tbuckley/cabot-search huggingface dataset:
Big boys don't cry
Authors: I. Robertson
Journal: BMJ (1996)

The furore over compensation for 14 policemen traumatised by what they witnessed at Hillsborough Stadium is strange indeed. One general practitioner wrote to The Times saying, more or less, that she had had to witness some gruesome things in her life but no one gave her any extra money. The tabloids howled insinuations about nambypambiness, and the general response showed that matters psychological and psychiatric are still primitively misunderstood in Britain, even among the medical profession.

Anybody who has actually spent some time with a person who truly suffers from post-traumatic stress disorder will know how it can break someone more completely than …
Abstract 3053: Identification of a novel cytoplasmic role for MTDH/AEG-1 in chemoresistance as a RNA binding protein
Authors: Xiangbing Meng, Danlin Zhu, Xinjun Wang, Shujie Yang, Yuping Zhang, Zhi Xiong, Kimberly K. Leslie
Journal: Cancer Research (2012)

Abstract Overexpression of metadherin (MTDH/AEG-1) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in solid tumors, and this localization has been shown to correlate with poor prognosis. In this study, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized to the cytoplasm in endometrial cancer cells, and the N-terminal region of MTDH was required to maintain cytoplasmic localization. Depletion of cytoplasmic MTDH in endometrial cancer cells restored chemosensitivity to various DNA damaging agents including mitomycin C (MMC) and doxorubicin. Next, we identified novel binding partners for cytoplasmic MTDH, including ribosome protein RPL4, ribosome biogenesis-related protein NPM1, and a component of the RNA induced silencing complex SND1. Association of MTDH with these cytoplasmic proteins was disrupted by nuclease treatment, demonstrating that nucleic acid is required for the interaction of cytoplasmic MTDH with these RNA metabolism and processing proteins. Furthermore, RNA binding protein-chromatin IP (RIP-chIP) analysis demonstrated that MTDH interacted with multiple mRNAs, and treatment with the PI3K and mTOR dual inhibitor BEZ235 altered the pattern of mRNAs that associate with MTDH. Knockdown of MTDH promoted an increase in protein levels of some MTDH-associated mRNAs. Finally, increased stress granule formation was observed in MTDH knockdown cells in response to heat shock, suggesting that one mechanism by which MTDH promotes chemoresistance is prevention of stress granule formation. Taken together, our data identify MTDH as an active RNA binding protein in the cytoplasm of cancer cells. Our findings suggest that the RNA binding properties of cytoplasmic MTDH serve to regulate genes involved in the drug resistance and metastasis of tumors and highlight MTDH as an ideal target for future drug development. Acknowledgements: This work was supported by NIH Grant R01CA99908 to K.K.L., and in part by the Department of Obstetrics and Gynecology Research Development Fund, the Institutional Research Grant Number IRG-77-004-31 from the American Cancer Society to XM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3053. doi:1538-7445.AM2012-3053
Case-control study of migraine and risk of ischaemic stroke in young women
Authors: C. Tzourio, A. Tehindrazanarivelo, S. Iglesias, A. Alperovitch, F. Chedru, J. d'Anglejan-Chatillon, M.-G. Bousser
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To determine whether migraine is a risk factor for ischaemic stroke in young women. <b>Design</b>: A case-control study. <b>Setting</b>: Five hospitals in Paris and suburbs. <b>Subjects</b>: 72 women aged under 45 with ischaemic stroke and 173 controls randomly selected from women hospitalised in the same centres. <b>Main outcome measures</b>: Ischaemic stroke confirmed by cerebral computerised tomography or magnetic resonance imaging; history of headache recorded with structured interview, and diagnosis of migraine assessed by reproducibility study. <b>Results</b>: Ischaemic stroke was strongly associated with migraine, both migraine without aura (odds ratio 3.0 (95% confidence interval 1.5 to 5.8)) and migraine with aura (odds ratio 6.2 (2.1 to 18.0)). The risk of ischaemic stroke was substantially increased for migrainous women who were using oral contraceptives (odds ratio 13.9) or who were heavy smokers (&gt;/=20 cigarettes/day) (odds ratio 10.2). <b>Conclusions</b>: These results indicate an independent association between migraine and the risk of ischaemic stroke in young women. Although the absolute risk of ischaemic stroke in young women with migraine is low, the reduction of known risk factors for stroke, in particular smoking and use of oral contraceptives, should be considered in this group.
Fluvastatin Lowers Atherogenic Dense Low-Density Lipoproteins in Postmenopausal Women With the Atherogenic Lipoprotein Phenotype
Authors: Winfried März, Hubert Scharnagl, Claudia Abletshauser, Michael M. Hoffmann, Aloys Berg, Joseph Keul, Heinrich Wieland, Manfred W. Baumstark
Journal: Circulation (2001)

