tbuckley/cabot-search huggingface dataset:
New Insights into Impaired Muscle Glycogen Synthesis
Authors: Leif Groop, Marju Orho-Melander
Journal: PLoS Medicine (2008)

Glucose is the most rapidly accessible substrate in the body. Its storage as glycogen in muscle and liver is of central importance as a first source of energy for muscle contractions and prevention against hypoglycemia. Glycogen synthesis and breakdown are regulated by insulin and catecholamines as well as by glucose-6-phosphate and the amount of glycogen. There are two isoforms of glycogen synthase (GS), one in muscle and one in liver, encoded by different genes (GYS1 and GYS2, respectively) [1]. Insulin stimulates glycogen synthesis by activating protein phosphatase 1 (PP1), which activates GS, inactivates glycogen phosphatase, and inactivates glycogen synthase kinase 3, an inhibitor of GS. PP1 has a glycogen-targeting subunit (PPP1R3A), which facilitates localization of PP1 to glycogen.
Two different metabolic responses to ischaemia: inherent variability or artefact?
Authors: S. C DENNIS, M. J SHATTOCK, D. J HEARSE, M. R BALL, M. SOCHOR, P. McLEAN
Journal: Cardiovascular Research (1983)

Journal Article Two different metabolic responses to ischaemia: inherent variability or artefact? Get access STEVEN C DENNIS, STEVEN C DENNIS § **From the Likoff Cardiovascular Institute, Hahnemann University, 230 North Broad Street, Philadelphia, PA 19102, USA §Address for reprint requests: Dr Steven C Dennis, Likoff Cardiovascular Institute Hahnemann University, 230 North Broad Street, Philadelphia, PA 19102. Search for other works by this author on: Oxford Academic PubMed Google Scholar MICHAEL J SHATTOCK, MICHAEL J SHATTOCK †The Rayne Institute, St Thomas' Hospital, London, SE1 UK Search for other works by this author on: Oxford Academic PubMed Google Scholar DAVID J HEARSE, DAVID J HEARSE †The Rayne Institute, St Thomas' Hospital, London, SE1 UK Search for other works by this author on: Oxford Academic PubMed Google Scholar MICHAEL R BALL, MICHAEL R BALL ‡Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, London, W1P, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar MILENA SOCHOR, MILENA SOCHOR ‡Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, London, W1P, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar PATRICIA McLEAN PATRICIA McLEAN ‡Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, London, W1P, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 17, Issue 8, August 1983, Pages 489–498, https://doi.org/10.1093/cvr/17.8.489 Published: 01 August 1983
Guidance has high priority in interventional procedures: Author's reply
Authors: Bruce Campbell
Journal: BMJ (2004)

EDITOR—I thank Anton Jacob for his comments on our editorial. The poor and scanty evidence on which many new interventions are based is self evident. We tried to explore some of the possible reasons. We made no claim that there were studies or “hard” evidence for the suggestion of “cultural and educational reasons”—this comment was simply proferred as one possible reason for …
Male Transsexualism: Uneasiness
Authors: ROBERT J. STOLLER
Journal: American Journal of Psychiatry (1973)

The author discusses sex reassignment in men. He points out that since 1953, when the procedures were first publicized, attitudes toward granting "sex change" have become increasingly liberal, resulting in a dearth of knowledge about the number of men who have received hormonal or surgical treatment; the frequency of surgical and postoperative complications and of morbidity and mortality; the nature and frequency of psychiatric complications; and the percentage of those treated who have benefited. Believing that sex reassignment should be restricted to the most feminine men, the author urges more scrupulous follow-up studies and more careful consideration of requests for change.
A Double-Blind Trial of Metoprolol in Acute Myocardial Infarction
Authors: L. Rydén, R. Ariniego, K. Arnman, J. Herlitz, Å. Hjalmarson, S. Holmberg, C. Reyes, P. Smedgård, K. Svedberg, A. Vedin, F. Waagstein, A. Waldenström, C. Wilhelmsson, H. Wedel, M. Yamamoto
Journal: New England Journal of Medicine (1983)

