tbuckley/cabot-search huggingface dataset:
Sitagliptin Improves Postprandial Hyperglycemia by Inhibiting Glucagon Secretion in Werner Syndrome With Diabetes
Authors: Kaneyuki Watanabe, Kazuki Kobayashi, Minoru Takemoto, Ryoichi Ishibashi, Masaya Yamaga, Harukiyo Kawamura, Masaki Fujimoto, Takahiro Ishikawa, Shunichiro Onishi, Emiko Okabe, Peng He, Koutaro Yokote
Journal: Diabetes Care (2013)

Werner syndrome (WS) is a typical progeria syndrome and often leads to diabetes (1). Here, we report a case in which sitagliptin, a dipeptidyl peptidase-4 inhibitor, normalized the postprandial glucagon secretion and improved postprandial blood glucose levels.

A 54-year-old female was admitted to our hospital. She developed bilateral cataracts at 35 years of age. Thereafter, at 44 years of age, because of her progeria-like face, she underwent genetic testing and was diagnosed with WS (mutation 4/6, compound heterozygote). At 49 years of age, she developed diabetes. Her height was 144 cm, weight 30.4 kg, and BMI 14.6 kg/m2. Her visceral fat area was 124.8 cm2. At the time of the hospitalization, she was prescribed 30 mg pioglitazone daily. The initial …
Points from Letters: Training in Infectious Diseases
Authors: R. J. Fallon
Journal: BMJ (1974)

1) That this commnittee agrees to ap- point an appropriate number of members to serve on its two District Medical Committees."(2) That if the General Medical Services Committee so advises, these members will not participate in-the work of the District Medical Committees until the ques- tion of remuneration or reimbursement for loss of earnings is agreed with the Depart- ment of Health and Social Security."-Weare, etc.,
Novel synthetic RORγ agonist compounds as a potential anti-tumor therapeutic approach
Authors: Xiao Hu, Xikui Liu, Rodney Morgan, Jacques Moisan, Ling-Yang Hao, Yahong Wang, Brian Sanchez, Charles Lesch, Dick Bousley, Clark Taylor, Thomas Aicher, Peter Toogood, Weiping Zou, Gary Glick, Laura Carter
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Selective enhancement (or activation) of the immune system by novel small molecules may be a potential therapeutic approach for the treatment of cancer. RORγt ( R etinoic Acid Receptor-related o rphan r eceptor) is the key transcription factor for the development of CD4+ Th17
Failure to Rescue
Authors: Jeffrey H. Silber
Journal: JAMA Surgery (2014)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
The J-Curve Phenomenon and the Treatment of Hypertension
Authors: Emanuel Cheraskin
Journal: JAMA (1991)

<h3>To the Editor.</h3> — Farnett and colleagues should be commended for refocusing our attention to the role of the parabola in clinical medicine. In the interest of accuracy and fairness, even the public (without scientific buzzwords) has long known that it is bad to be too tall or too short, too fat or too thin, too hot or too cold, and too mad or too glad. We took a hard look at this issue several years ago in an article entitled "If High Blood Cholesterol Is Bad... Is Low Good?"<sup>2</sup>It became obvious that the lipid story took on a different meaning as we switched from a dichotomy (high vs normal cholesterolemia) to a trichotomy of high, normal, and low. As a matter of fact, we have long studied the J-shaped curve. Specifically, the pattern has been confirmed in many areas. For example, the quasiparabolic picture applies in the
Effect of Saturated and Unsaturated Fats on the Concentration of Serum Cholesterol and Experimental Atherosclerosis
Authors: ALFRED STEINER, ARISTIDES VARSOS, PAUL SAMUEL
Journal: Circulation Research (1959)

