tbuckley/cabot-search huggingface dataset:
Histone deacetylases and their inhibitors: molecular mechanisms and therapeutic implications in diabetes mellitus
Authors: Xiaojie Wang, Xinbing Wei, Qi Pang, Fan Yi
Journal: Acta Pharmaceutica Sinica B (2012)

Epigenetic mechanisms such as DNA methylation, histone modification and microRNA changes have been shown to be important for the regulation of cellular functions. Among them, histone deacetylases (HDACs) are enzymes that balance the acetylation activities of histone acetyltransferases in chromatin remodeling and play essential roles in gene transcription to regulate cell proliferation, migration and death. Recent studies indicate that HDACs are promising drug targets for a wide range of diseases including cancer, neurodegenerative and psychiatric disorders, cardiovascular dysfunction, autoimmunity and diabetes mellitus. This review highlights the role of HDACs in diabetes mellitus and outlines several important cellular and molecular mechanisms by which HDACs regulate glucose homeostasis and can be targeted for the treatment of diabetic microvascular complications. It is hoped that our understanding of the role of HDACs in diabetes mellitus will lead to the development of better diagnostic tools and the design of more potent and specific drugs targeting selective HDAC proteins for the treatment of the disease.
Rise in legal action hits Britain's GPs
Authors: M. Halle
Journal: BMJ (1997)

An unprecedented rise in negligence cases in Britain means GPs face massive increases in premiums to protect against possible litigation.

The Medical Protection Society has just announced that it is to raise its membership rates by 18.5%. Other defence societies say that they are still reviewing their fees, but they are expected to follow suit.

This year's increase follows a 16% increase last year and a 9.5% increase in 1995. GP principals now pay £1950 ($3000) a year. …
Outcomes of neonatal intensive care
Authors: D. Field
Journal: BMJ (1995)

packed cell volumes with a lower limit in black American women may be due to the high frequency of oa thalassaemia in people of African descent and to total compensation for lifelong slightly lower haemoglobin concentrations.Steer and colleagues consider that it "remains possible that genuine anaemia . . .has adverse consequences on fetal growth and long term outcome."Obstetricians and others working in developing countries know well the severe conse- quences of matemal anaemia on placental size, fetal growth, length of gestation, fetal nutrition, infant morbidity and mortality, and maternal morbidity and ultimately mortality.4It remains the duty of obstetricians to try to bring maternal haemoglobin concentration into the optimal range for pregnancy.Evidence suggests that the optimal range is 110-140 g/l rather than the lower values proposed by Steer and colleagues.
Segmental chromosomal aberrations and centrosome amplifications: pathogenetic mechanisms in Hodgkin and Reed–Sternberg cells of classical Hodgkin's lymphoma?
Authors: J I Martín-Subero, U Knippschild, L Harder, T F E Barth, J Riemke, S Grohmann, S Gesk, J Höppner, P Möller, R M Parwaresch, R Siebert
Journal: Leukemia (2003)
LARYNGEAL PAPILLOMATA REQUIRING A SPECIAL INSTRUMENT.
Authors: SETH SCOTT BISHOP
Journal: JAMA (1900)

The following case presents a unique feature, in that it was impossible to remove all of the laryngeal growths with any instruments that were obtainable, but that no difficulty was found operating with the special instrument shown in the illustration. The case was that of a harness manufacturer, 50 years old, who had been in his present business thirty-two years. In 1895 he had experienced some annoyance from hoarseness; in December, 1897 he had a "cold in his throat," resulting in a loss of voice for two days; in the following summer the hoarseness returned and grew worse until, in November, 1898, there was complete suppression of the voice. The aphonia remained until the last of the papillomata were removed in January of the present year. The patient had been under the care of Dr. J. L. Eger, of Delphos, Ohio, who recognized the character of the tumors and referred
Toxicity of Irinotecan in Patients with Colorectal Cancer
Authors: Eric Van Cutsem, Jean-Yves Douillard, Claus-Henning Köhne
Journal: New England Journal of Medicine (2001)

