tbuckley/cabot-search huggingface dataset:
Sinoatrial Nodal Cell Ryanodine Receptor and Na <sup>+</sup> -Ca <sup>2+</sup> Exchanger
Authors: Konstantin Y. Bogdanov, Tatiana M. Vinogradova, Edward G. Lakatta
Journal: Circulation Research (2001)

Abstract —The rate of spontaneous diastolic depolarization (DD) of sinoatrial nodal cells (SANCs) that triggers recurrent action potentials (APs) is a fundamental aspect of the heart’s pacemaker. Here, in experiments on isolated SANCs, using confocal microscopy combined with a patch clamp technique, we show that ryanodine receptor Ca 2+ release during the DD produces a localized subsarcolemmal Ca 2+ increase that spreads in a wavelike manner by Ca 2+ -induced Ca 2+ release and produces an inward current via the Na + -Ca 2+ exchanger (NCX). Ryanodine, a blocker of the sarcoplasmic reticulum Ca 2+ release channel, in a dose-dependent manner reduces the SANC beating rate with an IC 50 of 2.6 μmol/L and abolishes the local Ca 2+ transients that precede the AP upstroke. In voltage-clamped cells in which the DD was simulated by voltage ramp, 3 μmol/L ryanodine decreased an inward current during the voltage ramp by 1.6±0.3 pA/pF (SEM, n=4) leaving the peak of L-type Ca 2+ current unchanged. Likewise, acute blockade of the NCX (via rapid substitution of bath Na + by Li + ) abolished SANC beating and reduced the inward current to a similar extent (1.7±0.4 pA/pF, n=4), as did ryanodine. Thus, in addition to activation/inactivation of multiple ion channels, Ca 2+ activation of the NCX, because of localized sarcoplasmic reticulum Ca 2+ release, is a critical element in a chain of molecular interactions that permits the heartbeat to occur and determines its beating rate.
Visual Hallucinations: More Diagnoses
Authors: Tallie Z. Baram
Journal: JAMA (1987)

<h3>To the Editor.—</h3> We must disagree with the answer given in response to Dr Babcock's inquiry to the QUESTIONS AND ANSWERS section about an 80-year-old man with visual hallucinations,<sup>1</sup>or at least suggest another alternative that should be strongly considered. We believe Dr Babcock's patient probably has the Charles Bonnet syndrome.<sup>2,3</sup>This is a constellation of formed visual hallucinations with visual loss, usually seen in elderly people, characterized by several diagnostic features that seem applicable to the patient under discussion: (1) The hallucinations are exclusively visual and are well formed, such as people and places. (2) They occur with insight and a clear consciousness—the patient is sane and aware he is hallucinating. The hallucinations are fairly devoid of emotional content and not sinister or threatening. (3) They are superimposed on or occur in combination with normal perceptions. The patient can still perceive events around him. (4) They are
Paying for bmj.com: Researchers will submit their articles elsewhere
Authors: G. Eysenbach
Journal: BMJ (2003)

Editor—The move to charge for access to bmj.com is sad.1 While I was not naive enough to believe that the BMJ would stay free forever, I had hoped that it would at least set a trend by keeping its open access policy and adopting an author pays model.

As a researcher I would be more than happy to spend money from my research grants to pay a fee for having an article processed by the BMJ. In closing the door and making the BMJ once again a subscription journal, the BMJ loses much of its appeal as the place for researchers to submit their high quality papers. At least for non-Britons, the high (international) visibility of articles published in the BMJ may have been the main motivation for submitting something there.

Researchers are interested in global impact, not in impact on BMA members alone. The BMJ—dubbed the “Better Medical Journal” by Richard Smith—becomes the “British Medical Journal” once more.
A Physician-Pharmacist Voluntary Program to Improve Prescription Practices
Authors: Calvin M. Kunin, J. Walter Dierks
Journal: New England Journal of Medicine (1969)

