tbuckley/cabot-search huggingface dataset:
Interleukin 4 or oncostatin M induces a prolonged increase in P-selectin mRNA and protein in human endothelial cells.
Authors: L Yao, J Pan, H Setiadi, K D Patel, R P McEver
Journal: The Journal of Experimental Medicine (1996)

During acute inflammation, P-selectin is transiently mobilized from Weibel-Palade bodies to the surface of histamine-activated endothelial cells, where it mediates rolling adhesion of neutrophils under hydrodynamic flow. During chronic or allergic inflammation, sustained expression of P-selectin on the endothelial cell surface has been observed. We found that the cytokines interleukin 4 (IL-4) or oncostatin M (OSM) induced a five- to ninefold increase in P-selectin messenger RNA (mRNA) in human umbilical vein endothelial cells (HUVEC) that persisted as long as 72 h. IL-4 elevated P-selectin mRNA by increasing its transcription rate rather than by prolonging its already long half-life. Stimulation of P-selectin transcription by IL-4 or OSM required new protein synthesis and tyrosine phosphorylation of cellular proteins. Tumor necrosis factor alpha, IL-1 beta, lipopolysaccharide, or IL-3 did not increase P-selectin mRNA in HUVEC, and did not augment the IL-4-induced increase in P-selectin transcripts. IL-4 or OSM increased P-selectin protein on the cell surface as well as in Weibel-Palade bodies. Under flow conditions, neutrophils rolled on P-selectin expressed by IL-4-treated HUVEC, and even more neutrophils rolled on P-selectin after IL-4-treated HUVEC were stimulated with histamine. These data demonstrate that IL-4 or OSM stimulates endothelial cells to synthesize more P-selectin over prolonged periods. The increased expression of P-selectin may facilitate the emigration of leukocytes into sites of chronic or allergic inflammation.
Disposal of Intravenously Administered Fat in Subjects with Atherosclerosis and in Normal Controls
Authors: M. L. MASHFORD, P. J. NESTEL
Journal: Circulation Research (1961)

A. series of experiments has been performed in which a standard dose of an artificial oil emulsion (Lipomul I.V.) was given to 5 groups of subjects and the disappearance of fat from their blood was observed by plasma optical density measurements. The groups were age-matched and consisted of a control group; 3 groups who had suffered a myocardial infarction and were respectively untreated, receiving heparin and receiving phenoprocoumon after recovery from the acute stage of the illness; and the last group which consisted of patients who suffered from intermittent claudication. The control, untreated infarct and peripheral vascular disease groups exhibited similar curves of optical density on time. The mean peak optical density was significantly lower in the heparin-treated than in the untreated group. Conversely, the mean peak optical density of the phenoprocoumontreated group was significantly higher than that of the untreated or control groups.
Hepatectomy-Related Hypophosphatemia
Authors: Kengo Nomura, Sawako Tatsumi, Atsumi Miyagawa, Yuji Shiozaki, Shohei Sasaki, Ichiro Kaneko, Mikiko Ito, Shinsuke Kido, Hiroko Segawa, Mitsue Sano, Tsutomu Fukuwatari, Katsumi Shibata, Ken-ichi Miyamoto
Journal: Journal of the American Society of Nephrology (2013)

Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal brush-border membrane vesicles isolated from PH rats, Na(+)-dependent phosphate (Pi) uptake decreased by 50%-60%. PH rats also exhibited significantly decreased levels of renal and intestinal Na(+)-dependent Pi transporter proteins (NaPi-IIa [NaPi-4], NaPi-IIb, and NaPi-IIc). Parathyroid hormone was elevated at 6 hours after PH. Hyperphosphaturia persisted, however, even after thyroparathyroidectomy in PH rats. Moreover, DNA microarray data revealed elevated levels of nicotinamide phosphoribosyltransferase (Nampt) mRNA in the kidney after PH, and Nampt protein levels and total NAD concentration increased significantly in the proximal tubules. PH rats also exhibited markedly increased levels of the Nampt substrate, urinary nicotinamide (NAM), and NAM catabolites. In vitro analyses using opossum kidney cells revealed that NAM alone did not affect endogenous NaPi-4 levels. However, in cells overexpressing Nampt, the addition of NAM led to a marked decrease in cell surface expression of NaPi-4 that was blocked by treatment with FK866, a specific Nampt inhibitor. Furthermore, FK866-treated mice showed elevated renal Pi reabsorption and hypophosphaturia. These findings indicate that hepatectomy-induced hypophosphatemia is due to abnormal NAM metabolism, including Nampt activation in renal proximal tubular cells.
Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones
Authors: M J Veysey, L A Thomas, A I Mallet, P J Jenkins, G M Besser, J A H Wass, G M Murphy, R H Dowling
Journal: Gut (1999)