During a double-blind trial in which patients with suspected myocardial infarction received metoprolol or placebo, we analyzed the occurrence of ventricular tachyarrhythmias. Metoprolol (15 mg intravenously) was given as soon as possible after admission, and thereafter 200 mg was given daily for three months. Antiarrhythmic drugs were given only for ventricular fibrillation and sustained ventricular tachycardia (greater than 60 beats per second). Definite acute myocardial infarction developed in 809 of the 1395 participants, and probable infarction in 162. Metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia. However, there were 17 cases of ventricular fibrillation in the placebo group (697 patients) and only 6 in the metoprolol group (698 patients, P less than 0.05). During the hospital stay significantly fewer patients receiving metoprolol (16) than placebo (38) (P less than 0.01) required lidocaine. In a separate analysis of 145 patients, metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia during the first 24 hours of treatment. Despite a lack of effect on less serious ventricular tachyarrhythmias, metoprolol had a prophylactic effect against ventricular fibrillation in acute myocardial infarction.
VWRPY motif–dependent and –independent roles of AML1/Runx1 transcription factor in murine hematopoietic development
Authors: Motohiro Nishimura, Yoko Fukushima-Nakase, Yasuko Fujita, Mitsushige Nakao, Shogo Toda, Nobuo Kitamura, Tatsuo Abe, Tsukasa Okuda
Journal: Blood (2003)
Evaluation of Anticoagulant Therapy in Cloth-Covered Prosthetic Valves
Authors: O. WAYNE ISOM, C. DAVID WILLIAMS, EMILY A. FALK, FRANK C. SPENCER, EPHRAIM GLASSMAN
Journal: Circulation (1973)

Over a period of four years, a series of 303 patients had prosthetic valve replacement with the Starr-Edwards cloth-covered metallic ball prosthesis. There were 135 aortic replacements, 105 mitral, 42 combined mitral and aortic, and 21 combined mitral and tricuspid. The frequency of thromboembolism and hemorrhage was studied in patients receiving warfarin sodium (Coumadin) and in those not receiving warfarin. No thromboemboli occurred during 2,052 patient-months of observation in patients with aortic prostheses who were receiving warfarin, but 10 episodes of hemorrhage occurred. By comparison, after anticoagulants were discontinued, there was 1 episode of thromboembolism during 786 months of patient observation. Among patients with mitral prostheses who were receiving warfarin, 3 episodes of thromboembolism occurred in 2,081 patient-months of observation, during which 5 hemorrhagic episodes also occurred. By comparison, after warfarin was discontinued, there were 3 episodes of thromboembolism during 402 months. In patients with mitral and aortic prostheses who were receiving warfarin, 1 episode of thromboembolism occurred in 670 patient-months, and no episodes of hemorrhage. Without anticoagulation, 2 episodes of thromboembolism occurred in 130 patient-months. In patients with mitral and tricuspid prostheses who were receiving warfarin, there were no episodes of thromboembolism during 186 patient-months, but there was 1 episode of hemorrhage. Without anticoagulation, however, there were 3 episodes of thromboembolism during 32 months of patient observation.
Islet Cell Autoantibodies: Pathobiology and Clinical Applications
Authors: Pnina Vardi, Elsie E Dibella, Timothy J Pasquarello, Sathyanarayana Srikanta
Journal: Diabetes Care (1987)

Autoimmunity directed against pancreatic islet cells results in slowly progressing β-cell destruction, culminating over years in clinically manifested insulin-dependent diabetes mellitus (IDDM). Circulating serum autoantibodies directed against the endocrine cells of the islets of Langerhans arean important hallmark of this disease. Assays for these islet cell antibodies (ICA) have facilitated the investigation and understanding of several facets in the pathogenesis of autoimmune diabetes. Their applications have begunto extend into clinical practice and have opened new avenues for early preclinical prediction and preventive prophylaxsis in IDDM.
Ketoconazole Blocks Adrenal Steroid Synthesis
Authors: ALLAN PONT
Journal: Annals of Internal Medicine (1982)

Ketoconazole, a broad-spectrum, antifungal drug that is administered orally, has been shown to inhibit sterol synthesis in fungi. When gynecomastia developed in some patients taking this drug, we investigated the effects of ketoconazole on steroid synthesis in humans and in isolated adrenal cells from rats. In healthy humans, the Cortisol response to adrenocorticotropic hormone was significantly blunted 4 hours after a 400-mg or 600-mg dose. The inhibition persisted for up to 8 hours and was absent by 16 hours. This finding indicated that adrenal androgen response was reduced. Easily achieved therapeutic concentrations of ketoconazole virtually eliminated corticosterone production by isolated adrenal cells from rats. Although ketoconazole at currently used doses has never been documented to cause clinical hypoadrenalism, caution is urged in high- or multiple-dose trials. The drug may prove useful as an agent to block steroid synthesis.
The 13 steps to community care
Authors: D. Hollander, R. B Powell
Journal: BMJ (1996)

EDITOR,—Social services departments and community projects have erected bureaucratic procedures that impede the process of discharging mentally ill people from hospital. For example, in one district the following steps must be fulfilled (this process is typical of the problem throughout London).

