tbuckley/cabot-search huggingface dataset:
Suppression of liver regeneration and hepatocyte proliferation in hepatocyte-targeted glypican 3 transgenic mice
Authors: Bowen Liu, Aaron W. Bell, Shirish Paranjpe, William C. Bowen, Jaspal S. Khillan, Jian-Hua Luo, Wendy M. Mars, George K. Michalopoulos
Journal: Hepatology (2010)

Abstract Glypican 3 (GPC3) belongs to a family of glycosylphosphatidylinositol-anchored, cell-surface heparan sulfate proteoglycans. GPC3 is overexpressed in hepatocellular carcinoma. Loss-of-function mutations of GPC3 result in Simpson-Golabi-Behmel syndrome, an X-linked disorder characterized by overgrowth of multiple organs, including the liver. Our previous study showed that GPC3 plays a negative regulatory role in hepatocyte proliferation, and this effect may involve CD81, a cell membrane tetraspanin. To further investigate GPC3 in vivo , we engineered transgenic (TG) mice overexpressing GPC3 in the liver under the control of the albumin promoter. GPC3 TG mice with hepatocyte-targeted, overexpressed GPC3 developed normally in comparison with their nontransgenic littermates but had a suppressed rate of hepatocyte proliferation and liver regeneration after partial hepatectomy. Moreover, gene array analysis revealed a series of changes in the gene expression profiles in TG mice (both in normal mice and during liver regeneration). In unoperated GPC3 TG mice, there was overexpression of runt related transcription factor 3 (7.6-fold), CCAAT/enhancer binding protein alpha (2.5-fold), GABA A receptor (2.9-fold), and wingless-related MMTV integration site 7B (2.8-fold). There was down-regulation of insulin-like growth factor binding protein 1 (8.4-fold), Rab2 (5.6-fold), beta-catenin (1.7-fold), transforming growth factor beta type I (3.1-fold), nodal (1.8-fold), and yes-associated protein (1.4-fold). Changes after hepatectomy included decreased expression in several cell cycle–related genes. Conclusion: Our results indicate that in GPC3 TG mice, hepatocyte overexpression of GPC3 suppresses hepatocyte proliferation and liver regeneration and alters gene expression profiles, and potential cell cycle–related proteins and multiple other pathways are involved and affected.
The Unique Morgue Ubiquitination Protein Is Conserved in a Diverse but Restricted Set of Invertebrates
Authors: Y. Zhou, Z. W. Carpenter, G. Brennan, J. R. Nambu
Journal: Molecular Biology and Evolution (2009)

Drosophila Morgue is a unique ubiquitination protein that facilitates programmed cell death and associates with DIAP1, a critical cell death inhibitor with E3 ubiquitin ligase activity. Morgue possesses a unique combination of functional domains typically associated with distinct types of ubiquitination enzymes. This includes an F box characteristic of the substrate-binding subunit in Skp, Cullin, and F box (SCF)-type ubiquitin E3 ligase complexes and a variant ubiquitin E2 conjugase domain where the active site cysteine is replaced by a glycine. Morgue also contains a single C4-type zinc finger motif. This architecture suggests potentially novel ubiquitination activities for Morgue. In this study, we address the evolutionary origins of this distinctive protein utilizing a combination of bioinformatics and molecular biology approaches. We find that Morgue exhibits widespread but restricted phylogenetic distribution among metazoans. Morgue proteins were identified in a wide range of Protostome phyla, including Arthropoda, Annelida, Mollusca, Nematoda, and Platyhelminthes. However, with one potential exception, Morgue was not detected in Deuterostomes, including Chordates, Hemichordates, or Echinoderms. Morgue was also not found in Ctenophora, Cnidaria, Placozoa, or Porifera. Characterization of Morgue sequences within specific animal lineages suggests that gene deletion or acquisition has occurred during divergence of nematodes and that at least one arachnid expresses an atypical form of Morgue consisting only of the variant E2 conjugase domain. Analysis of the organization of several morgue genes suggests that exon-shuffling events have contributed to the evolution of the Morgue protein. These results suggest that Morgue mediates conserved and distinctive ubiquitination functions in specific cell death pathways.
The Treatment of<i>Helicobacter pylori</i>Infection in the Management of Peptic Ulcer Disease
Authors: John H. Walsh, Walter L. Peterson
Journal: New England Journal of Medicine (1995)