BACKGROUND Treatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones. Prolongation of intestinal transit has been proposed as the mechanism for the increase in the proportion of deoxycholic acid in bile. AIMS To study the effects of octreotide on intestinal transit in acromegalic patients during octreotide treatment, and to examine the relation between intestinal transit and bile acid composition in fasting serum. METHODS Mouth to caecum and large bowel transit times, and the proportion of deoxycholic acid in fasting serum were measured in non-acromegalic controls, acromegalic patients untreated with octreotide, acromegalics on long term octreotide, and patients with simple constipation. Intestinal transit and the proportion of deoxycholic acid were compared in acromegalic patients before and during octreotide. RESULTS Acromegalics untreated with octreotide had longer mouth to caecum and large bowel transit times than controls. Intestinal transit was further prolonged by chronic octreotide treatment. There were significant linear relations between large bowel transit time and the proportion of deoxycholic acid in the total, conjugated, and unconjugated fractions of fasting serum. CONCLUSIONS These data support the hypothesis that, by prolonging large bowel transit, octreotide increases the proportion of deoxycholic acid in fasting serum (and, by implication, in bile) and thereby the risk of gallstone formation.
CHROMATOGRAPHIC PURIFICATION OF HUMAN SERUM ACCELERATOR GLOBULIN 1
Authors: Frederick M. Cox, Gerard F. Lanchantin, Arnold G. Ware
Journal: Journal of Clinical Investigation (1956)

There appears to be general agreement among investigators of blood clotting regarding the ex- istence in plasma of a heat-labile factor which po- tentiates the action of thromboplastin as a pro- thrombin converting agent (1).This clotting agent appears to be a protein which is not adsorbed on barium sulfate and which will correct the pro- longed prothrombin time of aged, oxalated, human plasma.There is a lack of agreement about its nomenclature; the terms accelerator globulin (2), proaccelerin (3), Factor V (4), and labile factor (5) being used predominately.Considerable confusion exists about the pres- ence and characteristics of accelerator globulin in serum.This is partly due to the fact that an- other accelerator has been identified in serum which can be readily removed by barium sulfate adsorption.This factor is most frequently re- ferred to as SPCA (6), proconvertin (7), stable factor *(8) or co-thromboplastin (9).2 Barium sulfate treatment of bovine serum does not remove the accelerator globulin (AcG) activity.In fact, after barium sulfate adsorption, considerably more AcG activity is demonstrable in bovine serum than in bovine plasma.Similarly, it is possible to produce a significant increase in plasma AcG activity by treatment of bovine plasma with puri- fied thrombin.To explain these phenomena, it was proposed by Ware, Murphy, and Seegers (11) that thrombin causes activation of AcG.Two forms of AcG were suggested to exist, plasma AcG and serum AcG.It seems probable that the AcG in plasma exists in a relatively inert form 1 This investigation was supported by grants from the U. S. Public Health Service (H-1649 C4) and
Thoracotomy and the Contralateral Lung: A Study of the Changes Occurring in the Dependent and Contralateral Lung during and after Thoracotomy in Lateral Decubitus
Authors: J. O. C. Craig, L. L. Bromley, R. Williams
Journal: Thorax (1962)

