tbuckley/cabot-search huggingface dataset:
The Spread of Sinus Activation During Potassium Administration
Authors: MARIO VASSALLE, BRIAN F. HOFFMAN
Journal: Circulation Research (1965)

Electrodes were chronically implanted in intact dogs at several locations on the atria and ventricles, and studies made of the effect of an elevated extracellular K + concentration on the spread of the sinus impulse throughout the atria. It was found that sinus activity propagates to the coronary sinus and ventricles at a time when the atrial muscle fibers have been rendered inexcitable. The finding of such a sino-ventricular rhythm supports the existence of a specialized conducting path between the sinus and the atrio-ventricular node; this path is particularly resistant to depolarization by potassium. Potassium-induced 2:1 sino-atrial block was described. In vitro experiments provided a demonstration that such block is frequency-dependent and due to marked prolongation of the refractory period provoked by high [K] 0 . It appears that the lengthened refractory period may be due to a marked reduction of the reactivation rate of the "sodium carrying system."
Targeting Aurora Kinase with MK-0457 Inhibits Ovarian Cancer Growth
Authors: Yvonne G. Lin, Anand Immaneni, William M. Merritt, Lingegowda S. Mangala, Seung Wook Kim, Mian M.K. Shahzad, Yvonne T.M. Tsang, Guillermo N. Armaiz-Pena, Chunhua Lu, Aparna A. Kamat, Liz Y. Han, Whitney A. Spannuth, Alpa M. Nick, Charles N. Landen, Kwong K. Wong, Michael J. Gray, Robert L. Coleman, Diane C. Bodurka, William R. Brinkley, Anil K. Sood
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The Aurora kinase family plays pivotal roles in mitotic integrity and cell cycle. We sought to determine the effects of inhibiting Aurora kinase on ovarian cancer growth in an orthotopic mouse model using a small molecule pan-Aurora kinase inhibitor, MK-0457. Experimental Design: We examined cell cycle regulatory effects and ascertained the therapeutic efficacy of Aurora kinase inhibition both alone and combined with docetaxel using both in vitro and in vivo ovarian cancer models. Results: In vitro cytotoxicity assays with HeyA8 and SKOV3ip1 cells revealed &amp;gt;10-fold greater docetaxel cytotoxicity in combination with MK-0457. After in vivo dose kinetics were determined using phospho-histone H3 status, therapy experiments with the chemosensitive HeyA8 and SKOV3ip1 as well as the chemoresistant HeyA8-MDR and A2780-CP20 models showed that Aurora kinase inhibition alone significantly reduced tumor burden compared with controls (P values &amp;lt; 0.01). Combination treatment with docetaxel resulted in significantly improved reduction in tumor growth beyond that afforded by docetaxel alone (P ≤ 0.03). Proliferating cell nuclear antigen immunohistochemistry revealed that MK-0457 alone and in combination with docetaxel significantly reduced cellular proliferation (P values &amp;lt; 0.001). Compared with controls, treatment with MK-0457 alone and in combination with docetaxel also significantly increased tumor cell apoptosis by ∼3-fold (P &amp;lt; 0.01). Remarkably, compared with docetaxel monotherapy, MK-0457 combined with docetaxel resulted in significantly increased tumor cell apoptosis. Conclusions: Aurora kinase inhibition significantly reduces tumor burden and cell proliferation and increases tumor cell apoptosis in this preclinical orthotopic model of ovarian cancer. The role of Aurora kinase inhibition in ovarian cancer merits further investigation in clinical trials.
Expression of the Ammonia Transporter, Rh C Glycoprotein, in Normal and Neoplastic Human Kidney
Authors: Ki-Hwan Han, Byron P. Croker, William L. Clapp, Dietrich Werner, Manisha Sahni, Jin Kim, Hye-Young Kim, Mary E. Handlogten, I. David Weiner
Journal: Journal of the American Society of Nephrology (2006)

