tbuckley/cabot-search huggingface dataset:
Differential ability of Tribbles family members to promote degradation of C/EBPα and induce acute myelogenous leukemia
Authors: Priya H. Dedhia, Karen Keeshan, Sacha Uljon, Lanwei Xu, Maria E. Vega, Olga Shestova, Meirav Zaks-Zilberman, Candice Romany, Stephen C. Blacklow, Warren S. Pear
Journal: Blood (2010)

Trib1, Trib2, and Trib3 are mammalian homologs of Tribbles, an evolutionarily conserved Drosophila protein family that mediates protein degradation. Tribbles proteins function as adapters to recruit E3 ubiquitin ligases and enhance ubiquitylation of the target protein to promote its degradation. Increased Trib1 and Trib2 mRNA expression occurs in human myeloid leukemia and induces acute myeloid leukemia in mice, whereas Trib3 has not been associated with leukemia. Given the high degree of structural conservation among Tribbles family members, we directly compared the 3 mammalian Tribbles in hematopoietic cells by reconstituting mice with hematopoietic stem cells retrovirally expressing these proteins. All mice receiving Trib1 or Trib2 transduced hematopoietic stem cells developed acute myeloid leukemia, whereas Trib3 mice did not. Our previous data indicated that Trib2-mediated degradation of the transcription factor, CCAAT/enhancer-binding protein-alpha (C/EBPalpha), is important for leukemogenesis. Similar to Trib2, Trib1 induced C/EBPalpha degradation and inhibited its function. In contrast, Trib3 failed to inactivate or promote efficient degradation of C/EBPalpha. These data reveal that the 3 Tribbles homologs differ in their ability to promote degradation of C/EBPalpha, which account for their differential ability to induce leukemia.
Letter: Umbilical arteries in smoking and nonsmoking mothers.
Authors: C G Caro
Journal: Circulation Research (1975)

Umbilical Arteries in Smoking andNonsmoking Mothers It would be interesting to know if Drs.Asmussen and Kjeldsen made quantitative studies of the appearance of the luminal surface of the endothelial cells in their electron micrographs of the umbilical arteries of children of smoking and nonsmoking mothers.One is impressed by seeing what they call cytoplasmic blebs on transmission electron micrographs from both sets of arteries (see their Figs. 2 and5).Comparable extensive fine folding of the plasma membrane of some endothelial cells has been pointed out previously (Caro et al., In Fluid Dynamic Aspects of Arterial Disease: Proceedings of a Specialists Meeting sponsored by NSF and The Ohio State University, Columbus, Ohio, 1974, pp 58-62) on transmission and scanning electron micrographs of excised carotid arteries from normal dogs when the arteries are fixed at relaxed length and zero transmural pressure.This folding is generally absent when the vessels are fixed at in vivo length and physiological transmural pressure.Furthermore, some investigators would question whether the large spaces seen between the endothelial cells are open clefts or simply arise as the result of corrugation of the wall.These points strengthen the case for making ultrastructural studies on vessels at physiological length and transmural pressure.
Herniated Lumbar Intervertebral Disk
Authors: Richard A. Deyo, John D. Loeser, Stanley J. Bigos
Journal: Annals of Internal Medicine (1990)

Low back pain is common, but a herniated intervertebral disk is the cause in only a small percentage of cases. Most symptomatic disk herniations result in clinical manifestations (pain, reflex loss, muscle weakness) that resolve with conservative therapy, and only 5% to 10% of patients require surgery. Sciatica is usually the first clue to disk herniation, but sciatica may be mimicked by other disorders that cause radiating pain. Because more than 95% of lumbar disk herniations occur at the L4-5 or L5-S1 levels, the physical examination should focus on abnormalities of the L5 and S1 nerve roots. Plain radiography is not useful in diagnosing disk herniation, but more sophisticated imaging (myelography, computed tomography, or magnetic resonance imaging) should generally be delayed until a patient is clearly a surgical candidate. Conservative therapy includes nonsteroidal anti-inflammatory drugs, brief bed rest (often for less than 1 week), early progressive ambulation, and reassurance about a favorable prognosis. Muscle relaxants and narcotic analgesics have a limited role, and their use should be strictly time-limited. Conventional traction and corsets are probably ineffective. Except for patients with the cauda equina syndrome, surgery is generally appropriate only when there is a combination of definite disk herniation shown by imaging, a corresponding syndrome of sciatic pain, a corresponding neurologic deficit, and a failure to respond to 6 weeks of conservative therapy.
Thyroid Analogue Therapy in Primary Hypercholesteremia with Xanthomatosis
Authors: Frederick L. Nichols
Journal: JAMA (1962)

