tbuckley/cabot-search huggingface dataset:
Viral Detection and Rhinovirus Strain Identification among Asthmatic Children During Peak Times of Asthma Exacerbations
Authors: J.P. Olenec, W.K. Kim, L. Salazar, T.E. Pappas, F. Vang, J. Bork, W.M. Lee, J.E. Gern
Journal: Journal of Allergy and Clinical Immunology (2009)

RATIONALE: There are predictable peaks in both asthma exacerbations and rhinovirus infections during the spring and fall among asthmatic children. The specific virology and strains of rhinoviruses during this time period are incompletely understood. METHODS: A total of 40 asthmatic children ages 6-8 years were enrolled, and 5 consecutive weekly samples of nasal lavage were collected during September 2006, April 2007, September 2007, and April 2008. Viruses were identified using multiplex PCR; rhinoviruses strains were identified using molecular typing. RESULTS: Viruses were detected in 38-51% of all the weekly specimens, and of the viruses detected, 72-99% were rhinoviruses in each collection period. Other viruses included enterovirus, adenovirus, coronavirus, influenza, metapneumovirus, bocavirus, and parainfluenza. There were 45 different strains detected among the 156 rhinovirus isolates, and 8 isolates were untypable. Each season, most RV strains were "new" (not found in the previous season): in April 2007, 68% (26/38); September 2007, 79% (27/34); and April 2008, 92% (12/13) were "new" strains. Comparing Sept 2006 and Sept 2007, 88% (30/34) were new strains, and comparing April 2007 and April 2008, 92% (12/13) were new strains. Conversely, the percentage of rhinovirus isolates that were carry-over strains, either from the previous season or previous year, ranged from 0-32%. There were no strains found in all four collection periods. CONCLUSIONS: These findings confirm that rhinoviruses are the most common virus found during the peak times of asthma exacerbations. In this group of children with asthma, the majority of rhinoviruses detected from season-to-season and year-to-year are new strains.
Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)—results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care
Authors: T.R. Asmis, E. Powell, C.S. Karapetis, D.J. Jonker, D. Tu, M. Jeffery, N. Pavlakis, P. Gibbs, L. Zhu, D.-A. Dueck, R. Whittom, C. Langer, C.J. O'Callaghan
Journal: Annals of Oncology (2010)
Two Sides of the Same Coin: <i>EGFR</i> Exon 19 Deletions and Insertions in Lung Cancer
Authors: Katerina Politi, Thomas J. Lynch
Journal: Clinical Cancer Research (2012)

Abstract Most lung adenocarcinoma-associated EGF receptor (EGFR) mutations confer sensitivity to specific EGFR tyrosine kinase inhibitors. The finding that exon 19 insertion mutations are also sensitive to this class of drugs suggests that testing for these mutations should be done and that these patients will benefit from treatment with tyrosine kinase inhibitors. Clin Cancer Res; 18(6); 1490–2. ©2012 AACR.
Patterns of Chromosomal Alterations in Breast Ductal Carcinoma <b> <i>In situ</i> </b>
Authors: E. Shelley Hwang, Sandy DeVries, Karen L. Chew, Dan H. Moore, Karla Kerlikowske, Ann Thor, Britt-Marie Ljung, Frederic M. Waldman
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Ductal carcinoma in situ (DCIS) is thought to be a nonobligate precursor of invasive cancer. Genomic changes specific to pure DCIS versus invasive cancer, as well as alterations unique to individual DCIS subtypes, have not been fully defined. Experimental Design: Chromosomal copy number alterations were examined by comparative genomic hybridization in 34 cases of pure DCIS and compared with 12 cases of paired synchronous DCIS and invasive ductal cancer, as well as to 146 additional cases of invasive breast cancer of ductal or lobular histology. Genomic differences between high-grade and low/intermediate-grade DCIS, as well as between pure DCIS and invasive cancer, were identified. Results: Pure DCIS showed almost the same degree of chromosomal instability as invasive ductal cancers. A higher proportion of low/intermediate-grade versus high-grade DCIS had loss of 16q (65 versus 12%, respectively; P = 0.002). When compared with lower grade DCIS, high-grade DCIS exhibited more frequent gain of 17q (65 versus 41%; P = 0.15) and higher frequency loss of 8p (77 versus 41%; P = 0.04). Chromosomal alterations in those cases with synchronous DCIS and invasive ductal cancer showed a high degree of shared changes within the two components. Conclusions: DCIS is genetically advanced, showing a similar degree of chromosomal alterations as invasive ductal cancer. The pattern of alterations differed between high- and low/intermediate-grade DCIS, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes. These regions of chromosomal alterations may be potential targets for treatment and/or markers of prognosis.
Acute cerebral oedema induced by methotrexate.
Authors: T. P. Enevoldson
Journal: BMJ (1989)