The recognition of gastritis due to Helicobacter pylori as a factor of major importance has revolutionized the therapeutic approach to peptic ulcer disease.1,2 The recurrence of ulcers can be more effectively prevented by a single course of antimicrobial treatment that eradicates H. pylori infection than by the continuous suppression of acid secretion. This concept received important support when a recent Consensus Development Conference of the National Institutes of Health (NIH) recommended that all patients with ulcers who are also infected with H. pylori receive antimicrobial therapy.3 Our review will focus on how to diagnose and treat H. pylori infection . . .
Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients.
Authors: H Bartsch, S Petruzzelli, S De Flora, E Hietanen, A M Camus, M Castegnaro, K Alexandrov, M Rojas, R Saracci, C Giuntini
Journal: Environmental Health Perspectives (1992)

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer.
Preventing iatrogenic pandemics of panic. Do it in a NICE way
Authors: L. Bonneux, W. V. Damme
Journal: BMJ (2010)

The decisions to stockpile antivirals and influenza vaccines to control avian flu (2005-6) and swine flu (2009) cost large amounts of money.1 2 Both epidemic threats were mostly iatrogenic pandemics of panic, which caused little human suffering, but the global plans to control them were largely a waste of money.1 Was this the consequence of rational risk management in conditions of uncertainty, of fear accompanying any epidemic threat,3 or of close working relationships between disease experts and the drugs industry?

Severe acute respiratory syndrome (SARS) in 2003 was an epidemic by an unknown and therefore scary new virus, but we know much more about influenza viruses.2 4 5 The new A/H1N1 swine flu was a far cry from the lethal A/H1N1 pandemic of 1918. There has never been evidence that the recent A/H1N1 virus was anything but mild,6 and it was not reasonable to consider it the first wave of a much more serious second wave. The theory that the 1918 influenza pandemic was caused by a second …
Gastroesophageal Reflux Disease in the Zollinger-Ellison Syndrome
Authors: Joel E. Richter, Stephen J. Pandol, Donald O. Castell, Denis M. Mccarthy
Journal: Annals of Internal Medicine (1981)

Gastroesophageal reflux has rarely been reported in the Zollinger-Ellison syndrome, presumably due to elevation in the lower esophageal sphincter pressure. We have evaluated 15 patients with the Zollinger-Ellison syndrome for evidence of esophageal disease. Five presented initially with esophageal disease: one, reflux symptoms; two, severe esophagitis; and two, strictures. Six of 15 had heartburn and nine of 15, objective evidence for reflux disease. Mean lower esophageal sphincter pressure was higher in the Zollinger-Ellison syndrome than in controls but was unrelated to serum gastrin levels. Zollinger-Ellison syndrome patients without heartburn had a higher mean sphincter pressure than did patients with heartburn (who had a mean sphincter pressure similar to that of controls but greater than that in patients with idiopathic gastroesophageal reflux). Four patients had biopsy evidence of esophagitis, one in association with Barrett's epithelium. Gastroesophageal reflux and its complications appear to be common in the Zollinger-Ellison syndrome.
The Diarrhea of Travelers
Authors: B. H. Kean
Journal: JAMA (1962)

Travelers to all lands have suffered attacks of diarrhea. A double-blind study tested the efficacy of 2 antimicrobial drugs in the prevention of tourist diarrhea among 473 American college students in Mexico City. One group of 168 received a lactose placebo, 137 received neomycin sulfate (1 gm. per day), and 168 received phthalylsulfathiazole (2 gm. per day), all under close supervision. Moderate or severe diarrhea occured in 17% (29) of those who took the placebo, 5% (7) of those who took neomycin, and 7% (11) of those who took phthalylsulfathiazole. Among these initially healthy and carefully supervised young persons no untoward reactions were observed, but if these drugs are to he used as prophylactic agents on a larger scale, their administration should be accompanied by similar medical precautions.
Ligation of the Mandibular (Inferior Dental) Artery
Authors: H. P. Pickerill
Journal: BMJ (1949)

