tbuckley/cabot-search huggingface dataset:
Chk1- and Claspin-Dependent but ATR/ATM– and Rad17-Independent DNA Replication Checkpoint Response in HeLa Cells
Authors: Verónica Rodríguez-Bravo, Sandra Guaita-Esteruelas, Roger Florensa, Oriol Bachs, Neus Agell
Journal: Cancer Research (2006)

Abstract When DNA synthesis is inhibited, DNA replication checkpoint is activated to prevent mitosis entry without fully replicated DNA. In Xenopus, caffeine-sensitive kinases [ataxia telangiectasia mutated (ATM) and ATM-related protein (ATR)] are essential in this checkpoint response, but in mammal cells an ATR/ATM–independent checkpoint response to DNA synthesis inhibition exists. Using HeLa cells, which have a caffeine-insensitive checkpoint response, we have analyzed here which molecules known to be involved in the DNA replication checkpoint participate in the caffeine-insensitive response. When DNA synthesis was inhibited in the presence of UCN01 or after knocking down Chk1 expression [Chk1 small interfering RNA (siRNA)], HeLa cells entered into aberrant mitosis. Consequently, Chk1 is essential for both the ATR/ATM–dependent and ATR/ATM–independent checkpoint response in HeLa cells. Neither wortmannin, Ly294002, nor SB202190 abrogated the caffeine-insensitive checkpoint response, indicating that DNA-PK and p38α,β are not involved in the ATR/ATM–independent Chk1 activation upon DNA synthesis inhibition. Using siRNA to knock down Rad17 and claspin, two molecules involved in sensing stalled replication forks, we also showed that claspin but not Rad17 is essential for the ATR/ATM–independent checkpoint response. Inhibition of DNA synthesis in HeLa cells led to a decrease in cyclin B1 protein accumulation that was abrogated when UCN01 was added or when claspin was knocked down. We conclude that upon DNA synthesis inhibition, Chk1 can be activated in a claspin-dependent manner independently of ATR and ATM, leading to cyclin B1 down-regulation and providing the cells of an additional mechanism to inhibit mitosis entry. (Cancer Res 2006; 66(17): 8672-9)
Letter: Vomiting with clonidine withdrawal.
Authors: J A Hopkirk, N B Simpson, W R Fitzgerald
Journal: BMJ (1975)

Vomiting with Clonidine Withdrawal SIR,-We would like to report a case of persistent vomiting in a patient after rapid withdrawal of clonidine (Catapres).The dangers of paroxysmal hypertension asso- ciated with raised catecholamine levels following rapid withdrawal of clonidine are well documented.'We have found no previous report of persistent vomiting occur- ring in this situation.
Danazol for the Treatment of Idiopathic Thrombocytopenic Purpura
Authors: Yeon S. Ahn, William J. Harrington, Sheryl R. Simon, Ravindra Mylvaganam, Lorraine M. Pall, Antero G. So
Journal: New England Journal of Medicine (1983)

Idiopathic thrombocytopenic purpura is an autoimmune disorder, most common in young women. We treated 22 patients with this disorder (12 of whom were women) with danazol, an androgen with reduced virilizing capability, for two months or longer. Fifteen had undergone splenectomy, all were receiving glucocorticoids, and 18 had also been given other treatments. Fifteen of the patients were benefited, 11 with sustained normalization of their platelet counts. Six of eight patients tested had initial increases in circulating platelet-reactive IgG; in all six there was a marked decrease concomitant with danazol therapy. Danazol was effective in both men and women, irrespective of previous treatments. The duration of remissions ranged from 2 to 13 months. The drug was well tolerated and appears to be better suited than glucocorticoids for long-term management of idiopathic thrombocytopenic purpura, but the exact indications for the use of danazol in this disorder remain to be determined.
Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: Effect of the lipid-lowering agents, atorvastatin and bezafibrate
Authors: J. Canudas, A. Cenarro, F. Civeira, A.L. Garcı́-Otı́n, R. Arı́stegui, C. Dı́az, X. Masramon, J.M. Sol, G. Hernández, M. Pocovı́
Journal: Metabolism (2001)
WHO swine flu review committee promises to probe links with drug industry
Authors: J. Zarocostas
Journal: BMJ (2010)

The chairman of the external expert review committee examining the World Health Organization’s management of the H1N1 pandemic said on 2 July that the panel will probe deeper into allegations that the drug industry may have unduly influenced key outcomes.