We need to be wary of recommending to our colleagues in district general hospitals high tech- nology procedures that are often not available and that require skill.Eighty one years ago James Mackenzie wrote in the preface of his marvellous book3: "In routine practice it is not usually neces- sary to take graphic records.If one-is trained to make careful and minute observations by the ordinary methods, and to have these checked by graphic records, one can ultimately acquire the power of recognising the majority of movements of the circulation without graphic records."Partly out of necessity but also out of kindness to our patients we need to remember his advice.Technology has made possible most of the spectacular advances in cardiology and cardiac surgery in the past 35 years.Once we have learnt from it, however, we can often dispense with it, par- ticularly if we wish to train our successors to be good doctors and not just high technologists.
Platinum-Based Chemotherapy for Variant Castrate-Resistant Prostate Cancer
Authors: Ana M. Aparicio, Andrea L. Harzstark, Paul G. Corn, Sijin Wen, John C. Araujo, Shi-Ming Tu, Lance C. Pagliaro, Jeri Kim, Randall E. Millikan, Charles Ryan, Nizar M. Tannir, Amado J. Zurita, Paul Mathew, Wadih Arap, Patricia Troncoso, Peter F. Thall, Christopher J. Logothetis
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Clinical features characteristic of small-cell prostate carcinoma (SCPC), “anaplastic,” often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined “anaplastic” clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low prostate-specific antigen levels relative to tumor burden, or short response to androgen deprivation therapy. Experimental Design: A 120-patient phase II trial of first-line carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Results: Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after four cycles of CD and EP, respectively. Median overall survival (OS) was 16 months [95% confidence interval (CI), 13.6–19.0 months]. Of the seven “anaplastic” criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Conclusion: Our findings support the hypothesis that patients with “anaplastic” prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with castration-resistant prostate cancer and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population. Clin Cancer Res; 19(13); 3621–30. ©2013 AACR.
Pathogenesis of Spontaneous and Pyelonephritic Hypertension in the Dog
Authors: J. I. KATZ, J. H. SKOM, G. E. WAKERLIN, L. Graham, B. Keith, R. Speer
Journal: Circulation Research (1957)

The upper limit of normotension in the trained, unanesthetized dog appears to be 145 (135-155) ± 7.5 mm. Hg mean femoral arterial pressure. The incidence of naturally occurring hypertension on the basis of this criterion was 0.9 per cent in 1000 dogs, 1 to 4 years of age. Six of the dogs had so-called spontaneous hypertension which may be similar to or the counterpart of essential hypertension in man. The other three had hypertension associated with chronic pyelonephritis. A renal, renin pathogenesis is indicated for both of these hypertensions by the antihypertensive effect produced by injections of hog renin with resulting antirenin and by passive transfer of high titre homologous antiserum containing antirenin to hog renin which also neutralizes dog renin.
Medical Ethics and the Law: Implications for Public Policy
Authors: Bruce L. Miller
Journal: JAMA (1982)

The title of this collection of essays is somewhat misleading; it suggests that the reader will find a lot of legal scholarship with ethical evaluation of the law and its implications for public policy. Rather, the book brings together three subdisciplines with their own perspectives on health and medical care: medical ethics, law and medicine, and health policy research. The avowed purpose of the editor is to bring ethical theory into closer contact with the study of public policy relating to health and medical care. All too often, medical ethics and the study of public policy pass each other without contact; the former is often abstract and frequently case oriented, and thus not in touch with specific policy problems; the latter is usually grounded in specifics, but makes no attempt to articulate and defend the ethical presuppositions of its analyses and evaluations. The 21 essays are organized into five general
Opposite Effects of Pressurized Steady Versus Pulsatile Perfusion on Vascular Endothelial Cell Cytosolic pH
Authors: Ilan S. Wittstein, Weiping Qiu, Roy C. Ziegelstein, Qinghua Hu, David A. Kass
Journal: Circulation Research (2000)

