tbuckley/cabot-search huggingface dataset:
Increased tyrosine phosphorylation of band 3 in hemoglobinopathies
Authors: H.T.M.B. Terra, M.J.A. Saad, C.R.O. Carvalho, D.L. Vicentin, F.F. Costa, S.T.O. Saad
Journal: American Journal of Hematology (1998)

In order to investigate the tyrosine phosphorylation of band 3, we performed immunoblotting of intact red cells using anti-phosphotyrosine antibody of 21 patients with sickle cell disorders (11 SS, 5 Sβ, 5 SC), 7 patients with β thalassemias (5 β thal intermedia, 2 δβ thal), 10 normal controls, and 1 patient with hereditary spherocytosis. They had not received transfusion for the last 4 months and all were clinically stable. Our results showed an increased tyrosine phosphorylation of two proteins, in the 100 and 80 kD regions, in sickle cell and β-thalassemic red cells when compared to the normal controls and to the patient with hereditary spherocytosis. Immunoprecipitation of the lysed red cells with anti-band 3 antibody and immunoblotting with anti-phosphotyrosine antibody confirmed that the 100 kD tyrosine phosphorylated protein was band 3. In the sickle cell disease group, the band 3 tyrosine phosphorylation varied from 2- to 10-fold increase compared to control (x ± SD; SS = 7.8- ± 2.7-fold; SC = 3.8- ± 1.3-fold; Sβ = 5.2- ± 2.0-fold). It was also higher in the β-thalassemic group (β-thal = 4.3- ± 3.7-fold). There was no significant difference in tyrosine phosphorylation among the various groups tested, except when we compared the phosphorylation in intact red cells of patients with sickle cell anemia and hemoglobinopathy SC (U = 6, P < 0.02). The tyrosine phosphorylation of band 3 was increased in hemoglobinopathies even in the absence of high reticulocyte count. At least two mechanisms might be involved in the increased tyrosine phosphorylation of band 3 in these hemoglobin disorders, probably related to the endogenous reactive oxygen intermediates generated by the abnormal erythrocyte: an inhibition of protein tyrosine phosphatase activity or an activation of the protein tyrosine kinase p72syk. Am. J. Hematol. 58:224–230, 1998. © 1998 Wiley-Liss, Inc.
A Wise and Able Governor.
Authors: J. A. Dibrell
Journal: JAMA (1895)

Little Rock, Ark., March 23, 1895. <h3>To the Editor:</h3> —I inclose herewith a cutting from the Little Rock<i>Daily Gazette</i>of this date. Up to two years ago a law had been in operation in this State, regulating the practice of medicine. It provided for a medical board in each county (about seventy-five of them) consisting of three "physicians," who were appointed by the county judges. They gave certificates of qualification to any and everybody who applied for them, and these "certificates," when once obtained, were good forever, and permitted the holder to practice medicine anywhere in the State. Two years ago this law was repealed and an Act was passed which required that all persons beginning practice after that date should be graduates of some reputable medical college, having not less than two full courses of lectures as a minimum requirement for graduation. It was a bill repealing this
Global analysis of B cell selection using an immunoglobulin light chain–mediated model of autoreactivity
Authors: Sarah F. Andrews, Qingzhao Zhang, Samuel Lim, Lie Li, Jane-Hwei Lee, Nai-Ying Zheng, Min Huang, William M. Taylor, A. Darise Farris, Dongyao Ni, Wenzhao Meng, Eline T. Luning Prak, Patrick C. Wilson
Journal: The Journal of Experimental Medicine (2012)

The important subtleties of B cell tolerance are best understood in a diverse immunoglobulin (Ig) repertoire context encoding a full spectrum of autoreactivity. To achieve this, we used mice expressing Igκ transgenes that confer varying degrees of autoreactivity within a diverse heavy chain (HC) repertoire. These transgenes, coupled with a biomarker to identify receptor-edited cells and combined with expression cloning of B cell receptors, allowed us to analyze tolerance throughout B cell development. We found that both the nature of the autoantigen and the Ig HC versus light chain (LC) contribution to autoreactivity dictate the developmental stage and mechanism of tolerance. Furthermore, although selection begins in the bone marrow, over one third of primary tolerance occurs in the periphery at the late transitional developmental stage. Notably, we demonstrate that the LC has profound effects on tolerance and can lead to exacerbated autoantibody production.
An American in London
Authors: John Lister
Journal: New England Journal of Medicine (1952)

