tbuckley/cabot-search huggingface dataset:
Cardiac Na+/Ca2+ exchange activity in patients with end-stage heart failure
Authors: H. Reinecke, R. Studer, R. Vetter, J. Holtz, H. Drexler
Journal: Cardiovascular Research (1996)

Objective: The aim of the present study was to investigate the functional activity and expression of the sarcolemmal Na+/Ca2+ -exchanger in the failing human heart. Methods: Left ventricular samples were taken from eleven patients with end-stage heart failure and six organ donors (normal controls). The Na+/Ca2+-exchanger activity was assessed by measuring Na+ gradient-induced 45Ca2+ transport into sarcolemmal vesicles of quantitatively collected crude membrane preparations. The abundance of the Na+/Ca2+-exchanger protein was determined by Western blot analysis using a specific antiserum and the results were normalized to myocyte specific β-myosin heavy chain protein content. Results: In membrane preparations of failing human hearts, both the Na+ gradient-induced 45Ca2+ transport activity and the level of immunoreactive Na+/Ca2+-exchanger protein were increased (P < 0.01) by 87% and 160% compared to controls, respectively. Conclusions: In human end-stage heart failure the increased sarcolemmal Na+/Ca2+-exchanger activity appears to be due to an elevated expression of this protein. An increase in the expression and activity of the Na+/Ca2+-exchanger in the failing human heart may be of important functional significance: while a resulting increase in Ca2+ extrusion across the sarcolemma may limit diastolic Ca2+ overload, a corresponding influx of Na+ may be associated with membrane depolarization and enhanced arrhythmogenesis if the Na+Ca2+-exchanger operates primarily in the forward mode.
Pulmonary hemorrhage and glomerulonephritis in primary biliary cirrhosis
Authors: François Bissuel, Thierry Bizollon, Frédérique Dijoud, Paul Bouletreau, Jean François Cordier, Charles Chazot, Christian Gouillat, Christian Trepo
Journal: Hepatology (1992)

We observed life-threatening intrapulmonary hemorrhages and focal proliferative glomerulonephritis in a 41-yr-old woman with primary biliary cirrhosis. The severity of the symptoms necessitated blood transfusions and mechanical ventilation; the patient improved with the help of corticosteroid therapy. No formal evidence of either Goodpasture's syndrome or any other well-defined systemic vasculitis could be found. Neutrophil cytoplasmic antibodies were initially positive and became undetectable after 3 mo of immunosuppressive treatment without relapse. This association has not been described previously and may be added to the list of extrahepatic immune-mediated conditions associated with primary biliary cirrhosis.
ACUTE EMERGENCIES OF ABDOMINAL DISEASE
Authors: R. A. Chisholm
Journal: BMJ (1911)

Prohibitin (PHB) is a critical protein involved in many cellular activities. In brain, PHB resides in mitochondria, where it forms a large protein complex with PHB2 in the inner TFmembrane, which serves as a scaffolding platform for proteins involved in mitochondrial structural and functional integrity. PHB overexpression at moderate levels provides neuroprotection in experimental brain injury models. In addition, PHB expression is involved in ischemic preconditioning, as its expression is enhanced in preconditioning paradigms. However, the mechanisms of PHB functional regulation are still unknown. Observations that nitric oxide (NO) plays a key role in ischemia preconditioning compelled us to postulate that the neuroprotective effect of PHB could be regulated by NO. Here, we test this hypothesis in a neuronal model of ischemia–reperfusion injury and show that NO and PHB are mutually required for neuronal resilience against oxygen and glucose deprivation stress. Further, we demonstrate that NO post-translationally modifies PHB through protein S-nitrosylation and regulates PHB neuroprotective function, in a nitric oxide synthase-dependent manner. These results uncover the mechanisms of a previously unrecognized form of molecular regulation of PHB that underlies its neuroprotective function. <b>SIGNIFICANCE STATEMENT</b> Prohibitin (PHB) is a critical mitochondrial protein that exerts a potent neuroprotective effect when mildly upregulated in mice. However, how the neuroprotective function of PHB is regulated is still unknown. Here, we demonstrate a novel regulatory mechanism for PHB that involves nitric oxide (NO) and shows that PHB and NO interact directly, resulting in protein S-nitrosylation on residue Cys<sup>69</sup> of PHB. We further show that nitrosylation of PHB may be essential for its ability to preserve neuronal viability under hypoxic stress. Thus, our study reveals a previously unknown mechanism of functional regulation of PHB that has potential therapeutic implications for neurologic disorders.
Cyanide-induced cytochrome a,a3 oxidation-reduction responses in rat brain in vivo.
Authors: C A Piantadosi, A L Sylvia, F F Jöbsis
Journal: Journal of Clinical Investigation (1983)

