tbuckley/cabot-search huggingface dataset:
Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.
Authors: M E Jessen, T E Kovarik, F M Jeffrey, A D Sherry, C J Storey, R Y Chao, W S Ring, C R Malloy
Journal: Journal of Clinical Investigation (1993)

The effect of aspartate and glutamate on myocardial function during reperfusion is controversial. A beneficial effect has been attributed to altered delivery of carbon into the citric acid cycle via substrate oxidation or by stimulation of anaplerosis, but these hypotheses have not been directly tested. 13C isotopomer analysis is well suited to the study of myocardial metabolism, particularly where isotopic and metabolic steady state cannot be established. This technique was used to evaluate the effects of aspartate and glutamate (amino acids, AA) on anaplerosis and substrate selection in the isolated rat heart after 25 min of ischemia followed by 30 or 45 min of reperfusion. Five groups of hearts (n = 8) provided with a mixture of [1,2-13C]acetate, [3-13C]lactate, and unlabeled glucose were studied: control, control plus AA, ischemia followed by 30 min of reperfusion, ischemia plus AA followed by 30 min of reperfusion, and ischemia followed by 45 min of reperfusion. The contribution of lactate to acetyl-CoA was decreased in postischemic myocardium (with a significant increase in acetate), and anaplerosis was stimulated. Metabolism of 13C-labeled aspartate or glutamate could not be detected, however, and there was no effect of AA on functional recovery, substrate selection, or anaplerosis. Thus, in contrast to earlier reports, aspartate and glutamate have no effect on either functional recovery from ischemia or on metabolic pathways feeding the citric acid cycle.
Active participation of CCR5+CD8+ T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease
Authors: Masako Murai, Hiroyuki Yoneyama, Akihisa Harada, Zhang Yi, Christian Vestergaard, Baoyu Guo, Kenji Suzuki, Hitoshi Asakura, Kouji Matsushima
Journal: Journal of Clinical Investigation (1999)

We examined the molecular pathogenesis of graft-versus-host disease–associated (GVHD-associated) liver injury in mice, focusing on the role of chemokines. At the second week after cell transfer in the parent-into-F1 model of GVHD, CD8+ T cells — especially donor-derived CD8+ T cells — infiltrated the liver, causing both portal hepatitis and nonsuppurative destructive cholangitis (NSDC). These migrating cells expressed CCR5. Moreover, macrophage inflammatory protein-1α (MIP-1α), one of the ligands for CCR5, was selectively expressed on intralobular bile duct epithelial cells, endothelial cells, and infiltrating macrophages and lymphocytes. Administration of anti-CCR5 antibody dramatically reduced the infiltration of CCR5+CD8+ T lymphocytes into the liver, and consequently protected against liver damage in GVHD. The levels of Fas ligand (FasL) mRNA expression in the liver were also decreased by anti-CCR5 antibody treatment. Anti–MIP-1α antibody treatment also reduced liver injury. These results suggest that MIP-1α–induced migration of CCR5-expressing CD8+ T cells into the portal areas of the liver plays a significant role in causing liver injury in GVHD; thus, CCR5 and its ligand may be the novel target molecules of therapeutic intervention of hepatic GVHD.
Environmental Arsenic Exposure and Diabetes
Authors: Molly L. Kile
Journal: JAMA (2008)

