tbuckley/cabot-search huggingface dataset:
Correction of characteristic abnormalities of microtubule function and granule morphology in Chediak-Higashi syndrome with cholinergic agonists.
Authors: J M Oliver, R B Zurier
Journal: Journal of Clinical Investigation (1976)

Chediak-Higashi (CH) syndrome is a genetic disorder of children and certain animal species including the beige mouse. We have previously described a membrane abnormality in CH mouse polymorphonuclear leukocytes (PMH). Whereas normal mouse PMN do not form surface caps with concanavalin A except after treatment with agents such as colchicine that inhibit microtubule assembly, CH mouse PMN show spontaneous cap formation. This capping is inhibited by 3',5 cyclic guanosine monophosphate and by the cholinergic agonists carbamylcholine and carbamyl beta-methylcholine that increase 3',5' cyclic guanosine monophosphate generation. These data suggested that microtubule function may be impaired in CH syndrome perhaps secondary to an abnormality in 3',5' cyclic guanosine monophosphate generation. The cholinergic agonists were also shown to prevent development of the giant granules that are pathognomonic of CH syndrome in embryonic fibroblasts isolated from CH mice and cultured in vitro. In this report it is shown that an extreme degree of spontaneous concanavalin A cap formation is also characteristic of peripheral blood PMN from two patients with CH syndrome. This indicates an abnormality of microtubule function in CH syndrome in man. 3',5' cyclic guanosine monophasphate, carbamylcholine, and carbamyl beta-methylcholine reduce spontaneous capping in CH cells. In addition, it is shown that monocytes isolated from the patients' blood and incubated in tissue culture generate a large complement of abnormal granules. When the same cells mature in vitro in the presence of carbamylcholine or carbamyl beta-methylcholine, the proportion of cells containing morphologically normal granules is significantly increased. These responses can be reproduced in vivo in the beige (CH) mouse. Animals treated for 3 wk and longer with carbamylcholine or carbamyl beta-methylcholline show normal granule morphology and a normal degree of concanavalin A cap formation in peripheral blood PMN leukocytes.
Roles of Various Organizations in Internal Medicine Curriculum Reform
Authors: Jordan J. Cohen
Journal: Annals of Internal Medicine (1992)

The curriculum in internal medicine for medical students and residents is being driven increasingly by the service demands of our teaching hospitals and is badly in need of fundamental reform. In reasserting the primacy of education as the driving force for the curriculum, numerous tasks must be done to achieve successful reform. These tasks are well within the scope of the several organizations that command leadership positions in the discipline of internal medicine and that represent the spectrum of activities required to discharge the specialty's public responsibility. These organizations include the Association of Professors of Medicine (APM), the Association of Program Directors in Internal Medicine (APDIM), the Society of General Internal Medicine (SGIM), The Residency Review Committee for Internal Medicine (RRC-IM), the American Board of Internal Medicine (ABIM), the American College of Physicians (ACP), the American Society of Internal Medicine (ASIM), and the Federated Council of Internal Medicine (FCIM). The challenge posed by the need for curriculum reform is to rouse these organizations to concerted action. Each of the seven organizations must assume a specific role and a unique set of responsibilities in the epic reforms envisioned.
DIAGNOSTIC AND PROGNOSTIC VALUE OF OSTEOPONTIN IN ACUTE CONGESTIVE HEART FAILURE -A PRELIMINARY STUDY
Authors: Michael Behnes, Florian Espeter, Siegfried Lang, Parviz Ahmad-Nejad, Michael Neumaier, Martina Brueckmann, Martin Borggrefe, Ursula Hoffmann
Journal: Journal of the American College of Cardiology (2012)
FURTHER REPORT OF THE SERUMTHERAPY IN TUBERCULOSIS.
Authors: PAUL PAQUIN
Journal: JAMA (1895)

Up to this date all of the reports which I have had the honor to make to the medical profession, bearing on the use of the horse-blood serum in the treatment of tuberculosis, cover a number of cases in which the improvement had been more or less marked. Our experiments up to the last report had not gone far enough to justify the statement that we had, in fact, cases of tuberculosis which had been cured. The present writing is chiefly for the purpose of reporting results of a more positive nature and, at the same time, to say a few words on the complications that may arise during serum injections; the conditions which militate against its use; also the extent, so far as I am able to present from past experience, of the expectations that may be based on the new treatment. I will begin with the latter propositions.
Endothelial Cell Surface ATP Synthase-Triggered Caspase-Apoptotic Pathway Is Essential for K1-5-Induced Antiangiogenesis
Authors: Niina Veitonmäki, Renhai Cao, Lin-Hua Wu, Tammy L. Moser, Bo Li, Salvatore V. Pizzo, Boris Zhivotovsky, Yihai Cao
Journal: Cancer Research (2004)