The feeding of a diet rich in unsaturated fats to rabbits produced no significant alteration of the serum cholesterol level, while the feeding of a diet rich in saturated fats produced an elevation of the serum cholesterol without the development of experimental atherosclerosis. The addition of unsaturated fats to a diet rich in cholesterol failed to prevent hypercholesterolemia and experimental atherosclerosis in rabbits.
The Effect of Copper on Red Cell Enzyme Activities
Authors: M. Boulard, K.-G. Blume, E. Beutler
Journal: Journal of Clinical Investigation (1972)

Previous studies have shown a marked effect of very high levels of copper on red cell glucose-6-phosphate dehydrogenase and glutathione. When the effect of more nearly physiological levels of copper were studied, red cell hexokinase, phosphofructokinase, phosphoglyceric kinase, pyruvate kinase, and 6-phosphogluconate dehydrogenase were found to be inhibited. Inhibition was observed both when copper was added directly to hemolysates or when hemolysates were prepared from red cells from whole blood which had been incubated with copper and washed. The inhibition of red cell enzymes by copper was completely reversed by the addition of EDTA.
Continuity and Change in Glycemic Control Trajectories From Adolescence to Emerging Adulthood
Authors: Koen Luyckx, Inge Seiffge-Krenke
Journal: Diabetes Care (2009)

To determine developmental classes of glycemic control in young people with type 1 diabetes throughout adolescence and emerging adulthood and assess relationships with general family climate and self-concept.In an eight-wave longitudinal study, 72 individuals (37 females) completed questionnaires assessing family climate (at times 1-4) and self-concept (at times 1-4 and 6). Times 1-4 covered adolescence (mean ages were 14-17 years, respectively); times 5-8 covered emerging adulthood (mean ages were 21-25 years, respectively). At each time point, patients visited their physicians to determine A1C values, and questionnaires were sent to the physicians to obtain these values. Latent class growth analysis was used to identify developmental classes of glycemic control.Latent class growth analysis favored a three-class solution, consisting of optimal control (n = 10), moderate control (n = 51), and deteriorating control (n = 11). From time 3 on and especially during emerging adulthood, mean A1C levels were substantially different among the classes. Additional ANOVAs indicated that at times 1, 2, and 4, the optimal control class was characterized by the most optimal family climate, whereas at times 3, 4, and 6, the deteriorating control class was characterized by the lowest score on positive self-concept.From late adolescence on, a multiformity of glycemic control trajectories emerged, which became more diversified throughout emerging adulthood. Family climate and self-concept in mid-to-late adolescence served as psychosocial markers of these developmental classes.
229 ASSESSMENT OF LIPOPROTEIN SUBFRACTIONS IN LIVER CIRRHOSIS: RELATIONSHIP WITH BASAL AND ACTH INDUCED CORTISOL
Authors: G. Privitera, T. Tomaselli, L. Spadaro, G. Fede, R. Scicali, F. Fayer, D. Noto, M. Averna, F. Purrello
Journal: Journal of Hepatology (2013)
Review: Isolated cardiac myocytes: II Functional aspects of mature cells
Authors: J. W DOW, N. G L HARDING, T. POWELL
Journal: Cardiovascular Research (1981)

Journal Article Review: Isolated cardiac myocytes: II Functional aspects of mature cells Get access JOCELYN W DOW, JOCELYN W DOW * *Correspondence and reprint requests should be addressed to: Dr Jocelyn Dow, Department of Biochemistry, University of Glasgow, Glasgow, GI2 8QQ. Search for other works by this author on: Oxford Academic PubMed Google Scholar NIGEL G L HARDING, NIGEL G L HARDING Search for other works by this author on: Oxford Academic PubMed Google Scholar TREVOR POWELL TREVOR POWELL Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 15, Issue 10, October 1981, Pages 549–579, https://doi.org/10.1093/cvr/15.10.549 Published: 01 October 1981
Dose-dependent Neuroprotection of VEGF165 in Huntington's Disease Striatum
Authors: Stuart M Ellison, Antonio Trabalza, Veronica Tisato, Evangelos Pazarentzos, Shirley Lee, Vasiliki Papadaki, Despoina Goniotaki, Sarah Morgan, Nazanin Mirzaei, Nicholas D Mazarakis
Journal: Molecular Therapy (2013)

