tbuckley/cabot-search huggingface dataset:
Risk of Major Adverse Cardiac Events Following Noncardiac Surgery in Patients With Coronary Stents
Authors: Mary T. Hawn, Laura A. Graham, Joshua S. Richman, Kamal M. F. Itani, William G. Henderson, Thomas M. Maddox
Journal: JAMA (2013)

Guidelines recommend delaying noncardiac surgery in patients after coronary stent procedures for 1 year after drug-eluting stents (DES) and for 6 weeks after bare metal stents (BMS). The evidence underlying these recommendations is limited and conflicting.To determine risk factors for adverse cardiac events in patients undergoing noncardiac surgery following coronary stent implantation.A national, retrospective cohort study of 41,989 Veterans Affairs (VA) and non-VA operations occurring in the 24 months after a coronary stent implantation between 2000 and 2010. Nonlinear generalized additive models examined the association between timing of surgery and stent type with major adverse cardiac events (MACE) adjusting for patient, surgery, and cardiac risk factors. A nested case-control study assessed the association between perioperative antiplatelet cessation and MACE.A composite 30-day MACE rate of all-cause mortality, myocardial infarction, and cardiac revascularization.Within 24 months of 124,844 coronary stent implantations (47.6% DES, 52.4% BMS), 28,029 patients (22.5%; 95% CI, 22.2%-22.7%) underwent noncardiac operations resulting in 1980 MACE (4.7%; 95% CI, 4.5%-4.9%). Time between stent and surgery was associated with MACE (<6 weeks, 11.6%; 6 weeks to <6 months, 6.4%; 6-12 months, 4.2%; >12-24 months, 3.5%; P < .001). MACE rate by stent type was 5.1% for BMS and 4.3% for DES (P < .001). After adjustment, the 3 factors most strongly associated with MACE were nonelective surgical admission (adjusted odds ratio [AOR], 4.77; 95% CI, 4.07-5.59), history of myocardial infarction in the 6 months preceding surgery (AOR, 2.63; 95% CI, 2.32-2.98), and revised cardiac risk index greater than 2 (AOR, 2.13; 95% CI, 1.85-2.44). Of the 12 variables in the model, timing of surgery ranked fifth in explanatory importance measured by partial effects analysis. Stent type ranked last, and DES was not significantly associated with MACE (AOR, 0.91; 95% CI, 0.83-1.01). After both BMS and DES placement, the risk of MACE was stable at 6 months. A case-control analysis of 284 matched pairs found no association between antiplatelet cessation and MACE (OR, 0.86; 95% CI, 0.57-1.29).Among patients undergoing noncardiac surgery within 2 years of coronary stent placement, MACE were associated with emergency surgery and advanced cardiac disease but not stent type or timing of surgery beyond 6 months after stent implantation. Guideline emphasis on stent type and surgical timing for both DES and BMS should be reevaluated.
Percutaneous arterial catheterization for multiple sampling
Authors: F. Moran, A. R. Lorimer, G. Boyd
Journal: Thorax (1967)

Two hundred and fifty instances of brachial artery catheterization using a simple percutaneous technique are reported. There have been no serious complications. Where multiple repeated arterial blood sampling is required, this method is superior to others available, particularly when the need for sampling extends over many days.
Over-expression of a modified bifunctional apoptosis regulator protects against cardiac injury and doxorubicin-induced cardiotoxicity in transgenic mice
Authors: C. C. Chua, J. Gao, Y.-S. Ho, X. Xu, I-C. Kuo, K.-Y. Chua, H. Wang, R. C. Hamdy, J. C. Reed, B. H.L. Chua
Journal: Cardiovascular Research (2008)