Type 2 diabetes mellitus emerged as a pandemic in the later half of the 20th century.In the United States alone, diabetes affects an estimated 7.8% of the US population (24 million individuals) and its prevalence is projected to almost double in the next 25 years. 1,2The complications associated with diabetes including cardiovascular disease, retinopathy, nephropathy, neuropathy, and lower limb amputation profoundly affect the quality of life and contribute to the high morbidity and mortality associated with this disease.Diabetes is ranked as the seventh leading cause of death in the United States in 2006 2 ; the economic costs of diabetes are also high.Approximately $1 of every $10 in US health care expenditures can be attributed to the direct costs associated with diabetes. 3When indirect costs to caregivers are included, it is estimated that the annual cost of diabetes in the United States is $174 billion. 3aracterized by a combination of deficient insulin secretion and a diminished response to insulin at the target tissue, which can progress to hyperglycemia, the risk of type 2 diabetes increases with age, obesity, and sedentary lifestyle. 4Clinical trials have shown that lifestyle modification including weight reduction and increased physical activity can reduce the prevalence of type 2 diabetes by as much as 58%, 5 and now these 2 behavioral issues have become the cornerstone of diabetes prevention programs.Yet the etiology of type 2 diabetes remains poorly understood and the role of environmental pollutants, specifically arsenic, in diabetogenesis has received little attention by the medical community.This is somewhat surprising because arsenic exposure has been linked to type 2 diabetes since 1950 when a case report documented a patient developing type 2 diabetes after receiving intravenous arsenical treatment for sexually transmitted diseases. 6However, research efforts on the role of arsenic in diabetogenesis did not intensify until populationbased epidemiologic studies published in the 1990s from Taiwan 7-9 and Bangladesh 10 demonstrated that chronic exposure to high levels of arsenic from drinking water is associated with a higher prevalence of type 2 diabetes.While the findings of these studies were consistent and indicated a dose-response relationship between chronic arsenic exposure and type 2 diabetes, these populations were considered somewhat unique.A proportion of the populations from Taiwan and Bangladesh
Book Review Molecular Nuclear Medicine: The Challenge of Genomics and Proteomics to Clinical Practice Edited by Ludwig E. Feinendegen, Walton W. Shreeve, William C. Eckelman, Yong-Whee Bahk, and Henry N. Wagner, Jr. 795 pp., illustrated. Berlin, Germany, Springer-Verlag, 2003. $325. 3-540-00132-8
Authors: Martin Schlumberger
Journal: New England Journal of Medicine (2004)
Correction: Posterior Interosseous Nerve
Authors: H. JOE PRYOR
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 November 1973Correction: Posterior Interosseous NerveH. JOE PRYOR, M.D.H. JOE PRYOR, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-5-765_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In regard to the review, "Rheumatoid Arthritis, 1970-1972," by Johnson, and associates (Ann Intern Med78:937-953, 1973) under the subheading "entrapment syndromes," two errors should be noted. First, the prosterior interosseous is a branch of the radial, not the ulnar, nerve. Second, the medial calcaneal is a branch of the posterior tibial (not the sural), which is the nerve occasionally entrapped in the tarsal tunnel. The only calcaneal branch of the sural nerve is the lateral calcaneal, which provides sensation to the lateral side of the heel. It does not penetrate the flexor retinaculum and therefore is...References1. HAYMAKERWOODHALL WB: Peripheral Nerve Injuries, 2nd ed. Philadelphia, W.B. Saunders Co., 1953, p. 290 Google Scholar2. JOHNSONORTIG EP: Electrodiagnosis of tarsal tunnel syndrome. Arch Phys Med Rehabil 47:776-780, 1966 MedlineGoogle Scholar3. GOLDMANHONETSOBEL SJR: Posterior interosseous nerve palsy in the absence of trauma. Arch Neurol 21:435-441, 1969 CrossrefMedlineGoogle Scholar1. CHANGGOWANSGRANGER LJC: Entrapment neuropathy of the posterior interosseous nerve. A complication of rheumatoid arthritis. Arthritis Rheum 15:350-352, 1972 CrossrefMedlineGoogle Scholar2. GRANT J: A Method of Anatomy. Descriptive and Deductive, 5th ed. Baltimore, The Williams & Wilkins Co., 1952, p. 23 Google Scholar3. CASAGRANDE T: Surgical rehabilitation of shoulder and elbow in rheumatoid arthritis. Semin Arthritis Rheum 1:3-6, 1971 CrossrefMedlineGoogle Scholar4. TUREK S: Orthopaedics. Principles and Their Application. Philadelphia, J.B. Lippincott Co., 1967, p. 264 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Physical Medicine and Rehabilitation University of Missouri Medical Center Columbia, Missouri PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1973Volume 79, Issue 5Page: 765-766KeywordsNervesRheumatoid arthritis ePublished: 1 December 2008 Issue Published: 1 November 1973 PDF downloadLoading ...
Reported inaccuracies about the UK Research Integrity Office
Authors: J. Parry
Journal: BMJ (2012)

We welcome the BMJ ’s focus on research misconduct, but this article contains serious errors about the UK Research Integrity Office (UKRIO).1

UKRIO is not “hosted by the University of Sussex.” Since December 2010 we have leased premises at the Sussex Innovation Centre on the university’s campus, but we remain an independent organisation.2 Although the university is one of many …
Management of hematological malignancies during pregnancy
Authors: Tina Rizack, Anthony Mega, Robert Legare, Jorge Castillo
Journal: American Journal of Hematology (2009)