1.  Refer patient for community living assessment (4 pages).

2.  Allocate worker to complete community living assessment.

3.  Complete community living assessment form (50 pages).

4.  Prepare summary …
Prostate Volume and Serum Prostate&amp;ndash;Specific Antigen as Predictors of Acute Urinary Retention
Authors: M.J. Marberger, J.T. Andersen, J.C. Nickel, M.-P. Malice, M. Gabriel, F. Pappas, A. Meehan, E. Stoner, J. Waldstreicher
Journal: European Urology (2000)
Radiation for Restenosis
Authors: Spencer B. King
Journal: Circulation (1999)

a sarandisis" is an ancient Greek admonition, which loosely translated means, "When meeting someone you are attracted to, wait 40 days and 40 nights prior to making the commitment."In the attempt to control restenosis, love at first sight has frequently led to disappointing and expensive outcomes.Endovascular radiation therapy to prevent restenosis has appeared very attractive, and Teirstein et al, in this issue of Circulation, 1 have contributed some of the "na sarandisis.
HIGH SENSITIVE TROPONIN T AND PEAK EARLY DIASTOLIC VELOCITY OF SEPTAL MITRAL ANNULUS PREDICT CARDIAC DAMAGE IN BREAST CANCER PATIENTS WITH ADJUVANT TRASTUZUMAB THERAPY
Authors: Kenichi Katsurada, Masaru Ichida, Yasuo Hozumi, Kazuomi Kario
Journal: Journal of the American College of Cardiology (2013)
GMC says doctors can give medical notes to patients who want to end their lives
Authors: C. Dyer
Journal: BMJ (2012)

Doctors who comply with patients’ valid requests for their medical records under the Data Protection Act but refrain from encouraging or helping them to end their lives will not normally face General Medical Council proceedings for assisting a suicide, the GMC says in new draft guidance.

Patients who travel to Switzerland for a legal assisted death are required to produce their medical records there, and some doctors have refused to hand over the notes if they know or suspect a patient’s motive, although patients have a legal right to their records under the act.

The draft guidance for GMC case examiners and members of investigation committees clarifies for …
Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress-induced hepatocellular injury
Authors: Akira Uchiyama, Jae-Sung Kim, Kazuyoshi Kon, Hartmut Jaeschke, Kenichi Ikejima, Sumio Watanabe, John J. Lemasters
Journal: Hepatology (2008)

Abstract Iron overload exacerbates various liver diseases. In hepatocytes, a portion of non-heme iron is sequestered in lysosomes and endosomes. The precise mechanisms by which lysosomal iron participates in hepatocellular injury remain uncertain. Here, our aim was to determine the role of intracellular movement of chelatable iron in oxidative stress-induced killing to cultured hepatocytes from C3Heb mice and Sprague-Dawley rats. Mitochondrial polarization and chelatable iron were visualized by confocal microscopy of tetramethylrhodamine methylester (TMRM) and quenching of calcein, respectively. Cell viability and hydroperoxide formation (a measure of lipid peroxidation) were measured fluorometrically using propidium iodide and chloromethyl dihydrodichlorofluorescein, respectively. After collapse of lysosomal/endosomal acidic pH gradients with bafilomycin (50 nM), an inhibitor of the vacuolar proton-pumping adenosine triphosphatase, cytosolic calcein fluorescence became quenched. Deferoxamine mesylate and starch-deferoxamine (1 mM) prevented bafilomycin-induced calcein quenching, indicating that bafilomycin induced release of chelatable iron from lysosomes/endosomes. Bafilomycin also quenched calcein fluorescence in mitochondria, which was blocked by 20 μM Ru360, an inhibitor of the mitochondrial calcium uniporter, consistent with mitochondrial iron uptake by the uniporter. Bafilomycin alone was not sufficient to induce mitochondrial depolarization and cell killing, but in the presence of low-dose tert -butylhydroperoxide (25 μM), bafilomycin enhanced hydroperoxide generation, leading to mitochondrial depolarization and subsequent cell death. Conclusion: Taken together, the results are consistent with the conclusion that bafilomycin induces release of chelatable iron from lysosomes/endosomes, which is taken up by mitochondria. Oxidative stress and chelatable iron thus act as two “hits” synergistically promoting toxic radical formation, mitochondrial dysfunction, and cell death. This pathway of intracellular iron translocation is a potential therapeutic target against oxidative stress–mediated hepatotoxicity. (Hepatology 2008.)
Russian doctors protest over state of nation's health
Authors: M. Ingram
Journal: BMJ (1997)

Doctors in Russia have written to the prime minister, Viktor Chernomyrdin, accusing the government of failing in its constitutional duty to provide free health care to all citizens.

