tbuckley/cabot-search huggingface dataset:
Multimodal Control of Cdc25A by Nitrosative Stress
Authors: Robert J. Tomko, John S. Lazo
Journal: Cancer Research (2008)

Abstract Cdc25A propels cell cycle progression, is overexpressed in numerous human cancers, and possesses oncogenic and antiapoptotic activities. Reactive oxygen species, such as hydrogen peroxide, regulate Cdc25A, but the physiologic and pathologic effects of nitric oxide (•NO) and •NO-derived reactive species are not well defined. Herein, we report novel independent mechanisms governing Cdc25A in response to nitrosative insult. We observed direct and rapid inhibition of Cdc25A phosphatase activity after in vitro treatment with the low molecular mass cell-permeable S-nitrosothiol S-nitrosocysteine ethyl ester (SNCEE). In addition, treatment of cancer cells with SNCEE induced nitrosative stress and decreased Cdc25A protein levels in a time-dependent and concentration-dependent manner. Similarly, iNOS-derived •NO was sufficient to suppress Cdc25A expression, consistent with its role in mediating nitrosative stress. Whereas a decrease in Cdc25A half-life was not observed in response to SNCEE, we found the translational regulator eukaryotic initiation factor 2α (eIF2α) was hyperphosphorylated and total protein translation was decreased with kinetics consistent with Cdc25A loss. Inhibition of eIF2α decreased Cdc25A levels, supporting the hypothesis that SNCEE suppressed Cdc25A translation through inhibition of eIF2α. Nitrosative stress decreased the Cdc25A-bound fraction of apoptosis signal-regulating kinase-1 (ASK-1) and sensitized cells to apoptosis induced by the ASK-1–activating chemotherapeutic cis-diaminedichloroplatinum (II), suggesting that nitrosative stress–induced suppression of Cdc25A primed cells for ASK-1–dependent apoptosis. Together these data reveal novel •NO-dependent enzymatic and translational mechanisms controlling Cdc25A, and implicate Cdc25A as a mediator of •NO-dependent apoptotic signaling. [Cancer Res 2008;68(18):7457–65]
The Big Fix: How the Pharmaceutical Industry Rips Off American Consumers
Authors: R. Moynihan
Journal: BMJ (2003)

<i>The Big Fix</i> opens with feisty 77 year old Melva McCuddy from Ohio struggling to find more than $6000 a year to pay for her multiple medications. We learn that she travels across the United States border to Canada, where her breast cancer drug, tamoxifen, is eight times cheaper than in her local pharmacy. Then we meet her son and grandson, both with medical troubles of their own, and discover that the family has three generations without any insurance cover for pharmaceuticals, and three generations forced to rely on handouts from their doctors. “The worst thing,” Melva told the audience at the book9s launch in Washington DC this month, “is being forced to beg doctors for free samples.”
Severe Transient Pancytopenia Associated With Procainamide Ingestion
Authors: Avrum Z. Bluming
Journal: JAMA (1976)