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by abnormal polyglutamine expansion in the huntingtin protein (Exp-Htt). Currently, there are no effective treatments for HD. We used bidirectional lentiviral transfer vectors to generate in vitro and in vivo models of HD and to test the therapeutic potential of vascular endothelial growth factor 165 (VEGF₁₆₅). Lentiviral-mediated expression of Exp-Htt caused cell death and aggregate formation in human neuroblastoma SH-SY5Y and rat primary striatal cultures. Lentiviral-mediated VEGF₁₆₅ expression was found to be neuroprotective in both of these models. Unilateral stereotaxic vector delivery of Exp-Htt vector in adult rat striatum led to progressive inclusion formation and striatal neuron loss at 10 weeks post-transduction. Coinjection of a lower dose VEGF₁₆₅ significantly attenuated DARPP-32(+) neuronal loss, enhanced NeuN staining and reduced Exp-Htt aggregation. A tenfold higher dose VEGF₁₆₅ led to overt neuronal toxicity marked by tissue damage, neovascularization, extensive astrogliosis, vascular leakage, chronic inflammation and distal neuronal loss. No overt behavioral phenotype was observed in these animals. Expression of VEGF₁₆₅ at this higher dose in the brain of wild-type rats led to early mortality with global neuronal loss. This report raises important safety concerns about unregulated VEGF₁₆₅ CNS applications.
Abstract IA16: Chemical inhibition of bromodomains
Authors: James E. Bradner
Journal: Cancer Research (2012)

Abstract In cancer, epigenetic proteins are among the most promising and intently pursued targets in drug discovery. This relates to the growing appreciation that cancer growth pathways are centrally influenced by proteins which modify chromatin. Already, inhibitors of DNA methyltransferases and histone deacetylases have demonstrated substantial clinical efficacy leading to regulatory approval for use in hematologic malignancies. These events have triggered intense competition to develop inhibitors of chromatin modifying enzymes, or so-called epigenetic “writers” and “erasers.” Perhaps owing to perceptions regarding the feasibility of targeting protein:protein interactions, small-molecule inhibitors of chromatin-binding modules or epigenetic “readers” have not been described. Recently, we reported the first potent, small-molecule inhibitor of human bromodomains, JQ1, which exhibits selectivity for the BET family of bromodomain-containing transcriptional co-activators. Of broad relevance to cancer, we will present research demonstrating that c-Myc expression is critically dependent on BRD4 function and localization to discrete upstream regulatory regions. Exposure of cancer cells to JQ1 prompts immediate downregulation of c-Myc expression leading to suppression of a transcriptional program associated with proliferation, survival and metabolic adaptation. In translational models of Myc-dependent hematologic malignancies, the efficacy of JQ1 treatment establishes a mechanistic rationale for the leveraged clinical development of drug-like JQ1 derivatives. Toward this objective, we have completed chemical optimization of novel, drug-like inhibitors of BET bromodomains as reagents capable of supporting human clinical investigation. This research has established the feasibility of inhibiting epigenetic reader proteins with efficient, cell-permeable, small molecules. In support of an open-innovation model of chemical biology, we have created a chemical probe allowing the broad study of chromatin biology, which has already been provided to more than 250 academic, governmental and industrial laboratories worldwide. Together, we have rapidly identified mechanism-based opportunities for clinical translation in cancer, inflammation, and metabolic diseases. Citation Format: James E. Bradner. Chemical inhibition of bromodomains [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr IA16.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Isaac Ginsburg, Zvi Bentwich, T. N. Harris
Journal: The Journal of Experimental Medicine (1965)

