tbuckley/cabot-search huggingface dataset:
Cellular pharmacology of potassium channel openers in vascular smooth muscle
Authors: U. Quast, J.-M. Guillon, I. Cavero
Journal: Cardiovascular Research (1994)

Journal Article Cellular pharmacology of potassium channel openers in vascular smooth muscle Get access Ulrich Quast, Ulrich Quast Pharmakologisches Institut, Eberhard-Karls-Universität, D-72074 Tübingen 1, Germany: U Quast; Rhône-Poulenc Rorer, Centre de Recherche Vitry-Alfortville, 13 quai Jules-Guesde, F-94403 Vitry sur Seine, France: J-M Guillon, I Cavero. Correspondence to Dr Cavero. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean-Michel Guillon, Jean-Michel Guillon Pharmakologisches Institut, Eberhard-Karls-Universität, D-72074 Tübingen 1, Germany: U Quast; Rhône-Poulenc Rorer, Centre de Recherche Vitry-Alfortville, 13 quai Jules-Guesde, F-94403 Vitry sur Seine, France: J-M Guillon, I Cavero. Search for other works by this author on: Oxford Academic PubMed Google Scholar Icilio Cavero Icilio Cavero Pharmakologisches Institut, Eberhard-Karls-Universität, D-72074 Tübingen 1, Germany: U Quast; Rhône-Poulenc Rorer, Centre de Recherche Vitry-Alfortville, 13 quai Jules-Guesde, F-94403 Vitry sur Seine, France: J-M Guillon, I Cavero. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 6, June 1994, Pages 805–810, https://doi.org/10.1093/cvr/28.6.805 Published: 01 June 1994
Targeting the BAF57 SWI/SNF Subunit in Prostate Cancer: A Novel Platform to Control Androgen Receptor Activity
Authors: Kevin A. Link, Sucharitha Balasubramaniam, Ankur Sharma, Clay E.S. Comstock, Sonia Godoy-Tundidor, Nathan Powers, Khanh H. Cao, Annemie Haelens, Frank Claessens, Monica P. Revelo, Karen E. Knudsen
Journal: Cancer Research (2008)

Abstract The androgen receptor (AR) is critical for disseminated prostate cancer proliferation and survival. AR activity is targeted either through prevention of ligand synthesis or through the use of antagonists that bind the COOH-terminal ligand-binding domain. Although initially effective, treatment fails due to restored AR activity in the presence of therapeutics. Thus, new means must be developed to target AR activity. The SWI/SNF chromatin remodeling complex is critical for AR transcriptional activity, and the BAF57 SWI/SNF subunit facilitates direct interaction with the receptor. Although selected SWI/SNF subunit expression is reduced in prostate cancer, we show that BAF57 is retained in human disease and is elevated in a subset of tumors. Functional analyses showed that BAF57 contributes uniquely to androgen-mediated stimulation of transcription without compromising the effectiveness of AR antagonists. Subsequent studies revealed that BAF57 is recruited to the AR DNA-binding domain/hinge region, which occurs concomitant with receptor activation. These data provided the basis for a novel inhibitor derived from BAF57 [BAF57 inhibitory peptide (BIPep)], which blocked AR residence on chromatin and resultant AR-dependent gene activation. Importantly, BIPep expression was sufficient to inhibit androgen-dependent prostate cancer cell proliferation in AR-positive cells. In summary, these data identify blockade of AR-BAF57 interaction as a novel means to target agonist-induced AR function in prostate cancer, and provide the first evidence that abrogation of SWI/SNF function can be developed as a point of therapeutic intervention in prostate cancer. [Cancer Res 2008;68(12):4551–8]
Interactions between a Pore-Blocking Peptide and the Voltage Sensor of the Sodium Channel: An Electrostatic Approach to Channel Geometry
Authors: Robert J. French, Elzbieta Prusak-Sochaczewski, Gerald W. Zamponi, Stefan Becker, A.Shavantha Kularatna, Richard Horn
Journal: Neuron (1996)

