tbuckley/cabot-search huggingface dataset:
Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart
Authors: E. Dale Abel, Helen C. Kaulbach, Rong Tian, James C.A. Hopkins, John Duffy, Thomas Doetschman, Timo Minnemann, Mary-Ellen Boers, Ed Hadro, Corinna Oberste-Berghaus, William Quist, Bradford B. Lowell, Joanne S. Ingwall, Barbara B. Kahn
Journal: Journal of Clinical Investigation (1999)

Glucose enters the heart via GLUT1 and GLUT4 glucose transporters. GLUT4-deficient mice develop striking cardiac hypertrophy and die prematurely. Whether their cardiac changes are caused primarily by GLUT4 deficiency in cardiomyocytes or by metabolic changes resulting from the absence of GLUT4 in skeletal muscle and adipose tissue is unclear. To determine the role of GLUT4 in the heart we used cre-loxP recombination to generate G4H–/– mice in which GLUT4 expression is abolished in the heart but is present in skeletal muscle and adipose tissue. Life span and serum concentrations of insulin, glucose, FFAs, lactate, and β-hydroxybutyrate were normal. Basal cardiac glucose transport and GLUT1 expression were both increased approximately 3-fold in G4H–/– mice, but insulin-stimulated glucose uptake was abolished. G4H–/– mice develop modest cardiac hypertrophy associated with increased myocyte size and induction of atrial natriuretic and brain natriuretic peptide gene expression in the ventricles. Myocardial fibrosis did not occur. Basal and isoproterenol-stimulated isovolumic contractile performance was preserved. Thus, selective ablation of GLUT4 in the heart initiates a series of events that results in compensated cardiac hypertrophy.
Practice Guidelines and malpractice Litigation
Authors: Edward E. Bartlett
Journal: Annals of Internal Medicine (1995)

Letters1 October 1995Practice Guidelines and malpractice LitigationEdward E. Bartlett, PhDEdward E. Bartlett, PhDGeorgetown University; Washington, DC 20007-2195Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-7-199510010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I am writing in response to the recent article by Hyams and colleagues [1].I have done many reviews of malpractice claims files. As a rule, legal proceedings are handled by lawyers outside the insurance company. Claims files contain only a summary of the case, not the details of the legal strategies or sources of evidence being considered. Thus, it is not surprising that only 6.6% of claims files reflect use of practice guidelines, when 48.1% of attorneys report such use per year.Of greater concern is the authors' conclusion, based on their review of claims files, ...References1. Hyams AL, Brandenburg JA, Lipsitz SR, Shapiro DW, Brennan TA. Practice guidelines and malpractice litigation: a two-way street. Ann Intern Med. 1995; 122:450-5. Google Scholar2. Felsenthal E. Doctors' own guidelines hurt them in court. Wall Street Journal. 19 October 1994: 1. Google Scholar3. Grilli R, Lomas J. Evaluating the message: the relationship between compliance rate and the subject of a practice guidelines. Med Care. 1994; 32:202-13. Google Scholar4. Bartlett EE. Practice guidelines: how risk managers can tap the benefits, avoid the pitfalls. Rockville, MD: Edward Bartlett Associates; 1995. Google Scholar5. Stephenson G. Guidelines take the pain out of malpractice premiums for anesthesiologists. Report on Medical Guidelines and Outcomes Research. 1990; 1:4-6. Google Scholar Author, Article, and Disclosure InformationAuthors: Edward E. Bartlett, PhDAffiliations: Georgetown University; Washington, DC 20007-2195 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGuidelines in Pulmonary MedicineEvaluation of a Critical Pathway for Pneumonia 1 October 1995Volume 123, Issue 7Page: 556KeywordsHealth care qualityPilot studies ePublished: 15 August 2000 Issue Published: 1 October 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Erythrocyte pyruvate kinase deficiency: A kinetic method for differentiation between heterozygosity and compound‐heterozygosity
Authors: Max Lakomek, Heinz Winkler, Sabine Linne, Werner Schröter
Journal: American Journal of Hematology (1989)