The relationship of the streptococcal hemolysin which is recognized on incubation of RBC with streptococcal cells (cell-bound hemolysin, CBH), to RNA hemolysin, a representative of oxygen-stable hemolysin (streptolysin S) has been studied. A number of similarities have been found in the conditions for optimal production of each of these hemolysins, a requirement for cysteine, Mg(++), and glucose; maximal production by streptococci in the stationary phase; similar curves of pH-dependence. In both systems, the production of hemolysin was inhibited by certain antibiotics, by ultraviolet irradiation, and by sonic disruption and was absent in the same streptococcal mutant strain. The hemolytic activity of both systems was inhibited by lecithin, trypan blue, and papain. Similarities were also found in relative susceptibilities to the two hemolytic systems of erythrocytes of a number of animal species. These data support a suggestion advanced in an earlier study that a streptococcal hemolytic moiety, which can be induced by, and carried on, a number of diverse agents to comprise the group of oxygen-stable hemolysins, serves, in its original attachment to a component of the streptococcal cell, to produce the hemolytic effect recognized as the cell-bound hemolysin.
Care of people with schizophrenia suffers as too much money is spent on secure units
Authors: Z. Kmietowicz
Journal: BMJ (2012)

Using PC12 cells that express transfected human growth hormone (hGH) as a secreted reporter protein, we have searched for Rab proteins that function in exocytosis. Among the Rab proteins tested, we found that besides the previously described Rab3 proteins, only members of the Rab11 family (Rab11a, 11b, and 25) impaired Ca<sup>2+</sup>-induced exocytosis. Rab11b, which is enriched in brain, had the strongest effect. Consistent with a role in exocytosis, Rab11 and Rab3 proteins were colocalized with other vesicle proteins on secretory vesicles in PC12 cells and on mature synaptic vesicles in brain. Rab11b mutants that fix Rab11b in the GTP- or GDP-bound state both effectively inhibited Ca<sup>2+</sup>-induced exocytosis but seemed to act by distinct mechanisms: whereas GDP-bound Rab11b greatly stimulated constitutive secretion of hGH and depleted hGH stores in secretory vesicles, GTP-bound Rab11b only had a moderate effect on constitutive secretion and no effect on vesicular hGH stores. These results suggest that, consistent with a GTP-dependent regulation of Rab function, GDP-bound Rab11b indirectly inhibits Ca<sup>2+</sup>-triggered exocytosis by causing the loss of hGH from the PC12 cells, whereas GTP-bound Rab11b directly impairs Ca<sup>2+</sup>-triggered exocytosis. In contrast to neuroendocrine PC12 cells in which GTP- and GDP-bound Rab11b inhibited Ca<sup>2+</sup>-induced, but not constitutive, exocytosis, in non-neuronal cells GTP- and GDP-bound Rab11b inhibited constitutive exocytosis and caused an accumulation of cellular hGH. Viewed together, our data suggest that, in addition to other functions, Rab11 has a specific role in neuronal and neuroendocrine but not in non-neuronal cells as a GTP-dependent switch between regulated and constitutive secretory pathways.
Diuretics and Sudden Cardiac Death
Authors: Arno W. Hoes
Journal: Annals of Internal Medicine (1996)