Recent studies have identified the presence of a novel Mep/Amt/Rh glycoprotein family of proteins that may play an important role in transmembrane ammonia transport. One of the mammalian members of this family, Rh C glycoprotein (RhCG), transports ammonia, is expressed in distal nephron sites that are critically important for ammonia secretion, exhibits increased expression in response to chronic metabolic acidosis, and originally was cloned as a tumor-related protein. The purpose of our studies was to determine the localization of RhCG in the normal and neoplastic human kidney. Immunoblot analysis of human renal cortical protein lysates demonstrated RhCG protein expression with a molecular weight of approximately 52 kD. Immunohistochemistry revealed both apical and basolateral Rhcg expression in the distal convoluted tubule, connecting segment, and initial collecting tubule and throughout the collecting duct. Co-localization with calbindin-D28k, H(+)-ATPase, aquaporin-2, and pendrin showed that distal convoluted tubule and connecting segment cells, A-type intercalated cells, and non-A, non-B cells express RhCG and that B-type intercalated cells, principal cells, and inner medullary collecting duct cells do not. In renal neoplasms, RhCG was expressed by chromophobe renal cell carcinoma and renal oncocytoma but not by clear cell renal cell carcinoma or by papillary renal cell carcinomas. These studies suggest that RhCG contributes to both apical and basolateral membrane ammonia transport in the human kidney. Furthermore, renal chromophobe renal cell carcinoma and renal oncocytoma seem to originate from the A-type intercalated cell.
Gaucher disease and comorbidities: B‐cell malignancy and parkinsonism
Authors: Timothy M. Cox, Barry E. Rosenbloom, Roger A. Barker
Journal: American Journal of Hematology (2015)

Data emerging from the International Collaborative Gaucher Group (ICGG) Gaucher Registry together with other contemporary clinical surveys have revealed a close association between Gaucher disease and non‐Hodgkin's B‐cell lymphoma and myeloma and Gaucher disease and Parkinson's disease. Several possible explanations for increased B‐cell proliferation and neoplasia in Gaucher disease have been proposed, including the possible influence of sphingosine (derived from the extra lysosomal metabolism of glucosylceramide), gene modifiers, splenectomy and immune system deregulation induced by cytokines, chemokines, and hydrolases released from Gaucher cells. Parkinson's disease is frequently seen in the otherwise‐healthy relatives of Gaucher disease patients leading to the finding that GBA mutations represent a genetic risk factor for Parkinson's disease. The mechanism of the association between GBA mutations and Parkinson's disease has yet to be elucidated but the pathogenesis appears distinct from that of Gaucher disease. Several pathogenic pathways have been proposed including lysosomal and/or mitochondrial dysfunction. The effect of Gaucher disease specific therapies on the incidence of cancer or Parkinson's disease are not clear and will likely be evaluated in future ICGG Gaucher Registry studies. Am. J. Hematol. 90:S25–S28, 2015. © 2015 Wiley Periodicals, Inc.
Assuring Access to State-of-the-Art Care for U.S. Minority Populations: the First 2 Years of the Minority-Based Community Clinical Oncology Program
Authors: A. Kaluzny, O. Brawley, D. Garson-Angert, J. Shaw, P. Godley, R. Warnecke, L. Ford
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Assuring Access to State-of-the-Art Care for U.S. Minority Populations: the First 2 Years of the Minority-Based Community Clinical Oncology Program Get access Arnold Kaluzny, Arnold Kaluzny Cecil G. Sheps Center for Health Services Research, Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., and School of Public Health, University of North Carolina at Chapel Hill Correspondence to : Arnold D. Kaluzny, Ph.D., Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, CB# 7590, 725 Airport Rd. Bldg., Chapel Hill, NC 27599-7590. Search for other works by this author on: Oxford Academic PubMed Google Scholar Otis Brawley, Otis Brawley Community Oncology and Rehabilitation Branch, Division of Cancer Prevention and Control, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan Garson-Angert, Dan Garson-Angert Cecil G. Sheps Center for Health Services Research, Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., and School of Public Health, University of North Carolina at Chapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar James Shaw, James Shaw Department of Medicine, University of North Carolina at Chapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul Godley, Paul Godley Department of Medicine, University of North Carolina at Chapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Warnecke, Richard Warnecke Survey Research Laboratory, University of IllinoisChicago Search for other works by this author on: Oxford Academic PubMed Google Scholar Leslie Ford Leslie Ford Community Oncology and Rehabilitation Branch, Division of Cancer Prevention and Control, National Cancer InstituteBethesda, Md * See "Notes" section following "References." Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 23, 1 December 1993, Pages 1945–1950, https://doi.org/10.1093/jnci/85.23.1945 Published: 01 December 1993 Article history Received: 19 May 1993 Revision received: 12 August 1993 Accepted: 07 September 1993 Published: 01 December 1993
Creating the Evidence Base for Quality Improvement Collaboratives
Authors: Brian S. Mittman
Journal: Annals of Internal Medicine (2004)