An American in LondonA Canadian doctor once remarked to me that, in many respects, Canadians regard themselves as occupying a position midway between the English and the Americans. He said he thought the situation was well illustrated by the time hospital-ward work is started in the respective countries. "In America" he said, "they start their ward rounds at 8 o'clock, in England you start at 10 o'clock — but in Canada we start at 9 o'clock!"With this in mind and with some slight experience of the 8 o'clock American ward round, I asked an American friend at present . . .
Rapid emergence of telaprevir resistant hepatitis C virus strain from wildtype clone in vivo
Authors: Nobuhiko Hiraga, Michio Imamura, Hiromi Abe, Nelson C. Hayes, Tomohiko Kono, Mayu Onishi, Masataka Tsuge, Shoichi Takahashi, Hidenori Ochi, Eiji Iwao, Naohiro Kamiya, Ichimaro Yamada, Chise Tateno, Katsutoshi Yoshizato, Hirotaka Matsui, Akinori Kanai, Toshiya Inaba, Shinji Tanaka, Kazuaki Chayama
Journal: Hepatology (2011)

Telaprevir is a potent inhibitor of hepatitis C virus (HCV) NS3-4A protease. However, the emergence of drug-resistant strains during therapy is a serious problem, and the susceptibility of resistant strains to interferon (IFN), as well as the details of the emergence of mutant strains in vivo, is not known. We previously established an infectious model of HCV using human hepatocyte chimeric mice. Using this system we investigated the biological properties and mode of emergence of mutants by ultra-deep sequencing technology. Chimeric mice were injected with serum samples obtained from a patient who had developed viral breakthrough during telaprevir monotherapy with strong selection for resistance mutations (A156F [92.6%]). Mice infected with the resistant strain (A156F [99.9%]) developed only low-level viremia and the virus was successfully eliminated with interferon therapy. As observed in patients, telaprevir monotherapy in viremic mice resulted in breakthrough, with selection for mutations that confer resistance to telaprevir (e.g., a high frequency of V36A [52.2%]). Mice were injected intrahepatically with HCV genotype 1b clone KT-9 with or without an introduced resistance mutation, A156S, in the NS3 region, and treated with telaprevir. Mice infected with the A156S strain developed lower-level viremia compared to the wildtype strain but showed strong resistance to telaprevir treatment. Although mice injected with wildtype HCV showed a rapid decline in viremia at the beginning of therapy, a high frequency (11%) of telaprevir-resistant NS3 V36A variants emerged 2 weeks after the start of treatment. Conclusion: Using deep sequencing technology and a genetically engineered HCV infection system, we showed that the rapid emergence of telaprevir-resistant HCV was induced by mutation from the wildtype strain of HCV in vivo. (HEPATOLOGY 2011;).
Iron Responsive Thrombocytopenia
Authors: HOWARD SCHER
Journal: Annals of Internal Medicine (1976)