Abstract A joint resolution prepared by a committee made up of physicians and pharmacists in Charlottesville-Albemarle County, Virginia, dealt with improvements in prescription writing, labeling of prescriptions and the use of generic drugs. Only eleven widely used generically available drugs were found to offer enough of a cost advantage to the patients to warrant inclusion in a list of recommended generic preparations. Nevertheless, it was demonstrated that when these were prescribed, pharmacists passed on savings to the consumer. Prescribing of recommended generic drugs increased from 36.4 per cent before the study to 59.8 and 49.5 per cent three and six months later. This experience may serve as a prototype for similar voluntary programs and may be extended to a wide variety of drugs to achieve realistic analysis of differential costs of generic and brand-name preparations. If the physician and pharmacist are to use generic drugs, they must also be assured that these agents have a biologic availability equal to that of brand-name preparations.
Dual controls, p-value plots, and the multiple testing issue in carcinogenicity studies.
Authors: M R Selwyn
Journal: Environmental Health Perspectives (1989)

The interpretation of statistically significant findings in a carcinogenicity study is difficult, in part because of the large number of statistical tests conducted. Some scientists who believe that the false positive rates in these experiments are unreasonably large often suggest that the use of multiple control groups will provide important insight into the operational false positive rates. The purpose of this paper is 2-fold: to present results from two carcinogenicity studies with dual control groups, and to present and illustrate a new graphical technique potentially useful in the analysis and interpretation of tumor data from carcinogenicity studies. The experimental data analyzed show that statistically significant differences between identically treated groups will occur with regular frequency. Such data, however, do not provide strong evidence of extrabinomial variation in tumor rates. The p-value plot is advocated as a graphical method that can be used to assess visually the ensemble of p values for neoplasm data from an entire study. This technique is then illustrated using several examples. Through computer simulation, we present p-value plots generated with and without treatment effects present. On average, the plots look substantially different depending on the presence or absence of an effect. We also evaluate decision rules motivated by the p-value plots. Such rules appear to have good power to detect treatment effects (i.e., have low false negative rates) while still controlling false positive rates.
Gapex-5, a Rab31 Guanine Nucleotide Exchange Factor that Regulates Glut4 Trafficking in Adipocytes
Authors: Irfan J. Lodhi, Shian-Huey Chiang, Louise Chang, Daniel Vollenweider, Robert T. Watson, Mayumi Inoue, Jeffrey E. Pessin, Alan R. Saltiel
Journal: Cell Metabolism (2007)
The Attacks on the American Medical Association.
Authors: C. E. Cantrell
Journal: JAMA (1906)

Greenville, Texas, Sept. 10, 1906. <h3>To the Editor:</h3> —I have just read Dr. Carstens' letter inThe Journal, September 1, and wish to correct the statements made therein regarding the Walker resolutions. I do not know from whom Dr. Carstens could have gotten his impression that the Board of Trustees or the officers of the Association opposed the Walker resolutions. He certainly could not have gotten this idea from any member of the House of Delegates who was present at the time. The moment the reading of the resolutions was concluded half a dozen men were on their feet (myself among the rest), trying to make motions. Dr. Jackson of Missouri was recognized by the President and moved to lay the resolutions on the table. This motion was immediately seconded by at least a dozen different men (myself among this number), was put to vote and carried unanimously, without any
EXTRA-ABDOMINAL CONDITIONS SIMULATING ACUTE ABDOMINAL DISEASES
Authors: DAVID RIESMAN
Journal: JAMA (1925)

Surgeons have coined the linguistically objectionable phrase  abdomen to express acute abdominal diseases requiring, as a rule, operative treatment. The abdomen, however, can be neither acute nor chronic any more than a leg or an arm can be acute or chronic.  The sudden onset of pain of severe character in the abdomen, together with signs and symptoms indicating an acute intra-abdominal lesion, imposes on the physician, since he is usually the first one to be called, the duty of making a correct diagnosis and of deciding whether the treatment shall or shall not be immediate operation.  Experience and experiment have taught us that, owing to the integrating action of the spinal cord centers, pain impulses coming from the periphery may be referred to areas of the body not in direct contact with the part from which the pain impulses primarily arise. Therefore, it happens that pain in the abdominal
Doctors demand apology for UK diplomat's involvement in Pakistan tobacco meeting
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Respiratory and public health specialists have said that they are “astonished” that a high ranking British diplomat based in Pakistan attended a meeting where a tobacco company tried to persuade the country’s government to repeal regulations that would require large graphic health warnings on cigarette packaging.