Bifunctional apoptosis regulator (BAR) is an endoplasmic reticulum protein that interacts with both the extrinsic and intrinsic apoptosis pathways. We hypothesize that over-expression of BAR Delta RING prevents apoptosis and injury following ischaemia/reperfusion (I/R) and attenuates doxorubicin (DOX)-induced cardiotoxicity.We generated a line of transgenic mice that carried a human BAR Delta RING transgene under the control of the mouse alpha-myosin heavy chain promoter. The RING domain, which binds ubiquitin conjugating enzymes, was deleted to prevent auto-ubiquitination of BAR and allow accumulation of the BAR protein, which binds apoptosis-regulating proteins. High levels of human BAR Delta RING transcripts and 42 KDa BAR Delta RING protein were expressed in the hearts of transgenic mice. When excised hearts were reperfused ex vivo for 45 min as Langendorff preparations after 45 min of global ischaemia, the functional recovery of the hearts, expressed as left ventricular developed pressure x heart rate, was 23 +/- 1.7% in the non-transgenic hearts compared with 51.5 +/- 4.3% in the transgenic hearts (P < 0.05). For in vivo studies, mice were subjected to 50 min of ligation of the left descending anterior coronary artery followed by 4 h of reperfusion. The infarct sizes following I/R injury, expressed as the percentage of the area at risk, were significantly smaller in the transgenic mice than in the non-transgenic mice (29 +/- 4 vs. 55 +/- 4%, P < 0.05). In hearts of mice subjected to cardiac I/R injury, BAR transgenic hearts had significantly fewer in situ oligo-ligation-positive cardiac cells (5.0 +/- 0.4 vs. 13.4 +/- 0.5%, P < 0.05). Over-expression of BAR Delta RING also significantly attenuated DOX-induced cardiac dysfunction and apoptosis.Our results demonstrate that over-expression of BAR Delta RING renders the heart more resistant to I/R injury and DOX-induced cardiotoxicity, and this protection correlates with reduced cardiomyocyte apoptosis.
Trypsinogen Copy Number Mutations in Patients With Idiopathic Chronic Pancreatitis
Authors: Emmanuelle Masson, Cédric Le Maréchal, Giriraj R. Chandak, Jérôme Lamoril, Stephane Bezieau, Swapna Mahurkar, Seema Bhaskar, D. Nageshwar Reddy, Jian-Min Chen, Claude Férec
Journal: Clinical Gastroenterology and Hepatology (2007)
Choline kinase inhibition in rheumatoid arthritis
Authors: M Guma, E Sanchez-Lopez, A Lodi, R Garcia-Carbonell, S Tiziani, M Karin, J C Lacal, G S Firestein
Journal: Annals of the Rheumatic Diseases (2014)

Objectives Little is known about targeting the metabolome in non-cancer conditions. Choline kinase (ChoKα), an essential enzyme for phosphatidylcholine biosynthesis, is required for cell proliferation and has been implicated in cancer invasiveness. Aggressive behaviour of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) led us to evaluate whether this metabolic pathway could play a role in RA FLS function and joint damage. Methods Choline metabolic profile of FLS cells was determined by 1 H magnetic resonance spectroscopy ( 1 HMRS) under conditions of ChoKα inhibition. FLS function was evaluated using the ChoKα inhibitor MN58b (IC 50 =4.2 μM). For arthritis experiments, mice were injected with K/BxN sera. MN58b (3 mg/kg) was injected daily intraperitoneal beginning on day 0 or day 4 after serum administration. Results The enzyme is expressed in synovial tissue and in cultured RA FLS. Tumour necrosis factor (TNF) and platelet-derived growth factor (PDGF) stimulation increased ChoKα expression and levels of phosphocholine in FLS measured by Western Blot (WB) and metabolomic studies of choline-containing compounds in cultured RA FLS extracts respectively, suggesting activation of this pathway in RA synovial environment. A ChoKα inhibitor also suppressed the behaviour of cultured FLS, including cell migration and resistance to apoptosis, which might contribute to cartilage destruction in RA. In a passive K/BxN arthritis model, pharmacologic ChoKα inhibition significantly decreased arthritis in pretreatment protocols as well as in established disease. Conclusions These data suggest that ChoKα inhibition could be an effective strategy in inflammatory arthritis. It also suggests that targeting the metabolome can be a new treatment strategy in non-cancer conditions.
Novel Mutation in Syntaxin-Binding Protein 2 (STXBP2) in Familial Hemophagocytic Lymphohistiocytosis Type 5 (FHL-5) Prevents IL-2-induced Natural Killer Cell Cytotoxicity and Degranulation
Authors: R.W. Saltzman, L. Monaco-Shawver, K.E. Sullivan, J.S. Orange
Journal: Journal of Allergy and Clinical Immunology (2011)
PET-CT findings of progressive massive fibrosis in retired coal miners
Authors: Meltem Tor, Tacettin Ornek, Bulent Altinsoy, Figen Atalay
Journal: European Respiratory Journal (2013)