SINCE THE ADVENT of thyroid analogues, clinical studies have shown a definite cholesterol-lowering effect with dosages that do not cause an appreciable calorigenic effect. However, to date, only an occasional reference has been made to therapeutic success in patients with xanthomatosis given thyroid analogues. The dietary approach to hypercholesteremic xanthomatosis has been reviewed and detailed elsewhere. It is not my intent to enter the controversy on the value of maintaining a normal level of serum cholesterol in relation to development of atherosclerosis. Rather, this study reports the use of 3,5,3' triiodothyropropionic acid (Triopron) over a 2†-year period in a patient with primary hypercholesteremia with tuberous and disseminated xanthomatosis. During the past 10 years many diverse scientific disciplines have collaborated to produce alterations of the thyroxin molecule, resulting in various analogues, and to study their physiological effects on animals and man. Definite dissociation of function by changes in the structure of
Comparison of Serum Bisphenol A Concentrations in Mice Exposed to Bisphenol A through the Diet versus Oral Bolus Exposure
Authors: Paizlee T. Sieli, Eldin Jašarevic´, Denise A. Warzak, Jiude Mao, Mark R. Ellersieck, Chunyang Liao, Kurunthachalam Kannan, Séverine H. Collet, Pierre-Louis Toutain, Frederick S. vom Saal, Cheryl S. Rosenfeld
Journal: Environmental Health Perspectives (2011)

Bisphenol A (BPA) is a widely produced endocrine-disrupting chemical. Diet is a primary route of exposure, but internal exposure (serum concentrations) in animals and humans has been measured only after single oral bolus administration.We compared serum concentrations of BPA over a 24-hr period after oral bolus administration or ad libitum feeding in mice and assessed for buildup with dietary exposure.Adult female mice were administered [dimethyl-d6]-BPA (BPA-d6) as a single oral bolus (20 mg/kg body weight) or fed a diet containing 100 mg BPA-d6/kg feed weight ad libitum for 1 week. Serum concentrations were analyzed using isotope dilution liquid chromatography coupled with electrospray tandem mass spectrometry and compared between exposure groups over the first 23 hr and after 7 days of dietary exposure.Maximum concentration (Cmax) for BPA-d6 during the first 24 hr was reached at 1 hr and 6 hr for oral bolus and diet groups, respectively. Relative BPA-d6 bioavailability (unconjugated BPA-d6) was higher in diet-exposed mice than in the bolus group despite a relative lower absorption, a phenomenon consistent with an inhibitory effect of food on first-pass hepatic metabolism. In mice with ongoing dietary exposure, unconjugated BPA-d6 was higher on day 7 than on day 1.This is the first report of serum BPA concentrations in an animal model exposed to this chemical via the diet. Although bolus administration of BPA-d6 led to peak concentrations within 1 hr, Cmax for diet-exposed mice was delayed for several hours. However, bolus administration underestimates bioavailable serum BPA concentrations in animals-and presumably humans-than would result from dietary exposure. Exposure via diet is a more natural continuous exposure route than oral bolus exposure and is thus a better predictor of BPA concentrations in chronically exposed animals and humans.
Sequester cuts will hit medical care and research
Authors: J. H. Tanne
Journal: BMJ (2013)

On 1 April $85bn (£56bn; €66bn) in this year’s mandatory budget cuts will kick in, affecting doctors, hospitals, research centers, Medicare, the Food and Drug Administration, the Centers for Disease Control and Prevention, and other essential parts of US healthcare. Only defense spending will be hit harder.

The cuts must be made in the current fiscal year, which ends on 30 September. More cuts will happen in the next 10 years as part of the $1.2 trillion reduction in spending spread over the next decade.

Nationally the sequester cuts will affect research and innovation, food safety, and mental health as well as payments to doctors and hospitals. The White House has estimated that the cuts would lead to 2100 fewer food inspections and 12 000 researchers and scientists losing their jobs. Cuts to mental health would leave nearly 400 000 mentally ill adults and severely emotionally disturbed children without treatment, leading to more hospitalizations, involvement with the criminal justice system, and homelessness, the White House said.

This year the sequester cuts will reduce Medicare payments to doctors and hospitals by 2%. Public health and research programs face big cuts.