Letters1 May 1976Iron Responsive ThrombocytopeniaHOWARD SCHER, M.D., ROBERT SILBER, M.D.HOWARD SCHER, M.D.Search for more papers by this author, ROBERT SILBER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-5-571 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRecent experimental and clinical studies have provided evidence that iron has a role in the regulation of thrombopoiesis (1). Gross, Keffer, and Newman (2), studying 60 iron-deficient infants, noted the occurrence of thrombocytopenia and thrombocytosis. Both groups responded with a rise in platelet count, independent of hemoglobin level, after iron therapy. With further administration of iron, the platelet count stabilized at a normal level. In 1974, two cases have been reported that describe iron deficiency and thrombocytopenia corrected by parenteral iron administration (3, 4). Recently, we had the opportunity to study a polycythemic patient whose platelet count appeared sensitive to...References1. KARPATKINGARGFREEDMAN SSM: The role of iron as a regulator of thrombopoiesis. Am J Med 57:521-525, 1974 CrossrefMedlineGoogle Scholar2. GROSSKEFFERNEWMAN SVA: The platelets in iron deficiency anemia. I. The response to oral and parenteral iron. Pediatrics 34:315-323, 1974 Google Scholar3. SAHUDOLSENPEDEMONT MHL: Thrombocytopenia and iron deficiency. Ann Intern Med 81:132-133, 1974 LinkGoogle Scholar4. SONNEBORN D: Thrombocytopenia and iron deficiency (letter). Ann Intern Med 80:111, 1974 LinkGoogle Scholar5. FREEDMANKARPATKIN MS: Requirement of iron for platelet protein synthesis. Biochem Biophys Res Commun 54:475-481, 1973 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine New York University Medical Center New York, NY 10016 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThrombocytopenia in severe iron deficiency anemia in childrenAn analysis of the relationship between severe iron deficiency anemia and thrombocytopeniaAn Unusual Case of ThrombocytopeniaThrombopénie ferriprive : un diagnostic différentiel rare du purpura thrombopénique auto-immunThrombocytopenia in Children With Severe Iron DeficiencyNIron Deficiency and Megaloblastic AnemiasThrombocytopenia Associated with Repletion of Lron in Lron-Deficiency AnemiaSevere thrombocytopenia in iron deficiency anemiaThe Hematopoietic System 1 May 1976Volume 84, Issue 5Page: 571-572KeywordsHemoglobinInfantsIron deficiencyPlateletsThrombocytosis Issue Published: 1 May 1976 PDF DownloadLoading ...
Sustained-Release Morphine
Authors: CYRIL BORODA
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 April 1984Sustained-Release MorphineCYRIL BORODACYRIL BORODASearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-4-617_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The letter by Weiler (1) on morphine administration cites a reference that states that a sustained-release form of morphine sulphate would be invaluable (2). It may interest your readers to know that a sustained-release form of morphine sulphate tablets, in strengths of 10 mg, 30 mg, 60 mg and 100 mg, has been available in the United Kingdom for some time and is available in some other European countries, although not currently in the United States....References1. WEILER J. Routes of morphine administration [Letter]. Ann Intern Med. 1983;99:736-7. LinkGoogle Scholar2. VERE D. Pharmacology of morphine drugs used in terminal care. In: Topics in Therapeutics. London: Pitman Medical Books; 1978:75-83. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Napp Laboratories Cambridge Science Park, Milton Road; Cambridge CB4 4BH United Kingdom PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1984Volume 100, Issue 4Page: 617-617KeywordsMorphine Issue Published: 1 April 1984 PDF downloadLoading ...
Abstract 2545: Roles of BIM induction and survivin down-regulation in lapatinib-induced apoptosis in breast cancer cells with HER2 amplification
Authors: Junko Tanizaki, Isamu Okamoto, Soichi Fumita, Wataru Okamoto, Kazuhiko Nakagawa
Journal: Cancer Research (2011)