Abstract The goal of the present study was to search for criteria that allow one to distinguish between normal individuals and heterozygotes as well as compound heterozygotes for pyruvate kinase (PK) deficiency. As the residual activity of PK with heterozygotes was between 35% and 110% of the normal activity, it was necessary to find other methods to prove heterozygosity. The PK in the hemolysates of 23 patients suffering from PK deficiency, 36 paternal and maternal enzymes as well as the enzymes of five heterozygous and four normal siblings together with those of 20 normal individuals, were studied according to the recommendations of the International Committee for Standardization in Haematology. The following hematological and enzyme kinetic parameters can serve to identify heterozygotes for PK deficiency: 1) a slight reticulocytosis, 2) an up‐to‐twofold increase of the intracellular concentrations of glucose‐6‐phosphate in the erythrocyte, 3) a mixed cooperativity of the phosphoenolpyruvate (PEP)‐binding process of PK, 4) a decreased nucleotide specificity with guanosine diphosphate and uridine diphosphate, and 5) a lowered affinity for adenosine diphosphate. The most significant criterium found with all heterozygotes was a mixed cooperativity of the PEP‐binding process caused by the presence of a mixture of normal and mutant PK.
Cortical Brain Lesions in Acute Intermittent Porphyria
Authors: Gordon Sze
Journal: Annals of Internal Medicine (1996)

Letters1 September 1996Cortical Brain Lesions in Acute Intermittent PorphyriaGordon Sze, MDGordon Sze, MDYale University School of Medicine, New Haven, CT 06520Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-5-199609010-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Kupferschmidt and colleagues [1] described two patients with acute intermittent porphyria who presented with cortical blindness. Magnetic resonance imaging showed bilateral occipital lesions, and the authors speculated that these lesions were caused by vasospasm-induced ischemia due to unopposed cerebral vasoconstriction resulting from a deficiency of nitrous oxide synthase, a major vascular dilator. The striking feature of the magnetic resonance findings in these cases and in those of acute intermittent porphyria described in the literature is that the lesions are bioccipital and partially or totally reversible [2]. These characteristics are typical of magnetic resonance findings seen in patients ...References1. Kupferschmidt H, Bont A, Schnorf H, Landis T, Walter E, Peter J, et al. Transient cortical blindness and bioccipital brain lesions in two patients with acute intermittent porphyria. Ann Intern Med. 1995; 123:598-600. Google Scholar2. King PH, Bragdon AC. MRI reveals multiple reversible cerebral lesions in an attack of acute intermittent porphyria. Neurology. 1991; 41:1300-2. Google Scholar3. Schwartz RB, Bravo SM, Klufas RA, Hsu L, Barnes PD, Robson CD, et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am J Ronentgenol. 1995; 165:627-31. Google Scholar4. Beausang-Linder M, Bill A. Cerebral circulation in acute arterial hypertension-protective effects of sympathetic nervous activity. Acta Physiol Scand. 1981; 111:193-9. Google Scholar5. Lai CW, Hung TP, Lin WS. Blindness of cerebral origin in acute intermittent porphyria. Arch Neurol. 1977; 34:310-2. Google Scholar Author, Article, and Disclosure InformationAuthors: Gordon Sze, MDAffiliations: Yale University School of Medicine, New Haven, CT 06520 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPorphyria Attack Manifesting as Delayed Emergence and Precipitated by Prolonged Cardiopulmonary BypassPosterior Reversible Encephalopathy Syndrome in Acute Intermittent PorphyriaPorphyria and its neurologic manifestationsThe PorphyriasApproaches to Treatment and Prevention of Human Porphyrias 1 September 1996Volume 125, Issue 5Page: 422-423KeywordsBrainBrain diseasesHypertensionIschemiaLesionsNervesPorphyriaSubarachnoid hemorrhageToxicityVasoconstriction ePublished: 15 August 2000 Issue Published: 1 September 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Importance of Tc-99m Sulfur Colloid Liver???Spleen Scans Performed Before Indium-111 Labeled Leukocyte Imaging for Localization of Abdominal Infection
Authors: I M. Youssef, R Milardovic, R W. Perone, S I. Heiba, H M. Abdel-Dayem
Journal: Clinical Nuclear Medicine (2005)