To the Editor: The early deaths reported by Sargent et al. (July 12 issue)1 among patients with colorectal cancer who were enrolled in trials N9741 and C89803 have aroused concern regarding the use of irinotecan in combination with fluorouracil and leucovorin. In these trials, a weekly bolus regimen of fluorouracil and leucovorin was combined with irinotecan. A different regimen of infusional fluorouracil and leucovorin, with or without irinotecan,2 is being used in three large, ongoing European trials. The Pan-European Trials in Adjuvant Colon Cancer 3 randomly assigned 1668 patients with stage III colon cancer to receive infusional fluorouracil and leucovorin . . .
Abstract 4897: Genome-wide analysis of CGIs in bladder cancer identifies novel epigenetic biomarkers for diagnosis and follow-up
Authors: Raju Kandimalla, Angela Van Tilborg, Lucie Kompier, Dominique J.P.M Stumpel, Ellen C. Zwarthoff
Journal: Cancer Research (2010)

Abstract Epigenetic modifications have been shown to contribute to the pathogenesis of various cancers including bladder cancer. Hypermethylation in cancer is often found in CGIs in the 5′ regions of genes. These DNA modifications may serve as useful biomarkers, both for diagnostic and prognostic purposes. Although the list of aberrantly methylated genes in cancer is expanding, only a few genes so far were investigated for their usefulness as tumor biomarkers for early diagnosis and risk assessment of bladder cancer. Thus, a large scale (genome wide) screening of aberrant methylation of CGIs is needed to identify bladder-specific epigenetic markers. In this study, we performed a genome wide screening for DNA methylation in different subtypes of bladder cancer using differential methylation hybridization (DMH) coupled with Agilent 244k human CpG island microarrays. We next validated the genome-wide data on a 384-plex custom Illumina Golden Gate Methylation Assay (GGMA), which is based on bisulfite conversion. We found and validated a large number of possible novel epigenetic biomarkers for early detection and prognosis of bladder cancer. We also observed that subgroups of bladder tumors cluster separately due to their different methylation patterns suggesting possible differences in pathogenesis. Our data clearly shown that the adjacent CpG loci within a CGI were co-methylated. In contrast, CGIs neighboring a methylated island were usually not methylated. The data showed no bias toward promoter methylation as the relative proportion of methylated islands in genes was similar to those encompassing promoter regions. We observed that 70% of the methylated genes are downregulated in bladder cancer. Moreover, gene body methylation also seems to be negatively correlated with gene expression. Interestingly, we found an overrepresentation of methylated genes in those genes that are the target of polycomb group protein complexes in embryonic stem cells. Further validation of selected CGIs on a separate group of bladder cancers on a custom Illumina Golden Gate Methylation assay (GGMA) allowed us to confirm 70 % of CGIs differentiating bladder cancers from normal cells, besides validating CGIs discriminating subgroups of bladder tumors. In conclusion, this is the first genome-wide study on bladder cancer which identified potential methylation target genes that provides putative biomarkers that may be correlated with disease course as well as insight into the pathogenesis of bladder cancer subtypes. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4897.
(22) Profuse hyperhidrosis localized to pretibial myxoedema
Authors: F.M. Tatnall, I. Sarkany
Journal: British Journal of Dermatology (1985)

Journal Article (22) Profuse hyperhidrosis localized to pretibial myxoedema Get access F.M. Tatnall, F.M. Tatnall Royal Free Hospital, London NW3 Search for other works by this author on: Oxford Academic Google Scholar I. Sarkany I. Sarkany Royal Free Hospital, London NW3 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 65–66, https://doi.org/10.1111/j.1365-2133.1985.tb13037.x Published: 01 July 1985
Abstract P6-04-11: Combination of PI3K-AKT-mTOR and MEK-ERK pathway inhibitors overcome acquired resistance to letrozole in ER+ breast cancer models
Authors: P De, Y Sun, LS Friedman, S Chen, N Dey, B Leyland-Jones
Journal: Cancer Research (2012)

