tbuckley/cabot-search huggingface dataset:
Study of C-C Chemokine Receptor 2 Alleles in Sarcoidosis, with Emphasis on Family-based Analysis
Authors: Ruta Valentonyte, Jochen Hampe, Peter J. P. Croucher, Joachim Müller-Quernheim, Eberhard Schwinger, Stefan Schreiber, Manfred Schürmann
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Prevailing models of sarcoidosis pathogenesis involve the activation of alveolar macrophages, aggregation of CD4+ T lymphocytes, and their accumulation in epithelioid cell granulomas. Increasing evidence suggests that each of these steps is modified by the host genetic constitution. Consequently, candidate susceptibility genes have been selected based on their potential function under this model. The C-C chemokine receptor 2 (CCR2) is involved in Th1 immune activity by recruiting competent cells and possibly by balancing response. CCR2 gene variants have been shown to be associated with sarcoidosis or, more specifically, with Löfgren's syndrome, a distinct form of acute sarcoidosis. We have studied three CCR2 gene polymorphisms (c.190G>A, c.840C>T, and c.4385A>T) in an extended sample of 1,203 patients with sarcoidosis and their relatives. Case-control comparisons and family-based genetic analyses did not support previous findings of an association between CCR2 gene variability and the risk of sarcoidosis. However, they confirmed linkage disequilibrium and showed positive linkage results (p = 0.034) and therefore suggest a susceptibility gene in the surrounding chromosomal region.
The Radiology of Skeletal Disorders: Exercises in Diagnosis
Authors: H. Andrew Wissinger
Journal: JAMA (1972)

This book contains a great quantity of information, offered to the reader in a very interesting and orderly manner. There are in excess of 2,000 radiographic illustrations, of sufficient size and clarity that the reader has no difficulty seeing what the authors intend for him. They are used to simulate the demands of radiologic interpretation. To achieve this, the authors provide the reader with an illustration, a brief clinical account and, no answer to the problem. This forces active participation on the part of the reader to search for the answer to the radiologic problem. On following pages one finds a clear, concise summary of the clinical and pathologic aspects of the problem confronting him. Also the answer, along with which the authors provide further examples of the same condition to illustrate other aspects of the problem, which may not have been evident on the initial test illustration. This method
A pilot, early angiographic patency study using a direct thrombin inhibitor as adjunctive therapy to streptokinase in acute myocardial infarction.
Authors: R M Lidón, P Théroux, J Lespérance, B Adelman, R Bonan, D Duval, J Lévesque
Journal: Circulation (1994)

BACKGROUND The success of streptokinase in acute myocardial infarction is hampered by the high failure rate to achieve early reperfusion. This study evaluates the possible benefit of Hirulog (Biogen, Cambridge, Mass), a direct thrombin inhibitor, as adjunct therapy to streptokinase to enhance early patency and prevent rethrombosis. Heparin has been shown to be of very limited benefits in this setting. METHODS AND RESULTS Forty-five patients were randomized to Hirulog or heparin (2:1 ratio). Coronary angiography documented a TIMI 2 or 3 flow after 90 minutes in 77% of the patients treated with Hirulog and streptokinase and in 47% of patients treated with heparin and streptokinase (P &lt; .05) and after 120 minutes in 87% and 47% of patients, respectively (P &lt; .01). TIMI 3 flow was established in 77% of patients with Hirulog compared with 40% with heparin (P &lt; .02). The clinical outcome and the bleeding rate was also favorable to Hirulog; no reocclusion was observed at late angiography performed 4.7 days later. CONCLUSIONS Hirulog in this pilot study significantly improved the early patency rate of the infarct-related artery with a favorable clinical profile. This new direct thrombin inhibitor exhibits promise as adjunctive therapy to thrombolysis.
Abstract 3363: Inhibition of glycolysis and proliferation of colon cancer cells by 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) an inhibitor of 6-phosphofructo-2-kinase (PFKFB3)
Authors: Michael A. Lea, Raymond Geherty, Rachelle David, Charles desBordes
Journal: Cancer Research (2014)

