compare the efficacy, safety and pump compatibility of insulin aspart (a rapid-acting insulin analog) and buffered regular human insulin in patients with type 1 diabetes undergoing continuous subcutaneous insulin infusion (CSII) therapy.This was a single-center randomized open-label study Patients received CSII therapy with insulin aspart (n = 19) or buffered regular human insulin (n = 10) for 7 weeks. Bolus doses of insulin aspart were administered immediately before meals and buffered regular human insulin 30 min before meals.Insulin aspart and buffered regular human insulin were both effective in controlling average daily blood glucose levels (8.2 +/- 1.9 and 8.5 +/- 2.1 mmol/l, respectively) (mean +/- SD) and maintaining serum fructosamine (343 +/- 25.7 and 336 +/- 27.4 micromol/l) and HbA1c (6.9 +/- 0.6 and 7.1 +/- 0.6%) levels. Possible obstructions and set leakages were infrequently reported in both groups. Similar numbers of patients experienced hypoglycemia (blood glucose <2.5 mmol/l): 14 (74%) insulin aspart patients versus 6 (60%) buffered regular human insulin patients. Patients receiving insulin aspart had fewer hypoglycemic events per patient (2.9) than those patients receiving buffered regular human insulin (6.2). There were no differences between the two insulins in the occurrence of hyperglycemic events (blood glucose >19 mmol/l) or in the number and type of adverse events.Insulin aspart and buffered regular human insulin were effective and well tolerated and provided similar pump compatibility when used in CSII therapy.
Molecular Pathways: BRAF Induces Bioenergetic Adaptation by Attenuating Oxidative Phosphorylation
Authors: Rizwan Haq, David E. Fisher, Hans R. Widlund
Journal: Clinical Cancer Research (2014)

Cancers acquire mutations in cooperating pathways that sustain their growth and survival. To support continued proliferation, tumor cells adapt their metabolism to balance energy production with their augmented biosynthetic needs. Although most normal differentiated cells use mitochondrial oxidative phosphorylation (OXPHOS) as the bioenergetic source, cancer cells have been proposed to rely principally on cytoplasmic glycolysis. The molecular basis for this shift, termed the Warburg effect, is the subject of intense investigation, because mechanistic understanding may lead to novel approaches to target the altered metabolism of cancer cells. Recently, mutations BRAF(V600E) have emerged as a major regulator of metabolic homeostasis. Melanoma cells may use a metabolic shift to circumvent BRAF(V600E)-induced senescence though limiting their reliance on OXPHOS and promote proliferation. Furthermore, BRAF(V600E) acts to suppress expression of the melanocyte master regulator microphthalmia-associated transcription factor (MITF) and the mitochondrial biogenesis coactivator PGC1α. Accordingly, therapeutic inhibition of BRAF(V600E) reverses metabolic reprogramming in melanoma cells and elevates OXPHOS through increased MITF-PGC1α levels. BRAF-targeted drugs modulate the metabolic state of malignant melanoma cells, and counteracting these adaptive responses using pharmacologic agents may prove useful in combinatorial therapeutic strategies. Clin Cancer Res; 20(9); 2257-63. ©2014 AACR.
Feedback on feedback on feedback: It's feedforward
Authors: Dennis Norris, James M. McQueen, Anne Cutler
Journal: Behavioral and Brain Sciences (2000)

The central thesis of our target article is that feedback is never necessary in spoken word recognition. In this response we begin by clarifying some terminological issues that have led to a number of misunderstandings. We provide some new arguments that the feedforward model Merge is indeed more parsimonious than the interactive alternatives, and that it provides a more convincing account of the data than alternative models. Finally, we extend the arguments to deal with new issues raised by the commentators such as infant speech perception and neural architecture.
Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Borja Ibanez, Carlos Macaya, Vicente Sánchez-Brunete, Gonzalo Pizarro, Leticia Fernández-Friera, Alonso Mateos, Antonio Fernández-Ortiz, José M. García-Ruiz, Ana García-Álvarez, Andrés Iñiguez, Jesús Jiménez-Borreguero, Pedro López-Romero, Rodrigo Fernández-Jiménez, Javier Goicolea, Borja Ruiz-Mateos, Teresa Bastante, Mercedes Arias, José A. Iglesias-Vázquez, Maite D. Rodriguez, Noemí Escalera, Carlos Acebal, José A. Cabrera, Juan Valenciano, Armando Pérez de Prado, María J. Fernández-Campos, Isabel Casado, Juan C. García-Rubira, Jaime García-Prieto, David Sanz-Rosa, Carlos Cuellas, Rosana Hernández-Antolín, Agustín Albarrán, Felipe Fernández-Vázquez, José M. de la Torre-Hernández, Stuart Pocock, Ginés Sanz, Valentin Fuster
Journal: Circulation (2013)

The effect of β-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion).Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean ± SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6 ± 15.3 versus 32.0 ± 22.2 g; adjusted difference, -6.52; 95% confidence interval, -11.39 to -1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was -8.13 (95% confidence interval, -13.10 to -3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21).In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI.http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.
Long-Distance Axonal Growth from Human Induced Pluripotent Stem Cells after Spinal Cord Injury
Authors: Paul Lu, Grace Woodruff, Yaozhi Wang, Lori Graham, Matt Hunt, Di Wu, Eileen Boehle, Ruhel Ahmad, Gunnar Poplawski, John Brock, Lawrence S.B. Goldstein, Mark H. Tuszynski
Journal: Neuron (2014)