Few experimental data illuminate the relationship between the molecular structures that mediate ion conduction through voltage-dependent ion channels and the structures responsible for sensing transmembrane voltage and controlling gating. To fill this void, we have used a strongly cationic, mutated μ-conotoxin peptide, which only partially blocks current through voltage-dependent sodium channels, to study voltage-dependent activation gating in both bound and unbound channels. When the peptide binds to the ion-conducting pore, it inhibits channel opening, necessitating stronger depolarization for channel activation. We show that this activation shift could result entirely from electrostatic inhibition of the movement of the voltage-sensing S4 charges and estimate the approximate physical distance through which the S4 charges move.
Low Heart Rate Variability in a 2-Minute Rhythm Strip Predicts Risk of Coronary Heart Disease and Mortality From Several Causes
Authors: Jacqueline M. Dekker, Richard S. Crow, Aaron R. Folsom, Peter J. Hannan, Duanping Liao, Cees A. Swenne, Evert G. Schouten
Journal: Circulation (2000)

Background —Low heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. Methods and Results —We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. Conclusions —Low HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.
Implementing the change in National Institute for Health and Clinical Excellence guidance on airflow obstruction grading in chronic obstructive pulmonary disease
Authors: R. C. M. Jones, K. Gruffydd-Jones, D. B. Price
Journal: Thorax (2010)

The updated National Institute for Health and Clinical Excellence (NICE) chronic obstructive pulmonary disease (COPD) guidelines1 and the draft national strategy for COPD2 have recommended a change in the classification of airflow obstruction severity to align them with international classifications. NICE's 2004 guidelines recognised that disease severity is not the same as the severity of airflow obstruction and has recommended using other measures such as the Medical Research Council (MRC) dyspnoea scale, exacerbation frequency and multicomponent indices.3 However, UK …
Flow-Induced Arterial Remodeling Relates to Endothelial Function in the Human Forearm
Authors: Joseph A. Vita, Monika Holbrook, Joseph Palmisano, Sherene M. Shenouda, William B. Chung, Naomi M. Hamburg, Benjamin R. Eskenazi, Lija Joseph, Oz M. Shapira
Journal: Circulation (2008)

Chronic changes in blood flow stimulate arterial remodeling, which contributes to the maintenance of vascular homeostasis. Experimental studies suggest that remodeling represents a response to local changes in endothelial shear stress and is nitric oxide-dependent.To investigate determinants of outward arterial remodeling in humans, we measured ulnar artery flow, diameter, and flow-mediated dilation before and after removal of the adjacent radial artery in 53 patients who were undergoing coronary bypass surgery (age 60+/-11 years; 13% female). Removal of the radial artery increased ulnar artery blood flow by 35% (P=0.009) and increased ulnar artery diameter by 9% (P<0.001) 4 to 8 weeks after surgery. At 1 week, ulnar artery shear stress was increased by 58% (P<0.001), but it was no longer different from baseline at longer-term follow-up. The contralateral ulnar artery was unaffected, which suggests that these findings were not attributable to the systemic effects of medications or the postoperative state. Extent of outward remodeling correlated with the increase in blood flow (r=0.50, P=0.001) and with flow-mediated dilation at baseline (r=0.50, P=0.001). Remodeling correlated inversely with baseline endothelial expression of P-selectin in the radial artery (r=-0.76, P=0.004, n=14).A sustained increase in blood flow in the ulnar artery induced outward arterial remodeling despite the presence of risk factors and coronary artery disease. The remodeling response was related to endothelial phenotype, as reflected by flow-mediated dilation and expression of P-selectin. These findings provide evidence that the endothelium plays an important role in the regulation of vascular structure in humans.
Advance care planning in primary care
Authors: Scott A Murray, Aziz Sheikh, Keri Thomas
Journal: BMJ (2006)

O f the various trajectories of physical decline, organ failure is often the most difficult to plan for in advance because of its unpredictability.1 The qualitative study by Davison and Simpson in this week's BMJ challenges the notion that early discussion of planning for the end of life will destroy hope rather than create it. Rather, it allowed patients dying of end stage renal failure and their carers to reflect on and reorient their aspirations.2 A wealth of evidence indicates that many elderly patients want to discuss these issues with their healthcare professionals, but this rarely happens even when (as in the United Kingdom) continuity of care with a trusted general practitioner is available.34 The main barrier is probably doctors' reluctance to raise the issue of planning for death because of the largely unfounded fear of destroying hope.