We have recently reported the identification of kringle 1-5 (K1-5) of plasminogen as a potent and specific inhibitor of angiogenesis and tumor growth. Here, we show that K1-5 bound to endothelial cell surface ATP synthase and triggered caspase-mediated endothelial cell apoptosis. Induction of endothelial apoptosis involved sequential activation of caspases-8, -9, and -3. Administration of neutralizing antibodies directed against the alpha- and beta-subunits of ATP synthase to endothelial cells attenuated activation of these caspases. Furthermore, inhibitors of caspases-3, -8, and -9 also remarkably blocked K1-5-induced endothelial cell apoptosis and antiangiogenic responses. In a mouse tumor model, we show that caspase-3 inhibitors abolished the antitumor activity of K1-5 by protecting the tumor vasculature undergoing apoptosis. These results suggest that the specificity of the antiendothelial effect of K1-5 is attributable, at least in part, to its interaction with the endothelial cell surface ATP synthase and that the caspase-mediated endothelial apoptosis is essential for the angiostatic activity of K1-5. Thus, our findings provide a mechanistic insight with respect to the angiostatic action and signaling pathway of K1-5 and angiostatin.
Abdominal Aortic Thrombosis in Association With an Attempted Heimlich Maneuver
Authors: Eric F. Roehm
Journal: JAMA (1983)

We report herein a case of an incorrectly applied Heimlich maneuver--to the best of our knowledge, the first reported fatal complication associated with a Heimlich maneuver, acute thrombosis of an abdominal aortic aneurysm, and the distal aorta. While the Heimlich maneuver is effective for the relief of foreign body-induced upper airway obstruction, increased efforts should be directed toward instructing the public in correctly recognizing and optimally treating airway obstruction.
The Presence of Venoarterial Shunts in Patients with Interatrial Communications
Authors: H. J. C. SWAN, HOWARD B. BURCHELL, EARL H. WOOD
Journal: Circulation (1954)

Evidence is presented which indicates that shunting of small amounts of blood from right to left occurs frequently through interatrial communications. Such right-to-left shunts are of small magnitude in the usual case of atrial septal defect, but it appears that of the fractions of blood shunted, a greater proportion has originated from the inferior vena cava than from the superior vena cava.
Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia
Authors: E McCormack, I Haaland, G Venås, R B Forthun, S Huseby, G Gausdal, S Knappskog, D R Micklem, J B Lorens, Ø Bruserud, B T Gjertsen
Journal: Leukemia (2011)
Ventricular Septal Defect with Altitude-Dependent Pulmonary Hypertension
Authors: James T. Willerson, A. Edward Baggett, Jackson W. Thomas, Allan Goldblatt
Journal: New England Journal of Medicine (1971)

EXPOSURE to high altitudes may result in increased pulmonary-artery pressure,1 2 3 which at least occasionally reverts toward normal with return to sea-level living.4 In the following case a ventricular septal defect with pulmonary hypertension occurred at moderately high altitude (Denver, Colorado), with a return to normal pulmonary-artery pressure at repeat cardiac catheterization in Boston, Massachusetts, four years later. Case Report J.W. (M.G.H. 147–92–84), a 6-year-old boy, was admitted to the Massachusetts General Hospital for cardiac catheterization in December, 1967. At birth in Denver, Colorado, a heart murmur had been noted. An electrocardiogram demonstrated right ventricular hypertrophy. At 2 years of age . . .
Injuries in professional horse racing in Great Britain and the Republic of Ireland during 1992-2000
Authors: M Turner, P McCrory, W Halley
Journal: British Journal of Sports Medicine (2002)

Professional horse racing is an exciting and demanding sport with high injury rates. Surprisingly few epidemiological studies have been published and no prospective studies have been reported. This paper reviews the literature and provides a detailed breakdown of injuries in Great Britain and the Republic of Ireland for 1992–2000. The introduction of protective equipment is discussed and evidence for its effectiveness put forward.
Sex hormone suppression and sexual impotence in hypoxic pulmonary fibrosis.
Authors: P D Semple, G H Beastall, T M Brown, K W Stirling, R J Mills, W S Watson
Journal: Thorax (1984)