Background —Although HMG-CoA reductase inhibitors (HMGRIs) are effective lipid-lowering agents, it remains controversial whether these agents also lower dense LDL (dLDL), a predominance of which is considered to contribute to the atherogenicity of the metabolic syndrome. Methods and Results —In a multicenter, double-blind, randomized, placebo-controlled study, we determined the effect of the HMGRI fluvastatin on lipids, apolipoproteins, and LDL subfractions (by equilibrium density gradient ultracentrifugation). A total of 52 postmenopausal women with combined hyperlipidemia and increased dLDL were treated with either fluvastatin 40 mg/d (n=35) or placebo (n=17). After 12 weeks’ treatment, significant reductions ( P &lt;0.001) in total cholesterol (−19%), IDL cholesterol (−35%), LDL cholesterol (−23%), apolipoprotein B (−21%), and apolipoprotein B in dLDL (−42%) were apparent among fluvastatin recipients. No significant changes in triglycerides or HDL cholesterol were observed. The effect of fluvastatin on dLDL was correlated with baseline values. There was no consistent relationship, however, between the effect of fluvastatin on triglycerides and the decrease in dLDL. Conclusions —Fluvastatin lowers total and LDL cholesterol and the concentration of dLDL. This profile may contribute to an antiatherogenic effect for fluvastatin that is greater than expected on the basis of changes in lipids and apolipoproteins.
Does it matter not only how much but also when we eat to induce fatty liver?
Authors: Claus Hellerbrand, Ralf Weiskirchen
Journal: Hepatology (2011)

Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent. Although amounts of HDAC3 are constant, its genomic recruitment in liver corresponds to the expression pattern of the circadian nuclear receptor Rev-erbα. Rev-erbα colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erbα in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbα directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis.
STUDIES ON THE NATURE OF THE VIRUS OF INFLUENZA
Authors: Leslie A. Chambers, Werner Henle
Journal: The Journal of Experimental Medicine (1943)

A considerable fraction of the influenza A virus contained in infected allantoic fluid of the developing chick is not sedimentable under conditions which remove virus activity almost completely from filtrates of emulsified mouse lung. The infectious unit from tissue suspensions is about 100 mmicro in diameter and is of the same chemical composition as particles of the same size and abundance separated from normal tissues by an identical procedure. Evidence has been presented showing that the infectivity can be, and probably is, carried on such normal cell components as an adsorbate. Other non-infective particles such as erythrocytes may also become infectious units through adsorption of the virus. The virus occurs in allantoic fluid in two states of dispersion. A variable percentage is associated with particles considerably less than 100 mmicro in diameter, probably more nearly 10 mmicro, while the remainder is reversibly aggregated. Reversal to the more disperse state may be effected by dilution, sonic vibration, or moderate heat treatment.
Abstract 157: Optimizing the flow cytometric analysis of cell signaling in heterogeneous samples
Authors: Guojian Gao, Christopher Coveney, Xiao Wang, Xiaowei Wu, Ai-Li Wei, Xiang-dong Ji, Lori Anderson, Nikesh Kotecha, Jurg Rohrer, Erika O'Donnell
Journal: Cancer Research (2012)