Advance care planning is practised in Australia, Canada, and the United States.5–7 It is also proposed …
EBP50, a β-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma
Authors: Tatsuhiro Shibata, Makoto Chuma, Akiko Kokubu, Michiie Sakamoto, Setsuo Hirohashi
Journal: Hepatology (2003)

Wnt signaling mediated by β–catenin plays crucial roles in the development of hepatocellular carcinoma and other cancers such as colorectal cancer. β–Catenin associates with T–cell factor (TCF) transcription factors and functions as a transcriptional activator in the nucleus. By protein interaction screening, we identified EBP50, a cytoplasmic protein with 2 PDZ domains, as a β–catenin–associating molecule. EBP50 interacted with β–catenin through its carboxyl–PDZ domain in vitro and in vivo . Northern blot and RT–PCR analysis revealed an increase of EBP50 messenger RNA (mRNA) in hepatocellular carcinoma (HCC) cell lines and surgical specimens of human HCC. Over–expression of EBP50 protein with focal nuclear localization was detected in human HCC. In human HCC and colorectal cancer cell lines, EBP50 enhanced β–catenin/TCF–dependent transcription in a dose–dependent manner. In an HCC cell line, over–expression of the carboxyl PDZ domain resulted in a decrease of endogenous β–catenin/TCF transactivation. EBP50 promoted β–catenin–mediated transactivation only in cells in which β–catenin was already stabilized, suggesting that EBP50 may work with stabilized β–catenin for transcriptional regulation. In conclusion, the EBP50/β–catenin complex promotes Wnt signaling, and over–expression of EBP50 may work cooperatively with β–catenin in the development of liver cancer.
Dropping liver fat droplets†
Authors: Sander Kersten, Michael Müller, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2009)

The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicle (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.
Skeletal Muscle Glycogenosis in Identical Twins
Authors: T. Lehoczky, M. Halasy, G. Simon, G. Harmos
Journal: BMJ (1964)

This drug is marketed by May and Baker under the name of Flagyl. Chemistry and PharmacologyMetronidazole (l-f3-hydroxyethyl-2-methyl-5-nitroimidazole) was discovered in France in 1959.It is a crystalline non- hygroscopic powder with a solubility in water of approximately 1 %.Its structural formula isCosar and Julou,1 who were first to demonstrate the anti-trichomonal activity of the drug in vitro, soon confirmed its effect in animal experiments and also demonstrated that its toxic effects were minimal even in high concentration.In the human subject, after a single oral dose of 500 mg., a high serum level is rapidly obtained and persists for at least three hours.The drug also reaches high concentration in the urine, saliva, breast milk, and seminal fluid.About 50% of the ingested metronidazole is excreted in the urine, which remains trichomonacidal in dilutions of up to 1 in 400 for four hours after a single oral dose.
THE pH OF THE SKIN SURFACE OF INFANTS AGED ONE TO SEVEN DAYS.
Authors: J. MARTIN BEARE, E. A. CHEESEMAN, A. A. H. GAILEY, D. W. NEILL, J. D. MERRETT
Journal: British Journal of Dermatology (1959)

Journal Article THE pH OF THE SKIN SURFACE OF INFANTS AGED ONE TO SEVEN DAYS. Get access J. MARTIN BEARE, M.D. M.R.C.P., J. MARTIN BEARE, M.D. M.R.C.P. Royal Victoria Hospital and Queen's University, Belfast, Northern Ireland Search for other works by this author on: Oxford Academic Google Scholar E. A. CHEESEMAN, Ph.D., E. A. CHEESEMAN, Ph.D. Royal Victoria Hospital and Queen's University, Belfast, Northern Ireland Search for other works by this author on: Oxford Academic Google Scholar A. A. H. GAILEY, M.D. M.R.C.P., A. A. H. GAILEY, M.D. M.R.C.P. Royal Victoria Hospital and Queen's University, Belfast, Northern Ireland Search for other works by this author on: Oxford Academic Google Scholar D. W. NEILL, M.Sc. F.R.I.C., D. W. NEILL, M.Sc. F.R.I.C. Royal Victoria Hospital and Queen's University, Belfast, Northern Ireland Search for other works by this author on: Oxford Academic Google Scholar J. D. MERRETT, B.Sc. J. D. MERRETT, B.Sc. Royal Victoria Hospital and Queen's University, Belfast, Northern Ireland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 71, Issue 5, 1 May 1959, Pages 165–180, https://doi.org/10.1111/j.1365-2133.1959.tb13402.x Published: 01 May 1959
How to make a silk purse from a sow's ear--a comprehensive review of strategies to optimise data for corrupt managers and incompetent clinicians
Authors: D. Pitches
Journal: BMJ (2003)