Abstract In human colon cancer cells, glycolytic activity shows a positive correlation with proliferation. PFKFB3 is an important enzyme regulating glycolysis in many tumor cells. We have studied the action of an established inhibitor of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) as a single agent and in combination with other molecules that affect glycolysis and proliferation in four colon cancer cell lines (Caco-2, HCT116, HT29 and SW1116). Glucose uptake and cell proliferation were inhibited by 3PO and butyrate and additive effects were seen with 10 µM 3PO and 1 mM butyrate. Induction of alkaline phosphatase activity serves as a marker of differentiation in colon cancer cells. The large induction of alkaline phosphatase activity by butyrate seen in most colon cancer cell lines was not observed with 3PO. Similar contrasting effects on induction of alkaline phosphatase activity were seen with rat Morris hepatoma 7777 cells where 2-3 fold induction was seen with 1 µM vorinostat or 1 mM butyrate but no significant effect was seen with 3PO in the range of 5-30 µM. The biguanides, metformin and phenformin, increase glycolysis but inhibit proliferation of colon cancer cells. After combination treatment with 3PO, glycolysis was inhibited, as judged by glucose uptake and acidification of the medium, and additive inhibitory effects on cell proliferation could be observed. For example, after a 72 hour incubation of Caco-2 cells with 10 µM 3PO, 25 µM phenformin or 1 mM metformin, as single agents, proliferation relative to controls was decreased 20%, 17% and 34%, respectively. For combinations of 3PO and phenformin or 3PO and metformin the decreases relative to controls were 48% and 58%, respectively. In conclusion, 3PO was an inhibitor of proliferation of colon cancer cells, especially the rapidly growing HCT116 and HT29 cell lines. 3PO may be a useful agent in combination with other drugs that inhibit colon cancer cell proliferation. Citation Format: Michael A. Lea, Raymond Geherty, Rachelle David, Charles desBordes. Inhibition of glycolysis and proliferation of colon cancer cells by 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) an inhibitor of 6-phosphofructo-2-kinase (PFKFB3). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3363. doi:10.1158/1538-7445.AM2014-3363
Abstract P3-14-11: Trastuzumab Cardiac Toxicity and HER2 Polymorphism: A Case-Control Study
Authors: A Mailliez, F Révillion, A Ploquin, V Servent, J. Bonneterre
Journal: Cancer Research (2010)

Abstract Background: Trastuzumab (T) is a very effective targeted therapy used in breast cancer patients but it can induce cardiac toxicity. Gene polymorphisms of Her 2 have been identified. According to a small report of Beauclair (2007), the polymorphism at codon 655 of the HER2 gene may represent a risk factor for cardiotoxicity induced by T. In this trial, we studied the incidence of the Val655Ile polymorphism in breast cancer patients with cardiac toxicity and in matched contol patients without cardiac toxicity. Patients and methods: In our institution, between January 1st, 2007 and April 15th, 2010, 26 patients developed cardiac toxicity potentially related to T and were referred to a cardiologist and treated with angiotensinconverting enzyme inhibitors, Beta-blockers. Their cardiac function was monitored. Twenty two control pts without cardiac toxicity were matched according to age, received dose of anthracyclin, BMI, cardiac risk factors, cardiac treatment and initial left ventricular ejection fraction. Her2 gene polymorphism in codon 655 was studied by PCR on lymphocyte DNA from blood samples in both populations. Genomic DNA was extracted from EDTA blood samples (300μl) on the MagNa Pure Compact instrument (Roche Diagnostics, Meylan, France), using the MagNA Pure Compact Nucleic Acid Isolation Kit according to the manufacturer's instructions. The HER2 Ile655Val (rs1163201) polymorphism was detected by sequencing using a 3730 DNA Analyzer (Applied Biosystems, Courtaboeuf, France) with the BigDye Terminator Cycle Sequencing kit and universal primers M13. Results: The mean age was 54.5 (31-72) and 52.5 (37-73) years respectively in the cardiac toxicity group and in the control group. In the cardiac toxicity group, 17 patients were in an adjuvant or a neoadjuvant setting, 9 were treated for a metastatic disease; 7 had cardiac risk factors (hypertension, diabetes, dyslipidemia or cardiac familial event). The control pts had similar characteristics. In the cardiac toxicity group 3.9% (1 patient) presented a genotype Val/Val at Her 2 codon 655, 42.3% (11)were heterozygous Ile and 53.8% (14) had the wild type. In the control population, the incidence was respectively 4.5% (1 patient), 31.8% (7) and 63.7% (14). No differences were found between the both groups. Discussion-Conclusion: The incidence of mutated, heterogeneous and wild type genotype was similar as the in the literature. We could not confirm the cardiac risk related to the Val allele at Her2 codon 655. Her2 polymorphism cannot be used in clinical practice to predict the risk of cardiac toxicity of Trastuzumab. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-11.
The ACLS score. Predicting survival from out-of-hospital cardiac arrest
Authors: M. Eisenberg
Journal: JAMA (1981)