While examining and reporting on the radiographs taken routinely following all thoracic surgical procedures at St. Mary's Hospital, it was noted that in a high proportion of cases extensive and diffuse peripheral opacification was present in that hemithorax which was dependent and unopened during the thoracotomy, i.e., in the lung and/or pleural cavity contralateral to that of the surgical approach.This opacification was frequently observed in the immediate post- operative radiograph and, in a number of cases, in radiographs taken on subsequent days.The operations were undertaken for a variety of cardiac and pulmonary lesions which may be grouped as follows: (1) Mitral valvotomy;(2) miscellaneous cardiac operations, including aortic valvotomy, resection of coarctation of aorta, pericardiectomy, and congenital heart operations;(3) pneumonectomy and lobectomy for bronchial carcinoma; (4) miscellaneous pulmonary and pleural operations, e.g., pulmonary biopsy, lobec- tomy for bronchiectasis, abscess and tuberculoma, and pleurodesis.It was apparent that the opacification which had stimulated our interest was found only in those patients who had been in a lateral decubitus position for the whole of the duration of the operative procedures.For all these procedures, the position of the patient on the operating table was as shown in Fig. 1.The duration of the operations varied from one to three hours.FIG. 1.-The operative position for left thoracotomy (right lateral decubitus).
Carcinomatous infiltration of cerebrospinal fluid with reactive lymphocytosis and granulocytosis
Authors: Parameswaran Anoop, Radovan Saso, Ayad Atra
Journal: American Journal of Hematology (2010)

Hematologists are frequently involved with morphological analysis of centrifuged cerebrospinal fluid (CSF) for the diagnosis of malignant infiltration of the central nervous system (CNS). Although malignant cells in the CSF are most often due to underlying hematological cancers, leptomeningeal carcinomatous infiltration from a solid tumor is not uncommon. A 46-year-old lady presented with focal neurological signs suggestive of cauda equina compression. She was on adjuvant therapy for invasive ductal carcinoma of breast with expression of human epidermal growth factor receptor-2 (HER-2). MRI scan confirmed a metastatic deposit in the conus medullaris with tumor nodules in the cauda equina and diffuse meningeal enhancement. Clear CSF was obtained from a diagnostic lumbar puncture and microscopy showed the presence of 50/mm3 white cells and 10/mm3 red cells, with no evidence of infection. A centrifuged cytospin preparation of CSF stained with May-Grunwald-Giemsa (MGG) showed numerous small lymphocytes, neutrophils, metamyelocytes, and metastatic breast carcinoma cells (Image 1). The latter cells were much larger than the hematological cells, with homogeneous nuclei containing open chromatin and abundant cytoplasm with prominent blebs from the cell surface (Image 1). Six large metastatic carcinoma cells on a background of hematological cells including two neutrophils (bottom left), a metamyelocyte (top right), and numerous small lymphocytes (MGG stained CSF cytospin; ×40). HER-2 positive breast cancers are known to carry a higher risk for CNS metastasis [1]. The presence of lymphocytosis and granulocytosis in this nonhemorrhagic CSF is a likely localized inflammatory response to metastasis from the breast carcinoma.
MPs question possible head of new English commission
Authors: Adrian O’Dowd
Journal: BMJ (2008)

The potential head of the new regulator for all health, mental health, and social care services in England has admitted that she has a lack of real knowledge of social care.

Barbara Young (Baroness Young of Old Scone) appeared last week before the parliamentary health select committee at its first ever pre-appointment hearing—a new type of session in which the committee vets people for posts relating to protecting public interests.

Baroness Young, currently chief executive of the Environment Agency, is the government’s candidate to chair the new Care Quality Commission, which from October will take over the regulatory work of the …
Anemia in Chronic Heart Failure
Authors: Yi-Da Tang, Stuart D. Katz
Journal: Circulation (2006)