Eight men with hypoxia associated with idiopathic pulmonary fibrosis were studied. Serum testosterone concentrations were low in two subjects and fell to subnormal levels in two others as the clinical condition and arterial oxygen tension deteriorated. There was a significant correlation between serum testosterone concentrations and arterial oxygen tensions (p less than 0.05). Three patients showed evidence of suppression of luteinising hormone secretion at the pituitary level. Only occasional abnormalities of thyroid and prolactin concentrations were noted. Most of the men suffered from organic sexual impotence, which is considered to be due at least in part to endocrine disturbance. These findings are similar to observations in patients with hypoxic chronic obstructive airways disease and support the hypothesis that hypoxia of lung disease suppresses the hypothalamo-pituitary-testicular axis.
Familial pyoderma gangrenosum in association with common variable immunodeficiency
Authors: L. Boussofara, R. Gammoudi, N. Ghariani, A. Aounallah, B. Sriha, M. Denguezli, C. Belajouza, R. Nouira
Journal: British Journal of Dermatology (2013)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Pyoderma gangrenosum (PG) is a rare skin disease characterized by noninfective, painful, necrotizing ulcerations. PG is extremely rare in the paediatric population; 4% of patients are infants and children.1 The occurrence of PG in a familial pattern is extremely rare. As far as we could ascertain, only three reports of familial predisposition in PG have been published previously in the English literature.2 3 4 The aetiopathogenesis of PG is still unclear. Its association with a variety of immunological disorders suggests an underlying defective immune system.5 6 However, to date, no cases of PG have been described in the context of common variable immunodeficiency (CVID). We report familial PG in two siblings with CVID, which we believe to be the first documentation of this kind. Patient 1, a 9‐year‐old boy born to nonconsanguineous parents, presented with painful ulcers that had appeared 2 months before. He had a history of recurrent episodes of lower respiratory tract infection since the age of 3 years leading to bronchiectasis. On clinical examination, the child was febrile, underweight and had multiple ulcers with undermined, violaceous margins and indurated bases on his neck, scalp, upper and lower extremities, groin and buttocks. The oral mucosa was particularly affected, presenting pustular exophytic lesions with an erythematous halo and friable membrane that easily disintegrated leading to exulcerated and vegetating lesions of the labial mucosa (Fig. 1). The rest of the clinical examination was unremarkable. Laboratory investigations revealed an elevated level of inflammatory markers. Cultures for bacteria and fungi from skin lesions and blood were repeatedly negative. A skin biopsy specimen revealed an ulcerated epidermis with a massive neutrophilic infiltrate in the upper and lower dermis. Based on the clinical and histological features, the diagnosis of PG was made and the patient was treated with oral prednisone 1 mg kg−1 daily, which induced a great improvement in his lesions and complete resolution in 4 weeks. The steroids were slowly tapered with no recurrence 1 year after the diagnosis. CVID was diagnosed when screening investigations revealed low IgG and IgM levels (IgG 5 g L−1, normal range 6·13–15·12; IgM 0·4 g L−1, normal range 0·7–2·84), absent response to polysaccharide and protein antigens, a reverse CD4:CD8 ratio, with normal complement levels and nitroblue tetrazolium test functional assays. The percentage of total B cells was within the lower normal range (5% of circulating lymphocytes) but with a reduced number of memory B cells identified by the surface marker CD27 (2% of B cells, normal range 6·5–29·2%).
Rigors with Vancomycin
Authors: N. Sharon Conley, Roy S. Weiner, John W. Hiemenz
Journal: Annals of Internal Medicine (1991)