The management of hematological malignancies during pregnancy is a challenging endeavor, which not only requires technical skills and knowledge by the clinicians but also requires sound clinical judgment and compassion, keeping in mind the patient and family preferences and, ultimately, the wellbeing of the neonate. The incidence of hematological malignancies during pregnancy is rare, ranging from 1 in 1,000 to 1 in 10,000 deliveries, impeding the design and execution of large prospective studies. The purpose of this review is to evaluate the limited existing data and make useful suggestions in the management of acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, plasma cell myeloma, and other hematological malignancies, such as myelodysplastic syndromes and hairy cell leukemia, during pregnancy.
Naloxone, Beta Endorphins, and High-Altitude Pulmonary Edema
Authors: DAVID BAR-OR
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 May 1982Naloxone, Beta Endorphins, and High-Altitude Pulmonary EdemaDAVID BAR-OR, M.D., JOHN A. MARX, M.D., JAMES T. GOOD JR., M.D.DAVID BAR-OR, M.D.Search for more papers by this author, JOHN A. MARX, M.D.Search for more papers by this author, JAMES T. GOOD JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-5-684_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: High-altitude pulmonary edema develops in certain unacclimatized and susceptible persons acutely exposed to extreme elevation. Since its original report the clinical manifestations have been well described, but despite numerous speculations the pathogenesis of this disorder remains unclear (1-3).We describe here an otherwise healthy man who presented with high-altitude pulmonary edema, in whom plasma beta endorphins were measured and found to be significantly elevated. Dramatic improvement in the patient's hypoxemia and clinical course occurred after administration of naloxone. We postulate that this opiate antagonist may be beneficial in the treatment of this disorder.A 22-year-old white man,...References1. SINGHKHANNASVIRASTAVALALROYSUBRAMANYAM IKMMSC. Acute mountain sickness. N Engl J Med. 1969;280:175-83. CrossrefMedlineGoogle Scholar2. HULTGRENSPICKARDHELLRIEGELHOUSTON HWHC. High altitude pulmonary edema. Medicine. 1961;40:289-313. CrossrefMedlineGoogle Scholar3. HACKETTRENNIELEVINE PDH. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet. 1976;2:1149-54. CrossrefMedlineGoogle Scholar4. MARTICORENAHULTGREN EH. Evaluation of therapeutic methods in high altitude pulmonary edema. Am J Cardiol. 1979;43:307-12. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: City and County of Denver Department of Health and Hospitals Denver, CO 80204 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEffects of Administration of Intravenous Naloxone on Gas Exchange in Brain-Dead Lung DonorsHigh-altitude pulmonary edema: A collective reviewNaloxone and NaltrexoneArachidonic acid metabolites and endorphinsNaloxone: Effects on hypoxic pulmonary vasoconstrictionThe pulmonary effects of opiate blockade in septic shockNaloxone: New therapeutic rolesThe Anecdotal AntidotesOpioid Peptides in Humans and Their Clinical SignificanceAcute Alveolar EdemaEndogenous opiates: 1982Endogenous Opiates, Pulmonary Edema, and Sleep Apnea SyndromeNaloxone, Itch, Asthma, Urticaria, and AngioedemaSIMON SMITZ, M.D., JEAN-JACQUES LEGROS, M.D., MARC LE MAIRE, PH.D. 1 May 1982Volume 96, Issue 5Page: 684-685KeywordsBlood plasmaEdemaHypoxiaOpiatesPathogenesis Issue Published: 1 May 1982 PDF downloadLoading ...
The Pathology and Treatment of Sexual Deviation: A Medhodological Approach
Authors: Jane E. Oltman
Journal: JAMA (1964)

