tbuckley/cabot-search huggingface dataset:
Chronotropic responsiveness of developing sinoatrial and ventricular rat myocytes to autonomic agonists following adrenergic and cholinergic innervation in vitro.
Authors: D L Atkins, W J Marvin
Journal: Circulation Research (1989)

The chronotropic responses of isolated sinoatrial node and ventricular muscle cells to neurotransmitters were compared in vitro with and without selective adrenergic and cholinergic innervation. Explants of either thoracolumbar sympathetic ganglion or sacrococcygeal spinal cord were added to cultures of newborn rat sinus node regions or ventricular apexes harvested before the onset of autonomic innervation in vivo. Catecholamine synthesis was detected by glyoxylic acid histofluorescence. Acetylcholine synthesis was indicated by monoclonal antibody labeling of choline acetyltransferase. After electrical or pharmacological stimulation of neurons, the chronotropic response of individual myocardial cells confirmed the presence of neuroeffector transmission; the nature of the myocyte response identified the stimulated neuron as either adrenergic or cholinergic. Chronotropic responses of all myocardial cells to norepinephrine or acetylcholine were transcribed on a recorder coupled to a video photoconductive cell monitor. Isolated sinoatrial node cells were supersensitive to norepinephrine and acetylcholine; thresholds were 3 x 10(-16) M and 6 x 10(-15) M, respectively. These sinoatrial node cells remained sensitive to both norepinephrine and acetylcholine after the development of innervation in vitro. Ventricular cells also were sensitive with thresholds of 3 x 10(-11) M and 6 x 10(-14) M to norepinephrine and acetylcholine, respectively. However, following in vitro innervation, ventricular cells were significantly less sensitive to norepinephrine and acetylcholine (thresholds 3 x 10(-9) M and 6 x 10(-11) M). These data are the first to demonstrate that neurotrophic modulation is not homogeneous throughout the myocardium and that it may be dependent on the specific myocardial cell innervated.
Circulating Visfatin Is Associated With Parameters of Iron Metabolism in Subjects With Altered Glucose Tolerance
Authors: José Manuel Fernández-Real, José María Moreno, Berta Chico, Abel López-Bermejo, Wifredo Ricart
Journal: Diabetes Care (2007)

OBJECTIVE—Visfatin is a novel adipokine that is predominantly secreted by visceral adipose tissue. Accumulation of visceral adipose tissue is also associated with iron metabolism. Despite the coincidence of visfatin expression in iron-rich tissues, no study has investigated the possible interaction of visfatin with parameters of iron metabolism. RESEARCH DESIGN AND METHODS—We evaluated insulin sensitivity and parameters of iron metabolism in 95 men with normal glucose tolerance (NGT) and 43 men with altered glucose tolerance. RESULTS—Men with newly diagnosed type 2 diabetes had significantly increased serum visfatin in parallel with increased serum prohepcidin and serum ferritin compared with the other groups. In all subjects as a whole, circulating visfatin was not found to be significantly linked to insulin sensitivity (r = 0.07, P = 0.4) but was significantly associated with serum prohepcidin concentration (r = 0.40, P &amp;lt; 0.0001). Obesity status and glucose tolerance status influenced the relationships among visfatin, insulin sensitivity, and parameters of iron metabolism. Among men with altered glucose tolerance, serum visfatin was strongly associated with serum prohepcidin (r = 0.61, P &amp;lt; 0.0001) and serum soluble transferrin receptor (sTfR) (r = −0.51, P &amp;lt; 0.0001). In nonobese subjects, sTfR (P = 0.02) and prohepcidin (P = 0.04) contributed independently to visfatin variance after controlling for age and BMI. When insulin sensitivity was added to the model, only the latter (P = 0.006) contributed to 17% of visfatin variance. In obese men, however, only sTfR (P = 0.04) contributed independently to visfatin variance in this latter model. CONCLUSIONS—Serum visfatin concentration is significantly associated with parameters of iron metabolism, especially in subjects with altered glucose tolerance.
Adenosine-Dependent Induction of Glutathione Peroxidase 1 in Human Primary Endothelial Cells and Protection Against Oxidative Stress
Authors: Yufeng Zhang, Diane E. Handy, Joseph Loscalzo
Journal: Circulation Research (2005)