The sensitivity of the brain to cyanide-induced histotoxic hypoxia and the protective effects of known cyanide antagonists, have been assessed in vivo by reflectance spectrophotometry. Cyanide-related changes in cytochrome a,a3 (cytochrome c oxidase) oxidation-reduction (redox) state, tissue hemoglobin saturation, and local blood volume were continuously monitored in cerebral cortex of rats. Noncumulative, dose-dependent inhibition of the in situ mitochondrial respiratory chain was evaluated directly by measuring increases in reduction levels of the terminal oxidase. These transient cytochrome a,a3 reductions were accompanied by increases in regional cerebral hemoglobin saturation and blood volume. Cytochrome redox responses were not altered either in magnitude or kinetics by hyperoxia; however, the cyanide-cytochrome dose-response curve was greatly shifted to the right by pretreatment with sodium nitrite, and the recovery rate of cytochrome a,a3 from cyanide-induced reduction was enhanced fourfold by pretreatment with sodium thiosulfate.
Noninvasive methods for assessment of airway inflammation in occupational settings
Authors: S. Quirce, C. Lemière, F. De Blay, V. Del Pozo, R. Gerth Van Wijk, P. Maestrelli, G. Pauli, P. Pignatti, M. Raulf‐Heimsoth, J. Sastre, T. Storaas, G. Moscato
Journal: Allergy (2009)

The present document is a consensus statement reached by a panel of experts on noninvasive methods for assessment of airway inflammation in the investigation of occupational respiratory diseases, such as occupational rhinitis, occupational asthma, and nonasthmatic eosinophilic bronchitis. Both the upper and the lower airway inflammation have been reviewed and appraised reinforcing the concept of 'united airway disease' in the occupational settings. The most widely used noninvasive methods to assess bronchial inflammation are covered: induced sputum, fractional exhaled nitric oxide (FeNO) concentration, and exhaled breath condensate. Nasal inflammation may be assessed by noninvasive approaches such as nasal cytology and nasal lavage, which provide information on different aspects of inflammatory processes (cellular vs mediators). Key messages and suggestions on the use of noninvasive methods for assessment of airway inflammation in the investigation and diagnosis of occupational airway diseases are issued.
Can Follow-up Sclerotherapy for Oesophageal Varices be Improved? Early Results of a New Technique
Authors: S.W. Hosking, P. Robinson, A.G. Johnson
Journal: Endoscopy (1986)

To help correctly identify varices as patent or thrombosed during follow-up sclerotherapy, a simple pressure device has been used to obtain intravariceal pressure. A high pressure denotes thrombosis and a low pressure (less than 50 mmHg) denotes patency. In 217 variceal assessments, conventional and pressure assessments agreed in 179 (82%). Over the 7 month study, a significant improvement was noted in correctly diagnosing thrombosed varices (p less than 0.01). No ulcers, bleeding or complications occurred. Pressure assessment of varices is simple and avoided 38 (18%) incorrect diagnoses and their consequences.
Fetal Outcomes Associated With Metoclopramide Use in Pregnancy
Authors: Nikolaos Vrachnis, Dimitrios Zygouris, Zoe Iliodromiti
Journal: JAMA (2014)

In the study on the use of metoclopramide during pregnancy and the risk of congenital malformations and fetal death,1 explicit details as to the dosage of metoclopramide were not reported. The only stratification made was women receiving 1 prescription vs 2 or more.

Specifically, information was lacking on the dose and the total amount of metoclopramide to which the fetuses were exposed, along with the duration of exposure and the form of administration. Because these factors can affect the molar concentration and the bioavailability of the drug,2 provision of this information is important to evaluate the actual exposure of the fetuses.
JAMA's new rule on whistleblowers creates controversy
Authors: J. H. Tanne
Journal: BMJ (2009)

The announcement by the editors of the Journal of the American Medical Association that, in future, anyone writing to the journal about a possible conflict of interest on the part of authors must keep silent while their allegations are investigated has aroused a storm of criticism.