We developed a score predictive of survival following out-of-hospital cardiac arrest from an analysis of factors associated with 611 cases. The score is calculated from four pieces of information readily obtainable by emergency personnel directly at the scene. The four items are as follow: A, arrest witnessed; C, cardiac rhythm; L, lay bystander cardiopulmonary resuscitation (CPR); S, speed (response time of paramedic unit). Among 22 patients with favorable findings on all four predictive variables (witnessed arrest, ventricular fibrillation, bystander CPR, paramedic response time less than four minutes), 15 (70%) were discharged alive. The ACLS score for this group of patients was 70%. Among 97 patients with the most unfavorable findings (whose ACLS score was 0), one (1%) was discharged. We believe the score can provide emergency personnel with a realistic appraisal of the likelihood of successful resuscitation.
Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1
Authors: Angélique Biancotto, Jean-Charles Grivel, Sarah J. Iglehart, Christophe Vanpouille, Andrea Lisco, Scott F. Sieg, Robert Debernardo, Kristen Garate, Benigno Rodriguez, Leonid B. Margolis, Michael M. Lederman
Journal: Blood (2007)
Control of the tissue inhibitor of metalloproteinases-1 promoter in culture-activated rat hepatic stellate cells: Regulation by activator protein-1 DNA binding proteins
Authors: Matthias J. Bahr, Karen J. Vincent, Michael J.P. Arthur, Andrew V. Fowler, David E. Smart, Matthew C. Wright, Ian M. Clark, Christopher R. Benyon, John P. Iredale, Derek A. Mann
Journal: Hepatology (1999)

In the injured liver hepatic stellate cells (HSCs) undergo a dramatic phenotypic transformation known as “activation” in which they become myofibroblast–like and express high levels of the tissue inhibitor of metalloproteinase 1 (TIMP–1). HSC activation is accompanied by transactivation of the TIMP–1 promoter. Truncation mutagenesis studies delineated a minimal active promoter consisting of nucleotides -102 to +60 relative to the major start site for transcription. Removal of an AP–1 site located at nucleotides -93 to -87 caused almost a complete loss of promoter activity. Analysis of AP–1 DNA binding activities during culture activation of HSCs initially indicated transient expression of proteins capable of forming a low mobility AP–1 DNA binding complex (lmAP–1). lmAP–1 was maximally induced at 24 hours of culture and then fell to undetectable levels at 120 hours. Western blot studies showed that both c–Fos and c–Jun underwent similar transient inductions. These temporal changes in c–Fos and c–Jun activities were unexpected because TIMP–1 mRNA expression is not detected in HSCs until culture day 3 to 5 and is thereafter sustained at a high level. Previous work in other cell lineages has established a key role for Pea3 binding proteins (Ets–1) in AP–1 mediated transactivation of the TIMP–1 promoter. We show that HSCs express relatively low levels Ets–1 and Ets–2 and show that mutagenesis of the Pea3 DNA binding site in the TIMP–1 promoter has less than a twofold effect on its activity in activated HSCs. Further analysis of AP–1 DNA binding activities in 7– to 14–day culture activated HSCs led to the discovery of high mobility AP–1 complexes (hmAP–1). hmAP–1 DNA binding activities were sequence specific with respect to AP–1 and absent from freshly isolated HSCs. Supershift EMSA and Western blot studies identified JunD, Fra2, and FosB as potential components of the HMAP–1. Mutations of the AP–1 site of the TIMP–1 promoter that prevented formation of hmAP–1 caused a 70% loss of activity in transfected activated HSCs. Taken together the data indicate that sustained upregulation of TIMP–1 gene expression may be at least partially controlled by a novel AP–1 dependent regulation of TIMP–1 promoter activity.
Personal Exposures to Traffic-Related Air Pollution and Acute Respiratory Health among Bronx Schoolchildren with Asthma
Authors: Ariel Spira-Cohen, Lung Chi Chen, Michaela Kendall, Ramona Lall, George D. Thurston
Journal: Environmental Health Perspectives (2011)