Endothelial cytosolic pH (pH(i)) modulates ion channel function, vascular tone, and cell proliferation. Steady shear induces rapid acidification in bicarbonate buffer. However, in vivo shear is typically pulsatile, potentially altering this response. We tested effects and mechanisms of pH(i) modulation by flow pulsatility, comparing pressurized steady versus pulse-flow responses in bovine aortic endothelial cells cultured within glass capillary tubes. Cells were loaded with the fluorescent pH(i) indicator carboxy seminaphthorhodafluor-1 and perfused with physiological pulsatile pressure and flow generated by a custom servo-control system. Raising mean pressure from 0 to 90 mm Hg at 0.5 mL/min steady flow in bicarbonate buffer induced sustained acidification (-0.33+/-0.09 pH units, P<0.01). A subsequent increase in steady flow resulted in further acidification. In contrast, if mean pressure and flow were unchanged but perfusion made pulsatile, pH(i) rose +0.3+/-0.03 (P<0. 0001) over 30 to 60 minutes. HCO(3)(-) removal and use of acid/base exchange inhibitors 5-(N-ethyl-N-isopropyl)amiloride or diisothiocyanato stilbene disulfonic acid identified both extracellular Na(+)-independent Cl(-)-HCO(3)(-) and Na(+)-H(+) exchangers as activated by static pressure, whereas pulsatility activated extracellular Na(+)-dependent Cl(-)-HCO(3)(-) and Na(+)-H(+) exchangers to raise pH(i). Pulse-perfusion alkalinization occurred with or without flow reversal and increased 1.6-fold in Ca(2+)-free buffer. Inhibition of c-Src tyrosine kinase (4-amino-5-[4-chlorophenyl]-7-[t-butyl]pyrazolo [3,4-d]pyrimidine; PP2) or MEK-1 (mitogen-activated protein kinase [MAP]/extracellular signal-regulated kinase [ERK]-1) (PD98059, blocking ERK1/2) blocked or reversed the pulsatile-flow pH(i) change to acidification. In contrast, PP2 had no effect on steady flow acidification, whereas MEK-1 inhibition converted it to alkalinization. Thus, pulsatile and steady flow trigger opposite effects on endothelial pH(i) by differential activation of acid/base exchangers linked to c-Src and MAP kinase phosphorylation, but not to Ca(2+). These data highlight specific signaling responses triggered by phasic shear profiles.
Medicine as a Planned Economy
Authors: R. D. Chalmers
Journal: BMJ (1948)