A 73-year-old woman was found to have clinically significant pancytopenia in association with procainamide hydrochloride ingestion. The syndrome, resembling systemic lupus erythematosus, which has been reported to develop in patients treated with this agent, is characterized by mild to moderate anemia and mild to moderate granulocytopenia. Severe granulocytopenia in patients taking procainamide and unrelated to a lupus syndrome has not previously been reported in association with significant thrombocytopenia. The clinical severity of this patient's presentation, suggesting an aleukemic leukemia, and its complete remission after cessation of procainamide administration occasional this report.
Epidemiology and detection of HIV-1 among pregnant women in the United Kingdom: results from national surveillance 1988-96
Authors: A. Nicoll, C. McGarrigle, A. R Brady, A E Ades, P. Tookey, T. Duong, J. Mortimer, S. Cliffe, D. Goldberg, D. Tappin, C. Peckham, C. Hudson
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To describe the epidemiology of HIV-1 infection in pregnant women in the United Kingdom. <b>Design:</b> Serial unlinked serosurveillance for HIV-1 in neonatal specimens and surveillance through registers of diagnosed maternal and paediatric infections from reporting by obstetricians, paediatricians, and microbiologists. <b>Setting:</b> United Kingdom, 1988-96. <b>Subjects:</b> Pregnant women proceeding to live births and their children <b>Main outcome measures:</b> Time trends in prevalence of HIV-1 seropositivity in newborn infants (as a proxy for infection in mothers); the proportions of mothers with diagnosed HIV-1 infections, and their characteristics. <b>Results:</b> HIV-1 prevalence among mothers in London rose sixfold between 1988 and 1996 (0.19% of women tested; 1 in 520 in 1996). Apart from in Edinburgh and Dundee, levels remained low in Scotland (0.025%; 1 in 3970) and elsewhere in the United Kingdom (0.016%; 1 in 1930). Over a third of births to infected mothers in 1996 occurred outside London. In London the reported infections were predominantly among black African women, whereas in Scotland most were associated with drug injecting. The contribution of reported infection among African women increased over time as that of drug injecting declined. In Scotland 51% of mothers9 infections were diagnosed before the birth. In England, despite a national policy initiative in 1992 to increase the antenatal detection rate of HIV, no improvement in detection was observed, and in 1996 only 15% of previously unrecognised HIV infections were diagnosed during pregnancy. <b>Conclusions:</b> HIV-1 infection affects mothers throughout the United Kingdom but is most common in London. Levels of diagnosis in pregnant women have not improved. Surveillance data can monitor effectively the impact of initiatives to reduce preventable HIV-1 infections in children. <h3>Key messages</h3> HIV-1 infections among pregnant women are commonest in London but they are found in all parts of the United Kingdom Black African ethnic group or a history of drug injecting are important risk factors, but HIV-1 infection occurs among women without either characteristic Identification of HIV infection in pregnant women, if combined with uptake of interventions, reduces the risk of mother to child transmission HIV testing should be universally available in all antenatal clinics without any obstacle All pregnant women in London should be offered and recommended HIV testing; elsewhere, HIV testing should be offered and recommended to those with risk characteristics
Plans for tackling research fraud may not go far enough
Authors: C. White
Journal: BMJ (2000)

The UK government is considering giving its support to a national body to tackle misconduct in biomedical research. But members of the Committee on Publication Ethics (COPE), which was set up three years ago by scientists, doctors, and the editors of medical journals to raise public awareness of research fraud, fear that the body's powers will not be strong enough.

The committee wants a national body to tackle research fraud similar to those operating in the United States and Scandinavia. The committee's latest report, published this week, expresses frustration at the lack of movement on the issue, despite support for the idea from the joint consensus conference on misconduct in biomedical research at the …
Rapid Stroke Treatment an Elusive Goal
Authors: Mike Mitka
Journal: JAMA (2008)

NEW ORLEANS—Although the availability of thrombolytic therapy in the form of tissue plasminogen activator (tPA) was seen as a potential milestone in treating ischemic stroke when it was approved by the US Food and Drug Administration in 1996, the reality is that few patients receive it. The failure of most individuals experiencing ischemic stroke to recognize their symptoms and promptly seek care, coupled with the delays by emergency departments to deliver timely care when such patients come through their doors, means that only a small proportion (estimated at less than 5%) of eligible patients with stroke receive tPA within the therapeutic window of 3 hours from symptom onset. At the American Stroke Association’s International Stroke Conference held here in February, researchers presented data about factors contributing to these roadblocks to swift treatment of this neurological emergency.
Aerosolized Surfactant in Sepsis-Induced Adult Respiratory Distress Syndrome
Authors: Christopher Doig
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The article by Dr Weg and colleagues<sup>1</sup>is important to all physicians treating patients with adult respiratory distress syndrome (ARDS). Though their article is listed under the heading Preliminary Communication and the primary objective is to assess drug safety, the authors have also assessed potential drug efficacy. It would be useful for readers to have further information before reaching any conclusion about this article. The authors comment that 51 patients were admitted from 20 tertiary care medical centers throughout the United States. Sepsis-induced ARDS is a common condition in most tertiary care intensive care units (ICUs). The authors do not comment on the study interval for patient enrollment, the number of patients screened for entry into the study, the number eligible for enrollment, and the reason for exclusion or refusal of subjects. These data are important if we are to be sure that the study sample
Herb medicine Inchin-ko-to (TJ-135) regulates PDGF-BB-dependent signaling pathways of hepatic stellate cells in primary culture and attenuates development of liver fibrosis induced by thioacetamide administration in rats
Authors: Yukihiro Imanishi, Naoto Maeda, Kohji Otogawa, Shuichi Seki, Hiroko Matsui, Norifumi Kawada, Tetsuo Arakawa
Journal: Journal of Hepatology (2004)
Effect of Digitalis Glycosides on the Myocardial Sodium and Potassium Balance
Authors: JOHN R. BLACKMON, HERMAN K. HELLERSTEIN, LOUIS GILLESPIE, ROBERT M. BERNE
Journal: Circulation Research (1960)