Contributors to this volume include members or former members of the Portman Clinic in England and other distinguished psychiatrists, scientists, and barristers. As with any edited book which owes its birth to many parents, it is somewhat uneven. However, there should be "something of value" to everyone interested in this complex and difficult field. It is problematical just how applicable Tinbergen's first chapter on "Aggression and Fear in the Normal Sexual Behaviour of Some Animals" is to human sexual deviation. On the other hand, the section on sociology, including among others Carstairs' "Cultural Differences in Sexual Deviation," Ginsberg's "Morality, Law and the Climate of Opinion," and Robinson's "Parliamentary and Public Attitudes" is of great interest and pertinence, although not directly clinical. The major portion of the book presents psychopathological material. Included here are the contributions of such well-known figures as Gillespie and Glover. The emphasis rests on psychoanalytic interpretation and
H_2-Antagonists and Hepatitis
Authors: DANIEL B. FISHBEIN
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 November 1986H2-Antagonists and HepatitisDANIEL B. FISHBEIN, M.D., JOSEPH E. MCDADE, Ph.D.DANIEL B. FISHBEIN, M.D.Search for more papers by this author, JOSEPH E. MCDADE, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-5-803_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We regret that Dr. Souza Lima's review (1) was incomplete and his deductions were invalid. The evidence from worldwide clinical experience shows that hepatitis is rarely associated with H2-antagonists and that the clinical characteristics are similar with ranitidine and cimetidine. Ranitidine was not hepatotoxic in rodents treated for over 2 years at doses 800 times higher than therapeutic ones. The clinical case reports also indicate a hypersensitivity reaction, rather than direct liver toxicity.The relative rate of occurrence of hepatitis with the two drugs can best be estimated from comparative clinical trials. The Glaxo research organization has...References1. SOUZA LM. Ranitidine and hepatic injury [Letter]. 1986;105:140. Google Scholar2. IRELANDCOLIN-JONESGEAR ADP. Ranitidine 150 mg twice daily vs. 300 mg nightly in treatment of duodenal ulcers. Lancet. 1984;2:274-5. CrossrefMedlineGoogle Scholar3. INMAN W. A preliminary study of Zantac (ranitidine). PEM News. 1983;1:9-13. Google Scholar4. POTTERJICKPERAR JHD. Long-term follow-up study of cimetidine. Pharmacotherapy. 1984;4:381-4. CrossrefMedlineGoogle Scholar5. KHALSA J. Cimetidine-associated cholestatic jaundice. ADR Highlight. 1983;10:1-7. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Centers for Disease Control Atlanta, GA 30333 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe Safety of Drugs Used in Acid-related Disorders and Functional Gastrointestinal DisordersHepatitis following Treatments with Famotidine and Then CimetIDINEFamotidine-Induced Mixed Hepatocellular Jaundice 1 November 1986Volume 105, Issue 5Page: 803-803KeywordsClinical trialsDrugsEmotionsHepatitisHypersensitivityLiverToxicity Issue Published: 1 November 1986 PDF DownloadLoading ...
Interleukin 6, adiponectin, leptin, and insulin resistance in nonobese Japanese type 2 diabetic patients
Authors: Ataru Taniguchi, Mitsuo Fukushima, Michihiro Ohya, Yoshikatsu Nakai, Satoru Yoshii, Shoichiro Nagasaka, Kazunari Matsumoto, Yoshiro Taki, Akira Kuroe, Fusanori Nishimura, Yutaka Seino
Journal: Metabolism (2006)
Adverse Reactions to Over-the-counter Analgesics Taken for Therapeutic Purposes
Authors: Brian L. Strom
Journal: JAMA (1994)

Over-the-counter mild analgesics are widely used. Acetaminophen hepatotoxicity has been well-recognized for many years to occur after overdose, and effective treatment has been developed that reduces the risk of this serious adverse outcome, if given sufficiently early in the course of the overdose.<sup>1</sup>In this issue ofThe Journal, Drs Whitcomb and Block report a study assessing possible etiologies of acetaminophen hepatotoxicity.<sup>2</sup>Prior reports suggest that alcoholics may suffer from acetaminophen-induced liver disease at doses lower than normally thought to be required for hepatotoxicity. The presumed cause was that chronic alcohol ingestion concomitantly induces cytochrome P450 2EI and depletes glutathione, by both the effects of alcohol and the malnutrition associated with alcoholism. In this article, the authors reviewed 126 779 discharge summaries from a university hospital over a 6.5-year period for cases of acetaminophen hepatotoxicity: 94 patients had documented acetaminophen ingestion or were evaluated for possible acetaminophen toxicity;
Abstract 5564: Lack of efficacy of metformin in several standard prevention models: Methylnitrosourea rat mammary (ER+), MMTV-Neu/p53 mouse mammary (ER−) and the Min mouse colon
Authors: Ronald A. Lubet, Margie Clapper, Ann Bode, Vernon Steele, Clinton Grubbs
Journal: Cancer Research (2011)