The new policy (http://jama.ama-assn.org/misc/jed90012pap\_E1\_E3.pdf) was announced after Jonathan Leo, professor of neuroanatomy at Lincoln Memorial University in Harrogate, Tennessee, and Jeffrey Lacasse, of Arizona State University, published a letter online in the BMJ in which they criticised a study published in JAMA and pointing out that the lead author had not reported a conflict of interest (http://bmj.com/cgi/eletters/338/feb05_1/b463#208503,9Feb2009).

The American Medical Association, JAMA ’s owner and publisher, has said in a press release that it is referring the controversy to JAMA ’s journal oversight committee. It said, “While we are ultimately responsible for these publications, as most …
Organochlorines, Breast Cancer, and GATT
Authors: David Perlmutter
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Breast cancer, which now affects one in eight American women, must truly be regarded as a modern epidemic. This year 180 000 American women will be diagnosed as having this disease and a third of them will die of it. In the past two decades, breast cancer has claimed the lives of more American women than the total fatalities of the Korean War, the Vietnam War, World War I, and World War II combined. Recent evidence strongly supports the relationship between tissue levels of organochlorines like dichlorodiphenyltrichloroethane (DDT) and the incidence of breast cancer, with some studies showing as much as a fourfold increase in the relative risk of breast cancer in women with high organochlorine compound concentrations.<sup>1,2,3</sup> Metabolites of DDT have been noted to be 50% to 60% higher in breast cancer patient specimens compared with controls (<i>P</i>&lt;.04).<sup>4</sup> The US government, hoping to
Book Review The Genetic Basis of Common Diseases (Oxford Monographs on Medical Genetics.) Second edition. Edited by Richard A. King, Jerome I. Rotter, and Arno G. Motulsky. 1076 pp., illustrated. New York, Oxford University Press, 2002. $195. 0-19-512582-7
Authors: Arnold Munnich, Josué Feingold
Journal: New England Journal of Medicine (2003)
Measuring up to shoulder pain
Authors: P. CROFT
Journal: Annals of the Rheumatic Diseases (1998)

See article on page 82 

Shoulder pain is common, affecting 15–30% of adults at any one time,1 of whom 1 in 20 will visit a general practitioner in the course of a year.2 What is the most useful way to categorise such a common symptom to measure its impact, study its aetiology, and determine the efficacy and effectiveness of treatment?

The clinical literature gives primacy to classifications based on presumed pathology. There is little concrete evidence that exalting most shoulder pain with terms such as tendonitis, bursitis or impingement syndrome is either reliable or useful, and such classifications cannot anyway provide a measure of outcome. Clinical measures of shoulder function, such as range of movement, provide a means to classify shoulder problems into subgroups and to assess change over time. However, they do not necessarily reflect patient well being or the ability to carry out usual activities. So the field is open for self completed questionnaires that assess symptom severity and the impact of shoulder pain on everyday living.

At least four instruments that measure function in this way have appeared recently.3-7 They include one (the Dutch Shoulder Disability Questionnaire or SDQ), which has received further study in this issue,6 7 two American schedules: the SPADI,3 and the Shoulder Rating Questionnaire or SRQ,4 and a British disability questionnaire.5 A number of others, such as the Dutch Shoulder Function Assessment,8 incorporate range of movement measurements by an observer, in addition to items completed by the patient. Each, like many new scales accepted for publication these days, have met some or all of the technical criteria of a “good” instrument (repeatability, validity, and responsiveness to change). Readers who are seeking a simple standard tool for use in clinical practice, audit or research, may justifiably …
GATA transcription factors in the developing and adult heart
Authors: S PIKKARAINEN
Journal: Cardiovascular Research (2004)