In an annotation in the Journal (1948, 1, 989) it was suggested that nomograms for use with the Assmann and the sling or whirling psychrometers might be welcomed, as these are the instruments of choice for the measurement of the hygrometric properties of the atmosphere with scientific accuracy.The accompanying nomograms have been designed accordingly.
Antihypertensive Therapy and Incidence of Type 2 Diabetes in an Elderly Cohort
Authors: Norman N. Chan, Peter C.Y. Tong, Alice P.S. Kong, Wing-bun Chan, Juliana C.N. Chan
Journal: Diabetes Care (2005)

We read the study by Padwal et al. (1) with great interest and feel that it warrants comment. In this retrospective observational cohort study of a large number of elderly patients ( n = 725,469, mean age 72–73 years) but of short duration (mean follow-up period of 9.5–11.6 months), the authors found that incidence of new-onset type 2 diabetes …
α-Sulfoquinovosylmonoacylglycerol Is a Novel Potent Radiosensitizer Targeting Tumor Angiogenesis
Authors: Ippei Sakimoto, Keisuke Ohta, Takayuki Yamazaki, Seiji Ohtani, Hiroeki Sahara, Fumio Sugawara, Kengo Sakaguchi, Masahiko Miura
Journal: Cancer Research (2006)

Angiogenesis is a promising target for the treatment of cancer, and varying types of antiangiogenic agents have been developed. However, limitations and problems associated with antiangiogenic therapy have recently arisen. Although radiotherapy can be combined with antiangiogenic compounds to overcome these difficulties, almost all previously described angiogenesis inhibitors could still cause side effects at effective doses, and only additive effects are seen in current combination therapy. In this study, we identified a member of the sulfoquinovosylacylglycerols, alpha-sulfoquinovosylmonoacylglycerol (alpha-SQMG), originally derived from sea urchins, as a potent radiosensitizer. The agent synergistically inhibits angiogenesis at low doses when combined with ionizing radiation. Combined treatment with alpha-SQMG and radiation seems to promote the adoption of a senescence-like phenotype by vascular endothelial cells. Finally, the agent remarkably enhances the radioresponse of human tumors transplanted into nude mice, accompanied by a significant reduction in the vascularity of the tumors. Collectively, alpha-SQMG may be a novel potent radiosensitizer targeting angiogenesis.
1233 T-regulatory lymphocytes in hepatocellular carcinoma
Authors: E UNITT, S RUSHBROOK, A MARSHALL, S DAVIS, L MORRIS, N COLEMAN, G ALEXANDER
Journal: Hepatology (2003)

Childhood Idiopathic Nephrotic Syndrome (INS) responds to glucocorticoid therapy, however, 60–80% of patients relapse and some of them become steroid non responsive. INS may occur because of T cell dysfunction, abnormal cytokines and podocytopathies which reverse on steroid treatment. The reason of relapses could be imbalances in T cells phenotypes and respective cytokines. Herein, we hypothesize that relapses in INS may occur due to imbalance in T-regulatory and T-effector cell with their respective cytokines and overexpression of P-gp on lymphocytes.The frequency of peripheral blood CD4+CD25+FoxP3+ Treg, CD4+IFN-γ+ Th1 and CD4+IL-4+ Th2 lymphocytes and their respective cytokines and P-gp expression on peripheral blood lymphocytes (PBLs) were analyzed in INS patients at baseline (n = 26), during remission (n = 24) and at relapse (n = 15).Compared to baseline, the frequency of Tregs was significantly increased at remission and decreased during relapse. In contrast, the frequency of Th1 and Th2 lymphocytes was significantly decreased during remission and increased at the time of relapse. Similarly, expression of P-gp was significantly high at baseline and at the time of relapse as compared to remission. Levels of cytokines IL-10 and TGF-β in the supernatant of stimulated PBMCs was increased during remission and decreased during relapse. In contrast, levels of IFN-γ and IL-4 were decreased during remission and increased at the time of relapse.Steroid therapy in INS induces decreased P-gp expression on PBLs along with increased frequency and cytokine response of T-regulatory cells, and reduced frequency and respective cytokine response of Th1 and Th2 cells during remission. However, reversal in the frequency and respective cytokines of T-regs, Th1 and Th2, and P-gp expression on PBLs occurs during relapses on follow-up.
Aspirin Versus Low-Molecular-Weight Heparin for Extended Venous Thromboembolism Prophylaxis After Total Hip Arthroplasty
Authors: David R. Anderson, Michael J. Dunbar, Eric R. Bohm, Etienne Belzile, Susan R. Kahn, David Zukor, William Fisher, Wade Gofton, Peter Gross, Stephane Pelet, Mark Crowther, Steven MacDonald, Paul Kim, Susan Pleasance, Nicki Davis, Pantelis Andreou, Philip Wells, Michael Kovacs, Marc A. Rodger, Tim Ramsay, Marc Carrier, Pascal-Andre Vendittoli
Journal: Annals of Internal Medicine (2013)

