tbuckley/cabot-search huggingface dataset:
Glibenclamide, a putative ATP-sensitive K+ channel blocker, inhibits coronary autoregulation in anesthetized dogs.
Authors: T Narishige, K Egashira, Y Akatsuka, Y Katsuda, K Numaguchi, M Sakata, A Takeshita
Journal: Circulation Research (1993)

We tested the hypothesis that ATP-sensitive K+ channels are involved in the mechanism mediating coronary autoregulation in open-chest dogs. We perfused the left anterior descending coronary artery with arterial blood from an extracorporeal circuit and measured steady-state coronary blood flow (CBF) with stepwise changes in coronary perfusion pressure (CPP) between 50 and 150 mm Hg during an intracoronary infusion of vehicle or glibenclamide (a putative blocker of ATP-sensitive K+ channels). CBF was relatively stable over CPP between 50 and 110 mm Hg during vehicle infusion, indicating the presence of autoregulation at the CPP range. During glibenclamide infusion (10 micrograms.min-1 x kg-1), CBF progressively decreased with reduction in CPP below 110 mm Hg, whereas the CPP-CBF relation at CPP above 110 mm Hg was not altered by glibenclamide. The autoregulation index [1-(delta F/F)/(delta P/P), where F indicates CBF and P indicates CPP] was greater than 0 over the CPP range between 50 and 100 mm Hg during vehicle infusion and was less than 0 during glibenclamide infusion. Glibenclamide did not alter systemic arterial pressure, heart rate, left ventricular pressure, and changes in regional myocardial oxygen consumption associated with changes in CPP. In the absence of glibenclamide, the CPP-CBF relation was reproducible in the repeated studies for time control. These results suggest that ATP-sensitive K+ channels play an important role in mediating coronary autoregulation at the lower range of CPP in the blood-perfused dog heart.
Three-year follow-up results of argentine randomized study coronary angioplasty with stenting versus bypass surgery in patients with multiple vessel disease (ERACI II)
Authors: Alfredo E. Rodriquez, Máximo Rodriguez Alemparte, Julio Baldi, José Navia, Jorge Martinez, Daniel Vogel, Alejandro Delacasa, Victor Bernardi, Carlos Fernández Pereira, Igor Palacios, William O'Neill
Journal: Journal of the American College of Cardiology (2002)
Should disadvantaged people be paid to take care of their health? No
Authors: J. Popay
Journal: BMJ (2008)

Many countries are turning to cash incentives to encourage people to look after their health. <b>Richard Cookson</b> (doi: 10.1136/bmj.a589) argues that such schemes can save money in the long run, but <b>Jennie Popay</b> believes the problems need a deeper solution
Physicians in the Making: Personal, Academic, and Socioeconomic Characteristics of Medical Students From 1950 to 2000
Authors: Norman D. Anderson
Journal: JAMA (1985)

In a decade when American medical education faces gloomy prospects of continually rising costs, limited financial support, and declining student enrollments compounded by uncertainties over an impending "physician glut" and heightening societal demands for cost containment in the "health care industry," there may be cogent reasons to try to divine the future. This timely book attempts to meet such needs by incorporating results of the<i>Delphi Survey of the Characteristics of Future U.S. Medical Students</i>, conducted by the Association of American Medical Colleges (AAMC) in 1981, onto background analyses of changing patterns in medical school applicants and students as viewed from the author's perspective after his 30 years of service as an admissions dean and AAMC staff member. The strength of this book rests on its scholarly recitation of composite national statistics describing demographic and socioeconomic trends in student applicants and matriculants. However interesting such data may be, this approach
Small intestinal obstruction by a Peutz-Jeghers polyp - double-balloon enteroscopic removal
Authors: H. Ullerich, C. Maaser, W. Domschke, T. Kucharzik
Journal: Endoscopy (2007)