Speaking at the end of the second round of hearings at WHO headquarters Harvey Fineberg, the head of the 27 member review committee, told reporters that, “Part of [our] concern is dealing with the accusations of undue influence by pharmaceutical companies on the decisions.”

Asked if that included looking into …
Cholesterol, Primary and Secondary Prevention, and All-Cause Mortality
Authors: Michael H. Criqui
Journal: Annals of Internal Medicine (1991)

Clinical trials of cholesterol lowering in apparently healthy persons (primary prevention) and in persons with known coronary disease (secondary prevention) routinely show a decrease in the incidence of nonfatal and fatal coronary events. Primary prevention trials, however, generally have failed to show a beneficial effect of cholesterol lowering on total mortality, because of both low overall death rates and a disturbingly high number of deaths from noncoronary causes in the treatment groups. Studies of secondary prevention give more clear-cut evidence of benefit. The rate of death from coronary heart disease is extremely high in these studies, overwhelming the rates for other causes of death. Thus, a possible increase in noncoronary deaths is of much less concern in secondary prevention studies. A possible link between cholesterol lowering and noncoronary causes of death should be explored using dose-response analyses of existing data sets, in both individual studies and aggregate meta-analysis; such analyses should be similar to those that have been done to study the relation between cholesterol lowering and coronary events. These analyses would greatly assist us in developing safe, efficacious ways to prevent coronary heart disease.
Residual DNA methylation at remission is prognostic in adult Philadelphia chromosome–negative acute lymphocytic leukemia
Authors: Hui Yang, Tapan Kadia, Lianchun Xiao, Carlos E. Bueso-Ramos, Koyu Hoshino, Deborah Ann Thomas, Susan O'Brien, Elias Jabbour, Sherry Pierce, Gary L. Rosner, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2008)
Cardiac preservation is enhanced in a heterotopic rat transplant model by supplementing the nitric oxide pathway.
Authors: D J Pinsky, M C Oz, S Koga, Z Taha, M J Broekman, A J Marcus, H Liao, Y Naka, J Brett, P J Cannon
Journal: Journal of Clinical Investigation (1994)

Nitric oxide (NO) is a novel biologic messenger with diverse effects but its role in organ transplantation remains poorly understood. Using a porphyrinic microsensor, the first direct measurements of coronary vascular and endocardial NO production were made. NO was measured directly in the effluent of preserved, heterotopically transplanted rat hearts stimulated with L-arginine and bradykinin; NO concentrations fell from 2.1 +/- 0.4 microM for freshly explanted hearts to 0.7 +/- 0.2 and 0.2 +/- 0.08 microM for hearts preserved for 19 and 38 h, respectively. NO levels were increased by SOD, suggesting a role for superoxide-mediated destruction of NO. Consistent with these data, addition of the NO donor nitroglycerin (NTG) to a balanced salt preservation solution enhanced graft survival in a time- and dose-dependent manner, with 92% of hearts supplemented with NTG surviving 12 h of preservation versus only 17% in its absence. NTG similarly enhanced preservation of hearts stored in University of Wisconsin solution, the clinical standard for preservation. Other stimulators of the NO pathway, including nitroprusside, L-arginine, or 8-bromoguanosine 3',5' monophosphate, also enhanced graft survival, whereas the competitive NO synthase antagonist NG-monomethyl-L-arginine was associated with poor preservation. Likely mechanisms whereby supplementation of the NO pathway enhanced preservation included increased blood flow to the reperfused graft and decreased graft leukostasis. NO was also measured in endothelial cells subjected to hypoxia/reoxygenation and detected based on its ability to inhibit thrombin-mediated platelet aggregation and serotonin release. NO became undetectable in endothelial cells exposed to hypoxia followed by reoxygenation and was restored to normoxic levels on addition of SOD. These studies suggest that the NO pathway fails during preservation/transplantation because of formation of oxygen free radicals during reperfusion, which quench available NO. Augmentation of NO/cGMP-dependent mechanisms enhances vascular function after ischemia and reperfusion and provides a new strategy for transplantation of vascular organs.
Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma
Authors: Javeed Iqbal, George Wright, Chao Wang, Andreas Rosenwald, Randy D. Gascoyne, Dennis D. Weisenburger, Timothy C. Greiner, Lynette Smith, Shuangping Guo, Ryan A. Wilcox, Bin Tean Teh, Soon Thye Lim, Soon Yong Tan, Lisa M. Rimsza, Elaine S. Jaffe, Elias Campo, Antonio Martinez, Jan Delabie, Rita M. Braziel, James R. Cook, Raymond R. Tubbs, German Ott, Eva Geissinger, Philippe Gaulard, Pier Paolo Piccaluga, Stefano A. Pileri, Wing Y. Au, Shigeo Nakamura, Masao Seto, Francoise Berger, Laurence de Leval, Joseph M. Connors, James Armitage, Julie Vose, Wing C. Chan, Louis M. Staudt
Journal: Blood (2014)
Isoniazid in Tuberculous Psychotic Patients
Authors: Michael A. Ferrara, Eloise B. Peterson
Journal: New England Journal of Medicine (1953)