The role of aspirin in thromboprophylaxis after total hip arthroplasty (THA) is controversial.To compare extended prophylaxis with aspirin and dalteparin for prevention of symptomatic venous thromboembolism (VTE) after THA.Multicenter randomized, controlled trial with a noninferiority design based on a minimal clinically important difference of 2.0%. Randomization was electronically generated; patients were assigned to a treatment group through a Web-based program. Patients, physicians, study coordinators, health care team members, outcome adjudicators, and data analysts were blinded to interventions. (Current Controlled Trials: ISRCTN11902170).12 tertiary care orthopedic referral centers in Canada.778 patients who had elective unilateral THA between 2007 and 2010.After an initial 10 days of dalteparin prophylaxis after elective THA, patients were randomly assigned to 28 days of dalteparin (n = 400) or aspirin (n = 386).Symptomatic VTE confirmed by objective testing (primary efficacy outcome) and bleeding.Five of 398 patients (1.3%) randomly assigned to dalteparin and 1 of 380 (0.3%) randomly assigned to aspirin had VTE (absolute difference, 1.0 percentage point [95% CI, -0.5 to 2.5 percentage points]). Aspirin was noninferior (P < 0.001) but not superior (P = 0.22) to dalteparin. Clinically significant bleeding occurred in 5 patients (1.3%) receiving dalteparin and 2 (0.5%) receiving aspirin. The absolute between-group difference in a composite of all VTE and clinically significant bleeding events was 1.7 percentage points (CI, -0.3 to 3.8 percentage points; P = 0.091) in favor of aspirin.The study was halted prematurely because of difficulty with patient recruitment.Extended prophylaxis for 28 days with aspirin was noninferior to and as safe as dalteparin for the prevention of VTE after THA in patients who initially received dalteparin for 10 days. Given its low cost and greater convenience, aspirin may be considered a reasonable alternative for extended thromboprophylaxis after THA.Canadian Institutes of Health Research.
Microscopic haematuria Examine urinary deposite before cystoscopy
Authors: J R C Bowen, P Miller, J Stabler, L Luzzatto, T Sherwood
Journal: BMJ (1994)

EDITOR, - The algorithm of diagnostic tests for microscopic haematuria in Fritz H Schroder's editorial is illogical.1 Once microscopic haematuria has been detected and infection excluded the next stage is to locate the site of bleeding. Practically this is either renal or urological, and the distinction can be made by light microscopy of a freshly provided centrifuged urinary deposit. Phase contrast microscopy can help distinguish dysmorphic from non-dysmorphic erythrocytes in difficult cases. The recommendation to perform cystoscopy before this simple, non-invasive, cheap, and effective procedure will condemn many patients with readily demonstrable glomerular haematuria to an unpleasant, uninformative, and unnecessary investigation. This is especially important in the younger age group, in which glomerular disease causes haematuria in a higher proportion of cases.