A 38-year-old woman with Peutz-Jeghers syndrome was admitted due to a 2-week history of intermittent abdominal pain and symptoms of incomplete intestinal obstruction. She had experienced symptoms of incomplete intestinal obstruction 2 years previously, and had undergone explorative laparotomy, which revealed a large polyp of the jejunum that required resection. On admission, laboratory results of the patient were unremarkable. Physical examination revealed a mild distension of the upper abdominal quadrants. Abdominal radiograph gave no hint of bowel obstruction.
Parkinsonism--Physiology and Pharmacology
Authors: D. B. Calne
Journal: BMJ (1971)

and basal ganglia, but the detailed anatomical connexions and physiological role of these areas of the central nervous system are so complex that at present their function in motor control remains uncertain. The term extrapyramidal was coined 70 years ago130 to embrace all motor pathways other than the direct projection from the motor cortex to the spinal cord via the medullary pyramid (the pyramidal or corticospinal pathway). Functional disturbance of the extrapyramidal system, in particular the basal ganglia, was thought to result in a group of clinical disorders characterized by invol untary movements. Probably many features of this simple scheme will prove to be incorrect as neurophysiology develops. Already the concept of an extrapyramidal system is beginning to appear redundant, as one of the important output pathways from the basal ganglia is the pyramidal tract131?and even such simple entities as involuntary movements are proving difficult to define in physiological terms because, for example, Parkinsonian tremor can often be temporarily abolished by conscious effort, while voluntary movement, such as walking, can be executed without conscious effort. If these examples seem contrived, how should such movements as those involved in breathing be classified ? While acknowledging these difficulties, it is still desirable to consider the physiology of the basal ganglia, and its disturbance in Parkinsonism.
Regulation of prorenin secretion in cultured human transfected juxtaglomerular cells.
Authors: F Pinet, J Mizrahi, I Laboulandine, J Menard, P Corvol
Journal: Journal of Clinical Investigation (1987)

The regulation of renin secretion was studied in continuous culture of human juxtaglomerular cells (JGC), which provided a permanent source of human renin production (Pinet, F., M. T. Corvol, F. Dench, J. Bourguignon, J. Feunteun, J. Ménard, and P. Corvol, 1985, Proc. Natl. Acad. Sci. USA, 82:8503-8507). 95% of the renin species secreted was prorenin, and therefore this study concerned primarily prorenin secretion. Renin production was stable, since the cells had been maintained in culture for more than two years. In culture, these human cells formed colonies of smooth musclelike cells, and electron microscopy showed the presence of cytoskeleton structures including myofibrils and attachment bodies. This human model was used to investigate the control of prorenin secretion in vitro at cellular level. Various pharmacological agents known to stimulate or inhibit renin secretion were tested in the cell cultures. The variations in prorenin secretion were measured in the supernatant. Forskolin, an independent receptor activator of adenylate cyclase, stimulated prorenin secretion in a dose-dependent manner and this stimulation was mediated by 3',5' cyclic-AMP (cAMP). Angiotensin II (AII) was found to inhibit prorenin secretion directly in a dose-dependent manner and atrial natriuretic factor (ANF), whose effects on human JGC were characterized for the first time, was also shown to exert such inhibition. When the effects of this inhibition by AII and ANF were tested on forskolin-mediated stimulation of prorenin secretion, the latter was inhibited and no change occurred in cAMP release. When JGC were treated with histamine, bradykinin, or one or two bradykinin analogues, the responses suggested that in these cells, H2-histamine receptors and kinin receptors are dependent on adenylate cyclase. One peptide, substance P, had an inhibitory effect on prorenin secretion but it was less important than AII and ANF. The present results demonstrate that the adenylate cyclase system of human JGC remains intact during culture and supports the hypothesis that cAMP is the second messenger and Cai2+, the final messenger involved in renin secretion. The cell system used here permits the evaluation of cellular responses and intracellular events in granulated cells in a human model.
Abrogation of MAPK and Akt Signaling by AEE788 Synergistically Potentiates Histone Deacetylase Inhibitor-Induced Apoptosis through Reactive Oxygen Species Generation
Authors: Chunrong Yu, Bret B. Friday, Jin-Ping Lai, Andrea McCollum, Peter Atadja, Lewis R. Roberts, Alex A. Adjei
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To evaluate the effects of combining the multiple receptor tyrosine kinase inhibitor AEE788 and histone deacetylase (HDAC) inhibitors on cytotoxicity in a broad spectrum of cancer cell lines, including cisplatin-resistant ovarian adenocarcinoma cells. Experimental Design: Multiple cancer cell lines were treated in vitro using AEE788 and HDAC inhibitors (LBH589, LAQ824, and trichostatin A), either alone or in combination. Effects on cytotoxicity were determined by growth and morphologic assays. Effects of the combination on cell signaling pathways were determined by Western blotting, and the results were confirmed using pathway-specific inhibitors and transfection of constitutively active proteins. Results: Cell treatment with AEE788 and HDAC inhibitors (LBH589, LAQ824, and trichostatin A) in combination resulted in synergistic induction of apoptosis in non–small cell lung cancer (MV522, A549), ovarian cancer (SKOV-3), and leukemia (K562, Jurkat, and ML-1) cells and in OV202hp cisplatin-resistant human ovarian cancer cells. AEE788 alone or in combination with LBH589 inactivated mitogen-activated protein kinase (MAPK) and Akt cascades. Inhibition of either MAPK and/or Akt enhanced LBH589-induced apoptosis. In contrast, constitutively active MAPK or Akt attenuated LBH589 or LBH589 + AEE788–induced apoptosis. Increased apoptosis was correlated with enhanced reactive oxygen species (ROS) generation. The free radical scavenger N-acetyl-l-cysteine not only substantially suppressed the ROS accumulation but also blocked the induction of apoptosis mediated by cotreatment with AEE788 and LBH589. Conclusion: Collectively, these results show that MAPK and Akt inactivation along with ROS generation contribute to the synergistic cytotoxicity of the combination of AEE788 and HDAC inhibitors in a variety of human cancer cell types. This combination regimen warrants further preclinical and possible clinical study for a broad spectrum of cancers.
Identification of a T-Type Ca <sup>2+</sup> Channel Isoform in Murine Atrial Myocytes (AT-1 Cells)
Authors: Jonathan Satin, Leanne L. Cribbs
Journal: Circulation Research (2000)