Introduction: There is limited data on the Positron Emission Tomography (PET) findings of lung lesions in coal worker9s pneumoconiosis and its utility to rule out lung cancer from progressive massive fibrosis (PMF) lesions.  Aims and objectives:In this preliminary study, we wanted to report the FDG-PET features of PMF lesions and to determine the ability of PET-CT to differentiate pure PMF in coal workers from PMF-associated lung cancer.  Methods: Six male retired coal miners potential PMF lesions, who were referred to our clinic to rule out lung cancer, were enrolled. Diagnostic workup including bronchoscopy and/or transthoracic lung biopsy were performed to confirm pathological diagnosis. PET-CT was also performed to rule out lung cancer  Results: Patients were all males, aged between 63 and 82 (mean age: 74.3 +/- 7.4). They had a mean underground coal mining history of 27 years (20-33 years). All but two were exsmokers with a mean 57.5+/-34.6 packyears of smoking history.Two were nonsmokers. All lesions were pathologically confirmed as PMF/ anthracosis. All patients had right upper lobe lesions and two patients had bilateral upper lobe lesions. FDG-PET scans identified metabolically active lesions in all patients. Mean standardized uptake values (SUVs) of abnormalities depicted on PET scan were 4.2 to 11.0 (mean +/- SD, 6.88+/-2.63), which were >3.0 on all occasions.  Conclusions: We conclude that FDG PET can identify PMF lesions as hypermetabolic lesions even without associated malignancy and thus PETCT has a limited role in ruling out cancer in exminers with a PMF lesion in case of suspicion of a possible concurrent lung cancer.
Impairment of the Diurnal Fibrinolytic Response in Man
Authors: DOUGLAS R. ROSING, DAVID R. REDWOOD, PIETER BRAKMAN, TAGE ASTRUP, STEPHEN E. EPSTEIN
Journal: Circulation Research (1973)

Diurnal patterns of plasma euglobulin fibrinolytic activity, estimated by the fibrin plate method, were determined in groups of young normal and older normal subjects, in subjects with type IV hyperlipoproteinemia, and in subjects with coronary artery disease who had normal lipid profiles. The marked diurnal increases in fibrinolytic activity observed in the young normal subjects were significantly reduced in a large percent of the older normal subjects and in most of the subjects with coronary artery disease or type IV hyperlipoproteinemia. Although not conclusive, these findings were compatible with the hypothesis that an impairment in the responsiveness of the fibrinolytic system may be related to the development of coronary artery disease.
Inhibition of sterile danger signals, uric acid and ATP, prevents inflammasome activation and protects from alcoholic steatohepatitis in mice
Authors: Arvin Iracheta-Vellve, Jan Petrasek, Abhishek Satishchandran, Benedek Gyongyosi, Banishree Saha, Karen Kodys, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Gyongyi Szabo
Journal: Journal of Hepatology (2015)
Assessment of Human Health Vulnerability to Climate Variability and Change in Cuba
Authors: Paulo Lázaro Ortíz Bultó, Antonio Pérez Rodríguez, Alina Rivero Valencia, Nicolás León Vega, Manuel Díaz Gonzalez, Alina Pérez Carrera
Journal: Environmental Health Perspectives (2006)