WHEN isoniazid (iso-nicotinic acid hydrazide) was first introduced in the treatment of tuberculosis, it was noted that, in contrast to other antituberculosis drugs, it was of low toxicity. Such toxic manifestations as were observed in the early days of its use (involuntary twitching, hyperreflexia, irritability, transient loss of memory, constipation, vertigo, insomnia and difficulty in starting the urinary stream) were transitory and mild, even with the continued use of the drug, and little clinical significance was attached to them. However, with more patients receiving the drug and with increases in dosage, it became apparent that isoniazid could have serious toxic . . .
Richard Leach Maddox (1816–1902)
Authors: Edward Shapiro
Journal: New England Journal of Medicine (1961)

BECAUSE of Richard Leach Maddox, M.D., photography was given an early impetus to become a disseminator of medical knowledge. His interest in the camera, combined with his poor health and his medical training, enabled him to invent the gelatin bromide negative that is the backbone of today's photographic film.Born in Bath, England, in 1816, Maddox studied medicine at University College, London. For unknown reasons, he took his degree at Edinburgh. Ill-health from early childhood prompted a voyage around the world before he settled in Constantinople, where he married and practiced medicine for some years. Here, in 1846, he purchased . . .
Parity and Primary Liver Cancer Among Young Women
Authors: A. W. Hsing, J. K. McLaughlin, R. N. Hoover, H. T. C. Chien, W. J. Blot, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Parity and Primary Liver Cancer Among Young Women Get access Ann W. Hsing, Ann W. Hsing * Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. * Correspondence to: Ann W. Hsing, Ph.D., Executive Plaza North, Rm. 415, National Institutes of Health, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph K. McLaughlin, Joseph K. McLaughlin Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert N. Hoover, Robert N. Hoover Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Harvey T. Co Chien, Harvey T. Co Chien Westat, Rockville, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar William J. Blot, William J. Blot Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph F. Fraumeni, Jr. Joseph F. Fraumeni, Jr. Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 14, 15 July 1992, Pages 1118–1119, https://doi.org/10.1093/jnci/84.14.1118 Published: 15 July 1992 Article history Received: 08 April 1992 Revision received: 13 May 1992 Accepted: 14 May 1992 Published: 15 July 1992
A CASE OF DIFFUSE, PURULENT, VENTRIC-ULO-SEPTAL MYOCARDITIS WITH ADAMS-STOKES' SYNDROME
Authors: HARVEY G. BECK
Journal: JAMA (1910)