A nemia occurs commonly in patients with chronic heart failure (CHF) and has been proposed as a novel therapeutic target in this patient population.The present review will summarize the current knowledge of the prevalence, causative factors, and pathophysiological correlates of anemia in CHF.Potential risks and benefits of therapy with erythropoietic agents for the treatment of anemia in CHF will also be discussed. Prevalence of Anemia in CHF][3][4][5][6][7][8][9][10][11][12][13][14][15] Variability in estimated prevalence is partly attributable to use of inconsistent definitions of anemia in individual reports.The World Health Organization definition of anemia (hemoglobin concentration Ͻ13.0 g/dL in men and Ͻ12.0 g/dL in women) takes into account known gender differences in distribution of hemoglobin values, 16 whereas the National Kidney Foundation defines anemia as hemoglobin Յ12 g/dL in men and postmenopausal women. 17These standard definitions of anemia are not based on wellestablished physiological or population norms.Published reports in CHF populations have used these and other study-specific definitions of anemia (including other arbitrary or statistically defined hemoglobin and hematocrit categories and administrative diagnostic codes from hospital records).Despite these inconsistencies in the definition of anemia cases, most studies indicate that the prevalence of anemia is increased in CHF populations with comorbid kidney disease, advanced age, and more severe symptoms (range, 30% to 61%) when compared with less symptomatic ambulatory populations (range, 4% to 23%).In patients with CHF and preserved ejection fraction, the few published reports indicate that anemia is also highly prevalent in this group.
5-Year Prognostic Value of No-Reflow Phenomenon After Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction
Authors: Gjin Ndrepepa, Klaus Tiroch, Massimiliano Fusaro, Dritan Keta, Melchior Seyfarth, Robert A. Byrne, Jürgen Pache, Patricia Alger, Julinda Mehilli, Albert Schömig, Adnan Kastrati
Journal: Journal of the American College of Cardiology (2010)
Cough Aerosols of <i>Mycobacterium tuberculosis</i> Predict New Infection. A Household Contact Study
Authors: Edward C. Jones-López, Olive Namugga, Francis Mumbowa, Martin Ssebidandi, Olive Mbabazi, Stephanie Moine, Gerald Mboowa, Matthew P. Fox, Nancy Reilly, Irene Ayakaka, Soyeon Kim, Alphonse Okwera, Moses Joloba, Kevin P. Fennelly
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Airborne transmission of Mycobacterium tuberculosis results from incompletely characterized host, bacterial, and environmental factors. Sputum smear microscopy is associated with considerable variability in transmission.To evaluate the use of cough-generated aerosols of M. tuberculosis to predict recent transmission.Patients with pulmonary tuberculosis (TB) underwent a standard evaluation and collection of cough aerosol cultures of M. tuberculosis. We assessed household contacts for new M. tuberculosis infection. We used multivariable logistic regression analysis with cluster adjustment to analyze predictors of new infection.From May 2009 to January 2011, we enrolled 96 sputum culture-positive index TB cases and their 442 contacts. Only 43 (45%) patients with TB yielded M. tuberculosis in aerosols. Contacts of patients with TB who produced high aerosols (≥10 CFU) were more likely to have a new infection compared with contacts from low-aerosol (1-9 CFU) and aerosol-negative cases (69%, 25%, and 30%, respectively; P = 0.009). A high-aerosol patient with TB was the only predictor of new M. tuberculosis infection in unadjusted (odds ratio, 5.18; 95% confidence interval, 1.52-17.61) and adjusted analyses (odds ratio, 4.81; 95% confidence interval, 1.20-19.23). Contacts of patients with TB with no aerosols versus low and high aerosols had differential tuberculin skin test and interferon-γ release assay responses.Cough aerosols of M. tuberculosis are produced by a minority of patients with TB but predict transmission better than sputum smear microscopy or culture. Cough aerosols may help identify the most infectious patients with TB and thus improve the cost-effectiveness of TB control programs.
Guidelines for the diagnosis and treatment of pulmonary hypertension
Authors: Marius M. Hoeper, Marc Humbert, Adam Torbicki, Jean-Luc Vachiery, Joan Albert Barbera, Maurice Beghetti, Paul Corris, Sean Gaine, J. Simon Gibbs, Miguel Angel Gomez-Sanchez, Guillaume Jondeau, Walter Klepetko, Andrew Peacock, Lewis Rubin, Michael Zellweger, Gerald Simonneau, Angelo Auricchio, Jeroen Bax, Claudio Ceconi, Veronica Dean, Gerasimos Filippatos, Christian Funck-Brentano, Richard Hobbs, Peter Kearney, Theresa McDonagh, Keith McGregor, Bogdan A. Popescu, Zeljko Reiner, Udo Sechtem, Michal Tendera, Panos Vardas, Petr Widimsky, Felicita Andreotti, Michael Aschermann, Riccardo Asteggiano, Ray Benza, Rolf Berger, Damien Bonnet, Marion Delcroix, Luke Howard, Anastasia N Kitsiou, Irene Lang, Aldo Maggioni, Jens Erik Nielsen-Kudsk, Myung Park, Pasquale Perrone-Filardi, Maria Teresa Subirana Domenech, Anton Vonk-Noordegraaf, Jose Luis Zamorano
Journal: European Respiratory Journal (2009)