Nearly two thousand delegates from across Russia attending the Pirogov congress, Russia's most prestigious medical gathering, also called on Russia's prosecutor general and constitutional court to investigate the legal implications of the government's breach of article 41 of the constitution, which guarantees health …
Early midzonal cell death during low-flow hypoxia in the isolated, perfused rat liver: Protection by allopurinol
Authors: Mark E. Marotto, Ronald G. Thurman, John J. Lemasters
Journal: Hepatology (1988)

Trypan blue uptake and lactate dehydrogenase release were measured as indices of irreversible cell damage in isolated, perfused rat livers during low-flow hypoxia. In livers from fasted rats perfused in the anterograde direction, trypan blue uptake took place beginning at about 45 min of hypoxia. Cells which took up trypan blue first were located in narrow bands at the border between anoxic pericentral areas and normoxic periportal regions of the liver lobule. After longer periods of hypoxia, trypan blue uptake progressed towards the central vein until after 120 min virtually all cells in the pericentral regions were stained. Under these conditions, cells in periportal regions were spared. In perfusions in the retrograde direction, cell death began in midzonal regions and spread towards the portal vein. Release of lactate dehydrogenase into the effluent paralleled trypan blue uptake, beginning at about 40 min of low-flow hypoxia and peaking at 80 min. In contrast to livers from fasted rats, trypan blue was not taken up, and lactate dehydrogenase was not released in livers from fed rats exposed to low-flow hypoxia for as long as 120 min. To test the hypothesis that xanthine oxidase-mediated oxygen-free radical formation was involved in cell injury at the border between anoxic and normoxic regions (anoxic edge), allopurinol, an inhibitor of xanthine oxidase, was studied. Allopurinol (0.2 to 5 mM) delayed the release of lactate dehydrogenase during low-flow hypoxia in a dose-dependent fashion (e.g., 5 mM allopurinol delayed hypoxia-induced lactate dehydrogenase release by about 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Blood pressure influences end-stage renal disease of Cd151 knockout mice
Authors: Norman Sachs, Nike Claessen, Jan Aten, Maaike Kreft, Gwendoline J.D. Teske, Anneke Koeman, Coert J. Zuurbier, Hans Janssen, Arnoud Sonnenberg
Journal: Journal of Clinical Investigation (2011)

Podocytes of the kidney adhere tightly to the underlying glomerular basement membrane (GBM) in order to maintain a functional filtration barrier. The clinical importance of podocyte binding to the GBM via an integrin-laminin-actin axis has been illustrated in models with altered function of α3β1 integrin, integrin-linked kinase, laminin-521, and α-actinin 4. Here we expanded on the podocyte-GBM binding model by showing that the main podocyte adhesion receptor, integrin α3β1, interacts with the tetraspanin CD151 in situ in humans. Deletion of Cd151 in mouse glomerular epithelial cells led to reduced adhesive strength to laminin by redistributing α3β1 at the cell-matrix interface. Moreover, in vivo podocyte-specific deletion of Cd151 led to glomerular nephropathy. Although global Cd151-null B6 mice were not susceptible to renal disease, as has been shown previously, increasing blood and transcapillary filtration pressure induced nephropathy in these mice. Importantly, blocking the angiotensin-converting enzyme in renal disease-susceptible global Cd151-null FVB mice prolonged their median life span. Together, these results establish CD151 as a crucial modifier of integrin-mediated adhesion of podocytes to the GBM and show that blood pressure is an important factor in the initiation and progression of Cd151 knockout-induced nephropathy.
Should research fraud be a crime?
Authors: Z. A. Bhutta, J. Crane
Journal: BMJ (2014)

<b>Zulfiqar A Bhutta</b> says that criminal sanctions are necessary to deter growing deliberate research misconduct, which can ultimately harm patients. <b>Julian Crane</b> disagrees: he doubts that sanctions will have any deterrent effect and worries that criminalisation would undermine trust
Neural Regulation of Luteinizing Hormone Secretion in the Rat*
Authors: SATYA P. KALRA, PUSHPA S. KALRA
Journal: Endocrine Reviews (1983)