During the past decade, emerging evidence has accumulated of different nuclear transcription factors in regulation of cardiac development and growth as well as in cardiac hypertrophy and heart failure. GATA-4, -5 and -6 are zinc finger transcription factors that are expressed in the developing heart and GATA-4 and -6 continue expression in the adult cardiac myocytes. GATA-4 and -6 regulate expression of several cardiac-specific genes, and during murine embryonic development, GATA-4 is essential for proper cardiac morphogenesis. In support of this, mutations of gene for GATA-4 or for its cofactors have been associated with human congenital heart disease. Pressure overload of the heart in vivo as well as hypertrophic stimulation of cardiac myocytes in vitro provide adequate stimulus for activation of GATA-4. Activity of GATA-4 transcription factor is subject to regulation at the level of gene expression and through post-translational modifications of GATA-4 protein. A number of genes induced during cardiac hypertrophy possess functional GATA sites in their promoter region and cardiac-specific overexpression of GATA-4 or -6 leads to cardiac hypertrophy. In addition, a pattern of interactions between GATA-4 and its numerous cofactors have been identified, showing an increasing complexity in regulatory mechanisms. The present review discusses current evidence of the role and regulation of GATA transcription factors in the heart, with an emphasis in the GATA-4 and development of cardiac hypertrophy.
1918 Flu Vaccine Effective in Mice
Authors: Tracy Hampton
Journal: JAMA (2006)

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A day Sheffield will never forget
Authors: E. Walker
Journal: BMJ (1996)

I magine for a moment that Hillsborough never happened. Imagine that Jimmy McGovern's drama was pure fiction. The review might read: “A powerful film, but let down by an incredible storyline of conspiracies and cover ups and the crass, cliched portrayal of the police as insensitive and incompetent. A very poor show indeed from the man who penned Cracker.”

But Hillsborough did happen, and the Granada drama on Thursday night was based on interviews with families of the victims, telling the truth as they see it. McGovern has attempted to tell the “story never told” about the day and its aftermath, the story that was effectively buried under piles of paperwork and statements. Not a story of drunken ticketless yobs, but a story of incompetent ill judged policing. It is easy to see why some would want to bury such a story. If South Yorkshire police feel hard done by, they …
Cyclosporine-Induced Sympathetic Activation and Hypertension after Heart Transplantation
Authors: Urs Scherrer, Susanne F. Vissing, Barbara J. Morgan, Julia A. Rollins, Richard S.A. Tindall, Steves Ring, Peter Hanson, Pramod K. Mohanty, Ronald G. Victor
Journal: New England Journal of Medicine (1990)

Hypertension is a frequent complication of cyclosporine-induced immunosuppression, but the underlying mechanism is unknown. In anesthetized animals, the administration of cyclosporine increases sympathetic-nerve discharge, which may contribute to hypertension.
Posttranscriptional regulation of IL-13 in T cells: Role of the RNA-binding protein HuR
Authors: Vincenzo Casolaro, Xi Fang, Brian Tancowny, Jinshui Fan, Fan Wu, Subramanya Srikantan, S. Yukiko Asaki, Umberto De Fanis, Shau-Ku Huang, Myriam Gorospe, Ulus X. Atasoy, Cristiana Stellato
Journal: Journal of Allergy and Clinical Immunology (2008)
Azathioprine-Induced Plasmacytosis
Authors: Roger C. Kathol
Journal: JAMA (1981)

AN INCREASE in bone marrow plasma cells is most commonly associated with plasma cell dyscrasias. Klein and Block,<sup>1</sup>however, showed that multiple myeloma accounted for only 20% of those with this finding. We report a case in which plasmacytosis was augmented in both bone marrow and peripheral smear by azathioprine overdose. <h3>Report of a Case</h3> A middle-aged woman had a 30-year history of rheumatoid arthritis; she had required aspirin, prednisone, indomethacin, surgery, and acupuncture for severe rheumatoid disease. She had a polyclonal gammopathy and high-titer rheumatoid factor (1:4,120). For four weeks prior to our evaluation, she mistakenly took 300 mg (5.66 mg/ kg/day) rather than 85 mg (1.42 mg/ kg/day) of azathioprine daily for exacerbation of her rheumatoid symptoms. She had not received indomethacin in four years and was receiving prednisone and aspirin prior to starting azathioprine treatment. She was admitted with bloody emesis. Oral temperature was 38.8 °C.
P10 The Effect Of Naltrexone, An Opioid Receptor Antagonist, On Capsaicin Evoked Cough, In Healthy Male Subjects
Authors: I. Satia, K. Holt, E. Hilton, A. Woodcock, J. Smith
Journal: Thorax (2014)