Abstract Background: Approximately 60–70% of breast cancers (BC) express estrogen receptor (ERα) and/or progesterone receptor (PR), the most common malignancy in women in the US and Europe. Many though not all patients with ER+ BC respond to hormonal therapy (e.g. tamoxifen and aromatase-inhibitor) but a large number will eventually develop resistance to long term therapy. Purpose: Development of resistance to endocrine therapy is a clinical issue in ER+ BC. Studies with human cell lines have shown that upregulation of PI3K-AKT-mTOR and MEK-ERK pathways contributes to resistance to endocrine therapy (Miller TW et al JCO 2011; Sanchez CG et al Breast Cancer Res 2011). Using leterozole-resistant ER+ BC model, we investigated the effects of PI3K-AKT-mTOR pathway inhibitor alone and in combination with MEK1/2 inhibitor. Methodology: The anti-proliferative, anti-migratory, and intracellular signaling (pAKT, pS6RP, p4EBP1 and pERK) effects of GDC-0941 (Class I PI3K inhibitor) or GDC-0980 (dual PI3K/mTOR inhibitor) alone and in combination with GDC-0973 (MEK1/2 inhibitor) were evaluated in aromatase overexpressed (MCF-7aro), letrozole-resistant (MCF-7aro/LetR) and long-term-estrogen-deprived (LTEDaro) BC cell lines by MTT assays, integrin-mediated migration assay and Western blots. Results: 1) Both GDC-0980 and GDC-0941 exhibited excellent in vitro cell killing activity in MTT assay in all cell lines with IC50's 10–30 nM &amp; 0.2–1.5 µM respectively. PI3K pathway inhibitors were more potent when combined with GDC-0973; 2) Integrin-mediated migration was significantly higher in both MCF-7aro/LetR andLTEDaro cells than MCF-7 and MCF-7aro cells; 3) Both MCF-7aro/LetR and LTEDaro cells movement were significantly abrogated following the treatment of GDC-0980, and the combination of GDC-0980 plus GDC-0973 more effectively blocked integrin-mediated migration; 4) Inhibition of phosphorylation of AKT (S473/T308), S6RP and 4EBP1 (T37/46) was observed following PI3K pathway inhibitors; 5) pERK was upregulated following the treatment of GDC-0941 (PI3K inhibitor); 6) Basal level of pERK was significantly high in MCF7/LetR and MCF7/LTED cells, and GDC-0980 failed to change the level of pERK in those cell lines; and 7) Combination of PI3K pathway inhibitor plus MEK1/2 inhibitor significantly blocked activation of both pathways. Conclusion: Our in vitro data suggest that therapeutic targeting of the PI3K-AKT-mTOR and the MEK-ERK signaling pathways should be effective in abrogating aromatase-inhibitor-resistance in ER+ BC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-11.
"Primum non nocere" and the principle of non-maleficence.
Authors: R Gillon
Journal: BMJ (1985)

The physician's duty of "primum non nocere," or avoiding harm to the patient, has often been given moral priority over other duties in discussions of medical ethics. In this article in a British Medical Journal series written for nonphilosophers on the philosophical foundations of medical ethics, Gillon takes issue with the prominence given the obligation of nonmaleficence over that of beneficence. He argues that risking harm is often necessary to obtain therapeutic benefit, and that always giving nonmaleficence priority over beneficence in clinical decision making results in "therapeutic nihilism." These two important principles should counterbalance one another in medical care, with due respect for patient autonomy.
A Progestogen for Treatment of Advanced Endometrial Cancer
Authors: B. J. Kennedy
Journal: JAMA (1963)

An esterized derivative progesterone was given to 27 patients who had advanced endometrial carcinoma. Objective improvement occurred in eight patients. A comparison of the patients in the responding group and those in the nonresponding (refractory) group showed an apparent biological difference in the cancer with respect to the natural pattern of growth and subsequent response to hormonal therapy. The disease in the responders was of long duration and slow growth, whereas that of the nonresponders appeared to be of short duration and rapid growth.
Modeling movement variability in space and time
Authors: Dagmar Sternad, Karl M. Newell
Journal: Behavioral and Brain Sciences (1997)

Plamondon &amp; Alimi propose a universal account of trajectory formation and speed/accuracy trade-off in rapid movements but fail, because: (1) the kinematic model ignores the more fundamental dynamics of movement generation, and (2) it does not capture the essential space-time constraints of movement accuracy. Hence, the modeling lacks a biologically and behaviorally principled foundation and is driven by pragmatic function fitting.
Abstract 1718: ErbB-2 acts as coactivator of Stat3 in heregulin-induced breast cancer growth
Authors: Wendy Béguelin, María C. Díaz Flaqué, Cecilia J. Proietti, Martín A. Rivas, Mercedes Tkach, Eduardo H. Charreau, Roxana Schillaci, Patricia V. Elizalde
Journal: Cancer Research (2010)