Idiosyncratic drug-induced liver injury (IDILI) typically occurs in a small fraction of patients and has resulted in removal of otherwise efficacious drugs from the market. Current preclinical testing methods are ineffective in predicting which drug candidates have IDILI liability. Recent results suggest that immune mediators such as tumor necrosis factor-<i>α</i> (TNF) and interferon-<i>γ</i> (IFN) interact with drugs that cause IDILI to kill hepatocytes. This proof-of-concept study was designed to test the hypothesis that drugs can be classified according to their ability to cause IDILI in humans using classification modeling with covariates derived from concentration-response relationships that describe cytotoxic interaction with cytokines. Human hepatoma (HepG2) cells were treated with drugs associated with IDILI or with drugs lacking IDILI liability and cotreated with TNF and/or IFN. Detailed concentration-response relationships were determined for calculation of parameters such as the maximal cytotoxic effect, slope, and EC<sub>50</sub> for use as covariates for classification modeling using logistic regression. These parameters were incorporated into multiple classification models to identify combinations of covariates that most accurately classified the drugs according to their association with human IDILI. Of 14 drugs associated with IDILI, almost all synergized with TNF to kill HepG2 cells and were successfully classified by statistical modeling. IFN enhanced the toxicity mediated by some IDILI-associated drugs in the presence of TNF. In contrast, of 10 drugs with little or no IDILI liability, none synergized with inflammatory cytokines to kill HepG2 cells and were classified accordingly. The resulting optimal model classified the drugs with extraordinary selectivity and specificity.
1406 ALISPORIVIR (ALV) PLUS PEG-INTERFERON/RIBAVIRIN (PR) IN HCV G1 TREATMENT-EXPERIENCED PATIENTS ACHIEVES PRIMARY ENDPOINT WITH SUPERIOR EFFICACY AT TREATMENT WEEK 12 COMPARED TO RETREATMENT WITH PR
Authors: A. Alberti, W.-L. Chuang, R. Flisiak, G. Mazzella, A. Horban, T. Goeser, P. Calistru, M. Buti, G. Davis, Y. Gong, C. Avila, J.-H. Kao
Journal: Journal of Hepatology (2012)
An integrated computational pipeline and database to support whole-genome sequence annotation
Authors: CJ Mungall, S Misra, BP Berman, J Carlson, E Frise, N Harris, B Marshall, S Shu, JS Kaminker, SE Prochnik, CD Smith, E Smith, JL Tupy, C Wiel, GM Rubin, SE Lewis
Journal: Genome biology (2002)

We describe here our experience in annotating the Drosophila melanogaster genome sequence, in the course of which we developed several new open-source software tools and a database schema to support large-scale genome annotation. We have developed these into an integrated and reusable software system for whole-genome annotation. The key contributions to overall annotation quality are the marshalling of high-quality sequences for alignments and the design of a system with an adaptable and expandable flexible architecture.
Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.
Authors: Z S Galis, G K Sukhova, M W Lark, P Libby
Journal: Journal of Clinical Investigation (1994)

Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular remodeling during the development and complication of human atherosclerotic lesions. We investigated the expression of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components in human atherosclerotic plaques (n = 30) and in uninvolved arterial specimens (n = 11). We studied members of all three MMP classes (interstitial collagenase, MMP-1; gelatinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) by immunocytochemistry, zymography, and immunoprecipitation. Normal arteries stained uniformly for 72-kD gelatinase and TIMPs. In contrast, plaques' shoulders and regions of foam cell accumulation displayed locally increased expression of 92-kD gelatinase, stromelysin, and interstitial collagenase. However, the mere presence of MMP does not establish their catalytic capacity, as the zymogens lack activity, and TIMPs may block activated MMPs. All plaque extracts contained activated forms of gelatinases determined zymographically and by degradation of 3H-collagen type IV. To test directly whether atheromata actually contain active matrix-degrading enzymes in situ, we devised a method which allows the detection and microscopic localization of MMP enzymatic activity directly in tissue sections. In situ zymography revealed gelatinolytic and caseinolytic activity in frozen sections of atherosclerotic but not of uninvolved arterial tissues. The MMP inhibitors, EDTA and 1,10-phenanthroline, as well as recombinant TIMP-1, reduced these activities which colocalized with regions of increased immunoreactive MMP expression, i.e., the shoulders, core, and microvasculature of the plaques. Focal overexpression of activated MMP may promote destabilization and complication of atherosclerotic plaques and provide novel targets for therapeutic intervention.
An unusual cause of gastric outlet obstruction
Authors: J P Y Ha, C N Tang, H Y S Cheung, G P C Yang, M K W Li
Journal: Gut (2007)