Essentially, two modalities of luteinizing hormone (LH) secretion have been identified in the rat. The basal mode is characterized by episodic bursts of pituitary LH discharge whose frequency and amplitude may vary considerably during the day in male (1, 2) and according to different phases of the estrous cycle in female rats (4). This low level of pulsatile LH secretion is established early in the juvenile period (5). With advancing age, subtle and progressive disintegration of several compo-nents of the LH episodes seems to account for the near cessation of rhythmicity in old rats (6). Additionally, in adult female rats, the periodic mode of LH secretion is interrupted on the afternoon of proestrus by fast, high amplitude pulses constituting the preovulatory LH surge lasting for 4–6 h (7–9). The cyclic pattern of LH secretion is fully established by the 5th week of pubertal life (5). Abnormalities in periodicity, onset, duration and magnitude of the preovulatory LH discharge during middle age precede reproductive senescence (10–14).
Dyslipidemia in type II Diabetes: Implications for Therapeutic Intervention
Authors: Michael P Stern, Steven M Haffner
Journal: Diabetes Care (1991)

Cardiovascular disease, and in particular ischemic heart disease, is the principal cause of morbidity, functional disability, and mortality in patients with non-insulin-dependent (type II) diabetes. The main risk factors for the macrovascular complications of diabetes are dyslipidemia, hypertension, and cigarette smoking. Although degree of hyperglycemia is a risk factor for microvascular complications, it is not a prominent risk factor for macrovascular complications. Nevertheless, there are theoretical reasons for believing that glycemic control could lower cardiovascular risk. For example, glycemic control may both improve clearance and suppress hepatic overproduction of very-low-density lipoprotein. Moreover, there is direct empirical evidence that improved glycemic control can favorably alter lipid profiles in type II diabetic patients. Despite this, the only clinical trial that has assessed cardiovascular mortality as an end point in diabetic subjects (i.e., the University Group Diabetes Program) failed to demonstrate a benefit of glycemic control. In this study, the insulin-variable group, which achieved sustained glycemic control relative to the placebo group, had essentially the same cardiovascular mortality as the latter group. All of the conventional lipid-lowering agents have been shown to produce favorable changes in lipid profiles in diabetic subjects. However, the optimum regimen remains to be defined. Metabolic differences between diabetic and nondiabetic subjects mean that the optimum lipid-lowering regimens for the two categories of patients may differ. For example, nicotinic acid, which is a powerful lipid-altering drug, may worsen glucose intolerance. The characteristic lipid abnormalities in type II diabetic subjects are hypertriglyceridemia and low high-density lipoprotein cholesterol, not hypercholesterolemia. Although the role of hypertriglyceridemia as a cardiovascular risk factor in the general population has been questioned, there is evidence that this lipid abnormality may play a stronger role in diabetic subjects. For all of the above reasons, there is an urgent need for large-scale clinical trials assessing cardiovascular end points and testing various strategies of improving lipid profiles in diabetic subjects, particularly given the fact that all of the current generation of lipid-lowering trials have systematically excluded diabetic patients.
Low incidence of rifampicin-resistant tubercle bacilli.
Authors: C H Collins, M D Yates
Journal: Thorax (1982)

In a six-year survey 10(0.15%) of 6849 patients with European names and 31 (1.0%) of 3079 patients with non-European names yielded cultures of Mycobacterium tuberculosis that were resistant to rifampicin. Only two of each group had organisms resistant to rifampicin alone. Resistance to one or more other antituberculous drugs was found in eight of the European and 29 of the non-European group. Two patients in each group were known to have received treatment for the first time in the United Kingdom; 17 of the non-Europeans were known to have been treated abroad; precise information was not available for the other 12. The overall six-year incidence of patients with rifampicin-resistant M tuberculosis was only 0.41%. The very low incidence among Europeans is probably the result of stricter regimens than are possible in some other areas.
Health Care Needs of Transgendered Patients-Reply
Authors: James R. Allen
Journal: JAMA (1996)

In Reply.  —Dr Lawrence and colleagues properly view the recent Council on Scientific Affairs report on health care for gay men and lesbians as a work in progress. The health care needs of transgendered patients would be appropriate for consideration by the Council in a future report. Quality research on transgendered persons is lacking. We strongly encourage further research on the relation of health care needs and all sexual orientations.