Letters15 August 1991Rigors with VancomycinN. Sharon Conley, MD, PhD, Roy S. Weiner, MD, John W. Hiemenz, MDN. Sharon Conley, MD, PhDSearch for more papers by this author, Roy S. Weiner, MDSearch for more papers by this author, John W. Hiemenz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-4-330_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:A 51-year-old woman with metastatic breast cancer was hospitalized for high-dose chemotherapy and autologous bone marrow transplantation. On hospital day 7, she developed a fever of 38.6 °C lasting for 8hours. Empiric therapy with ceftazidime, 2 g every 8 hours, and vancomycin (Vancoled, Lederle, Pearl River, New York), 1 g hours,was instituted. After the third dose of vancomycin, the patient developed severe rigors, which resolved with intravenous administration of diphenylhydramine and meperidine. Rigors again developed with the fourth and fifth doses. Before receiving her sixth dose, the patientreceived premedication with meperidine, diphenylhydramine, and promethazine, and no rigors...References1. FarberMoellering BR. Retrospective study of the toxicity of preparations of vancomycin from 1974-1981. Antimicrob Agents Chemother. 1983;23:138-41. CrossrefMedlineGoogle Scholar2. New Preparations of vancomycin. Med Lett Drugs Ther. 1986;28:121-2. MedlineGoogle Scholar3. High performance liquid chromatography data. Available on request from EH Lilly and Company, Indianapolis, Indiana. Google Scholar4. MuoghaluLattimer BG. Delayed redneck syndrome with generic vancomycin. Drug Intell Clin Pharm. 1988;22:173. CrossrefMedlineGoogle Scholar5. PirainoBernadiniJohnston BJJ. Chemical peritonitis due to intraperitoneal vancomycin (Vancoled). Peritoneal Dialysis Bull. 1987;7:156-9. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Florida Gainesville, FL 32610 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByLife-Threatening Reaction to Vancomycin Given for Noninfectious FeverComparative safety of teicoplanin and vancomycin 15 August 1991Volume 115, Issue 4Page: 330-330KeywordsBone marrow transplantationBreast cancerFeversHigh-dose chemotherapyRiversVancomycin Issue Published: 15 August 1991 PDF DownloadLoading ...
715 BASELINE GENOTYPE AND HBSAG WERE FOUND TO HAVE SIGNIFICANT ASSOCIATION WITH HBEAG SEROCONVERSION FOLLOWING UP TO 4 YEARS OF TENOFOVIR DISOPROXIL FUMARATE TREATMENT
Authors: J. Heathcote, M. Manns, P. Mathurin, R. Ebrahimi, J. Anderson, L. Lou, C. Ng
Journal: Journal of Hepatology (2011)
Protein Arginine Methyltransferase 6 Enhances Polyglutamine-Expanded Androgen Receptor Function and Toxicity in Spinal and Bulbar Muscular Atrophy
Authors: Chiara Scaramuzzino, Ian Casci, Sara Parodi, Patricia M.J. Lievens, Maria J. Polanco, Carmelo Milioto, Mathilde Chivet, John Monaghan, Ashutosh Mishra, Nisha Badders, Tanya Aggarwal, Christopher Grunseich, Fabio Sambataro, Manuela Basso, Frank O. Fackelmayer, J. Paul Taylor, Udai Bhan Pandey, Maria Pennuto
Journal: Neuron (2015)

Polyglutamine expansion in androgen receptor (AR) is responsible for spinobulbar muscular atrophy (SBMA) that leads to selective loss of lower motor neurons. Using SBMA as a model, we explored the relationship between protein structure/function and neurodegeneration in polyglutamine diseases. We show here that protein arginine methyltransferase 6 (PRMT6) is a specific co-activator of normal and mutant AR and that the interaction of PRMT6 with AR is significantly enhanced in the AR mutant. AR and PRMT6 interaction occurs through the PRMT6 steroid receptor interaction motif, LXXLL, and the AR activating function 2 surface. AR transactivation requires PRMT6 catalytic activity and involves methylation of arginine residues at Akt consensus site motifs, which is mutually exclusive with serine phosphorylation by Akt. The enhanced interaction of PRMT6 and mutant AR leads to neurodegeneration in cell and fly models of SBMA. These findings demonstrate a direct role of arginine methylation in polyglutamine disease pathogenesis.
Abstract 2400: Differential phosphorylation of signaling targets as a function of RAS mutation status and tumor histology in non-small cell lung cancer.
Authors: Sang-Won Um, Jingxiang Chen, Carrie Lee, Norman E. Sharpless, Patrick J. Roberts, D. Neil Hayes
Journal: Cancer Research (2013)

