tbuckley/cabot-search huggingface dataset:
Identification of putative gene based markers of renal toxicity.
Authors: Rupesh P Amin, Alison E Vickers, Frank Sistare, Karol L Thompson, Richard J Roman, Michael Lawton, Jeffrey Kramer, Hisham K Hamadeh, Jennifer Collins, Sherry Grissom, Lee Bennett, C Jeffrey Tucker, Stacie Wild, Clive Kind, Victor Oreffo, John W Davis, Sandra Curtiss, Jorge M Naciff, Michael Cunningham, Raymond Tennant, James Stevens, Bruce Car, Timothy A Bertram, Cynthia A Afshari
Journal: Environmental Health Perspectives (2004)

This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants--cisplatin, gentamicin, and puromycin--to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity.
A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): Study design and baseline characteristics
Authors: John Kjekshus, Peter Dunselman, Malin Blideskog, Christina Eskilson, Åke Hjalmarson, John V. McMurray, Finn Waagstein, Hans Wedel, Peter Wessman, John Wikstrand
Journal: European Journal of Heart Failure (2005)
The Transcription Factor STAT3 Is Required for T Helper 2 Cell Development
Authors: Gretta L. Stritesky, Rajarajeswari Muthukrishnan, Sarita Sehra, Ritobrata Goswami, Duy Pham, Jared Travers, Evelyn T. Nguyen, David E. Levy, Mark H. Kaplan
Journal: Immunity (2011)
Evaluating Psychiatric Treatment
Authors: Edith T. Shapiro
Journal: JAMA (1978)

PSYCHIATRISTS, like everyone else, win some and lose some.<sup>1(pp722-756)</sup>The inability of a psychiatrist to cure or to alleviate a patient's illness may reflect the psychiatrist's limitations with a refractory illness, or it may reflect some difficulty the patient is having in perceiving the benefit of therapy. Occasionally, failure is due to the psychiatrist's lack of skill or to the interference of the psychiatrist's own problems in the therapy.<sup>2</sup>More often, failure is due to obstacles inherent in the nature of psychotherapy as a treatment technique. In many of these instances, one psychiatrist may succeed where a colleague has failed, since a patient who gives a detailed description of his disappointment with his former psychiatrist provides his new physician with valuable information. The patient or his family, angered or disappointed by failure, may ask our opinion about the psychotherapy. We should be able to distinguish proper psychiatric treatment
Kenneth Hugh Nickol
Authors: M. Brill
Journal: BMJ (2009)

Kenneth Hugh Nickol (“Ken”) was a distinguished physician in occupational medicine who made a large contribution to education and training in the specialty. He died peacefully from a mesothelioma. He was born in Walthamstow, London, on the Essex border, and was educated in the county at St Aubyn’s and Felsted Schools.

He qualified MB BS in 1946 from the London Hospital Medical School and gained the Charrington prize in practical anatomy. He retained close ties with the Royal London Hospital throughout his career and was honorary clinical assistant in respiratory medicine for some 20 years.

He completed his national service in the Royal Air Force. Extensive hospital experience followed in general and respiratory medicine at a number …
Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders
Authors: Bethan Jones, Emma L. Jones, Stephanie A. Bonney, Hetal N. Patel, Arjen R. Mensenkamp, Sophie Eichenbaum-Voline, Mats Rudling, Urban Myrdal, Grazia Annesi, Sandhia Naik, Nigel Meadows, Aldo Quattrone, Suhail A. Islam, Rossitza P. Naoumova, Bo Angelin, Recaredo Infante, Emile Levy, Claude C. Roy, Paul S. Freemont, James Scott, Carol C. Shoulders
Journal: Nature Genetics (2003)
Thirty Years on — Should Doctors Strike? — Sundry Clippings
Authors: John Lister
Journal: New England Journal of Medicine (1978)

MR. Enoch Powell may be remembered for having pointed out in his book on medicine and politics1 that, because the demand for medical care is infinite but resources finite, some form of rationing is inevitable. Or he may be remembered for having remarked that ministers of health soon learn that money is the only topic that they ever discuss with the doctors.In recent years he has had less to say on medical matters, and it was with some interest that I read his contribution to the Spectator 2 at the time of the 30th anniversary of the inception of the . . .
Natriuretic Peptides—Relevance in Cardiovascular Disease
Authors: Bernard M. Y. Cheung
Journal: JAMA (1998)