Abstract Breast cancer is the leading cause of cancer death among women worldwide. Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 25 to 30% of breast cancers, and HER2 is thus an attractive target for the development of therapeutic drugs. Lapatinib, a dual tyrosine kinase inhibitor of HER2, is clinically active in patients with breast cancer positive for HER2 amplification. The mechanism of this antitumor action has remained unclear, however. Although lapatinib improved the overall outcome for such patients, not all patients benefited from the treatment. Characterization of the molecular basis of the response to lapatinib will thus be important to maximize the clinical efficacy of this drug. Mutations in PIK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been identified in 8 to 40% of breast cancers. Although a positive correlation between HER2 overexpression and the presence of PIK3CA mutations has been described, the relation between the efficacy of lapatinib and such mutations has remained unclear. We have now investigated the effects of lapatinib in HER2 amplification-positive breast cancer cells with or without an activating PIK3CA mutation. By using immunoblot analysis and Annexin V assay, we found that lapatinib induced apoptosis in association with up-regulation of the proapoptotic protein BIM through inhibition of the MEK-ERK signaling pathway in breast cancer cells with HER2 amplification. RNA interference-mediated depletion of BIM inhibited lapatinib-induced apoptosis, implicating BIM induction in this process. The proapoptotic effect of lapatinib was less pronounced in cells with a PIK3CA mutation than in those without one. Lapatinib failed to inhibit AKT phosphorylation in PIK3CA mutant cells, likely because of hyperactivation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway by the mutation. Depletion of PIK3CA (a catalytic subunit of PI3K) by si-RNA revealed that survivin expression is regulated by the PI3K pathway in these cells, suggesting that insufficient inhibition of PI3K-survivin signaling is responsible for the limited proapoptotic effect of lapatinib in HER2 amplification-positive cells with a PIK3CA mutation. Consistent with this notion, depletion of survivin by RNA interference or treatment with a PI3K inhibitor markedly increased the level of apoptosis in PIK3CA mutant cells treated with lapatinib. Our results thus suggest that inhibition of both PI3K-survivin and MEK-ERK-BIM pathways is required for effective induction of apoptosis in breast cancer cells with HER2 amplification. 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 2545. doi:10.1158/1538-7445.AM2011-2545
Reply to Ian Beckley and Masood A. Khan’s Letter to the Editor re: Felix K.-H. Chun, Thomas Steuber, Andreas Erbersdobler, et al. Development and Internal Validation of a Nomogram Predicting the Probability of Prostate Cancer Gleason Sum Upgrading Between Biopsy and Radical Prostatectomy Pathology. Eur Urol 2006;49:820–26
Authors: Felix K.-H. Chun, Markus Graefen, Nazzareno Suardi, Pierre I. Karakiewicz
Journal: European Urology (2007)
Lessons from the Johns Hopkins Multi-Disciplinary Venous Thromboembolism (VTE) Prevention Collaborative
Authors: M. B. Streiff, H. T. Carolan, D. B. Hobson, P. S. Kraus, C. G. Holzmueller, R. Demski, B. D. Lau, P. Biscup-Horn, P. J. Pronovost, E. R. Haut
Journal: BMJ (2012)

<b>Problem</b> Venous thromboembolism (VTE) is a common cause of potentially preventable mortality, morbidity, and increased medical costs. Risk-appropriate prophylaxis can prevent most VTE events, but only a small fraction of patients at risk receive this treatment. <b>Design</b> Prospective quality improvement programme. <b>Setting</b> Johns Hopkins Hospital, Baltimore, Maryland, USA. <b>Strategies for change</b> A multidisciplinary team established a VTE Prevention Collaborative in 2005. The collaborative applied the four step TRIP (translating research into practice) model to develop and implement a mandatory clinical decision support tool for VTE risk stratification and risk-appropriate VTE prophylaxis for all hospitalised adult patients. Initially, paper based VTE order sets were implemented, which were then converted into 16 specialty-specific, mandatory, computerised, clinical decision support modules. <b>Key measures for improvement</b> VTE risk stratification within 24 hours of hospital admission and provision of risk-appropriate, evidence based VTE prophylaxis. <b>Effects of change</b> The VTE team was able to increase VTE risk assessment and ordering of risk-appropriate prophylaxis with paper based order sets to a limited extent, but achieved higher compliance with a computerised clinical decision support tool and the data feedback which it enabled. Risk-appropriate VTE prophylaxis increased from 26% to 80% for surgical patients and from 25% to 92% for medical patients in 2011. <b>Lessons learnt</b> A computerised clinical decision support tool can increase VTE risk stratification and risk-appropriate VTE prophylaxis among hospitalised adult patients admitted to a large urban academic medical centre. It is important to ensure the tool is part of the clinician's normal workflow, is mandatory (computerised forcing function), and offers the requisite modules needed for every clinical specialty.
Failure of bile acids to control hepatic cholesterogenesis: evidence for endogenous cholesterol feedback
Authors: Hans J. Weis, John M. Dietschy
Journal: Journal of Clinical Investigation (1969)