In this study we assessed the potential effects of climate variability and change on population health in Cuba. We describe the climate of Cuba as well as the patterns of climate-sensitive diseases of primary concern, particularly dengue fever. Analyses of the associations between climatic anomalies and disease patterns highlight current vulnerability to climate variability. We describe current adaptations, including the application of climate predictions to prevent disease outbreaks. Finally, we present the potential economic costs associated with future impacts due to climate change. The tools used in this study can be useful in the development of appropriate and effective adaptation options to address the increased climate variability associated with climate change.
A patient with insidious onset of exertional dyspnoea
Authors: P Eller
Journal: Thorax (2005)

The case history is presented of a 42 year old woman with pulmonary artery occlusion due to tuberculous vasculitis that masqueraded as chronic pulmonary artery embolism and led to severe life threatening haemoptysis necessitating emergency pneumonectomy. It is concluded that obliterative tuberculous endarteritis of the pulmonary arteries should be considered in the differential diagnosis of any acquired obstruction of pulmonary arteries.
E400P in advanced seminoma of good prognosis according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification: The Spanish Germ Cell Cancer Group experience
Authors: J.A. Arranz Arija, X. García del Muro, J. Gumà, J. Aparicio, R. Salazar, A. Saenz, J. Carles, M. Sánchez, J.R. Germà-Lluch
Journal: Annals of Oncology (2001)
SUBSTANCES STIMULATING GLUCOSE CATABOLISM BY THE OXIDATIVE REACTIONS OF THE PENTOSE PHOSPHATE PATHWAY IN HUMAN ERYTHROCYTES*
Authors: Arieh Szeinberg, Paul A. Marks
Journal: Journal of Clinical Investigation (1961)

Mature human erythrocytes possess the enzymes necessary to catabolize glucose to CO2 via pentose phosphate pathway or to lactic acid via the Emb- den-Meyerhof pathway.These cells are deficient in certain enzymes of the tricarboxylic acid cycle.In the non-nucleated red cells, the oxidative reac- tions of pentose phosphate pathway appear to be the sole mechanism for glucose conversion to CO2 and for the generation of TPNH (2, 3).Several investigators have suggested that a major factor in the control of the rate of glucose catabo- lism via the pentose phosphate pathway is the meta- bolic demand for TPNH (4-6).It has been dem- onstrated that addition of dyes capable of acting as electron acceptors from TPNH (i.e., methylene blue, phenazine methosulphate, pyocyanin) in- creases the rate of activity of this pathway in eryth- rocytes, liver slices and mammary glands (7-9).Stimulation of the pentose phosphate pathway by pyruvate in bovine corneal epithelium, by insulin in rat mammary tissue, and by ammonium salts in yeasts has been ascribed to supply of substrates requiring TPNH for their metabolism or to stim- ulation of enzyme systems which utilize TPNH (8, 10-12).Among the systems requiring TPNH is that involved in the maintenance of glutathione in the reduced state (13).It has been demonstrated that human erythrocytes deficient in glucose-6- phosphate dehydrogenase (G6PD) are unable to maintain their level of reduced glutathione upon incubation with a variety of agents, such as acetylphenylhydrazine, primaquine, ascorbic acid, alpha naphthol, nitrofurantoin, cysteine and fava
Effects of environmental and occupational pesticide exposure on human sperm: a systematic review
Authors: M. J. Perry
Journal: Human Reproduction Update (2008)