Previous studies have reported relationships between adverse respiratory health outcomes and residential proximity to traffic pollution, but have not shown this at a personal exposure level.We compared, among inner-city children with asthma, the associations of adverse asthma outcome incidences with increased personal exposure to particulate matter mass ≤ 2.5 μm in aerodynamic diameter (PM(2.5)) air pollution versus the diesel-related carbonaceous fraction of PM2.5.Daily 24-hr personal samples of PM(2.5), including the elemental carbon (EC) fraction, were collected for 40 fifth-grade children with asthma at four South Bronx schools (10 children per school) during approximately 1 month each. Spirometry and symptom scores were recorded several times daily during weekdays.We found elevated same-day relative risks of wheeze [1.45; 95% confidence interval (CI), 1.03-2.04)], shortness of breath (1.41; 95% CI, 1.01-1.99), and total symptoms (1.30; 95% CI, 1.04-1.62) with an increase in personal EC, but not with personal PM(2.5) mass. We found increased risk of cough, wheeze, and total symptoms with increased 1-day lag and 2-day average personal and school-site EC. We found no significant associations with school-site PM(2.5) mass or sulfur. The EC effect estimate was robust to addition of gaseous pollutants.Adverse health associations were strongest with personal measures of EC exposure, suggesting that the diesel "soot" fraction of PM(2.5) is most responsible for pollution-related asthma exacerbations among children living near roadways. Studies that rely on exposure to PM mass may underestimate PM health impacts.
Bile acid synthesis from newly synthesized vs. preformed cholesterol precursor pools in the rat
Authors: Jürgen Scheibner, Michael Fuchs, Michael Schiemann, Gisela Tauber, Erwin Hörmann, Eduard F. Stange
Journal: Hepatology (1993)

The present study defines the origin of cholesterol subserving bile acid synthesis in male rats with an extracorporal bile duct by labeling newly formed cholesterol with tritiated water. Within 6 hr after interruption of the enterohepatic circulation, the bile acid pool was depleted. At this early time point the proportion from de novo cholesterol was 8% and 12% for biliary cholesterol and cholate, but 18% and 19% for muricholate and chenodeoxycholate, respectively. This proportion gradually rose to 40%, 34%, 51% and 51%, respectively, at 15 to 30 hr. At 78 hr after bile diversion, 64% of cholate was labeled, compared with 84% to 88% of the other biliary lipids and 71% of plasma cholesterol. Total and labeled bile acid secretion exhibited the same diurnal rhythm. To allow differentiation between direct hepatocytic de novo synthesis of bile acids from acetate and recycling of labeled plasma cholesterol, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (pravastatin) was infused from 54 to 78 hr. It suppressed total synthesis of primary bile acids by 60% to 80% but decreased the tritium label of bile acids only from a range of 74% to 92% (54 hr) to a range of 54% to 63% (78 hr), which was in the range of plasma cholesterol (58%). We conclude that bile acids and biliary cholesterol are synthesized mostly from preformed (i.e., plasma) cholesterol, both immediately after depletion of the pool in enterohepatic circulation and after derepression. Moreover, the hepatic cholesterol pools subserving the synthesis of different bile acids and biliary cholesterol secretion are not identical.
Activation of Lung p53 by Nutlin-3a Prevents and Reverses Experimental Pulmonary Hypertension
Authors: Nathalie Mouraret, Elisabeth Marcos, Shariq Abid, Guillaume Gary-Bobo, Mirna Saker, Amal Houssaini, Jean-Luc Dubois-Rande, Laurent Boyer, Jorge Boczkowski, Geneviève Derumeaux, Valérie Amsellem, Serge Adnot
Journal: Circulation (2013)