Cellular glutathione peroxidase (GPx-1), a selenocysteine-containing enzyme, plays a central role in protecting cells from oxidative injury. GPx-1 is ubiquitously expressed in eukaryotic cells where it reduces hydrogen and lipid peroxides to alcohols. Adenosine, which is released from stressed or injured cells, protects against ischemia/reperfusion injury and apoptosis. In this study, we hypothesize that the cytoprotective effect of adenosine involves an increase in the activity of GPx-1. Treatment of human primary pulmonary artery endothelial cells (HPAECs) with 50 micromol/L adenosine in the presence of 10 micromol/L erytho-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, for 48 hours increased GPx-1 mRNA levels 2-fold. GPx-1 protein and enzyme activity also increased approximately 2-fold after treatment. The induction of GPx-1 expression was found to be a consequence of increased mRNA stability and not an increase in transcription. Bisindolylmaleimide I (BIM), a protein kinase C signaling pathway inhibitor, significantly attenuated the induction of GPx-1 mRNA by approximately 36%. The adenosine/EHNA-treated cells were more resistant to hydrogen peroxide stress. Both pharmacological inhibition and siRNA knockdown of GPx-1 attenuated the protective affect of adenosine/EHNA treatment, indicating that the adenosine-induced increase in GPx-1 contributes to an increase in cellular protection against oxidative stress. These data suggest that adenosine may protect the cardiovascular system from ischemia/reperfusion injury, in part, by enhancing the expression of the central intracellular antioxidant enzyme, GPx-1.
T6 Impact Of Environmental Differences In The Prevalence Of Airway Dysfunction In Elite Athletes: Gb Boxing Vs. Gb Swimming
Authors: I. Levai, J. Dickinson, M. Loosemore, J. Greenwell, J. Hull, G. Whyte
Journal: Thorax (2014)

<h3>Objectives</h3> Exercising in a provocative environment (e.g. indoor swimming pool) at sustained high minute ventilation rates may increase the prevalence of airway dysfunction in athletic populations. The purpose of the study was to evaluate the impact of environmental differences in the prevalence of airway dysfunction in two cohorts of elite GB athletes. <h3>Methods</h3> Airway dysfunction was evaluated in the GB boxing (n = 39, Mean (SD) age: 22.0 (3.2) yrs.) and swimming squads (n = 33, Mean (SD) age: 21.0 (3.0) yrs.). All participants completed a Eucapnic Voluntary Hyperpnoea (EVH) challenge test, an indirect bronchoprovocation test, to characterise airway dysfunction (defined as abnormal if &gt;10% fall in FEV<sub>1</sub> post­­-challenge). Fraction of exhaled Nitric Oxide (FeNO) was measured and participants completed a symptom and medication questionnaire. <h3>Results</h3> The prevalence of airway dysfunction was greater in elite swimmers (70%) than boxers (8%) (p &lt; 0.001) (Figure 1). The EVH assessment process revealed missed and incorrect diagnosis of airway dysfunction; specifically 65% (17 of 26) of those with airway dysfunction had no prior diagnosis of asthma or exercise induced bronchoconstriction. Moreover, a prior diagnosis of asthma was not supported by testing in 9% (4 of 46) of the athletes. These athletes were prescribed one or a combination of short-acting β2-agonists, long-acting β2-agonists and inhaled corticosteroids. Neither symptoms nor baseline lung function were predictive of a positive EVH-challenge in swimmers. No correlation between change in lung function or airway dysfunction and FeNO value. <h3>Conclusions</h3> The prevalence of airway dysfunction was nine fold greater in elite swimmers when compared with boxers. This finding emphasises the high proportion of EVH-positive elite swimmers and the importance of strategies needed to ensure their respiratory health is optimised. These results also suggest that airway dysfunction is not only related to intensity and frequency of exertional hyperpnoea but also environmental conditions.
Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells
Authors: Marjorie Côte, Mickaël M. Ménager, Agathe Burgess, Nizar Mahlaoui, Capucine Picard, Catherine Schaffner, Fahad Al-Manjomi, Musa Al-Harbi, Abdullah Alangari, Françoise Le Deist, Andrew R. Gennery, Nathalie Prince, Astrid Cariou, Patrick Nitschke, Ulrich Blank, Gehad El-Ghazali, Gaël Ménasché, Sylvain Latour, Alain Fischer, Geneviève de Saint Basile
Journal: Journal of Clinical Investigation (2009)

Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous autosomal recessive immune disorder characterized by the occurrence of uncontrolled activation of lymphocytes and macrophages infiltrating multiple organs. Disease-causing mutations in the perforin (PRF1; also known as FHL2), Munc13-4 (UNC13D; also known as FHL3), and syntaxin-11 (STX11; also known as FHL4) genes have been identified in individuals with FHL. These genes all encode proteins involved in the cytotoxic activity of lymphocytes. Here, we show that the gene encoding syntaxin-binding protein 2 (Munc18-2; official gene symbol STXBP2) is mutated in another subset of patients with FHL (designated by us as "FHL5"). Lymphoblasts isolated from these patients had strongly decreased STXBP2 protein expression, and NK cells exhibited impaired cytotoxic granule exocytosis, a defect that could be overcome by ectopic expression of wild-type STXBP2. Furthermore, we provide evidence that syntaxin-11 is the main partner of STXBP2 in lymphocytes, as its expression required the presence of STXBP2. Our work shows that STXBP2 deficiency causes FHL5. These data indicate that STXBP2 is required at a late step of the secretory pathway for the release of cytotoxic granules by binding syntaxin 11, another component of the intracellular membrane fusion machinery.
Clinical Interpretation of the One-Stage Prothrombin Time
Authors: ARMAND J. QUICK
Journal: Circulation (1961)

BlIRT'H of the idea of the one-stage prothrombin time test came with the speed of tlhought its development, perfection, and full appraisal have not been entirely com- l)leted in a quarter of a century.'Its initial success is attributable to the fortuitious dis- covery of an active thromboplastie material.Rabbit lung was the first tissue tested and w\hile it was found moderately satisfactory, it was soon replaced by rabbit brain.The lat- ter material could readily be made almost bloodless mnerely by mechanically removing the pia and the larger blood vessels.In the earlier studies, air-dried rabbit brain was used.It had, however, the disadvantages of not having a uniform potency and being difficult to preserve.By a simple process of dehydrating the rabbit brain with acetone, a product was obtained with a high and constant potency and a remarkable stability.A prep- aration made and sealed in vacuum in April 1-938 still gave 12 seconds on human plasma ill a recent test as it had 22 years ago.Since this product gives very prolonged prothroin- b)in times on plasmas from patients with severe hypoprothrombinemia2 and with defi- cieiicmes of factors V,3 V l,4 and X4 (Stuart-
Results from a Phase I Clinical Study of the Novel Ii-Key/HER-2/<i>neu</i>(776–790) Hybrid Peptide Vaccine in Patients with Prostate Cancer
Authors: Sonia A. Perez, Nikoletta L. Kallinteris, Stratos Bisias, Panagiotis K. Tzonis, Katerina Georgakopoulou, Marighoula Varla-Leftherioti, Michael Papamichail, Anastasios Thanos, Eric von Hofe, Constantin N. Baxevanis
Journal: Clinical Cancer Research (2010)

Active immunotherapy is emerging as a potential therapeutic approach for prostate cancer. We conducted the first phase I trial of an Ii-Key/HER-2/neu(776-790) hybrid peptide vaccine (AE37) with recombinant granulocyte macrophage colony-stimulating factor as adjuvant in patients with HER-2/neu(+) prostate cancer. The primary end points of the study were to evaluate toxicity and monitor patients' immune responses to the vaccine.Thirty-two HER-2/neu(+), castrate-sensitive, and castrate-resistant prostate cancer patients were enrolled. Of these, 29 patients completed all six vaccination cycles with AE37. Immunologic responses in the total patient population were monitored by delayed-type hypersensitivity and IFN-gamma ELISPOT and intracellular staining. Regulatory T-cell (Treg) frequency and plasma HER-2/neu and transforming growth factor-beta levels were also determined. Immunologic responses were also analyzed among groups of patients with different clinical characteristics. Local/systemic toxicities were monitored throughout the study.Toxicities beyond grade 2 were not observed. Seventy-five percent of patients developed augmented immunity to the AE37 vaccine and 65% to the unmodified AE36 peptide as detected in the IFN-gamma-based ELISPOT assay. Intracellular IFN-gamma analyses revealed that AE37 elicited both CD4(+) and CD8(+) T-cell responses. Eighty percent of the patients developed a positive delayed-type hypersensitivity reaction to AE36. Additionally, significant decreases could be detected in circulating Treg frequencies, plasma HER-2/neu, and serum transforming growth factor-beta levels. Patients with less extensive disease developed better immunologic responses on vaccination.AE37 vaccine is safe and can induce HER-2/neu-specific cellular immune responses in patients with castrate-sensitive and castrate-resistant prostate cancer, thus emphasizing the potential of AE37 to target HER-2/neu for the immunotherapy of prostate cancer.
To perform or not to perform liver biopsy: an alternative view
Authors: R W Chapman
Journal: Gut (2003)