Relatively recent discoveries of the hormone disrupting properties of some pesticides have raised interest in how contemporary pesticide exposures, which primarily take the form of low level environmental or occupational exposures, impact spermatogenesis. The objective of the present review was to summarize results to date of studies examining pesticide effects on human sperm. Outcomes evaluated included sperm parameters, DNA damage and numerical chromosome aberrations (aneuploidy (disomy, nullisomy) or diploidy). Studies investigating sperm in men environmentally and/or occupationally exposed to any types of pesticides were included in the review. The targeted literature search over the last 15 years showed a range of pesticide classes have been investigated including pyrethroids, organophosphates, phenoxyacetic acids, carbamates, organochlorines and pesticide mixtures. None of the studies involved acute exposure events such as chemical accidents. There were 20 studies evaluating semen quality, of which 13 studies reported an association between exposure and semen quality; 6 studies evaluating DNA damage, of which 3 reported an association with exposure; and 6 studies assessing sperm aneuploidy or diploidy, of which 4 reported an association with exposure. Studies varied widely in methods, exposures and outcomes. Although suggestive for semen parameters, the epidemiologic evidence accumulated thus far remains equivocal as to the spermatotoxic and aneugenic potential of pesticides given the small number of published studies. This question warrants more investigation and suggestions for future studies are outlined.
Enumeration and Molecular Characterization of Circulating Tumor Cells in Lung Cancer Patients Using the Gilupi Cellcollector™, An Effective in Vivo Device for Capturing Ctcs
Authors: N. Scheumann, T. Gorges, N. Penkalla, B. Nowack, T. Schalk, S. Riethdorf, K. Lücke, K. Pantel, T. Krahn, C. Schumann
Journal: Annals of Oncology (2015)
DEGRANULATION OF POLYMORPHONUCLEAR LEUCOCYTES FOLLOWING PHAGOCYTOSIS OF MICROORGANISMS
Authors: James G. Hirsch, Zanvil A. Cohn
Journal: The Journal of Experimental Medicine (1960)

A marked reduction in numbers of cytoplasmic granules in rabbit and human polymorphonuclear leucocytes takes place following ingestion of various microorganisms or of a yeast cell wall preparation. The degranulation occurs within 30 minutes of phagocytosis, and is directly related to the quantity of material engulfed. White cells completely degranulated following phagocytosis of large numbers of microorganisms remain viable for at least 1 hour. The granules of polymorphonuclear leucocytes contain the antimicrobial agent, phagocytin, and various digestive enzymes. These substances thus are released into the cytoplasm or into vacuoles following ingestion of foreign material. The granule system and granule lysis mechanism may well play a central role in the primary function of these specialized cells; namely, that of destroying invading microorganisms.
Sox4 Is a Key Oncogenic Target in C/EBPα Mutant Acute Myeloid Leukemia
Authors: Hong Zhang, Meritxell Alberich-Jorda, Giovanni Amabile, Henry Yang, Philipp B. Staber, Annalisa Di Ruscio, Robert S. Welner, Alexander Ebralidze, Junyan Zhang, Elena Levantini, Véronique Lefebvre, Peter J.M. Valk, Ruud Delwel, Maarten Hoogenkamp, Claus Nerlov, Jörg Cammenga, Borja Saez, David T. Scadden, Constanze Bonifer, Min Ye, Daniel G. Tenen
Journal: Cancer Cell (2013)
Medical Costs of Abnormal Serum Sodium Levels
Authors: Alisa M. Shea, Bradley G. Hammill, Lesley H. Curtis, Lynda A. Szczech, Kevin A. Schulman
Journal: Journal of the American Society of Nephrology (2008)

An abnormal serum sodium level is the most common electrolyte disorder in the United States and can have a significant impact on morbidity and mortality. The direct medical costs of abnormal serum sodium levels are not well understood. The impact of hyponatremia and hypernatremia on 6-mo and 1-yr direct medical costs was examined by analyzing data from the Integrated HealthCare Information Services National Managed Care Benchmark Database. During the period analyzed, there were 1274 patients (0.8%) with hyponatremia (serum sodium <135 mmol/L), 162,829 (97.3%) with normal serum sodium levels, and 3196 (1.9%) with hypernatremia (>145 mmol/L). Controlling for age, sex, region, and comorbidities, hyponatremia was a significant independent predictor of costs at 6 mo (41.2% increase in costs; 95% confidence interval, 30.3% to 53.0%) and at 1 yr (45.7% increase; 95% confidence interval, 34.2% to 58.2%). Costs associated with hypernatremia were not significantly different from those incurred by patients with normal serum sodium. In conclusion, hyponatremia is a significant independent predictor of 6-mo and 1-yr direct medical costs.
Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function
Authors: Teunis B.H. Geijtenbeek, Sandra J. van Vliet, Estella A. Koppel, Marta Sanchez-Hernandez, Christine M.J.E. Vandenbroucke-Grauls, Ben Appelmelk, Yvette van Kooyk
Journal: The Journal of Experimental Medicine (2002)