The localization of intraabdominal abscesses is a difficult imaging problem in nuclear medicine, especially when the location of the abscess is in the area of the liver and spleen. The need for performing Tc-99m sulfur colloid liver-spleen scans before injecting indium-111 leukocytes for improved lesion detection and characterization versus performing In-111 leukocyte scans alone has been questioned in the literatureWe present 3 patients with intraabdominal abscesses in the liver-spleen area, in which liver-spleen scans were performed before In-111 leukocyte scans. The findings of all were correlated with computed tomography and interventional procedures.In all patients, the Tc-99m liver-spleen scan helped for accurate recognition of the location of the abscess, correlated with computed tomography findings, and were helpful for intervention and exclusion of the other sources of infection.Data from these 3 patients reinforces the need for Tc-99m sulfur colloid liver-spleen scans before performing In-111 WBC scans for better localization and interventional treatment of intraabdominal abscesses.
Intoxication from an Accidentally Ingested Lead Shot Retained in the Gastrointestinal Tract
Authors: Per Gustavsson, Lars Gerhardsson
Journal: Environmental Health Perspectives (2005)

A 45-year-old woman was referred to the Department of Occupational and Environmental Health in January 2002 because of increased blood lead concentrations of unknown origin. She suffered from malaise, fatigue, and diffuse gastrointestinal symptoms. She had a blood lead level of 550 μg/L (normal range < 40 μg/L). The patient had not been occupationally exposed to lead, and no potential lead sources, such as food products or lead-glazed pottery, could be identified. Her food habits were normal, but she did consume game occasionally. Clinical examination, including standard neurologic examination, was normal. No anemia was present. Laboratory tests showed an increased excretion of lead in the urine, but there were no signs of microproteinuria. An abdominal X ray in October 2002 revealed a 6-mm rounded metal object in the colon ascendens. Before the object could be further localized, the patient contracted winter vomiting disease (gastroenteritis) and the metal object was spontaneously released from the colon during a diarrhea attack. The object was a lead shot pellet, possibly but not normally used in Sweden for hunting wild boar or roe deer. Blood lead levels slowly decreased. Nine months later the patient's blood lead levels were almost normal (~ 70 μg/L) and her symptoms had almost completely disappeared. In this case, a rare source of lead exposure was found. In investigations of blood lead elevations of unknown origin, we recommend abdominal X ray in parallel with repeated blood lead determinations.
Different hematological phenotypes caused by the interaction of triplicated α-globin genes and heterozygous β-thalassemia
Authors: C. Camaschella, A.C. Kattamis, D. Petroni, A. Roetto, P. Sivera, L. Sbaiz, A. Cohen, K. Ohene-Frempong, P. Trifillis, S. Surrey, P. Fortina
Journal: American Journal of Hematology (1997)

The pathophysiology and clinical severity of β-thalassemia are related to the degree of α/non-α-chain imbalance. A triplicated α-globin gene locus can exacerbate effects of excess α-chains caused by a defective β-globin gene, although this is not observed in all cases. Extensive studies on this condition are lacking. We report a group of 17 patients who are heterozygous for both the αααanti-3.7 allele and a mutation in the β-globin gene cluster. Their clinical phenotypes varied: six had mild anemia with microcytosis and hypochromia, while 11 had more severe anemia with splenomegaly requiring splenectomy (three cases) and blood transfusions (four cases). Different phenotypes were also evident in the presence of the same β-thalassemia mutation: in one family, two individuals had the same α- and β-globin genotypes but presented with different hematologic phenotypes. In addition, the complex interaction involving a triplicated α-globin gene, β39- and δ+27-thalassemia mutations is studied in a family with two siblings presenting with hemolytic anemia, normal Hb A2 and increased Hb F. Analysis of this series of patients suggests that additional genetic determinants play a role in modulating phenotypic expression in individuals with identical α- and β-globin genotypes. Interaction with a triplicated α-gene can play a role in the clinical presentation of patients with defective β-globin gene expression and should be considered in the diagnosis of atypical cases. Am. J. Hematol. 55:83-88, 1997. © 1997 Wiley-Liss, Inc.
Maintained stroke volume but impaired arterial oxygenation in man at high altitude with supplemental CO2.
Authors: R F Grover, J T Reeves, J T Maher, R E McCullough, J C Cruz, J C Denniston, A Cymerman
Journal: Circulation Research (1976)