A joint report from the American Medical Association, the American Hospital Association, and the American Nurses Association estimated that 766 000 healthcare and related jobs could be lost by 2021 as a result of the 2% cut to Medicare.1

Jeremy Lazarus, president of the AMA, said, “The across the board cut will hit physicians particularly hard because of the fundamentally flawed Medicare physician payment system. Since 2001 Medicare payments for physician services have only increased by …
Guidelines for the management of chronic venous leg ulceration. Report of a multidisciplinary workshop
Authors: W.S DOUGLAS, N.B SIMPSON
Journal: British Journal of Dermatology (1995)

This document is the product of a multidisciplinary workshop held in November 1991 between the audit subcommittee of the British Association of Dermatologists and the Research Unit of the Royal College of Physicians. Partieipants included dermatologists, vascular surgeons, general practitioners, community nurses and physicians involved in care of the elderly. The text is based on papers submitted to, and presented and discussed at, the workshop, and on comments received in response to subsequent wide dissemination of the proceedings to speciality associations. Participants in the workshop, and contributors to the guidelines are: Dr B.R.Allen (Nottingham), Sister S.Bainsborough (Exeter), Professor K.Burnand (London), Professor D.Burrows (Belfast), Mr M.J.Caflam (Bedford), Dr G.W.Cherry (Oxford), Dr R.P.R.Dawber (Oxford). Dr W.S.Douglas (Airdrie), Dr A.Y.Finlay (Cardiff), Dr D.Gawkrodger (Sheffield), Dr D.J.Gould (Truro), Dr A.Hopkins (Royal College of Physicians, London), Dr D.McGibbon (London), Dr A.M.Middleton (London), Dr L.Millard (Nottingham), Dr L.Rhodes (Liverpool), Professor T.J.Ryan (Oxford), Dr N.B.Simpson (Newcastle), Dr F.D.Skerrett (Fowey). Dr J.M.Sowden (Nottingham), Miss L.A.Stone (London), Dr R.Williams (Rhyl). Papers presented to the workshop (copies available from the Royal College of Physicians of London):
Marathon Group Therapy
Authors: C.V. Martin, F.M. Banks
Journal: Psychotherapy and Psychosomatics (1972)

One of the new methods of sensitivity training in the United States is the weekend Marathon group. This technique has been used by therapists as an adjunct to the usual course of psychotherapy with extremely good results. The Marathon usually takes place midway in the course of therapy, thus enabling the therapist to be fully acquainted with the patient's problems and also continue therapy after the Marathon. Another feature of the Marathon presented is the use of closed circuit television and instant replay for self-confrontation experiences as well as the usual 'other' object confrontations.
SUPPURATING CYST DEVELOPED FROM ADHERENT OVARIES, AFTER REPEATED ATTACKS OF INFLAMMATION. SECONDARY OPERATION FOR THE REMOVAL OF INTRA-LIGAMENTOUS CYSTS.Read before the American Association of Obstetrics and Gynecologists at New York, September, 17, 18, and 19, 1891.
Authors: RUFUS B. HALL
Journal: JAMA (1892)

In presenting this paper I have selected three cases from my work of the past few months, which illustrate some interesting points, and teach a very valuable lesson, which, in the judgment of the writer, cannot be too forcibly emphasized by men engaged in abdominal and pelvic surgery. I report the cases as illustrating three as difficult abdominal operations as it has ever been my misfortune to have seen. While it is not a pleasant task for an operator to report the cases which have not recovered, it is my practice to do so, for it almost always occurs that from the careful study of these unfortunate results much valuable information is gained, and I am quite certain that we shall not be disappointed in the present instance in that particular. Even though the task be an unpleasant one it is one which every operator should do as promptly and
Abstract 2944: Genome-wide transcriptional modulation screening in non-smoking female lung cancer in Taiwan
Authors: Tzu-Pin Lu, Pei-Chun Chen, Jang-Ming Lee, Chung-Ping Hsu, Shin-Kuang Chen, Mong-Hsun Tsai, Chuhsing K. Hsiao, Eric Y. Chuang, Liang-Chuan Lai
Journal: Cancer Research (2010)