Mycobacterium tuberculosis represents a world-wide health risk and immunosuppression is a particular problem in M. tuberculosis infections. Although macrophages are primarily infected, dendritic cells (DCs) are important in inducing cellular immune responses against M. tuberculosis. We hypothesized that DCs represent a target for M. tuberculosis and that the observed immuno-suppression results from modulation of DC functions. We demonstrate that the DC-specific C-type lectin DC-SIGN is an important receptor on DCs that captures and internalizes intact Mycobacterium bovis bacillus Calmette-Guérin (BCG) through the mycobacterial cell wall component ManLAM. Antibodies against DC-SIGN block M. bovis BCG infection of DCs. ManLAM is also secreted by M. tuberculosis-infected macrophages and has been implicated as a virulence factor. Strikingly, ManLAM binding to DC-SIGN prevents mycobacteria- or LPS-induced DC maturation. Both mycobacteria and LPS induce DC maturation through Toll-like receptor (TLR) signaling, suggesting that DC-SIGN, upon binding of ManLAM, interferes with TLR-mediated signals. Blocking antibodies against DC-SIGN reverse the ManLAM-mediated immunosuppressive effects. Our results suggest that M. tuberculosis targets DC-SIGN both to infect DCs and to down-regulate DC-mediated immune responses. Moreover, we demonstrate that DC-SIGN has a broader pathogen recognition profile than previously shown, suggesting that DC-SIGN may represent a molecular target for clinical intervention in infections other than HIV-1.
Cotargeting Androgen Receptor and Clusterin Delays Castrate-Resistant Prostate Cancer Progression by Inhibiting Adaptive Stress Response and AR Stability
Authors: Hiroaki Matsumoto, Yoshiaki Yamamoto, Masaki Shiota, Hidetoshi Kuruma, Eliana Beraldi, Hideyasu Matsuyama, Amina Zoubeidi, Martin Gleave
Journal: Cancer Research (2013)

Abstract Although androgen receptor (AR) pathway inhibitors prolong survival in castrate-resistant prostate cancer (CRPC), resistance rapidly develops and is often associated with increased stress-activated molecular chaperones like clusterin (CLU) and continued AR signaling. Because adaptive pathways activated by treatment facilitate development of acquired resistance, cotargeting the stress response, activated by AR inhibition and mediated through CLU, may create conditional lethality and improve outcomes. Here, we report that CLU is induced by AR antagonism and silencing using MDV3100 and antisense, respectively, to become highly expressed in castrate- and MDV3100-resistant tumors and cell lines. CLU, as well as AKT and mitogen-activated protein kinase (MAPK) signalosomes, increase in response to MDV3100-induced stress. Mechanistically, this stress response is coordinated by a feed-forward loop involving p90rsk (RPS6KA)-mediated phosphoactivation of YB-1 with subsequent induction of CLU. CLU inhibition repressed MDV3100-induced activation of AKT and MAPK pathways. In addition, when combined with MDV3100, CLU knockdown accelerated AR degradation and repressed AR transcriptional activity through mechanisms involving decreased YB-1–regulated expression of the AR cochaperone, FKBP52. Cotargeting the AR (with MDV3100) and CLU (with OGX-011) synergistically enhanced apoptotic rates over that seen with MDV3100 or OGX-011 monotherapy and delayed CRPC LNCaP tumor and prostate-specific antigen (PSA) progression in vivo. These data indicate that cotargeting adaptive stress pathways activated by AR pathway inhibitors, and mediated through CLU, creates conditional lethality and provides mechanistic and preclinical proof-of-principle to guide biologically rational combinatorial clinical trial design. Cancer Res; 73(16); 5206–17. ©2013 AACR.