Nontoxic and toxic doses of digitalis glycoside produced a rapid release of potassium from the myocardium and from extracardiac tissues of the dog. For approximately 25 minutes after the administration of a digitalis glycoside the myocardium was in negative potassium balance and within an hour returned to positive balance. The most serious electrocardiographic changes transpired when the myocardium approached or attained potassium balance. Pretreatment with potassium chloride protected the heart against arrhythmias by increasing Ko + . Pretreatment with glucose and insulin enhanced the arrhythmic action of the digitalis glycosides presumably by producing a low serum potassium (Ko + ) and possibly by modifying the state of intracellular potassium (Ki + ).
Erythropoietic protoporphyria: hepatic cirrhosis
Authors: DEREK J. CRIPPS, STANLEY S. GOLDFARB
Journal: British Journal of Dermatology (1978)

Observations on liver pathology and function were made on 12 patients with erythropoietic protoporphyria (EPP). Needle liver biopsies in 3 of 11 patients showed mild portal or periportal fibrosis without evidence of abnormal liver function. One patient (Case 12) died from hepatic cirrhosis and failure at the age of 11 years, the youngest yet reported. He was not suspected of pending liver disease until 3 months before death. The quantity of protoporphyrin present in his liver was approximately 575% of total liver weight. Fatal liver disease in EPP has occurred in 13 patients, 7 male and 6 female, in which the mean age of death was 38 years. The pathology of the liver in EPP is characteristic and is described.
TWO CASES OF TULAREMIA
Authors: W. W. G. Maclachlan
Journal: JAMA (1926)

These cases are, according to Dr. Francis of the United States Public Health Service, the first to be reported from Pennsylvania. It is interesting that both were recognized within a few days of each other. <h3>Case 1.</h3> —A man, aged 49, a butcher, admitted to the Mercy Hospital, Dec. 8, 1925, complained of fever, weakness and coughing. His illness began, November 24, two days before Thanksgiving. He had been preparing rabbits for the market and had cut his right index finger about two days before he began to feel ill. His finger became infected and was very sore, and remained so until shortly before admission to the hospital. Since the onset he had been feverish and had had many chills. He felt very weak and ached generally over the body. There was a good deal of coughing, but little sputum. He never had any bloody sputum. There were no gastro-intestinal
Geriatrician questions prescribing for stroke prevention in people over 80
Authors: Z. Kmietowicz
Journal: BMJ (2014)

People in their 80s are being overtreated for the prevention of stroke with statins and antihypertensives, whose benefit is marginal at best, an article in the journal Evidence Based Medicine has claimed.

Kit Byatt, a geriatrician at the County Hospital in Hereford, said that doctors “need actively to rethink [their] priorities and beliefs about stroke prevention” among this age group.1

He said research showed that among people in their 80s …
Application of the Statistical Process Control Method for Prospective Patient Safety Monitoring During the Learning Phase: Robotic Kidney Transplantation with Regional Hypothermia (IDEAL Phase 2a–b)
Authors: Akshay Sood, Khurshid R Ghani, Rajesh Ahlawat, Pranjal Modi, Ronney Abaza, Wooju Jeong, Jesse D Sammon, Mireya Diaz, Vijay Kher, Mani Menon, Mahendra Bhandari
Journal: European Urology (2014)
How automatic and representational is empathy, and why
Authors: Martin L. Hoffman
Journal: Behavioral and Brain Sciences (2002)

The claim that empathy is both automatic and representational is criticized as follows: (a) five empathy-arousing processes ranging from conditioning and mimicry to prospective-taking show that empathy can be either automatic or representational, and only under certain circumstances, both; (b) although automaticity decreases, empathy increases with age and cognitive development; (c) observers' causal attributions can shift rapidly and produce more complex empathic responses than the theory allows.
P1185 INTERIM SVR12 RESULTS FROM THE TELAPREVIR PHASE 3B REPLACE STUDY IN TREATMENT-NAIVE STABLE LIVER TRANSPLANT PATIENTS WITH GENOTYPE 1 HCV INFECTION
Authors: X. Forns, D. Samuel, D. Mutimer, S. Fagiouli, M. Navasa, K. Agarwal, M. Berenguer, M. Colombo, K. Herzer, F. Nevens, R. Van Solingen-Ristea, D. Luo, I. Dierynck, J. Witek
Journal: Journal of Hepatology (2014)
Pancreatic Fat Content and β-Cell Function in Men With and Without Type 2 Diabetes
Authors: Maarten E. Tushuizen, Mathijs C. Bunck, Petra J. Pouwels, Michaela Diamant
Journal: Diabetes Care (2008)

We thank Saisho, Butler, and Butler (1) for their interest in our study (2). They confirm and extend our findings by providing additional data on pancreatic fat content in individuals with and without type 2 diabetes using different technologies, i.e., computed tomography (CT) to measure pancreas volume and morphometric analyses of intrapancreatic fat spaces to estimate fat in postmortem pancreas sections (3).