Calcium channels are important targets for therapeutics, but their molecular diversity complicates characterization of these channels in native heart cells. In this study, we identify a new splice variant of a low-voltage activated, or T-type Ca(2+), channel in murine atrial myocytes. To date, alpha1G and alpha1H are the only 2 T-type Ca(2+) channel isoforms found in cardiovascular tissue. We compared alpha1G and alpha1H channel current heterologously expressed in HEK 293 cells with T-type current from the murine atrial tumor cell, AT-1. AT-1 cell T-type current (I(T)) has the same voltage dependence of activation and inactivation as alpha1G and alpha1H. The cloned T-type channels and AT-1 T-type current share similar kinetics of macroscopic inactivation and deactivation. The kinetics of recovery from inactivation of T-type currents serves as an electrophysiological signature for T-channel isoform. alpha1G and AT-1 I(T) have a similar recovery from inactivation time course that is faster than that for alpha1H. In all cases, T-type current recovers with a biexponential time course, and the relative amplitude of fast and slow time courses explains the slower alpha1H recovery kinetics, rather than differences in the time constants of the individual transitions. Thus, the T-type channels may be an important contributor to automaticity in heart cells, and molecular diversity is reflected in the pathway of recovery from inactivation.
A Study of the Coevolutionary Patterns Operating within the env Gene of the HIV-1 Group M Subtypes
Authors: S. A. A. Travers, D. C. Tully, G. P. McCormack, M. A. Fares
Journal: Molecular Biology and Evolution (2007)

The env gene of human immunodeficiency virus (HIV) is a functionally important gene responsible for the production of protein products (gp120 and gp41) involved in host cell recognition, binding, and entry. This occurs through a complex and, as yet, not fully understood process of protein-protein interaction and within and between protein functional communication. Exposure on the surface of active HIV virions means the gp120-gp41 complexes are subjected to intense immune system pressure and have, therefore, evolved mechanisms to avoid neutralization. Using protein-coding sequences representing all the HIV type-1 (HIV-1) group M subtypes, we have identified amino acids within the env gene whose evolution is inextricably linked over the entire HIV-1 group M epidemic. We identified 848 pairs of coevolving residues (involving 263 out of 764 amino acid sites), which represent 0.29% of all possible pairs. Of the coevolving pairs, 68% were significantly correlated by hydrophobicity, molecular weight, or both hydrophobicity and molecular weight. Subsequent grouping of coevolving pairs resulted in the identification of 290 groups of amino acid residues, with the size of these groups ranging from 2 to 10 amino acid residues. Many of these dependencies are correlated by function including CD4 binding, coreceptor binding, glycosylation, and protein-protein interaction. This analysis provides important information regarding the functional dependencies observed within all the HIV-1 group M subtypes and may assist in the identification of functional protein domains and therapeutic targets within the HIV-1 env gene.
Detection of Anti-Acetylcholine Receptor Factors in Serum and Thymus from Patients with Myasthenia Gravis
Authors: Thomas Mittag, Peter Kornfeld, Anne Tormay, Charles Woo
Journal: New England Journal of Medicine (1976)