<h3>Introduction</h3> Chronic cough is a troublesome condition that reduces patient quality of life. Recent evidence suggests that healthy females cough more than healthy males but the mechanism underlying this in unclear.<sup>1</sup> We hypothesise that opiate-sensitive inhibitory control mechanisms determine capsaicin-evoked cough responses in healthy subjects. <h3>Aim</h3> To show that in healthy males the number of capsaicin-evoked coughs is increased following administration of naltrexone, an opiate receptor antagonist, compared with placebo. <h3>Method</h3> 15 male subjects (median age 30 yrs (21–59)) were recruited in to a randomised double blind cross-over trial of single doses of naltrexone vs. placebo given 1 week apart. A capsaicin inhalational challenge (doubling doses 0.48 to 125[micro]M) was performed 60 min after ingestion of naltrexone/placebo using a dosimeter. Four inhalations 30 seconds apart were performed at each concentration and the total coughs evoked at each dose were recorded and verified using a cough monitor. <h3>Results</h3> There was a tendency for subjects to cough more when treated with naltrexone (16.7 ± 2.7 (SEM) compared with placebo (13.7 ± 1.6), (p = 0.11, general estimating equations). See Figure 1 <h3>Conclusion</h3> This small pilot study suggest that opiate sensitive inhibitory mechanisms may have a role in controlling the cough reflex even in healthy subjects. <h3>References</h3> Hilton EC, Baverel PG, Woodcock A, Van Der Graaf PH, Smith JA. <i>J Allergy Clin Immunol</i>. 2013 Oct;132(4):847–55
EVALUATION OF RECOMBINANT ACTIVATED FACTOR VII, PROTHROMBIN COMPLEX CONCENTRATE AND FIBRINOGEN CONCENTRATE TO REVERSE APIXABAN IN A RABBIT MODEL
Authors: Martin Anne-C&eacute;line, Le-Bonniec Bernard, Lecompte thomas, Fischer Anne-Marie, Emmerich Joseph, Samama Charles marc, Godier Anne
Journal: Journal of the American College of Cardiology (2012)
Estimating xenobiotic half-lives in humans from rat data: influence of log P.
Authors: J G Sarver, D White, P Erhardt, K Bachmann
Journal: Environmental Health Perspectives (1997)

The nature of empirical allometric expressions relating dispositional and kinetic parameters for a given xenobiotic across multiple mammalian species is well known. It has also been demonstrated that a simple allometric relationship may be used to predict kinetic parameters for humans based merely on data for multiple xenobiotics from rats. We decided to explore reasons for the variance in the data arising from the latter method. We were particularly interested in learning whether any physicochemical characteristics of xenobiotics might account for outlying data points (i.e., poor prediction of human half-life from rat half-life). We have explored the influence of lipid solubility as reflected by a xenobiotic's log P value because adipose tissue comprises a significantly larger percentage of total body weight in humans than in rats. We used half-life data from the literature for 127 xenobiotics. A data subset of 102 xenobiotics for which we were able to find estimates of log P values, including several with extremely large log P values, was also analyzed. First and second order models, including and excluding log P, were compared. The simplest of these models can be recast as the familiar allometric relationship having the form Y = a(Xb). The remaining models can be seen as extensions of this relationship. Our results suggest that incorporation of log P into the prediction of xenobiotic half-life in humans from rat half-life data is important only for xenobiotics with extremely large log P values such as dioxins and polychlorinated biphenyls. Moreover, a second order model in logarithm of rat half-life accommodates all data points very well, without specifically accounting for log P values.
Bone metastasis targeting: A novel approach to reach bone using Zoledronate anchored PLGA nanoparticle as carrier system loaded with Docetaxel
Authors: Kiran Ramanlal Chaudhari, Abhinesh Kumar, Vinoth Kumar Megraj Khandelwal, Mukesh Ukawala, Arehalli S. Manjappa, Anil Kumar Mishra, Jukka Monkkonen, Rayasa S. Ramachandra Murthy
Journal: Journal of Controlled Release (2011)