4In contrast, the increase in intravascular volume from dietary salt loading results in the expected increase in BNP. 4 Similarly, a change in a patient’s pacemaker mode from atrial to ventricular pacing leading to uncoordinated atrial contractions and high pressure waves causes a greater acute increase in plasma ANP than BNP. 5 It therefore appears that BNP level reflects long-term intravascular volume status rather than momentary volume. Moreover, BNP is more stable than ANP in plasma and has a longer half-life, 6 which may be attributable to its lesser affinity for clearance receptors. CNP is synthesized in the endothelium and has vasodilatory and antiproliferative effects on vascular smooth muscle. It has a local action in the blood vessels or within the organ where it is produced. The natriuretic peptides are cleared from the circulation by at least 2 mechanisms. They bind to widely distributed natriuretic peptide clearance receptors (NPR-Cs) on endothelial cells and are then internalized and degraded. 7 They are also metabolized by neutral endopeptidases that are widely distributed on cells of various tissues. 2 Actions Intravenous infusion of ANP or BNP has a potent natriuretic and diuretic effect in healthy subjects, and infusions of supraphysiological concentrations of these peptides also show some hypotensive effect and suppression of the reninangiotensin-aldosterone system. 6,8,9 The effects of ANP and BNP seem to be additive, which may be because ANP and BNP share a common receptor (NPR-A). 6 Activation of this receptor leads to formation of cyclic guanosine monophosphate (cGMP), the second messenger mediating the effects of the natriuretic peptides. Plasma ANP and BNP levels are markedly increased in congestive heart failure, the magnitude of increase being related to the degree of heart failure. 2 Because their actions include vasodilation, natriuresis, and suppression of the renin-angiotensin-aldosterone system, ANP and BNP may be endogenous hormones counteracting the development of heart failure. The physiological effects of exogenous ANP are blunted in patients with congestive heart failure compared with its effects in normal subjects. 9 Proposed explanations for this resistance include receptor down-regulation and increased cGMP phosphodiesterase activity. 2 In contrast, BNP infused intravenously in patients with chronic congestive heart failure leads to a dose-dependent natriuretic response, a decrease in pulmonary capillary wedge pressure, and an increase in cardiac output. 10
Natriuretic response to the combination of atrial natriuretic peptide and terlipressin in patients with cirrhosis and refractory ascites
Authors: Adrián Gadano, Richard Moreau, Florence Vachiery, Thierry Soupison, Song Yang, Steéphane Cailmail, Philippe Sogni, Antoine Hadengue, François Durand, Dominique Valla, Didier Lebrec
Journal: Journal of Hepatology (1997)
Abstract 4760: ER-β/Sp/NFκB/FLIP axis: Potential therapeutic target in prostate cancer
Authors: Huiyoung Yun, Jianping Xie, Izhar Singh Batth, Rong Li, Rita Ghosh, Addanki Pratap Kumar
Journal: Cancer Research (2014)

Abstract Emergence of hormone-refractory prostate cancer is fatal for lack of effective, durable systemic therapeutic strategies. Therefore, discovery of novel approaches and agents that can prevent development of therapeutically resistant disease and its progression is critical for successful management of prostate cancer (PCA). One of the reasons for the inability to implement such strategies is an incomplete understanding of molecular events associated with the development of therapeutically resistant disease. Previously, we reported the anti-tumorigenic potential of 2-methoxyestradiol (2-ME2) both in vitro and in vivo. We showed that (i) transcription factor Sp1 activates while Sp3 inhibits Sp1-mediated transactivation of anti-apoptotic gene FLIP in androgen independent prostate cancer PC-3 cells, and that (ii) 2-ME2-mediated tumor growth inhibitory effects were accompanied by transcriptional down-regulation of FLIP through 745 bp (-503/+242) sequence elements. In order to fully understand the underlying molecular mechanism of 2-ME2 induced down-regulation of FLIP, we generated exonuclease deletion constructs and performed transient transfection assays. These studies led to identification of -121/+242 sequence containing putative bindings sites for NFκB, CREB and AR in addition to Sp1 with maximal promoter activity in androgen responsive (LNCaP) and androgen independent (PC-3 and DU145) cells. Using ChIP assays, we also observed the enrichment of these factors to the endogenous FLIP promoter. Furthermore, androgen stimulation enhanced promoter activity and recruitment of Sp1, NFκB to the FLIP promoter region in LNCaP cells. Surprisingly, we found DHT but not R1881 decreased FLIP promoter activity in DU145 cells. Further molecular investigations indicated enhanced expression of AKR1C3 (aldo-keto reductase) that catalyzes the conversion of DHT to 3β-Adiol (a potent ligand for ER-β) in response to 2-ME2 treatment in DU145 cells. In addition, not only 3β-Adiol treatment reduced proliferation of prostate cancer cell significantly but co-transfection with ER-β reduced FLIP promoter activity. Taken together, these results implicate an important role for ER-β/Sp/NFκB/FLIP in mediating 2-ME2 induced tumor growth inhibitory effects. Supported by VA-Merit Award and CA 135451 (APK). Citation Format: Huiyoung Yun, Jianping Xie, Izhar Singh Batth, Rong Li, Rita Ghosh, Addanki Pratap Kumar. ER-β/Sp/NFκB/FLIP axis: Potential therapeutic target in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4760. doi:10.1158/1538-7445.AM2014-4760
THE SO-CALLED MEDICAL COMPLICATIONS OF PREGNANCY
Authors: PHIL A. DALY
Journal: JAMA (1931)