The subject of suppurative myocarditis has received some attention from ancient writers, since Whittaker<sup>1</sup>states that Galen described this malady in gladiators and Benevenus and Bonetus have also described abscesses in the walls of the heart. Later, Laennec and Meckel cited similar cases. These cases of suppurative myocarditis are called "myocarditis purulenta" by Aschoff,<sup>2</sup>who shows that they are usually produced by ulcerative endocarditis, intracardiac thrombosis, pericarditis and septic infarction and abscess formation in cases of general pyemia. It will be seen that these purulent infiltrations or abscesses in the heart muscle are secondary processes caused by an antecedent infection. The case we shall later describe is a primary condition and cannot, therefore, be compared to the above mentioned processes. The condition known as acute interstitial myocarditis, which follows such infectious diseases as diphtheria, scarlet fever and rheumatism, first described by von Hayen,<sup>3</sup>also differs from our
A FURTHER EXPERIMENTAL STUDY ON EXCITATION OF INFECTIONS OF THE THROAT
Authors: Samuel B. Grant, Stuart Mudd, Alfred Goldman
Journal: The Journal of Experimental Medicine (1920)

Improvements are described in the method of following temperature changes, and thus alterations in vasomotor tone, in exposed mucous membranes. Invention of an applicator holder, by means of which more sure and stable apposition of the thermopile terminals to the mucous surface may be effected has been the chief advance. Minor improvements have been the use of a saliva ejector and of better calibration technique. The palatine tonsils, like the palate, pharynx, and skin, react to chilling of the body surface with reflex vasoconstriction and ischemia. On rewarming the subject the tonsils quickly more than recover their former blood supply, actually becoming hyperemic; the skin returns to about its control condition; the pharynx and palate remain somewhat ischemic. The hypothesis is advanced that one factor in the beneficial hardening effect of cold bathing and outdoor living, with its incident heightened immunity to respiratory infection, may be the training of the vasomotor system in the direction of development in the pharynx of a reaction of hyperemia following chilling, similar to that observed in the tonsils of the present subjects. With inhalation of amyl nitrite, the skin temperature has always shown a sharp transient rise. The mucous membrane, if relatively ischemic, responds by a rise corresponding to the skin flush. If already hyperemic, local vasodilation in the mucous membrane with amyl nitrite is more than counterbalanced by the lowering of the general blood pressure, and the temperature falls. The flora of the pharynx and tonsils, studied by the unsatisfactory method described, showed, in several instances, after experimentation changes apparently due to proliferation of one of the microorganisms already present. In one case Streptococcus haemolyticus, in one Micrococcus catarrhalis, and in a third Bacillus influenzae was the organism showing a relative increase in numbers. The first two instances were associated with sore throat, the third with slight constitutional symptoms. The chilling in the experiments in no instance produced albuminuria or glycosuria, although a more dilute urine was apparently excreted during the experiments. A fall in hydrogen ion concentration, referable to the forced respiration, was noted.
A Multi-Individual Pharmacokinetic Model Framework for Interpreting Time Trends of Persistent Chemicals in Human Populations: Application to a Postban Situation
Authors: Roland Ritter, Martin Scheringer, Matthew MacLeod, Urs Schenker, Konrad Hungerbühler
Journal: Environmental Health Perspectives (2009)

Human milk and blood are monitored to detect time trends of persistent organic pollutants (POPs) in humans. It is current practice to use log-linear regression to fit time series of averaged cross-sectional biomonitoring data, here referred to as cross-sectional trend data (CSTD).The goals of our study are to clarify the interpretation of half-lives derived from fitting exponential functions to declining CSTD and to provide a method of estimating human elimination half-lives from CSTD collected in a postban situation.We developed a multi-individual pharmacokinetic model framework and present analytical solutions for a postban period. For this case, the framework quantitatively describes the relationships among the half-life for reduction of body burdens of POPs derived from CSTD, the half-life describing decline in daily intake, and the half-life of elimination from the human body.The half-life derived from exponential fitting of CSTD collected under postban conditions describes the exposure trend and is independent of human elimination kinetics. We use a case study of DDT (dichlorodiphenyltrichloroethane) to show that CSTD can be combined with exposure data obtained from total diet studies to estimate elimination kinetics of POPs for humans under background exposure conditions.CSTD provide quantitative information about trends in human exposure and can be combined with exposure studies to estimate elimination kinetics. The full utility of these data has not been exploited so far. An efficient and informative monitoring strategy for banned POPs in humans would coordinate sampling of consistent sets of CSTD from young adults with total diet studies.
Plasma prolactin levels during a simulated dive.
Authors: R A Karmali, C J Weatherly, L Parke, D F Horrobin
Journal: BMJ (1976)