Hypobaric hypoxia causes hypocapina and alkalosis, hemoconcentration and increased hematocrit, and a decreased cardiac stroke volume. To assess the role of the hypocapnic alkalosis in causing these other changes, five men were exposed to hypobaric hypoxia at a barometric pressure (PB) of 440 torr with an alveolar O2 tension of 55 torr for 5 days with 3.77% CO2 added to the atmosphere to prevent alkalosis. They did not lose weight, and arterial CO2 tension, pH, and cardiac stroke volume were unchanged. An unchanged hematocrit implied an unchanged plasma volume. During exercise to maximum, stroke volumes equaled sea level values but arterial hypoxemia was profound, the arterial O2 tension being 39 torr. By contrast, three men at high altitude without CO2 supplementation (PB=455 torr; alveolar PO2=56 torr) had weight loss, hypocapnia, alkalosis, and decreased stroke volume. Increased hematocrits suggested decreased plasma volumes. During exercise, arterial PO2 (48 torr) was higher than in the group receiving CO2. Maximum oxygen uptakes were decreased to a similar degree in the two groups. Catecholamine excretion doubled in the group with CO2 but in the group without CO2 catechoamine excretion was unchanged. A normal pH at high altitude apparently maintained plasma volume, which, with the increased catecholamine excretion, may have prevented a decrease in stroke volume. However, the subjects with CO2 added did not have enhanced oxygen transport, because their arterial oxygenation was impaired.
Abstract 1558: Innovative biotherapy for brain tumors: Myxoma virus accelerates NK clearance of malignant gliomas
Authors: Henry Ogbomo, Xueqing Lun, Jiqing Zhang, Franz J. Zemp, Grant Mcfadden, Christopher H. Mody, Peter A. Forsyth
Journal: Cancer Research (2012)

Abstract Innovative biotherapeutic approaches for experimental malignant gliomas (MGs) and brain tumor stem cells (BTSCs) include using oncolytic viruses such as Myxoma Virus (Myxv) or immune cells such as Natural Killer (NK) cells. In this study, we combined the individual strengths of using NK cells and Myxv to treat MGs with a view of overcoming the potential limitations posed when each is used as monotherapy. All MGs (U87, U251) and BTSCs (25EF and 48EF) investigated expressed varying levels of NK ligands including inhibitory MHC-I, activating ULBP1-3, MICA/B, and co-activating nectin-2, poliovirus receptor. Infection of MGs and BTSCs with Myxv resulted in the downregulation of MHC-I expression both on the cell surface and intracellularly. No effect was observed on the expression of NK activating ligands except for the downregulation of nectin-2. The downregulation of MHC-I and nectin-2 by Myxv was specifically mediated by M153 gene of Myxv as loss of M153 restored MHC-I and nectin-2 expression. Subsequently, NK cell degranulation and killing of MGs was enhanced in Myxv-infected cells. Loss of M153 inhibited NK degranulation and lysis of MGs. In vivo, using luciferase-expressing U87 cells in a mouse intracranial model, Myxv accelerated tumor size reduction/clearance by NK cell lysis. Combined intratumoral treatment with Myxv and NK of established U87 tumor accelerated tumor clearance when compared with single treatment with Myxv or NK. Tumor in 66% of mice (4 out of 6 mice) were cleared or significantly reduced within 14 days following combination treatment with Myxv and NK. No significant effect was observed in Myxv or NK singly-treated mice within the same time frame. Clearance of tumors was only first observed in 50% (2 out of 4) of Myxv-treated mice after 25 days Myxv treatment. In NK treated mice, the tumor size rather increased. The enhanced tumor clearance in the combined Myxv and NK treated mice was possibly due to the down-regulation of MHC-I by Myxv since combined treatment with NK cells and mutant Myxv (gene M153 which is responsible for MHC-I down-regulation was deleted) did not result in clearance of tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1558. doi:1538-7445.AM2012-1558
Thymidine-phosphorothioate oligonucleotides induce activation and apoptosis of CLL cells independently of CpG motifs or BCL-2 gene interference
Authors: J E Castro, C E Prada, R A Aguillon, S Kitada, T Fukuda, M Motta, C Wu, F Dicker, G Sun, J Y J Wang, D A Carson, J C Reed, T J Kipps
Journal: Leukemia (2006)
Rabbit polymorphonuclear neutrophils elicit endothelium-dependent contraction in vascular smooth muscle.
Authors: E H Ohlstein, A J Nichols
Journal: Circulation Research (1989)