Abstract Metformin, an anti-diabetic drug, activates AMP-activated protein kinase (AMPK), and has generated considerable interest as a potential preventive agent for a variety of cancers. This interest is based both on epidemiologic studies showing that diabetics treated with metformin have a lower incidence of a variety of cancers, and on mechanistic considerations arguing that activation of AMPK is likely to be relevant to cancer treatment and prevention. The preventive efficacy of metformin was examined in three commonly employed in rodent prevention models of breast and intestinal cancers. Treatment of female Sprague-Dawley rats at 50 days of age with a single dose of MNU (75 mg/kg BW) resulted in the development of multiple ER+ mammary cancers. This model has been highly responsive to a wide variety of agents or hormonal alterations that affect ER+ tumors in humans (SERMs, aromatase inhibitors, pregnancy, and ovariectomy). Metformin was administered by gavage (7x/week) at either 150 or 50 mg/kg BW/day; beginning seven days after MNU treatment and continuing for the duration of the study. Metformin failed to decrease mammary cancer incidence and, in fact, increased tumor multiplicity in this model by approximately 35%. In addition, the ability of metformin to inhibit mammary cancer in MMTV-Neu/p53 KO mice (which spontaneously develop ER− cancers) was evaluated. In this study, metformin was administered in the diet at a dose level of 1500 mg/kg diet. Initial supplementation of the diet with this agent began when the mice were 60 days of age, and continued for 10 months. This study similarly showed no efficacy of metformin (average tumors/mouse: 2.7 in both controls and metformin-treated mice). Finally the effect of metformin was examined in the Min model of intestinal neoplasia, in which mice have a germline APC mutation. Again, we failed to observe any efficacy of metformin. In contrast, naproxen (a non-specific NSAID) was highly effective in this model when used as a positive control. Thus, these initial studies failed to detect any chemopreventive efficacy of metformin in three commonly employed prevention models. One major caveat to these studies is that the animals were not diabetic nor were they administered an altered diet containing high fat or carbohydrates. Supported by NCI contract number HHSN261200433001C. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5564. doi:10.1158/1538-7445.AM2011-5564
THE ANTIGENIC PROPERTIES OF SPLIT PRODUCTS OF CASEIN
Authors: Frederick P. Gay, T. Brailsford Robertson
Journal: The Journal of Experimental Medicine (1912)

We draw the following conclusions from our experiments on the antigenic properties of chemically pure casein and some of its split products. Casein and paranuclein have distinct antigenic properties, particularly as shown by their ability to sensitize guinea pigs for subsequent anaphylactic intoxication by each other or by milk. This sensitizing ability and a corresponding ability to intoxicate are indistinguishably equivalent, under the conditions employed. On immunizing rabbits by repeated injections of paranuclein or of casein, and subsequently testing their sera for precipitins and fixation antibodies, it was found that casein apparently produces them much more readily, giving an antiserum that reacted (fixation) in very high dilution with casein (0.000,000,1 of a 1 per cent. solution), but much less strongly with paranuclein. Only one of two antiparanuclein sera showed the presence of antibodies to paranuclein by the delicate fixation reaction, and that in relatively small amounts. The two antibodies to casein and to paranuclein are, in the case of casein quantitatively, and in the case of paranuclein absolutely specific. A solution of the products of complete peptic digestion of casein fails to sensitize to paranuclein and gives no fixation reaction with an anticasein or antiparanuclein serum. It intoxicates animals sensitized to paranuclein but no more markedly than it does normal animals. It also fails to show specific intoxication in an animal that has been sensitized by the same substance. The amino acids, glutamic acid, and leucin, the principal components of their kind in casein, and in the same proportion therein present, likewise failed to show antigenic properties. They do not sensitize animals to milk intoxication or to intoxication by themselves, and likewise failed to produce precipitins in rabbits in a preliminary experiment. These experiments are regarded as a fairly systematic analysis of the antigenic properties of split products of a single protein. They are analogous to, though less complete than the work of Wells (6) on egg-white. They seem to present the additional advantage of dealing with what is probably the only protein certainly known chemically, and in its purest form. They serve, moreover, as an introduction to the following study of the antigenic properties of a combined protein.