From an historical point of view it has been interesting to study published opinions of authorities on obstetrics concerning the question of so-called medical complications encountered in their specialty. In the first edition of DeLee's Obstetrics<sup>1</sup>(1913) "glycosuria" is considered as an entity, and the prognosis of diabetes (50 per cent mortality) is discussed without reference to any collateral features such as the simple one of proper treatment of diabetes. The fifth edition<sup>2</sup>(1928) states that "today with proper treatment mortality is much lower, and in most cases pregnancy may be carried through to term." Proper treatment naturally means treatment by men trained in the field of metabolism. The earlier pessimistic statistics regarding the outlook for the pregnant woman with heart disease or diabetes are almost completely lacking in what might be called comparative control. The gloomy prognoses are based almost entirely on comparisons of pregnant ill women
Early contact with infant siblings reduces risk of multiple sclerosis
Authors: Susan Mayor
Journal: BMJ (2005)

People who had more exposure to infant siblings during the first six years of life have a lower risk of developing multiple sclerosis than people with less exposure, potentially because of increased childhood infection and related immune responses, says a study published this week.

The study looked at 136 adults (average age 43.5 years) with multiple sclerosis confirmed by magnetic resonance imaging and 272 controls (average age 43.6 years) matched by sex and year of birth. The participants, all residents of Tasmania, were interviewed between March 1999 and June 2001.

The aim was to assess whether a range of factors, including exposure to infant siblings in early life, was associated with the risk of developing …
Keratodermia blenorrhagica in Reiter's disease.
Authors: R Howell
Journal: BMJ (1971)

in Reiter's Disease SIR,-The case of keratodermia blennor- rhagica in a woman with Reiter's disease (19 December, p. 723) illustrates the difficulty that may arise in differentiating this condi- tion from arthropathic psoriasis.The patient subsequently came under my care on 15 July 1970, three months after discharge from the Westminster Hospital.Prednisone had been discontinued two weeks previously, but relapse had occurred several on 20 July
Insight into Graves’ Hyperthyroidism from Animal Models
Authors: Sandra M. McLachlan, Yuji Nagayama, Basil Rapoport
Journal: Endocrine Reviews (2005)

Graves’ hyperthyroidism can be induced in mice or hamsters by novel approaches, namely injecting cells expressing the TSH receptor (TSHR) or vaccination with TSHR-DNA in plasmid or adenoviral vectors. These models provide unique insight into several aspects of Graves’ disease: 1) manipulating immunity toward Th1 or Th2 cytokines enhances or suppresses hyperthyroidism in different models, perhaps reflecting human disease heterogeneity; 2) the role of TSHR cleavage and A subunit shedding in immunity leading to thyroid-stimulating antibodies (TSAbs); and 3) epitope spreading away from TSAbs and toward TSH-blocking antibodies in association with increased TSHR antibody titers (as in rare hypothyroid patients). Major developments from the models include the isolation of high-affinity monoclonal TSAbs and analysis of antigen presentation, T cells, and immune tolerance to the TSHR. Studies of inbred mouse strains emphasize the contribution of non-MHC vs. MHC genes, as in humans, supporting the relevance of the models to human disease. Moreover, other findings suggest that the development of Graves’ disease is affected by environmental factors, including infectious pathogens, regardless of modifications in the Th1/Th2 balance. Finally, developing immunospecific forms of therapy for Graves’ disease will require painstaking dissection of immune recognition and responses to the TSHR.
Exercise training: can it improve cardiovascular health in patients with type 2 diabetes?
Authors: K J Stewart
Journal: British Journal of Sports Medicine (2004)

Exercise training is an essential component of the management of patients with type 2 diabetes

Most exercise training studies of patients with diabetes have focused on glycaemic control and less on the effects of exercise on cardiovascular health. Yet there are data from a variety of studies that provide strong, albeit not perfect, evidence that exercise training should be a standard of care not only for glycaemic control but for also improving the cardiovascular system in these patients.