The present studies were designed to investigate the interaction between activated polymorphonuclear neutrophils (PMNs) and endothelial regulation of vascular smooth muscle function. Rabbit peritoneal PMNs (4 x 10(3)-4 x 10(5) cells/ml) added to muscle bath chambers containing phenylephrine-precontracted rabbit isolated aortic rings produced no effect on vascular tone. However, when PMNs were activated with the chemotactic peptide, f-met-leu-phe (0.1 microM), PMNs produced concentration-dependent vascular contraction, which was dependent on the presence of the endothelium. Aortic rings denuded of endothelium were unaffected by activated PMNs. Superoxide dismutase (100 units/ml) treatment of tissues blocked completely PMN-induced vascular contraction, whereas mannitol (20 mM) had no significant effect on PMN-induced vascular contraction. Pyrogallol (a generator of superoxide anion) produced a response that was similar to that observed with activated PMNs. Superoxide anion production was measured separately, and the time of peak rate of superoxide anion production corresponded to the time of the maximal vascular contractile responses. Activated PMNs added to vascular tissues undergoing endothelium-dependent relaxation mediated by either acetylcholine or A23187 produced a reversal of vascular relaxation. Furthermore, activated PMNs did not have any effect on endothelium-independent vascular relaxation produced by either isoproterenol or nitroglycerin. The present investigation reveals that activated PMNs can release superoxide anion and produce endothelium-dependent contraction. The endothelium-dependent contraction may be the result of superoxide anion inactivation of endothelium-derived relaxing factor.
Clinical and immunologic evaluation of<i>Cedrus deodara</i>pollen:a new allergen from India
Authors: A. Rawat, A. Singh, A. B. Singh, S. N. Gaur, L. Kumar, I. Roy, P. Ravindrun
Journal: Allergy (2000)

Background: Allergy to pollen from gymnosperms is well documented in the West. However, many allergenic species are native to the Himalayan region of India, and Cedrus deodara (Pinaceae) was selected for allergologic investigation. The objective was to define the allergologic and immunochemical aspects of C. deodara pollen. Methods: Pollen antigen from C. deodara (CD) was prepared and characterized by biochemical and biologic assays. Specific IgE binding was determined by means of ELISA and immunoblotting. Results: CD pollen antigen caused marked skin sensitivity in 7.5% of an atopic population. A significantly elevated level of CD‐specific IgE antibodies was observed in 65.8% of the skin‐positive patients. Immunoblotting showed protein fractions of 37, 44, 58, and 78 kDa with 100% binding with the patients’ sera suspected to be due to carbohydrate moieties. Conclusions: Patients from the Himalayan region, where CD occurs naturally, were sensitized more than patients from distant places. The immunochemical characterization revealed multiple protein fractions from low to very high molecular mass (14–126 kDa) mostly in the acidic pI range. CD pollen has been recognized as a new allergen from India for the first time.
Comparison of actions of disodium cromoglycate and ketotifen on exercise-induced bronchoconstriction in childhood asthma.
Authors: J D Kennedy, F Hasham, M J Clay, R S Jones
Journal: BMJ (1980)

Comparison of actions of disodium cromoglycate and ketotifen on exercise-induced bronchoconstriction in childhood asthma Ketotifen (Zaditen), a benzocycloheptathiophene derivative, is a new oral agent for treating asthma, with action similar in some respects to that of sodium cromoglycate.It is well established that sodium cromoglycate protects against antigen challenge by inhibiting the release of chemical mediators from mast cells.It also inhibits exercise- induced bronchoconstriction and has bronchodilator properties.' Ketotifen has a similar capacity to inhibit the release of chemical mediators from mast cells.2Its clinical effectiveness is still uncertain.3Patients, methods, and resultsTwenty-three children with a clinical history of asthma and a value on the Jones lability index greater than 20 % were examined.The decrease in peak expiratory flow rate (PEFR) below the resting value was examined and remeasured on another day after the child had been given 20 mg sodium cromoglycate solution via a Wright nebuliser and mains-driven compressor (Aerosol Products Ltd) 15 minutes before running.On a third day the test was repeated with 20 mg sodium cromoglycate powder given 15 minutes before exercise.It was repeated on a fourth day after the patient had received three days' treatment with ketotifen (1 mg twice a day by mouth).The last dose was given two hours before the test.The percentage fall index ((PEFR at rest-PEFR after exercise/PEFR at rest) x 100) was measured in each case. CommentMany patients with rheumatological disorders are treated with ibuprofen.From this case apparently a depressed level of conscious- ness and hypotension may result soon after ingestion of more than the maximum dose.Side effects when taking the normal dose include headache, amblyopia, and lightheadedness but there is no record of depressed consciousness.The findings of Adams et all in animals on 20 August