Abstract Lung cancer has become the leading cause of cancer death in Taiwan and in most countries. Although smoking has been the major risk factor for lung cancer, less than 20% smokers develop lung cancer. In Taiwan, only about 50% of lung cancer cases were related to smoking, while more than 90% lung cancer females were non-smokers. In this study, we collected gene expression microarrays to investigate the pathogenesis process. One hundred and twenty lung tumor samples and their normal counterparts from non-smoking females were collected from National Taiwan University Hospital and Taichung Veterans General Hospital. RNAs from 60 paired samples were examined using Affymetrix Human U133 plus2.0 microarray. Paired t-tests were used to identify differentially expressed genes between tumor and normal tissues. The preliminary results showed there were 791 differentially expressed genes (p-value &amp;lt; 10−14). Ingenuity Pathway Analysis (IPA) was utilized for further functional and pathway analyses on these genes, and the axon guidance signaling pathway was the most significantly enriched pathway. Among genes in the axon guidance signaling pathway, SEMA5A was chosen for further investigation because it was the most significant down-regulated gene in tumor tissue. Its down-regulation was validated by both real-time PCR and immunohistochemistry (IHC). Furthermore, Kaplan-Meier survival analysis showed that patients with low SEMA5A expression had poor overall survival as compared to those who had high SEMA5A expression. This significant association was also observed in two published studies. Therefore, these results indicated that the SEMA5A may play an important role in the carcinogenesis and can be a potential prognosis biomarker for non-smoking lung cancer females in Taiwan. 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 2944.
The Connective-Tissue Diseases and Symptoms Associated with Hashimoto's Thyroiditis
Authors: Kenneth L. Becker, Richard H. Ferguson, William M. McConahey
Journal: New England Journal of Medicine (1963)

THE relation between the thyroid gland and rheumatic disorders has long excited interest.1 2 3 4 5 6 7 In particular, an association between some of the connective-tissue diseases and Hashimoto's thyroiditis (lymphadenoid goiter) has recently seemed likely.6 , 8 , 9 Many reports of this coexistence have consisted of studies of only 1 or several patients. For this reason, study of a large group of cases of Hashimoto's disease was undertaken to determine the incidence of concomitant rheumatic symptoms and musculoskeletal disease.MethodsThe clinical records of 506 patients with the diagnosis of Hashimoto's thyroiditis seen at the Mayo Clinic from the years 1958 through 1960 were studied. In . . .
Gall bladder emptying in normal subjects--a data base for clinical cholescintigraphy.
Authors: C R Mackie, J N Baxter, J S Grime, G Hulks, A Cuschieri
Journal: Gut (1987)

Biliary excretion scintigraphy with a cholagogic test meal may be used to assess patients with suspected disorders of gall bladder motility. The interpretation of results is frustrated, however, by the lack of information about the range of normal responses in a form suitable for comparative analysis. We present the results of 41 gall bladder emptying studies on 32 normal healthy subjects (14 men, 18 women) 30 minutes after intravenous injection of 74 MBq 99Tcm-EHIDA. Gall bladder emptying was provoked by the ingestion of 300 ml milk. Gamma camera scintigraphy was used to plot gall bladder activity against time. Gall bladder emptying occurred within 10 minutes in all men and 12/18 women (p = 0.02). Gall bladder ejection fractions were significantly greater in women (p less than 0.05). Duplicate studies in nine subjects showed good reproducibility (r = 0.959). A plot of mean and (m + 2 SD) values of gall bladder activity against time has been derived. The data provide an estimate of normal gall bladder emptying response, which may be used to aid interpretation of clinical studies.
S122 Statin use is associated with improved long term outcomes after community-acquired pneumonia
Authors: GB Fleming, A Singanayagam, AR Akram, JK Taylor, M Restrepo, AT Hill, JD Chalmers
Journal: Thorax (2013)