I would like to thank Joy and Scott for their comments in their letter in response to my review ( Gut 2002; 51 :9–10).1 I entirely agree with their view that ultrasound is highly specific and sensitive for the diagnosis of fatty liver. However, I do not feel that the presence or absence of fatty liver is the issue …
EXPERIMENTAL INFECTION OF THE SKIN IN THE HAMSTER SIMULATING HUMAN IMPETIGO
Authors: Adnan S. Dajani, Lewis W. Wannamaker
Journal: The Journal of Experimental Medicine (1971)

The interaction between staphylococci and Group A beta hemolytic streptococci in mixed lesions was investigated in an experimental impetigo model. A strain of staphylococcus of phage Type 71, which has been shown in vitro to produce a bacteriocin for streptococci and other Gram-positive organisms, eliminates or reduces Group A streptococci in mixed lesions. In contrast, staphylococcal strains of phage Types 75 and 81, which do not produce a demonstrable bacteriocin in vitro, exhibit no such effect. Some variation was noted in the in vivo response of two different streptococcal M Types to the bactericidal effect of phage Type 71 staphylococci. Bacterial antagonism is more pronounced when staphylococci and streptococci are injected simultaneously into animals than when staphylococci are superimposed on preexisting streptococcal lesions. Marked variations were found in the numbers of viable streptococci (colony-forming units) recovered from individual lesions containing identical mixtures of streptococci and phage Type 71 staphylococci. The frequency of a demonstrable bactericidal effect was related to the number of streptococci injected. With small inocula of streptococci, the tendency towards an all-or-none effect was particularly striking. No evidence of selection of streptococcal or staphylococcal mutants which might explain this phenomenon was obtained. These observations suggest that the bactericidal effect of phage Type 71 staphylococci on other Gram-positive organisms, previously demonstrated in vitro, appears to operate also in vivo.
Neuromuscular and vascular hamartoma of small bowel presenting as inflammatory bowel disease.
Authors: C E Smith, M I Filipe, W J Owen
Journal: Gut (1986)

We present the case of a rare hamartomatous condition of the small intestine clinically mimicking inflammatory bowel disease. Disorganised fascicles of smooth muscle derived from both muscularis mucosae and propria, bundles of non-myelinated nerve fibres with groups of abnormal ganglion cells, and haemangiomatous vessels were present within the submucosa of a long segment of small intestine causing subacute obstruction.
Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan
Authors: C.I. Ripamonti, M. Maniezzo, T. Campa, E. Fagnoni, C. Brunelli, G. Saibene, C. Bareggi, L. Ascani, E. Cislaghi
Journal: Annals of Oncology (2008)
Paradoxical Reduction of Fatty Streak Formation in Mice Lacking Endothelial Nitric Oxide Synthase
Authors: Weibin Shi, Xuping Wang, Diana M. Shih, Victor E. Laubach, Mohamad Navab, Aldons J. Lusis
Journal: Circulation (2002)

Background — The endothelial isoform of nitric oxide synthase (eNOS) has been considered to exert an antiatherosclerotic role through synthesis of NO. However, eNOS has been shown to generate superoxide, which could oxidize LDL and promote atherosclerosis. We sought to determine the role of eNOS in diet-induced fatty streak formation through the use of eNOS-deficient mice. Methods and Results — Mice were fed an atherogenic diet containing 15% fat, 1.25% cholesterol, and 0.5% sodium cholate for 12 weeks, and atherosclerotic lesions at the aortic root were measured after oil-red O staining. Unexpectedly, eNOS-deficient mice developed much smaller aortic lesions than did wild-type control mice (2544±1107 versus 7023±1569 μm 2 /section; P =0.03). This reduction in lesion formation could not be explained by changes in plasma levels of lipids and susceptibility of lipoproteins to oxidation. To examine whether eNOS contributed to the oxidation of LDL within the arterial wall, endothelial cells were isolated from the aorta of mice and incubated with native LDL in the absence or presence of N-Ω-nitro- l -arginine methyl ester (L-NAME), a specific NOS inhibitor. L-NAME significantly inhibited LDL oxidation by endothelial cells from wild-type animals ( P &lt;0.05), but it had no effect on LDL oxidation by endothelial cells from eNOS-deficient mice. Conclusions — These data indicate that absence of eNOS-mediated LDL oxidation may contribute to the reduction of fatty-streak formation in eNOS-deficient mice.
Iatrogenic injury to the intercostal artery: aetiology, diagnosis and therapeutic intervention
Authors: Ioannis Psallidas, Emma J Helm, Nick A Maskell, Lonny Yarmus, David J Feller-Kopman, Fergus V Gleeson, Najib M Rahman
Journal: Thorax (2015)