The introduction of performance league tables for UK surgeons and hospitals has forced them to learn how to present data in the best possible light. Though there is anurgent need for guidance, official guidelines on how to optimise performance data are lacking 

Surgeons' and hospitals' positions in league tables can make or break their reputations. They therefore need to learn how to present data in the best possible light. Although some may protest about “sexing up” poor performance data, “creative accounting” adds a positive spin. In contrast to the plethora of clinical guidelines, there is still no official advice on how to optimise performance data, and wide variations in practice persist. This review provides a timely, evidence based response to the urgent need for guidance.

We searched Medline for empirical examples of creative accounting (using the search terms “gaming”, “mortality“, “league

table$”, “upcoding”, “fraud$”, “quality“, and “quality indicators, health care/”) and identified 284 papers, of which we reviewed the most relevant for suitable examples. We also searched the web with Google using “examples hospital healthcare fiddling figures.” We included anecdotes from personal experience.

In addition to fraudulent or biased research, which has been thoroughly reviewed elsewhere,1 we identified three broad categories of creative accounting:

### Manipulation of non-clinical performance targets

This is particularly important for managers when meeting so called P-45 targets—an expression used by Tony Wright MP while examining Sir Nigel Crisp for the House of Commons Select Committee on Public Administration2 and meaning targets for which failure to meet can result in redundancy (in Britain the P-45 is the tax form people receive when leaving employment). A House of Commons investigation in 2002 uncovered strategies to bring waiting times and numbers of patients waiting for treatment within national targets.3 …
Diffuse large-cell B-cell lymphoma in a pituitary adenoma: An unusual cause of pituitary apoplexy
Authors: W.Y. Au, Y.L. Kwong, T.W.H. Shek, G. Leung, C. Ooi
Journal: American Journal of Hematology (2000)

With the C282Y Mutation in the HFE GeneTo the Editor: The association between hereditary hemochromatosis and thalassemia syndrome might lead to a severe iron overload [1,2], but the results are still controversial.By PCR and restriction enzyme digestion [3], we analyzed the C282Y and H63D mutations in the HFE gene in one family whose propositus carried the ␤-thalassemia trait.The patient was a female, 38 years old, presenting weakness and arthralgia.She had 4 children and received transfusion (1 unit of red cell) during her last gestation.She did not present diabetes or cardiac disease and her hepatic enzymes were normal.Her mother and 2 sons also carried the ␤-thalassemia trait.
Medical Journals in the Continuing Education of the Student and Physician
Authors: Joseph Garland
Journal: New England Journal of Medicine (1964)

EDUCATION, as many educators will admit, is an intriguing and usually a baffling adventure. The faults in human behavior that are attributed to its lack are frequently not corrected by its application, leading one to suspect that some more basic form of influence than mere pedagogy is necessary.Education, according to Webster, is, first, "the act or process of educating"; the "discipline of mind or character through study or instruction." Its second definition is that of a "science dealing with the principles and practice of teaching and learning." Knowing little about the vagaries and complexities of formal education, which continue . . .
Cardiac-Specific Overexpression of Caveolin-3 Attenuates Cardiac Hypertrophy and Increases Natriuretic Peptide Expression and Signaling
Authors: Yousuke T. Horikawa, Mathivadhani Panneerselvam, Yoshitaka Kawaraguchi, Yasuo M. Tsutsumi, Sameh S. Ali, Ravi C. Balijepalli, Fiona Murray, Brian P. Head, Ingrid R. Niesman, Timo Rieg, Volker Vallon, Paul A. Insel, Hemal H. Patel, David M. Roth
Journal: Journal of the American College of Cardiology (2011)
Rheumatoid arthritis in a rural South African Negro population.
Authors: P Beighton, L Solomon, H A Valkenburg
Journal: Annals of the Rheumatic Diseases (1975)