Pakistan’s Ministry of National Health Services announced in February that it was introducing new regulations from 31 March that required graphic images on cigarette packages to cover 85% of the packs, up from 40% previously.

Newspapers in Islamabad reported that a meeting on 13 March attended by Philip Barton, British high commissioner for Pakistan, resulted in ministers constituting a committee to review the regulations. The meeting was called by British American Tobacco …
Difference Between Patients' and Doctors' Interpretation of Some Common Medical Terms
Authors: C. M. Boyle
Journal: BMJ (1970)

Multiple-choice questionaries completed by 234 outpatients were compared with those completed by 35 doctors to evaluate differences between their interpretation of some commonly used medical terms. There were significant differences between the "majority doctors' definition" and the number of patients agreeing with that definition in all cases except the term "a good appetite." It is suggested that unless the patient is cross-examined recording of symptoms-particularly in computer studies-may be unreliable.
Self-Tolerance and Autoimmunity in the Thyroid
Authors: Anthony C. Allison
Journal: New England Journal of Medicine (1976)

Among the fundamental observations and concepts on which the science of immunology was founded in the beginning of the 20th century was the recognition that animals do not as a rule make antibodies against their own body constituents. In 1900 Ehrlich and Morgenroth1 described how they injected goats intraperitoneally with blood of other goats and looked for the development of lysins in the blood of the recipients. These lysins were regularly found, and, moreover, reacted with blood of many other goats but never with that of the recipients. Ehrlich recognized that "the organism has contrivances by means of which the . . .
Grosse Nervenärzte. Band III. 22 Lebensbilder
Authors: F. T. Jung
Journal: JAMA (1963)

This is the third of a series of volumes of biographies of great neurologists and psychiatrists. It contains 22 chapters grouped as follows: investigators of basic problems of structure and function ( Bielschowsky, Edinger, Obersteiner, Spielmeyer, and Bethe), psychiatrists (Flemming, Gruhle, Janet, Korsakow, Lombroso, Maudsley, Möbius, and Moreira), neurologists (Dejerine, Goldflam, von Monakow, Nonne, Sicard, Strümpell, and Wallenberg), a neurosurgeon (Krause), and a clinical psychologist (Binet). The preceding volumes were reviewed in the May 19, 1956, and April 4, 1959 issues ofThe Journal. Like them, the present volume lives up to a most commendable standard for scientific biographers. Each chapter has been written by a contributor fully qualified to trace the course of the scientific thinking and development of his propositus and, at the same time, sufficiently acquainted with the subject's personality to paint a wordpicture of the man. The reader finds himself constantly wondering what it was in the
Polycythemia Secondary to Hamartoma of the Liver
Authors: Burrill N. Josephs
Journal: JAMA (1962)

This report adds another type of tumor to those already described as associated with and probably causing a secondary polycythemia. A 28-year-old woman with severe polycythemia and a large hamartoma of the liver was cured of her polycythemia by partial hepatectomy. There is convincing evidence for the theory that an erythropoietic-stimulating substance is produced in various tumors, especially in hypernephroma and renal cysts. It is logical to assume that this hamartoma was the site of production of erythropoietin and that in the future other tumors causing a secondary polycythemia will be described. Preoperative treatment by venesection and the expectation of ultimate cure of the polycythemia by ablation of such tumors must be recognized by surgeons.
Menstrual Function and Bone Mass in Elite Women Distance Runners
Authors: ROBERT MARCUS
Journal: Annals of Internal Medicine (1985)

Bone mass and metabolic features were studied in 17 women distance runners. Eleven of the women had secondary amenorrhea for 1 to 7 years. Six women have maintained regular menses since menarche. Both groups were matched for aerobic capacity, body fat, exercise intensity, and age of menarche. Mineral density of lumbar spine in the amenorrheic runners was lower than that in the cyclic women and age-matched controls, but higher than that in runners with secondary amenorrhea who are less physically active. Mineral density of the radius was normal in both groups. Running-related fractures were more frequent in amenorrheic women. Metabolic assessment showed no differences between groups, except that serum triiodothyronine was lower in the amenorrheic group, perhaps reflecting low calorie intake. Intense exercise may reduce the impact of amenorrhea on bone mass; however, amenorrheic runners remain at high risk for exercise-related fractures.
Abstract 1480: Characterization of C35, a novel protein binding partner of p73, in gynaecological cancers
Authors: Sanna Ching-shan Wong, Thomas Ho-yin Leung, Karen Kar-loen Chan, Hextan Yuen-sheung Ngan
Journal: Cancer Research (2010)