As repeatedly stated in our paper (2), proton magnetic resonance spectroscopy (1H-MRS) cannot discriminate between intracellular fat in adipocytes versus nonadipocytes. Similar to Saisho, Butler, and Butler, we reasoned that since islets constitute only ∼2% of the pancreas mass, the fat signal obtained by 1H-MRS …
GM‐CSF in the treatment of Felty syndrome
Authors: Geetha Joseph, David H. Neustadt, John Hamm, Michael Kellihan, Terence Hadley
Journal: American Journal of Hematology (1991)

Abstract Many therapeutic agents have been tried with variable success in the treatment of Felty neutropenia, but the reports are anecdotal. We now describe the second trial of recombinant granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), in a splenectomized, infected patient with Felty syndrome.
53 One-year treatment with clevudine demonstrated significant viral suppression and biochemical improvement
Authors: Y.H. Chung, K.S. Lee, J.H. Kim, S.H. Ryu, S.W. Paik, S.H. Um, B.H. Han, M. Cho, K.S. Byun, B.I. Kim, J.W. Park, H.J. Lee, J.Y. Han, H.C. Kim, S.G. Hwang, K. Yoo, Y.S. Lee, Y.J. Lee, Y.S. Kim, J.M. Yang, C.Y. Chon, S.H. Cho, S.K. Choi, Y.O. Kweon, C.J. Han, J.S. Hwang, M.S. Lee, D.G. Kim, H.Y. Lee, J.Y. Choi, H.W. Yoo, M.J. Otto, P.A. Furman, H.S. Lee, B.C. Yoo, Y.H. Chung
Journal: Journal of Hepatology (2006)
Comparison of Vitrectomy with Brilliant Blue G or Indocyanine Green on Retinal Microstructure and Function of Eyes with Macular Hole
Authors: Takayuki Baba, Akira Hagiwara, Eiju Sato, Miyuki Arai, Toshiyuki Oshitari, Shuichi Yamamoto
Journal: Ophthalmology (2012)
Efficient Cross-presentation Depends on Autophagy in Tumor Cells
Authors: Yuhuan Li, Li-Xin Wang, Guojun Yang, Fang Hao, Walter J. Urba, Hong-Ming Hu
Journal: Cancer Research (2008)

Abstract Cross-presentation of antigens is critical for the induction of adaptive immunity against tumor cells and infectious pathogens. Currently, it is not known how cross-presentation of tumor antigens is regulated by autophagy. Using both HEK 293T cells that expressed the model antigen OVA and melanoma cells as antigen donors, we show that macroautophagy in tumor cells is essential for cross-presentation by dendritic cells both in vitro and in vivo. Inhibition of autophagy abolished cross-presentation almost completely, whereas induction of autophagy dramatically enhanced the cross-presentation of tumor antigens. Moreover, purified autophagosomes were found to be efficient antigen carriers for cross-presentation. Our findings not only identified a novel role for autophagy as an active process in antigen sequestration and delivery to dendritic cells for cross-presentation, but also suggested, for the first time, that isolated autophagosomes may have potential as potent vaccines for immunotherapy against cancer and infectious diseases. [Cancer Res 2008;68(17):6889–95]
Granuloma Inguinale-Reply
Authors: Bernard M. Kalstone
Journal: JAMA (1962)

To the Editor:—  In rebuttal to the letter from Doctor Rangiah of India: What we have quoted was the opinion of Doctor Rangiah et al. concerning a case that was reported by Lyford, Scott, and Johnson, which, incidentally, we have listed in our article as reference number 7. On page 74 of Doctor Rangiah's paper it is stated, in reference to Doctor Lyford et al., that the case favours a diagnosis of either lymphogranuloma venereum ortuberculosisof the bone with a superimposed infection of the sinuses of the groin with granuloma venereum. In other words, we were not referring to the specific case which Doctor Rangiah reported in his article, rather we referred to his comment concerning the Lyford case.
In vivo natriuretic peptide reporter assay identifies chemical modifiers of hypertrophic cardiomyopathy signalling
Authors: Jason R. Becker, Tamara Y. Robinson, Chetana Sachidanandan, Amy E. Kelly, Shannon Coy, Randall T. Peterson, Calum A. MacRae
Journal: Cardiovascular Research (2011)