Studies were undertaken to define the role of bile acids in the control of hepatic cholesterogenesis from acetate. Both biliary diversion and biliary obstruction increase the rate of sterol synthesis by the liver 2.5- to 3-fold. After biliary diversion, however, the bile acid content of the liver is decreased, whereas after biliary obstruction, it is markedly increased. Thus, there is no relationship between the tissue content of bile acid and the rate of hepatic cholesterol synthesis. Furthermore, restoration of the enterohepatic circulation of bile acid in animals with biliary diversion fails to prevent the rise in synthetic activity seen after this manipulation. These data indicate that bile acid plays no direct inhibitory role in the regulation of cholesterol synthesis by the liver. Other experiments were therefore undertaken to evaluate the possibility that changes in cholesterogenic activity observed after manipulation of the enterohepatic circulation of bile acid actually are the result of changes in the enterolymphatic circulation of cholesterol. In support of this thesis it was found that intestinal lymphatic diversion causes the same specific enhancement of cholesterol synthetic activity as biliary diversion and that both of these operative procedures increase enzymatic activity at the step mediated by beta-hydroxy-beta-methyl glutaryl reductase. Furthermore, the increase in the rate of sterol synthesis by the liver seen in animals with biliary diversion can be prevented by the infusion of approximately 7 mg of cholesterol/24 hr in the form of chylomicrons. This is an amount of cholesterol circulating normally in the enterolymphatic circulation of the intact rat.These results indicate that bile acid plays no direct role in the control of hepatic cholesterogenesis, but rather, it is the enterohepatic circulation of endogenous cholesterol that determines directly the rate at which cholesterol is synthesized by the liver.
Treatment With Clopidogrel After Myocardial Infarction
Authors: Gen-Min Lin, Yi-Hwei Li, Chih-Lu Han
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Maharashtra government is told to end doctors' strikes over poor security in hospitals
Authors: P. Chatterjee
Journal: BMJ (2013)

The High Court in Mumbai has told the government of Maharashtra to act immediately to resolve a dispute with doctors in public hospitals who have been striking in protest at poor security against attacks from aggrieved relatives of patients they have treated.

The court has also issued a notice to the Maharashtra Association of Resident Doctors to withdraw its call for strikes once their grievances are dealt with.

The calls came as the court was considering a public interest litigation from a member of the …
OBSERVATIONS ON CAPILLARY MICROSCOPY IN PREGNANCY
Authors: JOSEPH L. BAER
Journal: JAMA (1924)

Clinical studies of capillary circulation received a marked impetus when Lombard, 1 in 1912, elaborated his method of direct visual examination of the capillaries of the skin. The capillary system is probably the most important unit of the entire circulatory apparatus, and yet, to quote Krogh, 2  is a little strange that... the capillaries have been neglected in an extraordinary degree. Since microscopy of the capillaries has permitted a study of their morphology, distribution and behavior in health and disease, a new field has been opened to physiologists as well as to clinicians.  The function of the circulatory system is twofold; viz., to carry nourishment to the tissues and to carry waste products away from the tissues. The capillaries are all-important since it is through their walls that this exchange of food and excretion products takes place. It must be apparent, therefore, that many pathologic conditions will be better
TCTAP A-001 Twelve-month Clinical Outcomes of Transradial Coronary Artery Intervention: Comparison of the Right and Left Radial Artery Approach
Authors: Ji Young Park, Seung-Woon Rha, Byoung Geol Choi, Dong Joo Oh, Jae Woong Choi, Sung Kee Ryu, Myung Ho Jeong, Sang Sik Jung, Moo Hyun Kim, Hyoung-Mo Yang, Junghan Yoon, Keum Soo Park, Kyoo Rok Han, Byung Ryul Cho, Kwang Soo Cha, Byung Ok Kim, Min Soo Hyun, Won Yong Shin, Hyunmin Choe, Jang-Whan Bae, Hee Yeol Kim
Journal: Journal of the American College of Cardiology (2014)