Type 2 diabetes is associated with dysfunction and failure of various organs, especially the heart and peripheral blood vessels. Both insulin resistance and β cell dysfunction are contributing factors to the disease,1,2 as are environmental influences and genetic factors.3,4 It has also become clear that the increasing prevalence of obesity1 and a sedentary lifestyle5 are also key contributors to the rising prevalence of type 2 diabetes in the United States and throughout the world. Two other metabolic conditions that precede the development of diabetes also have adverse effects on cardiovascular health and may also be prevented or delayed by regular exercise. Pre-diabetes is a metabolic condition that is between normal glucose homoeostasis and diabetes,6 and its prevalence in 2000 was estimated at nearly 12 million adults in the United States.7–9 The metabolic syndrome, which considerably increases the risk of developing diabetes, also stems from an underlying abnormality in insulin resistance.10–13 Although type 2 diabetes increases the risk of microvascular complications such as retinopathy and nephropathy,14,15 most diabetic patients die from macrovascular complications including coronary artery disease and stroke, with an increased risk of these conditions of 200–400%.16,17 Even before glucose concentrations reach the diagnostic threshold for diabetes, 25% of newly diagnosed patients may already have appreciable cardiovascular …
Can general practitioners influence exercise habits? Controlled trial.
Authors: M J Campbell, D Browne, W E Waters
Journal: BMJ (1985)

A health promotion campaign in the community organised by the general practitioner was evaluated by the use of a questionnaire before and after the campaign, both in the village where the campaign was based and in a control village. There was a general increase in the amount of exercise that people in both villages took. The results showed that having received a questionnaire, and been subject to the campaign, more people took exercise regularly.
Ventricular arrhythmias may not be primary cause of sudden death
Authors: William A. Check
Journal: JAMA (1981)

At a recent conference sponsored by the New York Academy of Sciences, physicians and scientists from several disciplines explored the topic of sudden coronary death, discussing its epidemiology, pathogenesis, and prevention. The purpose of the conference was not to present conclusions but "to start to define sudden death and identify predictors of it," according to co-chairman Edward M. Dwyer, Jr, MD, of Columbia University's College of Physicians and Surgeons, New York. Approximately 400,000 persons die suddenly of heart disease in the United States each year. Furthermore, it is estimated that about 50% die within one hour of symptom onset and that half of those over age 50 years never even reach the hospital. The concept of "sudden" cardiac death as a special category of death from heart disease arose largely in the early 1960s, recalled John Kastor, MD, director of the division of cardiovascular medicine at the University of Pennsylvania
Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21.
Authors: S B Patel, G Salen, H Hidaka, P O Kwiterovich, A F Stalenhoef, T A Miettinen, S M Grundy, M H Lee, J S Rubenstein, M H Polymeropoulos, M J Brownstein
Journal: Journal of Clinical Investigation (1998)

The molecular mechanisms regulating the amount of dietary cholesterol retained in the body as well as the body's ability to selectively exclude other dietary sterols are poorly understood. Studies of the rare autosomal recessively inherited disease sitosterolemia (OMIM 210250) may shed some light on these processes. Patients suffering from this disease appear to hyperabsorb both cholesterol and plant sterols from the intestine. Additionally, there is failure of the liver's ability to preferentially and rapidly excrete these non-cholesterol sterols into bile. Consequently, people who suffer from this disease have very elevated plasma plant sterol levels and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. Identification of this gene defect may therefore throw light on regulation of net dietary cholesterol absorption and lead to an advancement in the management of this important cardiovascular risk factor. By studying 10 well-characterized families with this disorder, we have localized the genetic defect to chromosome 2p21, between microsatellite markers D2S1788 and D2S1352 (maximum lodscore 4.49, theta = 0.0).
Finding the Primary Site of Metastatic Cancer
Authors: Richard B. Merlo
Journal: JAMA (1979)

<h3>To the Editor.—</h3> We do not judge the usefulness of electrocardiography on the basis of technically unsatisfactory ECGs; neither do we evaluate ultrasonography on the basis of technically unsatisfactory sonograms. So we should not conclude, as have Nystrom and his colleagues (241:381, 1979), that roentgenography is of little help in finding occult primary malignant neoplasms. The evaluation by Nystrom et al is based on single-contrast colon examinations and urograms done without routine tomographic scans, and these are technically unsatisfactory examinations. The potential of diagnostic roentgenography cannot be judged by such examinations. It seems likely that true-positive and true-negative detection of occult malignant neoplasms would have been much improved by the routine use of air-contrast colon examinations and the routine use of tomographic scans during intravenous urographic examinations.