Since the blood and thymus of patients with myasthenia gravis may contain inhibitors of neuromuscular transmission that affect acetylcholine receptors of striated muscle, we used denervated rat muscle to test for inhibitors in 43 serums and 18 thymus glands from such patients. Seven per cent of serums inhibited the binding of 125l alpha-bungarotoxin to triton-solubilized receptors; 65 per cent interfered with binding of toxin-labeled receptors to concanavalin-A coupled to Sepharose gel, and 85 per cent formed IgG-receptor complexes detectable by immunoprecipitation. Serum inhibitory activity varied widely among patients with similar clinical manifestations and was not correlated with duration of myasthenia gravis or thymectomy. Among thymus extracts, 44 per cent were inhibitory in the concanavalin-A binding assay, whereas 72 per cent contained anti-receptor IgG. Thus, serums from patients with myasthenia gravis contain more than one anti-receptor factor.
LEAD MARKERS IN ROENTGEN EXAMINATION OF DISEASES OF THE CHEST
Authors: Oscar W. Bethea
Journal: JAMA (1930)

One of the principal difficulties experienced in reaching an accumulation of fluid in the chest is selecting the most favorable point of entry on the chest wall.  The accompanying illustrations from films made by Dr. Magruder at the Baptist Hospital show my use of lead markers in roentgen examinations in pleurisy. I have been using them under two circumstances:  1. Before having the first picture made, if aspiration is considered a possibility, what appears to be the most favorable site is marked with a lead letter, held in place by a strip of adhesive tape. This is allowed to remain on the patient until after the film has been developed and the operator is then in a better position to judge as to whether or not the proposed site is the most desirable. Should the marker appear on the film as not in the proper position in relation to the
Sex Differences in Outcomes After Cardiac Catheterization
Authors: Kathryn M. King, William A. Ghali, Peter D. Faris, Michael J. Curtis, P. Diane Galbraith, Michelle M. Graham, Merril L. Knudtson
Journal: JAMA (2004)

Studies comparing outcomes of cardiac care in women vs men yield various results, with some suggesting worse outcomes for women and others suggesting equivalent outcomes.To determine whether extent of coronary disease, treatment strategy, and follow-up time influence the risk of death in women vs men among patients who have had cardiac catheterization.We studied a large inception cohort by using detailed clinical data from a registry of 37 401 patients undergoing cardiac catheterization in Alberta, Canada, from 1995-2000, with follow-up through December 31, 2001.The risk of death for women vs men was assessed for all patients combined and then in analyses stratified by degree of coronary anatomic risk and by treatment strategy (no revascularization, percutaneous coronary intervention [PCI], coronary artery bypass graft [CABG] surgery). The latter analysis included a graphic assessment of the changing relative risk over time for women vs men.Women had higher 1-year mortality than men did (5.6% vs 4.6%; P<.001). However, stratified analyses demonstrated that sex differences in risk occurred only early after catheterization and were most apparent among patients undergoing revascularization. The early risk-adjusted relative risks for women vs men were elevated at 3.49 (95% confidence interval [CI], 1.95-6.24) for CABG surgery and 2.38 (95% CI, 1.48-3.83) for PCI on day 1 after catheterization, with a subsequent decrease in relative risk over time to equivalence in risk between sexes before 1 year.Sex-based differences in death rates after cardiac catheterization are time- and treatment-specific. This finding may at least partially explain the discrepancies in results from earlier studies on sex differences in outcomes of cardiac care.
THE TREATMENT OF ANEURYSMS BY SUBCUTANEOUS GELATIN INJECTIONS.
Authors: THOMAS B. FUTCHER
Journal: JAMA (1900)

The year 1898 added still another to the many methods that have been advanced to the treatment and cure of aneurysms. To Lancereaux of Paris is due the credit of having introduced this method to the medical profession. The treatment in question consists in the injection of sterilized solutions of gelatin into the subcutaneous tissues. The method is based on the experimental work of Dastre and Floresco<sup>1</sup>, who studied the effect of gelatin solutions on the coagulability of the blood. These observers went only so far as to show that the coagulability of the blood was increased when the gelatin solution was brought into direct contact with it, whether this be the circulating blood of the animal or the blood of the animal after removal. They found that the injection of gelatin solutions into the blood-vessels of dogs and rabbits caused a rapid coagulation of the blood. They employed
Remarkable Specimen of Disease in Bone
Authors: G. F. Elliott
Journal: BMJ (1869)