Myasthenic syndrome during treatment with practolol SIR,-The myasthenic syndrome during treat- ment with large doses of practolol described by Drs R 0 Hughes and F J Zacharias (21 February, p 460) appears to be a clinical manifestation of the effect of 3-adrenoceptor blocking agents on the neuromuscular junction observed in animals.Like other members of this group of drugs' 2 practolol has a curare- like action, as shown in sciatic nerve- gastrocnemius preparations of the cat:' and frog and in the frog sciatic nerve-sartorius preparation and rectus abdominis muscle.2 4 The dosage required to depress neuromuscular transmission was larger for practolol than for propranolol.Though the patient's electromyogram, presumably taken in the resting state, was normai, it would be of great interest to know whether in the myasthenic state repetitive nerve stimulation evoked a gradually declining response of the muscle and whether even in the absence of the myasthenic syndrome the patient was particularly prone to fatigue.As in experimental animals the neuromuscular effects of '3-adrenoceptor blockers are readily reversible the risk of a relapse of the myas- thenic syndrome seems to be remote.How- ever, the patient may be hypersensitive to D-tubocurarine and related agents and also to drugs with a local anaesthetic action, like quinidine.
Relationship Between Physician and Hospital Coronary Angioplasty Volume and Outcome in Elderly Patients
Authors: James G. Jollis, Eric D. Peterson, Charlotte L. Nelson, Judith A. Stafford, Elizabeth R. DeLong, Lawrence H. Muhlbaier, Daniel B. Mark
Journal: Circulation (1997)

Background With the expectation that physicians who perform larger numbers of coronary angioplasty procedures will have better outcomes, the American College of Cardiology/American Heart Association guidelines recommend minimum physician volumes of 75 procedures per year. However, there is little empirical data to support this recommendation. Methods and Results We examined in-hospital bypass surgery and death after angioplasty according to 1992 physician and hospital Medicare procedure volume. In 1992, 6115 physicians performed angioplasty on 97 478 Medicare patients at 984 hospitals. The median numbers of procedures performed per physician and per hospital were 13 (interquartile range, 5 to 25) and 98 (interquartile range, 40 to 181), respectively. With the assumption that Medicare patients composed one half to one third of all patients undergoing angioplasty, these median values are consistent with an overall physician volume of 26 to 39 cases per year and an overall hospital volume of 196 to 294 cases per year. After adjusting for age, sex, race, acute myocardial infarction, and comorbidity, low-volume physicians were associated with higher rates of bypass surgery ( P &lt;.001) and low-volume hospitals were associated with higher rates of bypass surgery and death ( P &lt;.001). Improving outcomes were seen up to threshold values of 75 Medicare cases per physician and 200 Medicare cases per hospital. Conclusions More than 50% of physicians and 25% of hospitals performing coronary angioplasty in 1992 were unlikely to have met the minimum volume guidelines first published in 1988, and these patients had worse outcomes. While more recent data are required to determine whether the same relationships persist after the introduction of newer technologies, this study suggests that adherence to minimum volume standards by physicians and hospitals will lead to better outcomes for elderly patients undergoing coronary angioplasty.
Alcoholic Liver Disease: Pathobiology, Epidemiology and Clinical Aspects
Authors: Howard M. Spiro
Journal: JAMA (1985)

The most compelling section of this multiauthored book covers the epidemiology of alcoholic liver disease. More than a third of the book marshals evidence from all over the world that the incidence of liver disease is rapidly increasing in step with the increasing consumption of alcohol. One has only to look at the graphs to want to join the antialcohol forces, despite the gracious admission of Hans Popper that "many of the contributors to this volume, including myself, still believe that moderate drinking may add to the enjoyment of their lives." How to moderate drinking is the real problem, and one happily addressed in the last two chapters of the book, which deal with the treatment of alcoholism. Contemplating the scanty advances in the therapy of alcoholic liver disease over the past 40 years, I found these chapters an especially worthwhile reminder that in a rational society we would try