Guidelines and Expert Consensus Documents summarise and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk/benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.

A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organisations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines).

In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition.

Unpublished clinical trial results are not taken into account. A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk/benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in tables 1⇓ and 2⇓.

The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must …
Effect of influenza A virus infection on acid-induced cough response in children with asthma
Authors: T Shimizu, H Mochizuki, A Morikawa
Journal: European Respiratory Journal (1997)

Although it is well-known that some types of respiratory viral infections cause airway hyperresponsiveness in humans, the effect of viral infection on the cough threshold in asthmatics is not known. We, therefore, evaluated the effects of naturally-acquired influenza A virus infection on the cough threshold to inhaled acid in children with asthma. Twelve children with asthma (9 boys and 3 girls, mean +/- SEM age of 10.8 +/- 0.6 yrs), who had naturally-acquired influenza A virus infection in winter (January-February, 1992) during an epidemic of influenza A (H1N1), were enrolled in this prospective, uncontrolled study. All patients underwent acetic acid (AA) inhalation challenge 2, 4 and 6 weeks after the influenza infection. The cough threshold values (the lowest concentrations of AA eliciting coughs) after 2, 4 and 6 weeks of the illness were 3.7 +/- 0.9, 5.3 +/- 1.0 and 8.1 +/- 1.4% (mean +/- SEM), respectively. Cough threshold values 4 or 6 weeks after the illness improved significantly over that at 2 weeks (p < 0.05 and p < 0.01, respectively). In contrast, baseline forced expiratory volume in one second did not change throughout the study. These results indicate that influenza A virus infection attenuates the cough threshold independently of airway obstruction in children with asthma. The enhanced cough response following virus infection is probably mediated by damage to the airways epithelium.
Targeting SOD1 reduces experimental non–small-cell lung cancer
Authors: Andrea Glasauer, Laura A. Sena, Lauren P. Diebold, Andrew P. Mazar, Navdeep S. Chandel
Journal: Journal of Clinical Investigation (2013)

Approximately 85% of lung cancers are non–small-cell lung cancers (NSCLCs), which are often diagnosed at an advanced stage and associated with poor prognosis. Currently, there are very few therapies available for NSCLCs due to the recalcitrant nature of this cancer. Mutations that activate the small GTPase KRAS are found in 20% to 30% of NSCLCs. Here, we report that inhibition of superoxide dismutase 1 (SOD1) by the small molecule ATN-224 induced cell death in various NSCLC cells, including those harboring KRAS mutations. ATN-224–dependent SOD1 inhibition increased superoxide, which diminished enzyme activity of the antioxidant glutathione peroxidase, leading to an increase in intracellular hydrogen peroxide (H(2)O(2)) levels. We found that ATN-224–induced cell death was mediated through H(2)O(2)-dependent activation of P38 MAPK and that P38 activation led to a decrease in the antiapoptotic factor MCL1, which is often upregulated in NSCLC. Treatment with both ATN-224 and ABT-263, an inhibitor of the apoptosis regulators BCL2/BCLXL, augmented cell death. Furthermore, we demonstrate that ATN-224 reduced tumor burden in a mouse model of NSCLC. Our results indicate that antioxidant inhibition by ATN-224 has potential clinical applications as a single agent, or in combination with other drugs, for the treatment of patients with various forms of NSCLC, including KRAS-driven cancers.