Abstract The p53 family protein p73 encodes pro-apoptotic (TAp73) and anti-apoptotic (DNp73) isoforms. The functional role of the two isoforms in cancer development is still unclear. In this study, by yeast-2-hybrid screening using DNp73 as a bait, we identified C35 (C17orf37) as a novel protein interacting partner of p73. C35 was mapped to chromosome 17q12. It was overexpressed in breast cancer and prostate cancer. Its expression was positively correlated with the grade and stage of breast cancer progression. A recent study reported that C35 promotes cell migration and invasion in prostate cancer cells. However, the significance of C35 in cancer development remains to be elucidated. In this study, we focused on the functional role of C35 in gynaecological cancers. The binding of C35 and DNp73 was confirmed by co-immunoprecipitation. Quantitative real-time PCR revealed that mRNA expression of C35 in ovarian and cervical cancer cell lines was higher than that in normal cell lines. In addition, mRNA expression of C35 was significantly higher in ovarian cancer clinical samples than that in normal samples (p&amp;lt;0.0001, t-test). To investigate the function of C35, SiHa and OV2008 cells stably expressing C35 were established. The protein expression of C35 was confirmed by western blot analysis. In studying the effect of C35 on cell transforming ability, soft agar assay was performed. The result showed that the number of colonies formed by the C35 stable clones was significantly higher than those formed by the parental cells and control vector stably transfected cells. In addition, the size of the colonies formed by the C35 stable clones was larger. Wound healing assay and transwell migration assay were performed to investigate the effect of C35 on cell migration rate. We found that the migration rate of the C35 stable clones was higher than that of the parental cells and vector transfected cells. XTT assay revealed that the proliferation rate of the C35 stable clones was higher than that of the parental cells and vector controls. In summary, our findings suggested that C35 is overexpressed in ovarian cancer. C35 likely exerts its oncogenic roles to enhance transformation, cell migration and cell proliferation in gynaecological cancers. Further study of the significance of the DNp73-C35 interaction may give insight into their oncogenic properties. 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 1480.
Vitamin B<sub>12</sub>, Folic Acid, and the Prevention of Dementia
Authors: Robert Clarke
Journal: New England Journal of Medicine (2006)

Finding treatments for the prevention of dementia is an important challenge for medical research.1 Dementia currently affects about 4.5 million persons in the United States, and many more have cognitive impairment. The disorder is characterized by an insidious and progressive loss of memory and higher intellectual function, which ultimately leads to the inability of affected persons to live independently. The population distribution of cognitive impairment shows a continuum of severity, with dementia at one extreme of the distribution.1 Longitudinal, population-based studies of people who are 70 years of age or older show that cognitive function declines abruptly and irreversibly at . . .
Stress and neuroimmune regulation of gut mucosal function
Authors: J Santos
Journal: Gut (2000)

The intestinal mucosa is composed of three layers: the innermost muscularis mucosae, lamina propria, and the epithelial layer which is exposed to the lumen. Besides being the structural support for the epithelium, the lamina propria contains elements important for immunological and absorptive functions. Thus in the lamina propria we find blood and lymph vessels, nerve varicosities, and a plethora of immune cells (plasma cells, lymphocytes, macrophages, eosinophils, mast cells, dendritic cells, etc).1 The lamina propria is densely innervated via both intrinsic (mainly from the submucosal plexus) and extrinsic nerve fibres. From the lamina propria, chemical messengers from nerves and immune cells reach and act on epithelial cell receptors.