(1) An epidemiological study of an urban South African Negro community has been carried out in Johannesburg. Altogether 964 respondents were examined and in each case radiographs of the hands and feet were obtained. Rheumatoid factor tests were carried out on 404 serum samples. (2) Rheumatoid arthritis (RA) was graded 'definite' or 'probable' on the basis of a modification of the Rome criteria (Kellgren, Jeffrey, and Ball, 1963a). (3) In marked contrast to the findings in rural Africans the prevalence of RA in this community was similar to that in Caucasian populations. Five respondents (all elderly women) had 'definite' RA, giving a prevalence of 1.4% of the females and 0.9% of the total population sample over 15 years old. The prevalence of 'definite' and 'probable' RA combined was 2.6% for males, 3.7% for females, and 3.3% for all individuals over 15 years old. Prevalence increased with age, reaching a maximum in the 65- to 74-year cohort. (4) The form and severity of the clinical and radiological features were unlike the mild manifestations seen in rural African peoples and closely resembled the usual clinical picture of rheumatoid disease. (5) The latex fixation test was positive in 12.1% of the sera tested, which is similar to the high titres found in other African populations. No obvious cause for this phenomenon was found. (6) Several reasons for the marked difference in prevalence of RA between this urban African population and a rural African population are considered. Marked intraracial differences such as this point to the importance of sociological and environmental factors in the pathogenesis of rheumatoid arthritis.
Methotrexate Therapy of Wegener's Granulomatosis
Authors: ROBERT L. CAPIZZI
Journal: Annals of Internal Medicine (1971)

Two patients with advanced Wegener's granulomatosis, one with nose, sinus, and skin involvement and the other with pulmonary, renal, and skin involvement, experienced marked improvement with intermittent methotrexate therapy. Initial treatment consisted of weekly intravenous injections of 50 mg. This was subsequently decreased to 15 and 25 mg as a single, weekly oral dose. Responses consisted of marked and rapid subjective relief of symptoms, healing of skin lesions, total clearing of pulmonary infiltrates, and lack of progression of nasal, sinus, and renal lesions. Remission of the disease, for more than 30 and 26 months, respectively, has occurred without evidence of oral or hematologic toxicity of methotrexate.
Shape and Volume Changes During "Isovolumetric Relaxation" in Normal and Asynergic Ventricles
Authors: MICHAEL S. RUTTLEY, DOUGLASS F. ADAMS, PETER F. COHN, HERBERT L. ABRAMS
Journal: Circulation (1974)

Clinically suspected coronary artery disease was assessed in 52 patients by 16-mm biplane left ventriculography. Outward movement of the left ventricular wall was observed prior to mitral valve opening in normal patients and those with coronary artery disease. In the normal ventriculogram, outward movement was usually visible in the anterior wall and the apex. In the asynergic ventricle, the outward movement almost invariably occurred at the region of optimal contraction. Outward movement of the ventricular wall during protodiastole and isovolumetric relaxation was accompanied by a significant volume increase over the end-systolic volume. The volume increase was greater in the abnormal than in the normally contracting ventricle. The altered ventricular volume was probably associated with the return to the ventricle of blood contained between the patent aortic leaflets at the end of ventricular ejection. This event occurs during aortic valve closure when ventricular pressure is falling more rapidly than aortic pressure. It accounts for the alteration in volume between end ejection and pre-mitral valve opening. The stroke volume, which is generally calculated from end-systolic and end-diastolic volumes, may therefore be inaccurate by at least 10% because ventricular volume immediately before mitral valve opening is not utilized in the calculation. Some of the discrepancies between angiocardiographic stroke volume and ejection fraction measurements and those obtained by other methods may be explained by failure to use preinflow volume (PIV) in the calculations.