Intensive efforts are under way to improve health care quality and safety throughout the United States and abroad. Many of these efforts use the quality improvement collaborative method, an approach emphasizing collaborative learning and exchange of insights and support among a set of health care organizations. Unfortunately, the widespread acceptance and reliance on this approach are based not on solid evidence but on shared beliefs and anecdotal affirmations that may overstate the actual effectiveness of the method. More effective use of the collaborative method will require a commitment by users, researchers, and other stakeholders to rigorous, objective evaluation and the creation of a valid, useful knowledge and evidence base. Development of this evidence base will require improved conceptions of the nature of quality problems, quality improvement processes, and the types of research needed to elucidate these processes. Researchers, journal editors, and funding agencies must also cooperate to ensure that published evaluations are relevant, comprehensive, and cumulative.
Function and Distribution of Apolipoprotein A1 in the Artery Wall Are Markedly Distinct From Those in Plasma
Authors: Joseph A. DiDonato, Ying Huang, Kulwant S. Aulak, Orli Even-Or, Gary Gerstenecker, Valentin Gogonea, Yuping Wu, Paul L. Fox, W.H. Wilson Tang, Edward F. Plow, Jonathan D. Smith, Edward A. Fisher, Stanley L. Hazen
Journal: Circulation (2013)

Background— Prior studies show that apolipoprotein A1 (apoA1) recovered from human atherosclerotic lesions is highly oxidized. Ex vivo oxidation of apoA1 or high-density lipoprotein (HDL) cross-links apoA1 and impairs lipid binding, cholesterol efflux, and lecithin-cholesterol acyltransferase activities of the lipoprotein. Remarkably, no studies to date directly quantify either the function or HDL particle distribution of apoA1 recovered from the human artery wall. Methods and Results— A monoclonal antibody (10G1.5) was developed that equally recognizes lipid-free and HDL-associated apoA1 in both native and oxidized forms. Examination of homogenates of atherosclerotic plaque–laden aorta showed &gt;100-fold enrichment of apoA1 compared with normal aorta ( P &lt;0.001). Surprisingly, buoyant density fractionation revealed that only a minority (&lt;3% of total) of apoA1 recovered from either lesions or normal aorta resides within an HDL-like particle (1.063≤d≤1.21). In contrast, the majority (&gt;90%) of apoA1 within aortic tissue (normal and lesions) was recovered within the lipoprotein-depleted fraction (d&gt;1.21). Moreover, both lesion and normal artery wall apoA1 are highly cross-linked (50% to 70% of total), and functional characterization of apoA1 quantitatively recovered from aorta with the use of monoclonal antibody 10G1.5 showed ≈80% lower cholesterol efflux activity and ≈90% lower lecithin-cholesterol acyltransferase activity relative to circulating apoA1. Conclusions— The function and distribution of apoA1 in human aorta are quite distinct from those found in plasma. The lipoprotein is markedly enriched within atherosclerotic plaque, predominantly lipid-poor, not associated with HDL, extensively oxidatively cross-linked, and functionally impaired.
How Do You Tell Whether a Breast Cancer is HER2 Positive? Ongoing Studies Keep Debate in High Gear
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2010)