Letters15 August 1996Diuretics and Sudden Cardiac DeathArno W. Hoes, MD, PhD and Diederick E. Grobbee, MD, PhDArno W. Hoes, MD, PhDErasmus University Medical School, Rotterdam, the NetherlandsSearch for more papers by this author and Diederick E. Grobbee, MD, PhDErasmus University Medical School, Rotterdam, the NetherlandsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-4-199608150-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Aursnes and others question the use of a nonexperimental study design to evaluate drug effects. We are aware of the limitations of nonexperimental assessment of efficacy or side effects of medications, including the methods we applied to limit bias that resulted from lack of random allocation. We emphasize, however, that the case–control method has important advantages over randomized trials and may be the only way to study rare outcomes, such as sudden death, different antihypertensive medications, and the influence of dosage and duration of drug use [1]. Obviously, the published trials lacked the power to address these ...References1. Hoes AW, Grobbee DE, Lubsen J. Primary prevention in hypertension. Valid conclusions from observational studies. Circulation. 1991; 84(Suppl VI):78-83. Google Scholar2. Grobbee DE, Hoes AW. Non-potassium-sparing diuretics and risk of sudden cardiac death. J Hypertens. [In press]. Google Scholar3. Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ. 1992; 304:405-12. Google Scholar4. Siscovick DS, Raghunathan TE, Psaty BM, Koepsell TD, Wicklund KG, Lin X, et al. Diuretic therapy and the risk of primary cardiac arrest. N Engl J Med. 1994; 330:1852-7. Google Scholar Author, Article, and Disclosure InformationAffiliations: Erasmus University Medical School, Rotterdam, the Netherlands PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1996Volume 125, Issue 4Page: 348-349KeywordsCalciumCoronary heart diseaseDiureticsDrug usersDrugsElderlyMultivariate analysisRandomized trialsRelative riskSudden cardiac death ePublished: 15 August 2000 Issue Published: 15 August 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Biodegradable microspheres containing a colchicine analogue inhibit DNA synthesis in vascular smooth muscle cells.
Authors: K L March, S Mohanraj, P P Ho, R L Wilensky, D R Hathaway
Journal: Circulation (1994)

BACKGROUND Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local application of agents capable of modulating vascular responses, including smooth muscle cell proliferation, has been achieved, but difficulty in maintaining active levels locally has been a factor limiting the efficacy of such approaches. One strategy to maintain adequate levels is the local delivery of microspheres that release active agents over sustained time periods. METHODS AND RESULTS We incorporated a colchicine analogue into biodegradable microspheres composed of a lactic acid/glycolic acid copolymer and characterized their drug release behavior as well as their effects on bovine aortic smooth muscle cells (BASMCs) in culture. Drug release was evaluated by spectrophotometric assay. Drug effects on DNA synthesis were measured by thymidine incorporation after addition of serum to subconfluent cells synchronized by serum withdrawal as well as in asynchronous cell populations. Polymeric microspheres incorporating 10% to 17% drug by weight and averaging 6 microns in size were found to release the colchicine analog in buffered saline solutions over more than several weeks. Drug-loaded particles inhibited DNA synthesis completely, with EC50 values ranging from 0.001 to 0.005 g% (wt/wt). Morphological changes suggesting microtubule depolymerization were observed after drug particle treatment, with similar EC50 values. Microspheres allowed to contact the cell surface demonstrated effects similar to those seen with microspheres suspended in the nutrient medium by porous polycarbonate filters, at EC50 values approximately fivefold lower. In contrast, control microspheres composed only of polymer with no incorporated active drug demonstrated no observable toxicity to BASMCs and &lt; 40% inhibition of thymidine incorporation even in suspensions containing up to 0.5 g% particles. CONCLUSIONS Biodegradable microspheres were fashioned that release a colchicine analogue and inhibit DNA synthesis in smooth muscle cells. Drug-loaded polymeric particles are candidates for local delivery at sites of arterial injury to decrease restenosis.
The Freeman hospital: disillusionment sets in.
Authors: S Kingman
Journal: BMJ (1993)

tion of existing expenditure and top slicing of the funds.Although top slicing is an unpopular practice at present, the economies of scale achieved by concentrating the function into substantial groups would give better value for money.By making the function more visible it would give greater accountability than is evident at present.The only satisfactory altemative to top slicing at regional or subregional level would be the creation of a nationally managed service.Ideally we would prefer to retain the function at regional or subregional level. ConclusionWe need a system designed to cope with communicable diseases rather than with a "market," and this requires explicit legislation.Until this is done confusion will continue over responsibilities and powers leaving the public at risk.