Abstract We have previously demonstrated that heregulin (HRG), a ligand for ErbB receptors, activates signal transducer and activator of transcription 3 (Stat3) in primary cultures of ErbB-2 overexpressing C4HD cells, from a murine progestin-dependent mammary tumor. ErbB-2 activity is an absolute requirement in the mechanisms of HRG stimulation of Stat3 activity. Recent findings have demonstrated ErbB-2 nuclear migration and its function as a transcription factor. In this work, we studied whether HRG induces ErbB-2 nuclear migration and its interaction with Stat3 in breast cancer cells. We demonstrated that HRG induces ErbB-2 nuclear migration and colocalization with Stat3 in C4HD and human T47D breast cancer cells. Cyclin D1 is a cancer-related gene that contains Stat3 binding sites (GAS sites) but lacks ErbB-2 response elements (HAS sites). By chromatin immunoprecipitation assays (ChIP) and sequential ChIP, we demonstrated that HRG induces in vivo binding of Stat3 and ErbB-2 to the GAS sites of the cyclin D1 promoter. This finding prompted us to evaluate the ability of HRG to regulate cyclin D1 expression. By inhibiting ErbB-2 and Stat3 activation or silencing their expression, we demonstrated that ErbB-2 and Stat3 participate in the mechanism of HRG-induced cyclin D1 protein expression. Next, we explored whether HRG induces cyclin D1 promoter directly via Stat3 binding to its response elements. C4HD and T47D cells transiently transfected with a cyclin D1 promoter luciferase construct showed an enhanced transcriptional activity with HRG treatment. Overexpression of increasing amounts of ErbB-2 wt resulted in a dose-dependent ErbB-2 capacity to enhance Stat3 transcriptional activity induced by HRG. On the other hand, transfection with increasing amounts of an ErbB-2 mutant that is defective in nuclear entry but retains its cell-surface location and functions (ErbB-2ΔNLS) resulted in abrogation of HRG-induced Stat3 activation of cyclin D1 promoter. Finally, we addressed the effect of targeting ErbB-2 in in vivo HRG-dependent growth of C4HD breast tumors. Transfection of C4HD cells with the ErbB-2ΔNLS expression vector significantly inhibited these cells’ ability to form tumors in syngeneic mice. Taken together, these results suggest a new role of ErbB-2 as a coactivator in the mechanism of HRG-induced transcriptional activation of Stat3. We also found nuclear ErbB-2 to be a requisite for HRG stimulation of in vitro and in vivo breast cancer growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1718.
Access to computed tomography in British accident and emergency departments
Authors: P. Dorman, P. Sandercock
Journal: BMJ (1997)

Editor–Julien Bogousslavsky highlights the need for further trials of thrombolysis in patients presenting soon after the onset of acute ischaemic stroke.1 However, before randomisation the patient must have computed tomography to exclude intracranial haemorrhage as the cause of the stroke. Computed tomography has not been widely available in the United Kingdom.2 Accident and emergency departments are well placed to perform the initial triage and assessment of patients presenting with acute stroke, but a selective audit suggested that access to computed tomography in these departments was patchy.3 We …
European Association of Urology (@Uroweb) Recommendations on the Appropriate Use of Social Media
Authors: Morgan Rouprêt, Todd M. Morgan, Peter J. Bostrom, Matthew R. Cooperberg, Alexander Kutikov, Kate D. Linton, Joan Palou, Luis Martínez-Piñeiro, Henk van der Poel, Carl Wijburg, Andrew Winterbottom, Henry H. Woo, Manfred P. Wirth, James W.F. Catto
Journal: European Urology (2014)
LEFT VENTRICULAR SYSTOLIC TORSION BY TWO DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY PREDICTS LEFT VENTRICULAR DYSFUNCTION AFTER BALLOON MITRAL VALVULOPLASTY
Authors: Osama Rifaie, Mohamed Abdel-Rahman, Sameh Samir, Khalid Z. Malek, Alaa Mabrouk Salem Omar
Journal: Journal of the American College of Cardiology (2014)
Theophylline Blood Levels in Circulatory Shock
Authors: Parmjeet S. Randhawa
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 June 1989Theophylline Blood Levels in Circulatory ShockParmjeet S. Randhawa, MDParmjeet S. Randhawa, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-12-1035_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:A person with longstanding bronchial asthma who attempted suicide by theophylline over-dosage recently presented to the emergency department. The patient, a 46-year-old woman, swallowed an unspecified number of Theo-Dur tablets (Key Pharmaceuticals, Whippany, New Jersey) after a family fight. She had recurrent seizures, upper gastrointestinal bleeding, and peripheral vascular collapse. Laboratory studies showed metabolic acidosis (pH, 7.22; plasma bicarbonate, 13 mmol/L; pCO2, 28 mm Hg) and an initial plasma lactate of 12.4 mmol/L. A toxicology screen showed caffeine and theophylline in the urine. The laboratory received three paired, concurrently drawn arterial and venous samples for arterial blood... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Parmjeet S. Randhawa, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Significance of Marked “Universal” Dependence of Drug Concentration on Blood Sampling Site in Pharmacokinetics and Pharmacodynamics 15 June 1989Volume 110, Issue 12Page: 1035-1035KeywordsBloodBlood plasmaHemorrhageLactatesPartial pressure of carbon dioxideResearch laboratoriesShockSuicideToxicologyUrine ePublished: 1 December 2008 Issue Published: 15 June 1989 PDF downloadLoading ...
TREATMENT OF MENORRHALGIA OF PELVIC ORIGIN BY ELECTRICITY.
Authors: G. BETTON MASSEY
Journal: JAMA (1901)