Abstract Background: While the importance of RAS and mTOR signaling pathways in non-small cell lung cancer (NSCLC) is well known, the activation status of key components in the pathway as a function of histology and oncogene mutation status has been not completely described. The purpose of this study is to investigate phosphorylation status of signal transduction pathway members and to elucidate their prognostic significance in relation to adenocarcinoma and squamous cell carcinoma. Methods: Phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK), MEK 1 and 2 (pMEK), and mammalian target of rapamycin (pmTOR) were immunohistochemically examined using tissue microarray samples of 269 surgically resected primary NSCLC. Thyroid transcription factor-1 (TTF-1) expression and mutation status of EGFR and KRAS were also evaluated. The relationships between 5-year progression free survival (PFS) and phospho-protein expression were investigated by univariate analyses of log-rank test and multivariate analyses using Cox regression model. Results: A total of 98 adenocarcinomas and 134 squamous cell carcinomas were included in the analyses. In adenocarcinoma, pERK expression was significantly related to pMEK (P = 0.001), pmTOR (P &amp;lt; 0.001), and TTF-1 (P = 0.013) expression. In squamous cell carcinoma, pERK expression was significantly related to pMEK (P &amp;lt; 0.001) expression. EGFR or KRAS mutations were significantly associated with TTF-1 expression (P = 0.014) in adenocarcinoma. However, EGFR and KRAS mutation status were not significantly associated with pERK, pMEK, and pmTOR expressions in adenocarcinoma. By univariate analyses, high pERK expression was associated with better 5-year PFS (P = 0.018) in adenocarcinoma and high pMEK expression was associated with worse 5-year PFS (P = 0.043) in squamous cell carcinoma. In multivariate analyses, pERK (P = 0.040) and pMEK (P = 0.048) expression were independent prognostic factors. Conclusions: There were different patterns of phospho-protein expression in adenocarcinoma and squamous cell carcinoma. pERK expression was a good prognostic factor only in adenocarcinoma and pMEK expression was a poor prognostic factor only in lung squamous cell carcinoma. Citation Format: Sang-Won Um, Jingxiang Chen, Carrie Lee, Norman E. Sharpless, Patrick J. Roberts, D. Neil Hayes. Differential phosphorylation of signaling targets as a function of RAS mutation status and tumor histology in non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2400. doi:10.1158/1538-7445.AM2013-2400
Adiposity and weight change in mid-life in relation to healthy survival after age 70 in women: prospective cohort study
Authors: Q. Sun, M. K Townsend, O. I Okereke, O. H Franco, F. B Hu, F. Grodstein
Journal: BMJ (2009)

<b>Objective</b> To examine the hypothesis that mid-life adiposity is associated with a reduced probability of maintaining an optimal health status among those who survive to older ages. <b>Design</b> Prospective cohort study. <b>Setting</b> The Nurses' Health Study, United States. <b>Participants</b> 17 065 women who survived until at least the age of 70, provided information on occurrence of chronic disease, cognitive function, physical function, and mental health at older ages, and were free from major chronic diseases at mid-life (mean age was 50 at baseline in 1976). <b>Main outcome measures</b> Healthy survival to age 70 and over was defined as having no history of 11 major chronic diseases and having no substantial cognitive, physical, or mental limitations. <b>Results</b> Of the women who survived until at least age 70, 1686 (9.9%) met our criteria for healthy survival. Increased body mass index (BMI) at baseline was significantly associated with linearly reduced odds of healthy survival compared with usual survival, after adjustment for various lifestyle and dietary variables (P&lt;0.001 for trend). Compared with lean women (BMI 18.5-22.9), obese women (BMI ≥30) had 79% lower odds of healthy survival (odds ratio 0.21, 95% confidence interval 0.15 to 0.29). In addition, the more weight gained from age 18 until mid-life, the less likely was healthy survival after the age of 70. The lowest odds of healthy survival were among women who were overweight (BMI ≥25) at age 18 and gained ≥10 kg weight (0.18, 0.09 to 0.36), relative to women who were lean (BMI 18.5-22.9) and maintained a stable weight. <b>Conclusions</b> These data provide evidence that adiposity in mid-life is strongly related to a reduced probability of healthy survival among women who live to older ages, and emphasise the importance of maintaining a healthy weight from early adulthood.
UK ministers must "reconsider" decision on compensation to haemophiliacs
Authors: C. Dyer
Journal: BMJ (2010)

A British haemophiliac man who was infected with HIV and hepatitis C through contaminated blood products has won a legal challenge at the High Court in London over government compensation payments.

Andrew March, 36, an award winning composer, won a judicial review of the government’s decision not to increase ex gratia payments in line with much higher payments made by the Republic of Ireland.

Mr Justice Holman quashed UK ministers’ decision not to match the “very much higher” payments in Ireland, ruling that the government’s approach “had been, and remains, infected by an error.” The error was the belief that the Irish government decided to pay full compensation only …