More than a decade after the drug trastuzumab (Herceptin) won approval in 1998, scientists still disagree over how to identify breast cancer patients for treatment. Trastuzumab targets human HER2, which contributes to poor outcomes in breast cancer when amplified. HER2-positive cases account for up to 20% of all newly diagnosed breast cancers, and there is no argument about trastuzumab’s efficacy in these cases. The debate is over the assays used to determine HER2 positivity: Which is more accurate? Even more controversial, how should their results be interpreted? Breast cancer strikes more than 200,000 women in the United States every year, so even small discordance rates between HER2 assays can mean thousands of potentially inaccurate fi ndings. That’s worrisome not just because women misclassifi ed as false negative are denied trastuzumab but also because falsepositive results needlessly saddle HER2negative patients with the drug’s $100,000 annual price tag — not to mention its side effects, which can include heart failure. Michael Press, M.D. , a pathologist at the
Pulmonary-derived phosphoinositide 3-kinase gamma (PI3Kγ) contributes to ventilator-induced lung injury and edema
Authors: Vito Fanelli, Valeria Puntorieri, Barbara Assenzio, Erica L. Martin, Vincenzo Elia, Martino Bosco, Luisa Delsedime, Lorenzo Del Sorbo, Andrea Ferrari, Stefano Italiano, Alessandra Ghigo, Arthur S. Slutsky, Emilio Hirsch, V. Marco Ranieri
Journal: Intensive Care Medicine (2010)
Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301)
Authors: Shinji Atagi, Masaaki Kawahara, Akira Yokoyama, Hiroaki Okamoto, Nobuyuki Yamamoto, Yuichiro Ohe, Toshiyuki Sawa, Satoshi Ishikura, Taro Shibata, Haruhiko Fukuda, Nagahiro Saijo, Tomohide Tamura
Journal: The Lancet Oncology (2012)
Overlapping paclitaxel-eluting stents: Long-term effects in a porcine coronary artery model
Authors: G WILSON, J POLOVICK, B HUIBREGTSE, B POFF
Journal: Cardiovascular Research (2007)

At 4-year follow-up, paclitaxel-eluting stents (PES, TAXUS) have demonstrated clinical effectiveness in reducing restenosis without increasing death or myocardial infarction. Concerns remain with all drug-eluting stents, however, regarding potential interference with long-term healing, particularly in zones with adjacent stent overlap due to theoretical doubling in both drug release and tissue contact with coating polymer. Therefore, we evaluated long-term healing of overlapped TAXUS stents in an accepted animal model.Seventy-one non-injured swine underwent coronary artery placement of 138 overlapping stent-pairs (91 PES TAXUS Liberté 1 microg/mm(2) slow release formulation, 3.0 or 3.5 mm diameter pairs and 47 control bare metal Liberté pairs) deployed at a 1.1:1 to 1.2:1 target stent-to-artery diameter ratio. Pathological analysis was performed at 30 (9 bare, 10 paclitaxel), 90 (9 bare, 10 paclitaxel), 180 (10 bare, 16 paclitaxel), 360 (10 bare, 21 paclitaxel), and 580 (9 bare, 22 paclitaxel) days.At all time intervals overlapped TAXUS stents were consistently endothelialized and free of luminal thrombus or vascular dilatation. Full healing, however, was delayed compared to control, with macrophage processed para-strut fibrin and cellular debris still present, but reduced and sequestered from blood flow by an endothelialized neointima at 360 and 580 days. While neointimal thickness in TAXUS overlap zones was significantly less than control at 30 days, greater neointima formation was observed with TAXUS at > or =90 days, but was stable and did not progress further from 90 to 580 days.In this porcine model TAXUS stents demonstrated safety and acceptable healing with prolonged time to resolution of para-strut deposits, and did not produce the sustained neointimal suppression seen clinically.
The Effect of Rural-to-Urban Migration on Obesity and Diabetes in India: A Cross-Sectional Study
Authors: Shah Ebrahim, Sanjay Kinra, Liza Bowen, Elizabeth Andersen, Yoav Ben-Shlomo, Tanica Lyngdoh, Lakshmy Ramakrishnan, R. C. Ahuja, Prashant Joshi, S. Mohan Das, Murali Mohan, George Davey Smith, Dorairaj Prabhakaran, K. Srinath Reddy
Journal: PLoS Medicine (2010)