<h3>Introduction</h3> Long term outcomes after community-acquired pneumonia (CAP) are poor, with high rates of readmission, cardiovascular events and mortality. No intervention has previously been shown to alter the excess morbidity and mortality associated with CAP. Statins are effective in preventing cardiovascular disease, but may also have beneficial anti-inflammatory effects. We tested the hypothesis that statin users would have improved long term outcomes following CAP. <h3>Methods</h3> Secondary analysis of the Edinburgh pneumonia database, a prospective observational study of CAP (2005–2010). All discharged patients were included. Follow-up data were obtained from a database linked to national morbidity and mortality registers. Outcomes were assessed using cox proportional hazards regression adjusting for confounding variables (age, gender, previous cardiovascular events, ACE-inhibitor/anti-platelet use, smoking status and severity of pneumonia). <h3>Results</h3> Data from 1631 patients with complete follow-up were analysed. Readmissions occurred in 728 patients (44.6%) with 157 readmissions within 30 days of discharge. 133 patients had a further hospitalisation with CAP. The 1 year mortality rate was 12.8%. 523 patients were current statin users. There were significant differences between statin and non-statin users. Statin users were older, suffering more cardiovascular disease, stroke, diabetes, renal disease, COPD and a greater severity of pneumonia. 1 year mortality rates were similar in statin and non-statin users. After adjusting for baseline differences, statins were associated with a non-significant trend towards lower 1 year mortality HR 0.78(0.55–1.1). When adjusted for the propensity score, the difference in mortality became statistically significant HR 0.70(0.50–0.98). In the fully adjusted analysis, statins were not significantly associated with readmissions HR 0.85(0.70–1.03) but were associated with a significantly lower risk of recurrent pneumonia HR 0.60 (0.37–0.96). There was no association with reduced cardiovascular hospitalisations HR 0.94(0.65–1.34). There were no beneficial effects seen with either antiplatelet or ACE-inhibitor use following CAP. <h3>Conclusion</h3> Statins are associated with reduced 1 year mortality and a significantly lower rate of recurrent pneumonia. This is the first study to show that statins may improve long term outcomes in CAP, and that the associated morbidity and mortality can be modified.
Involvement of the interleukin 2 pathway in the rearrangement and expression of both alpha/beta and gamma/delta T cell receptor genes in human T cell precursors.
Authors: M L Toribio, A de la Hera, J Borst, M A Marcos, C Márquez, J M Alonso, A Bárcena, C Martínez
Journal: The Journal of Experimental Medicine (1988)

In this report, we have undertaken the phenotypic, functional and molecular characterization of a minor (less than 5%) subpopulation of adult thymocytes regarded as the earliest intrathymic T-cell precursors. Pro-T cells were immunoselected and shown to express different hematopoietic cell markers (CD45, CD38, CD7, CD5) and some activation-related molecules (4F2, Tr, HLA class II), but lack conventional T cell antigens (CD2-1-3-4-8-). TCR-gamma RNA messages are already expressed at this early ontogenic stage, while alpha and beta chain TCR genes remain in germline configuration. In vitro analyses of the growth requirements of pro-T cells demonstrated the involvement of the IL-2 pathway in promoting their proliferation and differentiation into CD3+ CD4+ or CD8+ mature thymocytes. Moreover, during the IL-2-mediated maturation process rearrangements and expression of both alpha and beta chain TCR genes occurred, and resulted in the acquisition of alpha/beta as well as gamma/delta (either disulphide-linked or non-disulphide-linked) heterodimeric TCR among the pro-T cell progeny.
Intracoronary thrombus formation causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease.
Authors: A M Zeiher, V Schächinger, S H Weitzel, H Wollschläger, H Just
Journal: Circulation (1991)

Experimental studies have demonstrated that intracoronary platelet aggregation and thrombus formation may induce marked vasoconstriction of epicardial arteries with endothelial injury.To examine the effects of intracoronary thrombus formation on coronary vasomotor tone of human epicardial arteries in vivo, we studied 15 patients who developed intracoronary thrombi adherent to the guide wire during balloon dilatation. Epicardial artery luminal area was evaluated by quantitative coronary angiography proximal and distal to the site of intracoronary thrombus formation and in a reference vessel before and after thrombus formation as well as after intracoronary injection of 0.2-0.3 mg nitroglycerin. All artery segments distal to the site of thrombus formation showed vasoconstriction with a luminal area reduction of -27.4 +/- 17.1% (p less than 0.001), whereas proximal vessel segments and reference vessels not manipulated during percutaneous transluminal coronary angioplasty did not demonstrate any significant luminal area changes during thrombus formation. Angiographic measurements after advancing the guide wire with the adherent thrombus (performed in six of the 15 patients) revealed in all patients that vasoconstriction did develop at a new site distal to the thrombus persistence of the initial vasoconstriction now residing proximal to the thrombus. Thus, there was a sequential association between thrombus formation and subsequent distal vasoconstriction. Intracoronary injection of nitroglycerin abolished the thrombus-induced vasoconstriction. No significant luminal area changes were observed in 20 patients without angiographic evidence of intracoronary thrombus formation.Intracoronary thrombus formation during percutaneous transluminal coronary angioplasty causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease. Although caution must be advised in the extrapolation of this phenomenon, which was observed in a manipulated artery during coronary angioplasty, the vasoconstrictor response to intracoronary thrombus formation in vivo may play an important role in the dynamic mechanisms of acute coronary heart disease syndromes.