Despite increased understanding of the fundamental biology regulating cardiomyocyte hypertrophy and heart failure, it has been challenging to find novel chemical or genetic modifiers of these pathways. Traditional cell-based methods do not model the complexity of an intact cardiovascular system and mammalian models are not readily adaptable to chemical or genetic screens. Our objective was to create an in vivo model suitable for chemical and genetic screens for hypertrophy and heart failure modifiers Using the developing zebrafish, we established that the cardiac natriuretic peptide genes (nppa and nppb), known markers of cardiomyocyte hypertrophy and heart failure, were induced in the embryonic heart by pathological cardiac stimuli. This pathological induction was distinct from the developmental regulation of these genes. We created a luciferase-based transgenic reporter line that accurately modelled the pathological induction patterns of the zebrafish nppb gene. Utilizing this reporter line, we were able to show remarkable conservation of pharmacological responses between the larval zebrafish heart and adult mammalian models. By performing a focused screen of chemical agents, we were able to show a distinct response of a genetic model of hypertrophic cardiomyopathy to the histone deacetylase inhibitor, Trichostatin A, and the mitogen-activated protein kinase kinase 1/2 inhibitor, U0126. We believe this in vivo reporter line will offer a unique approach to the identification of novel chemical or genetic regulators of myocardial hypertrophy and heart failure.
The Impact of HIV Infection on <i>Mycobacterium kansasii</i> Disease in South African Gold Miners
Authors: ELIZABETH L. CORBETT, GAVIN J. CHURCHYARD, MALCOLM HAY, PHILIP HERSELMAN, TIM CLAYTON, BRIAN WILLIAMS, RICHARD HAYES, DAAN MULDER, KEVIN M. DE COCK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The impact of human immunodeficiency virus (HIV) infection on Mycobacterium kansasii disease in miners was investigated with a retrospective study covering a single workforce. M. kansasii, isolated from 43 HIV-positive and 202 HIV-negative miners, was the most common nontuberculous mycobacterial (NTM) species in both HIV groups. CD4 counts were unusually high for M. kansasii disease (mean 490 × 106/L, from 14 HIV-positive men). Treatment outcomes were similar: mortality during treatment was higher in HIV-positive than in HIV-negative men (9% and 2%, respectively), but not significantly so. The majority of a sample of 31 HIV-positive and 92 HIV-negative men had radiological silicosis and/or old tuberculosis scarring prior to M. kansasii disease. A normal premorbid radiograph was more common in HIV-positive men (45% versus 24%; odds ratio [OR], 2.62; 95% confidence interval [95% CI], 1.01 to 6.67). New cavitation was less common (55% versus 78%; OR, 0.34; 95% CI, 0.13 to 0.88) and new hilar adenopathy more common (OR, 5.07; 95% CI, 1.24 to 21.9) in HIV-positive than in HIV-negative men. Miners, who have additional NTM risk factors, develop M. kansasii disease that occurs at an earlier stage of HIV infection and more closely resembles disease in HIV-negative men than has been found for HIV-associated M. kansasii disease in other settings.
Clinical governance in primary care: Improving quality in the changing world of primary care
Authors: R. Rosen
Journal: BMJ (2000)

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FULL-TERM ECTOPIC GESTATION
Authors: E. B. Low, H. J. McCurrich
Journal: BMJ (1934)

To take the opposite type of patient.Many years ago I saw an old W'elsh collier wrho insisted on resuming work a few months after a fracture of one of his lumbar bodies.He had a fracture of his pelvis also.He died suddenly at his work from aortic disease.Another man, who was an old bare-fist fighter, worked very shortly after fracturing his spine.But the most interesting case of all was that of a particularly well built younig collier who sustained a crush fracture of the second lumbar vertebra, w%ith considerable displacement and fractures of several trans- verse processes.He enlisted in the Guards and served for six years.At the end of that time he returned to South Wales and claimed for an injury to the spine, which had been found at Aldershot and as a result of which he had been discharged.He wAas paid a lump sum by the colliery company, and then announced that he was going round the world a.s a servant to his compainy officer, and that his spine was perfectly right.