Pleural interventions are commonly performed in both elective and emergency settings. They include simple thoracocentesis, closed pleural biopsy (with or without image guidance), intercostal drain (ICD) insertion, in-dwelling pleural catheter insertion and medical thoracoscopy. Complications of pleural procedures are common but their incidence is often under-recognised. Higher operator experience and the use of image guidance are key factors demonstrated to significantly reduce the frequency of complications.1

Injury to the intercostal artery (ICA) is an infrequent but potentially life-threatening complication of all pleural interventions. Pleural haemorrhage is reported to occur in up to 2% of thoracocenteses, up to 13% of ICD insertions and up to 4% of thoracoscopies.2 The true incidence of ICA laceration and consequent pleural haemorrhage is likely to be higher due to under-reporting of complications seen in retrospective case series.

The British Thoracic Society has published guidelines for the insertion of ICDs,1 aiming to reduce the potential harm of ICD insertion. Although these recommendations are likely to reduce certain complications such as drain insertion into abdominal or thoracic viscera, they do not specifically address the possibility of ICA injury. Proper site selection for pleural interventions is important as this minimises the likelihood of ICA laceration. In a recent large study, Helm et al 3 identified that ICA is exposed within the intercostal space in the first 6 cm lateral to the spine using CT pulmonary angiograph and mapping of the ICA course. The variability of ICA is greater in older people and in more cephalad rib spaces and decreases with lateral distance from the spinous process. Additionally, another important parameter is the management protocol for intrapleural haemorrhage. This should be in place prior to any pleural interventions to avoid life-threatening delays.

We present three cases of iatrogenic ICA injury in different clinical circumstances, from three different …
A dietary pattern characterized by high consumption of whole-grain cereals and low-fat dairy products and low consumption of refined cereals is positively associated with plasma adiponectin levels in healthy women
Authors: Mary Yannakoulia, Nikos Yiannakouris, Labros Melistas, Meropi D. Kontogianni, Ioannis Malagaris, Christos S. Mantzoros
Journal: Metabolism (2008)
Contemporary Impact of State Certificate-of-Need Regulations for Cardiac Surgery
Authors: Verdi J. DiSesa, Sean M. O’Brien, Karl F. Welke, Sarah M. Beland, Constance K. Haan, Mary S. Vaughan-Sarrazin, Eric D. Peterson
Journal: Circulation (2006)

Prior research using administrative data associated certificate-of-need (CON) regulation for open heart surgery with higher hospital coronary artery bypass grafting (CABG) volume and lower CABG operative mortality rates in elderly patients. It is unclear whether these findings apply in a general population and after controlling for detailed clinical characteristics and region.Using the Society of Thoracic Surgeons' (STS) National Cardiac Surgery Database, we examined isolated CABG surgery volume, operative mortality, and the composite end point of operative mortality or major morbidity for the years 2000 to 2003. The presence of CON regulations for open heart surgery was ascertained from the National Directory of the American Health Policy Association and by contacting CON administrators. Results were analyzed nationally, by state, and by region (West, Northeast, Midwest, South) and were adjusted for clinical factors and both population density and region with mixed-effects hierarchical logistic regression models. During 2000 to 2003, there were 314,710 isolated CABG surgeries performed at 294 STS hospitals in CON states (n=27, including Washington, DC) and 280 512 procedures at 343 STS hospitals in non-CON states (n=24). Patient clinical characteristics were similar among CON and non-CON hospitals. States with CON regulations tended to have higher population densities and had significantly higher median hospital annual CABG volumes in each of the years 2000 to 2003 (P<0.005). This difference remained significant after adjustment for region and population density. Operative mortality was 2.52% for CON versus 2.62% for non-CON states (P=0.32). There was a significant association between CON law and operative mortality in the South. After adjustment for patient risk factors and region, there was a marginally significant reduction of mortality risk in states with CON regulation (adjusted OR 0.92, 95% CI 0.86 to 1.00). However, this difference was not statistically significant when a revised model accounted for random state effects. Similar volume and outcomes results were seen when the analysis was repeated with data from the national Medicare database.CON states have significantly higher hospital CABG surgery volumes but similar mortality compared with non-CON states. CON regulation alone is not a sufficient mechanism to ensure quality of care for CABG surgery.
Increased Numbers of Eosinophils, Rather Than Only Etiology, Predict Histologic Changes in Patients With Esophageal Eosinophilia
Authors: Srividya Sridhara, Karthik Ravi, Thomas C. Smyrk, Hirohito Kita, Gail M. Kephart, Catherine R. Weiler, David A. Katzka
Journal: Clinical Gastroenterology and Hepatology (2012)