Background— Induction of cellular senescence through activation of the p53 tumor suppressor protein is a new option for treating proliferative disorders. Nutlins prevent the ubiquitin ligase MDM2 (murine double minute 2), a negative p53 regulator, from interacting with p53. We hypothesized that cell senescence induced by Nutlin-3a exerted therapeutic effects in pulmonary hypertension (PH) by limiting the proliferation of pulmonary artery smooth muscle cells (PA-SMCs). Methods and Results— Nutlin-3a treatment of cultured human PA-SMCs resulted in cell growth arrest with the induction of senescence but not apoptosis; increased phosphorylated p53 protein levels; and expression of p53 target genes including p21, Bax, BTG2, and MDM2. Daily intraperitoneal Nutlin-3a treatment for 3 weeks dose-dependently reduced PH, right ventricular hypertrophy, and distal pulmonary artery muscularization in mice exposed to chronic hypoxia or SU5416/hypoxia. Nutlin-3a treatment also partially reversed PH in chronically hypoxic or transgenic mice overexpressing the serotonin-transporter in SMCs (SM22-5HTT+ mice). In these mouse models of PH, Nutlin-3a markedly increased senescent p21-stained PA-SMCs; lung p53, p21, and MDM2 protein levels; and p21, Bax, PUMA, BTG2, and MDM2 mRNA levels; but induced only minor changes in control mice without PH. Marked MDM2 immunostaining was seen in both mouse and human remodeled pulmonary vessels, supporting the use of Nutlins as a PH-targeted therapy. PH prevention or reversal by Nutlin-3a required lung p53 stabilization and increased p21 expression, as indicated by the absence of Nutlin-3a effects in hypoxia-exposed p53 −/− and p21 −/− mice. Conclusions— Nutlin-3a may hold promise as a prosenescence treatment targeting PA-SMCs in PH.
MECHANISMS OF EDEMA FORMATION IN CHRONIC EXPERIMENTAL PERICARDITIS WITH EFFUSION 1
Authors: A. P. Fishman, J. Stamler, L. N. Katz, A. J. Miller, E. N. Silber, L. Rubenstein, F. Williams, A. Ellis
Journal: Journal of Clinical Investigation (1950)

Recent studies of the mechanism of congestive heart failure have brought forth new data on the changes in cardiac output, central venous pres- sure, renal blood flow, and salt and water excre- tion, which have led to new interpretations of the pathogenesis of this syndrome (1-10).Several basic problems remain unsolved, however.Their resolution has been handicapped by the inability to reproduce chronic congestive heart failure in laboratory animals (11).Chronic pericarditis with effusion resembles congestive heart failure in that both may exhibit congestion, fluid retention, edema and anasarca.We have recently produced chronic pericarditis with effusion in the dog by the introduction of ir- ritative cellophane into the pericardial sac (12).Animals so treated eventually exhibited a syn- drome of circulatory failure (insufficiency) with congestion.This experimental approach there- fore provides a means for the investigation of the alterations in cardiodynamics and in renal func- tion which lead to fluid accumulation.The changes observed in chronic experimental peri- carditis with effusion have been analyzed in an attempt to explain the pathogenesis of fluid re- tention in this syndrome.This information is of value in attempting to elucidate the mechanisms of edema formation in chronic congestive heart failure. METHODSThe production of pericarditis: 5 An irritative cello- phane was used to produce pericarditis with effusion.6
Learning Medicine through the Closet Door
Authors: J. Randall Curtis
Journal: Annals of Internal Medicine (1999)

On Being a Doctor21 September 1999Learning Medicine through the Closet DoorJ. Randall Curtis, MD, MPHJ. Randall Curtis, MD, MPHHarborview Medical Center; Seattle, WA 98104 (Curtis)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-6-199909210-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The year was 1986. I was on my first rotation as a third-year medical student. It was 7 p.m. on my first night on-call. I had picked up my patient for the night: a 35-year-old woman with a long history of type 1 diabetes who had suffered many of the ravages of that disease. As I leaned over Harrison's Principles of Internal Medicine in the team room trying to figure out what else to write in my admission note, the intern received a call about an admission coming from an outside hospital. The patient was a 42-year-old gay man who ... Author, Article, and Disclosure InformationAffiliations: Harborview Medical Center; Seattle, WA 98104 (Curtis)Corresponding Author: J. Randall Curtis, MD, MPH, Division of Pulmonary and Critical Care Medicine, University of Washington, Harborview Medical Center, Box 359762, 325 Ninth Avenue, Seattle, WA 98104. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEducating for Diversity: A Decade of Experience (1989-1999) 21 September 1999Volume 131, Issue 6Page: 470-471KeywordsAIDSBloodEmotionsHeterosexualsHospital medicineHuman sexual behaviorMeningitisPatientsType 1 diabetesWalking Issue Published: 21 September 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
On the psychological reality of parallel relational architectures: Whose knowledge system is it anyway?
Authors: Margaret Chalmers, Brendan McGonigle
Journal: Behavioral and Brain Sciences (1998)

We argue that Halford et al.'s characterisation of relational complexity offers an unadaptive principle in terms of cognitive economy, that its relation with the empirical evidence is highly selective, and that the task behaviours used in support of a multivector processing space are better described by linear serial processes which do not require n-dimensional mappings for their emergence.