ritation of the nerves, but afterward menstruation oc- curs without pain."I have heard gynecologists declare that they never make use of tents, that such methods are antiquated; but in this class of cases the laminaria tent unfolds a power that can be equaled by no other known plan of treatment.In cases complicated by chronic en- dometritis and in those in which a myoma is situated in the uterine wall I make use by preference of the dilator of Pryor, which possesses many advantages over the ordinary dilators, for the purpose of thorough dila- tation.The uterus is then curetted with the Sims sharp curette and tightly packed with strips of iodoform gauze.In this way the dysmenorrhea is cured with the endometritis.For the membranous form I use the same method of treatment with decided benefit.Fritsch recommends the prolonged use of uterine irrigations of lysol, 1 to 100, after thorough dilatation, and this method is well worthy of adoption.Finally, it should be mentioned that oophorectomy has been recommended as a last re- sort in cases of persistent and obstinate dysmenorrhea.Against this practice I must make my decided protest; in the first place we have no certain guarantee that the patient's condition will be better after the operation than before, and secondly with the less radical means at our command I am absolutely sure that we can attain the desired goal by persistence, patience, and wise dis- crimination.
VITAMIN THERAPY IN PULMONARY TUBERCULOSIS*
Authors: PAUL D. CRIMM
Journal: Annals of Internal Medicine (1933)

Article1 July 1933VITAMIN THERAPY IN PULMONARY TUBERCULOSISIV. COMPARISON OF THE H-ION CONCENTRATION OF THE BLOOD IN TUBERCULOSIS WITH NORMALS ON THE SAME DIETARYPAUL D. CRIMM, M.D., HERMAN L. WATSON, B.A.PAUL D. CRIMM, M.D.Search for more papers by this author, HERMAN L. WATSON, B.A.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-7-1-109 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn studying the effect of vitamin D upon the calcium equilibrium of the human body infected with tubercle bacilli, normal chemical relationships are prerequisite. A normal blood calcium and phosphorus is interwoven in the physico-chemical complex of a normal acid-base balance. One of the factors representing this balance is the H-ion concentration of the blood. That H-ion concentrations within normal limits exist during the clinical course of many diseases is obvious, otherwise they would present to us an accompanying state of acidosis or alkalosis. Although bio-chemical tests other than pH give us a wider range of analysis and interpretation, yet...Bibliography1. FOSBINDERSCHOONOVER RJJ: An improved method of measuring glass electrode potentials, Jr. Biol. Chem., 1930, lxxxviii, 605. CrossrefGoogle Scholar2. WOODWARDSCHOONOVERFRYTORRANCEMCDONALD GEJWEGEGE: The hydrogen-ion concentration of the blood in untreated cancer cases and its relation prognosis, Jr. Lab. and Clin. Med., 1931, xvi, 704. Google Scholar3. HASTINGSSENDROY ABJ: Studies of acidosis. XX. The colorimetric determination of blood pH at body temperature without buffer standards, Jr. Biol. Chem., 1924, lxi. Google Scholar4. CULLEN GE: Studies of acidosis: colorimetric determination of hydrogen-ion concentration of blood plasma, Jr. Biol. Chem., 1922, lii, 501. CrossrefGoogle Scholar5. KASTMYERSSCHMITZ LVCHW: Clinical conditions of alkalosis, Jr. Am. Med. Assoc., 1924, lxxxii, 1858. CrossrefGoogle Scholar6. PETERSVAN SLYKE JPDD: Quantitative clinical chemistry, Volume I, 1932, Williams and Wilkins Company, Baltimore. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Evansville, Indiana*Received for publication November 11, 1932. From Boehne Tuberculosis Hospital, Evansville, Indiana. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1933Volume 7, Issue 1Page: 109-113KeywordsAttentionBloodCalciumPhosphorusVitamin D Issue Published: 1 July 1933 PDF downloadLoading ...