347(articulation) was affected at times; the tongue felt too big for the mouth, and she talked thickly.At times she was not able to speak.There was great depression of spirits.Bowels regular; appetite good.The treatment was continued, and from this time she improved.On July 6th, she had no agitation of the limbs at all; but occasionally the mouth was affected.
Disentangling the order effect from the context effect: Analogies, homologies, and quantum probability
Authors: Elias L. Khalil
Journal: Behavioral and Brain Sciences (2013)

Abstract Although the quantum probability (QP) can be useful to model the context effect, it is not relevant to the order effect, conjunction fallacy, and other related biases. Although the issue of potentiality, which is the intuition behind QP, is involved in the context effect, it is not involved in the other biases.
Progesterone Receptor Expression in Human Saphenous Veins
Authors: M. Perrot-Applanat, K. Cohen-Solal, E. Milgrom, M. Finet
Journal: Circulation (1995)

Background Clinical and epidemiological observations regarding varicose veins, such as their predominance in women and the occurrence of venous stasis during sex-hormone therapy, the luteal phase of the menstrual cycle, and pregnancy, suggest a sex hormone–dependency of this venous pathology. In the present study, analysis of steroid receptors was used to determine if these effects were due to a direct hormonal action on the saphenous vein. Methods and Results Biopsy samples were obtained from patients undergoing stripping removal of varicose saphenous veins. Patients were men (n=5) and premenopausal (n=15) or postmenopausal (n=10) women. Progesterone receptors (PR) and estrogen receptors (ER) were determined by both enzyme immunoassay (EIA) and immunocytochemistry by use of monoclonal antibodies. Ninety percent of the biopsy samples showed PR positivity by EIA (range, 5 to 53 fmol/mg cytosol protein). When present, PR staining was observed in the cell nuclei of the tunica media and the subendothelial layer (neointima). No significant variation was observed in the PR content of different regions within the same saphenous vein. In contrast, no ER or extremely low levels of ER (&lt;5 fmol/mg cytosol protein) were detected by EIA in 25 of 30 varicose biopsy samples. Reverse transcription–polymerase chain reaction (RT-PCR) was used to analyze PR and ER mRNAs in biopsy samples that were PR positive/ER negative. With primers to the hormone-binding region encoded by PR mRNA, a RT-PCR product of the expected size was detected and its identity confirmed by Southern blot by use of a PR cDNA probe. In contrast, no RT-PCR product could be detected by use of primers to the DNA-binding domain, the hinge region, and the ligand-binding domain encoded by ER mRNA. Conclusions These results indicate that human saphenous veins from both sexes express PR, as previously described for arterial blood vessels. This observation suggests that progesterone acts directly on these veins via a classic receptor-mediated pathway.
Commissioners are restricting referrals for hip and knee surgery, says report
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Clinical commissioning groups in England should stop restricting access to hip and knee replacement surgery on the grounds of a patient’s age and weight, a report has recommended.

The Medical Technology Group found that 33 of 67 (49%) acute trusts across England that responded to a freedom of information request said that commissioners were applying more stringent conditions than is recommended before referring patients for surgery.1 The group is a coalition …
Step Care for Asthma
Authors: Roger C. Bone
Journal: JAMA (1988)

Asthma has classically been considered a disease characterized primarily by bronchospasm. In addition to bronchospasm, however, the pathologic characteristics of severe asthma include bronchial inflammation, consisting of lymphocytic and eosinophilic infiltration, as well as desquamation of ciliated epithelium. In fact, it has been proposed that asthma be renamed "chronic desquamative eosinophilic bronchitis."<sup>1</sup> Despite recent advances in the therapy for bronchial asthma, the morbidity and mortality associated with this disease are increasing,<sup>2</sup>with concomitant increases in the sale of bronchodilator medications.<sup>3</sup>Although the explanation of this disturbing trend is unknown, investigators and clinicians are reevaluating current concepts of asthma pathophysiologic characteristics and treatment, particularly the prevention and control of bronchial inflammation. To reverse the increased death rate in patients with asthma, treatment of bronchospasm must be combined with the control of chronic desquamative eosinophilic bronchitis.<sup>1</sup>Step-care treatment of asthma should be strongly considered as an approach to