The detection of microscopic haematauria of …
Christmas Disease-Reply
Authors: William J. Schaaf
Journal: JAMA (1961)

<h3>To the Editor:—</h3> In reply to Dr. Lamar, concerning my use of the eponym Christmas disease instead of hemophilia B, I might state that I could have also used the terms PTC deficiency or Factor IX deficiency and by so doing confused or at least discouraged the average reader. I would like to defend my use of the eponym Christmas disease. In the bibliography to my paper in<i>Hemophilia and Other Hemorrhagic States</i>, edited by Brinkhous and DeNicola, the eponym Christmas disease is mentioned at least 20 times. In the introduction to this book, there is a glossary of synonyms and symbols containing 72 definitions. I quote 2 of these: "Christmas disease, a hemophilioid disease; prototype a patient named Christmas, Factor IX deficiency." "Hemophilia B, PTC deficiency, Christmas Disease." These are the only definitions of hemophilia B in the glossary. In addition, in the index of this book under
Non-invasive mechanical ventilation
Authors: D VANPEE
Journal: Thorax (2001)

We read with interest the study by Moretti et al concerning the incidence and causes of failure of non-invasive mechanical ventilation (NIV) after initial success.1 It is an interesting study, but some important factors associated with the initial treatment of chronic obstructive pulmonary disease (COPD) which could influence the results of the study are not addressed. The aim of NIV includes not only the correction of alveolar hypoventilation, but also the unloading of inspiratory muscles. NIV reduces the work of breathing, allowing resting of respiratory muscles and recovery of muscle function. How long had the patients in the two groups been in an acute state before admission to the intensive care units? Where were they before being enrolled in the study—in an emergency unit or in a pneumology ward? Was it the same for the two groups? Perhaps the patients in …
Gene pioneers: Donald Brown and Thomas Maniatis win the 2012 Lasker~Koshland Special Achievement Award in Medical Science
Authors: Kathryn Claiborn
Journal: Journal of Clinical Investigation (2012)

The 2012 Lasker~Koshland Special Achievement Award in Medical Science recognizes Donald Brown (Carnegie Institute of Washington) and Thomas Maniatis (Columbia University) (Figure ​(Figure1),1), two scientists whose career-long contributions were seminal to our understanding of what genes are and our ability to study and manipulate them, and whose commitment to mentorship have had tremendous impact on a generation of scientists.
Mechanisms Determining Course and Outcome of Diabetic Patients Who Have Had Acute Myocardial Infarction
Authors: Doron Aronson
Journal: Annals of Internal Medicine (1997)

Purpose: To review the pathogenic mechanisms that lead to the poor prognosis of diabetic patients after myocardial infarction and to determine the efficacy of current interventions for myocardial infarction in these patients. Data Sources: Search of the MEDLINE database from 1985 to 1995, using the keywords diabetes, myocardial infarction, and cardiomyopathy, and a search of the reference citations of relevant articles. Study Selection: Experimental and clinical studies on myocardial infarction in diabetic patients and basic research studies relevant to this topic. Data Synthesis: The excess in-hospital mortality of diabetic patients results primarily from an increased incidence of congestive heart failure. Several combined mechanisms reduce the compensatory ability of the noninfarcted myocardium; such mechanisms include preexisting congestive heart failure caused by diabetic cardiomyopathy, severe coronary artery disease, decreased vasodilatory reserve of epicardial and resistance arteries, and possibly abnormal metabolism of myocardial substrate. Late mortality results from increased reinfarction rates caused by the diffuse nature of the atherosclerotic disease and hypercoagulable state.Platelet hyperactivity, reduced fibrinolytic capacity, increased concentrations of hemostatic proteins, and endothelial dysfunction promote thrombosis at the site of plaque rupture. Autonomic neuropathy predisposes patients to ventricular arrhythmias. Thrombolytic agents, aspirin, β-blockers, and angiotensin-converting enzyme inhibitors are effective in patients with diabetes. Conclusions: In the thrombolytic era, mortality rates of diabetic patients who have had acute myocardial infarction remain 1.5 to 2 times higher than those in nondiabetic patients. This increased mortality rate is caused by diverse mechanisms that affect myocardial function and blood supply and by the tendency toward thrombosis in diabetic patients. Current therapies for myocardial infarction are effective in these patients. Improved metabolic control may also decrease mortality rates.