The intestinal epithelium is a single layer of columnar cells. The most common cells are the enterocytes (absorptive cells). However, a rich variety of cells are also present, including goblet cells (secrete mucus), endocrine cells (secrete hormones and neuropeptides), Paneth cells, caveolated (tuft) and cup cells, M cells, stem cells (crypt), and intraepithelial lymphocytes. Epithelial cells are bound together by junctional complexes in the apical membrane1: the tight junction (zona occludens), the intermediate junction (zonula adherens), and the desmosomes (macula adherens). These structures define the paracellular space.

The epithelial lining serves several functions in the intestinal tract.2 The junctional complex acts as a physical barrier limiting the uptake of microbial and food derived antigens. However, in certain conditions macromolecules and even cells (mainly neutrophils) may be able to cross it to reach the lamina propria or the luminal surface, respectively. The presence of various enzymes on the apical surface and within epithelial cells contributes to the digestion and absorption of nutrients as well as to the degradation of immunogenic particles. Absorption and secretion of water and electrolytes is regulated by the epithelium. The epithelium maintains its own integrity …
COMPLETE CONSTIPATION OF THE BOWELS FOR TWENTY-EIGHT DAYS, TERMINATING FATALLY AFTER OPERATION
Authors: G. Norman
Journal: BMJ (1854)

ws f of this disorder we no n y he t ta ranltion, so to spea& Of the ss ca Smating fatally in my own practe, in tm s go by, oem VW the me compiment of acute inm atory aetie involvn th ubstce and peritonel sufc of the ute, he rs adjacent, and patiarly the parete of the descendng colon This w followed by absione of
Emotional Factors in Juvenile Diabetes Mellitus: A Study of Early Life Experience of Adolescent Diabetics
Authors: STEFAN P. STEIN, EDWARD CHARLES
Journal: American Journal of Psychiatry (1971)

The family backgrounds of a group of adolescent diabetics were compared with those of a matched group of nondiabetic chronically ill adolescents; both groups were predominantly from a low socioeconomic level. The diabetic group was found to have a significantly higher incidence of loss and of severe family disturbance. This finding is discussed in relation to findings from other psychosocial studies of juvenile diabetics. The authors advance the hypothesis that juvenile-onset diabetes occurs as a consequence of psychological stress in a physiologically susceptible individual.
What Fans the Fire
Authors: Amy S. Major, David G. Harrison
Journal: Circulation (2011)

I t is now widely accepted that inflammation and immunity play important roles in the pathogenesis of atherosclerosis and diabetes mellitus.Over the past 3 decades, it has been demonstrated that cells of both the innate and adaptive immune systems contribute to the progression of atherosclerosis and modulation of plaque stability. 1Similarly, recent studies in experimental models of obesity and type II diabetes mellitus have shown that not only macrophages, but also T cells and B cells are involved in the modulation of adipose depots and the development of insulin resistance. 2-5However, even with all that is known about the important cellular players in atherogenesis, a clear understanding of the mechanisms by which immune cells influence arterial plaque formation is lacking.
Clinical trials in the era of personalized oncology
Authors: Michael L. Maitland, Richard L. Schilsky
Journal: CA A Cancer Journal for Clinicians (2011)

Abstract The rapid pace of discoveries in tumor biology, imaging technology, and human genetics hold promise for an era of personalized oncology care. The successful development of a handful of new targeted agents has generated much hope and hype about the delivery of safer and more effective new treatments for cancer. The design and conduct of clinical trials has not yet adjusted to a new era of personalized oncology and so we are more in transition to that era than in it. With the development of treatments for breast cancer as a model, we review the approaches to clinical trials and the development of novel therapeutics in the prior era of population oncology, the current transitional era, and the future era of personalized oncology. CA Cancer J Clin 2011. © 2011 American Cancer Society.
Molecular Basis of Cardiology.
Authors: A. M KATZ
Journal: Cardiovascular Research (1993)

Molecular Basis of Cardiology. Get access ARNOLD M KATZ ARNOLD M KATZ Farmington, Connecticut, USA Edited by R Roberts. (Pp 518; £39.50.) Oxford: Blackwell Scientific Publications, 1993. ISBN 0-86542-196-X. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 9, September 1993, Page 1698, https://doi.org/10.1093/cvr/27.9.1698b Published: 01 September 1993