Shah Ebrahim and colleagues examine the distribution of obesity, diabetes, and other cardiovascular risk factors among urban migrant factory workers in India, together with their rural siblings. The investigators identify patterns of change of cardiovascular risk factors associated with urban migration.
Race by Sex Differences in Depression Symptoms and Psychosocial Service Use Among Non-Hispanic Black and White Patients With Lung Cancer
Authors: Lara Traeger, Sheila Cannon, Nancy L. Keating, William F. Pirl, Christopher Lathan, Michelle Y. Martin, Yulei He, Elyse R. Park
Journal: Journal of Clinical Oncology (2013)

This study examined race by sex differences in depression symptoms and psychosocial service use (pastors, social workers, mental health workers, support groups) among patients with lung cancer.The multiregional Cancer Care Outcomes Research and Surveillance study surveyed black and white adults with stages I to III lung cancer (n = 1,043) about depression symptoms, interest in help for mood, and psychosocial service use. Multivariable logistic regression was used to evaluate race/sex differences in depression symptoms (modified Center for Epidemiologic Studies Depression Scale ≥ 6) and psychosocial service use, independent of demographic, clinical, psychosocial, and behavioral covariates.A total of 18.2% screened positive for depression symptoms. This proportion was highest among black men (24.7%), followed by white women (20.6%), black women (15.8%), and white men (15.0%). In adjusted analyses, white women showed greater risk for depression symptoms relative to black women (P = .01) and white men (P = .002), with no other differences among groups. Black patients were less likely than white patients to receive desired help for mood from their doctors (P = .02), regardless of sex. Among all patients, black women were most likely to have contact with pastoral care and social work.Race and sex interacted to predict risk of depression symptoms. Covariates accounted for elevated risk among black men. White women showed greater risk than black women and white men, independent of covariates. Black patients may experience greater barriers to receiving help for mood from their doctors. Race by sex differences in contact with psychosocial services highlight potential differences in the extent to which services are available, acceptable, and/or sought by patients.
Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis
Authors: P Aurora
Journal: Thorax (2004)

Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden.Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6-16 years and in 33 healthy controls.LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI -0.1 to 0.4), p = 0.38)MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.
Pleural biopsy in the diagnosis of malignant mesothelioma.
Authors: A Herbert, P J Gallagher
Journal: Thorax (1982)

In an attempt to distinguish reactive from neoplastic mesothelial proliferation, the histological material and clinical records of 153 patients on whom open or closed pleural biopsies were performed during 1976 were reviewed. In six of the 10 patients subsequently shown to have malignant mesothelioma the specimens from closed pleural biopsy had been reported as negative or equivocal but in retrospect showed changes not observed in reactive pleurisy. These included papillary mesothelial proliferation, exfoliated papillae, sheets of atypical mesothelial cells, and abnormal fibroblastic proliferation. In contrast, in inflammatory conditions the mesothelial lining was usually replaced by granulation tissue, although sheets or clumps of exfoliated mesothelial cells were often present in the corresponding pleural fluid clot. Some multilayering of parietal mesothelium was occasionally seen in chronic pleurisy and around metastases.
Cytosolic and microsomal glutathione S-transferase isoenzymes in normal human liver and intestinal epithelium.
Authors: P C Hayes, D J Harrison, I A Bouchier, L I McLellan, J D Hayes
Journal: Gut (1989)

Glutathione S-transferases are a group of drug metabolising and detoxification enzymes. We have studied the distribution of four isoenzymes, acidic, basic, neutral, and microsomal GST in human liver, gall bladder, and small and large intestinal epithelium by immunohistochemistry. Antibodies were raised in rabbits to purified GST subunits and several formalin fixed paraffin sections of each human tissue studied using the peroxidase-antiperoxidase method. Staining density was graded from very strong (+++) to negative (-). All four enzymes were identified within the liver, the acidic GST being found almost exclusively within the biliary epithelium. The gall bladder epithelium stained strongly for acidic and basic GST. In the small intestinal epithelium the acidic and neutral GST were readily identified in villi and crypts, whilst basic GST was found only in the villi and microsomal only in the crypts. In the colonic mucosa only acidic GST could consistently be identified. This histological heterogeneity may have functional implications for these enzymes in human hepatobiliary and intestinal tissue.