<h3>Abstract</h3> The resilience of ecosystem function under global climate change is governed by individual species vulnerabilities and the functional groups they contribute to (e.g. decomposition, primary production, pollination, primary, secondary and tertiary consumption). Yet it remains unclear whether species that contribute to different functional groups, which underpin ecosystem function, differ in their vulnerability to climate change. It is important to examine if functional group vulnerability differs across space (e.g. tropical vs temperate latitudes) to determine if some regions will be more vulnerable to loss of ecosystem function than others, and to examine whether localized effects of particular community compositions override global patterns of functional group vulnerability. We used existing upper thermal limit data across a range of terrestrial species (N = 1,743) to calculate species warming margins (degrees distance between a species upper thermal limit and the maximum environmental temperature they inhabit), as a metric of climate change vulnerability, to determine whether species that comprise different functional groups exhibit differential vulnerability to climate change, and if vulnerability trends change across geographic space. We found that primary producers had the broadest warming margins across the globe (μ = 21.85 °C) and that tertiary consumers had the narrowest warming margins (μ = 4.37 °C), where vulnerability tended to increase with trophic level. Species that contribute towards primary production were more vulnerable in low-latitude than mid-latitude regions, but warming margins across all other functional groups did not differ across regions when evolutionary history was considered. However, when evolutionary history was excluded from the analyses (as closely related species often play similar functional roles within ecosystems demonstrating true variation in functional group warming margins) we found that pollinators are more vulnerable in mid-latitude regions and that primary producers are more vulnerable in low-latitude environments. This study provides a critical first step in linking individual species vulnerabilities with whole ecosystem responses to climate change.
Aminorex, Fenfluramine, and Chlorphentermine Are Serotonin Transporter Substrates
Authors: Richard B. Rothman, Mario A. Ayestas, Christina M. Dersch, Michael H. Baumann
Journal: Circulation (1999)

Coadministration of phentermine and fenfluramine (phen/fen) effectively treats obesity and possibly addictive disorders. The association of fenfluramine and certain other anorexic agents with serious side effects, such as cardiac valvulopathy and primary pulmonary hypertension (PPH), limits the clinical utility of these drugs. Development of new medications that produce neurochemical effects like phen/fen without causing unwanted side effects would be a significant therapeutic breakthrough.We tested the hypothesis that fenfluramine (and other anorexic agents) might increase the risk of PPH through interactions with serotonin (5-HT) transporters. Because 5-HT transporter proteins in the lung and brain are identical, we examined, in rat brain, the effects of selected drugs on 5-HT efflux in vivo and monoamine transporters in vitro as a generalized index of transporter function. Our data show that drugs known or suspected to increase the risk of PPH (eg, aminorex, fenfluramine, and chlorphentermine) are 5-HT transporter substrates, whereas drugs that have not been shown to increase the risk of PPH are less potent in this regard.We speculate that medications that are 5-HT transporter substrates get translocated into pulmonary cells where, depending on the degree of drug retention, their intrinsic drug toxicity, and individual susceptibility, PPH could develop as a response to high levels of these drugs or metabolites. Emerging evidence suggests that it is possible to develop transporter substrates devoid of adverse side effects. Such medications could have therapeutic application in the management of obesity, drug dependence, depression, and other disorders.
Linkage analysis of the murine interferon-alpha locus on chromosome 4.
Authors: F Dandoy, K A Kelley, J DeMaeyer-Guignard, E DeMaeyer, P M Pitha
Journal: The Journal of Experimental Medicine (1984)

Southern blot analysis with a murine interferon-alpha2 (MuIFN-alpha2) cDNA probe revealed restriction fragment polymorphism of EcoRI- and HindIII-digested C57BL/6 and BALB/cDNA. The inheritance pattern of this polymorphism was examined using DNA from each of the seven recombinant inbred strains derived from C57BL/6 and BALB/c; the strain distribution pattern suggests linkage of INF-alpha genes to two histocompatibility loci on chromosome 4. Southern blot analysis of DNA from six bilinear congenic strains carrying different fragments of the BALB/c chromosome 4 on a C57BL/6 background showed linkage of IFN-alpha genes to the histocompatibility locus H-15. It can therefore be concluded that the IFN-alpha gene cluster is situated on chromosome 4 near the H-15 locus, between loci Mup-1 and b.
Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease
Authors: Philippe Brouqui, Vincenzo Puro, Francesco M Fusco, Barbara Bannister, Stephan Schilling, Per Follin, René Gottschalk, Robert Hemmer, Helena C Maltezou, Kristi Ott, Renaat Peleman, Christian Perronne, Gerard Sheehan, Heli Siikamäki, Peter Skinhoj, Giuseppe Ippolito
Journal: The Lancet Infectious Diseases (2009)