Abstract Unlike conventional biochemical methods for cell signaling analysis, analyzing protein levels by flow cytometry allows measurements to be made at the single-cell level. Multiparameter flow cytometry provides a powerful tool for the analysis of protein expression and phosphorylation status within complex populations, such as those found in lymphoid tissues or blood. However, different intracellular and cell surface proteins often require different conditions for optimal detection, creating challenges for analyzing multiple protein types in a single sample. To facilitate the design of multiparameter staining panels for analysis of intracellular and cell surface proteins, we tested over 250 fluorescently conjugated antibodies in cells fixed and permeabilized under various conditions. Multiple fluorescent conjugates of each antibody were tested in human PBMCs, human whole blood, mouse spleen, and/or mouse bone marrow following fixation with BD Phosflow™ Lyse/Fix or BD Cytofix™ Fixation Buffer and permeabilization with one of the four BD Phosflow™ Perm buffers. These studies demonstrated that certain intracellular epitopes required harsh permeabilization conditions for optimal detection, whereas others were detectable under milder conditions. Surface marker stains often required optimization, particularly under harsh permeabilization conditions. Factors such as antibody clone, fluorophore, and concentration had a considerable impact on staining resolution, and alternative staining protocols were required for optimal staining of some surface markers. To facilitate the optimization of fixation, permeabilization, and staining conditions for multiparameter flow cytometry, experimental data and protocols from this study are available through an interactive database freely accessible at www.cytobank.org/facselect. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 157. doi:1538-7445.AM2012-157
Electrocardiographic Differentiation Between Left Ventricular Hypertrophy and Anterior Myocardial Infarction
Authors: P. M. KINI, E. E. EDDLEMAN, H. V. PIPBERGER
Journal: Circulation (1970)

Electrocardiograms recorded from patients with uncomplicated left ventricular hypertrophy (LVH) often show loss of initial anteriorly directed QRS forces. An attempt was made to differentiate these records from electrocardiograms showing a similar pattern as a result of anterior myocardial infarction (MI). Orthogonal ECGs (Frank system) obtained from 103 patients with LVH were compared to ECG obtained from 327 patients with MI. The ECG were selected on the basis of absence of Q waves in lead Z which in the conventional ECG corresponds to absence of the R wave in right precordial leads. With two simple scalar measurements, namely R amplitude in lead X ≥ 1.2 mv and the sum of amplitudes of R in leads X and Z ≥ 2.5 mv, 66% of LVH cases were recognized. With these criteria, 88% of the MI records were also correctly classified. The same measurements identified 59% of an independent sample of 66 cases of LVH with no Q in lead Z. By utilizing linear discriminant function analysis, 75% of the cases of LVH, 80% of the MI, and 70% of the independent group of LVH were correctly classified. Classification procedures were also tested on 48 autopsy cases with results slightly inferior to those obtained on clinical samples. Direction of initial instantaneous QRS vectors in the transverse plane proved to be much less efficient than scalar measurements or multivariate analysis in the separation between LVH and MI. This study confirms the difficulties concerning the correct interpretation of the significance of loss of anteriorly directed forces in the presence of LVH. However, the error rate in diagnosis can be considerably reduced by the use of criteria proposed on the basis of this investigation.
Scanning electron microscopy and replica studies of joint surfaces in experimental arthritis.
Authors: D L Gardner, G Sander, R Inoue, C Soria-Herrera, P Marriott
Journal: Annals of the Rheumatic Diseases (1971)

To determine whether the demonstrated hyperlipidaemia (and, possibly, an increased incidence of ischaemic vascular disease in gouty patients) was related to pathological platelet function, platelet adhesion studies were performed by two different methods in gouty and control subjects.The results in gouty patients, however, were not significantly different from those in controls.Discussion DR D. C. DUMONDE (London) Is there any relationship between diabetes mellitus and gout?DR. DARLINGTON This question has proved contro- versial in the past but most people do not now consider that such a relationship exists.DR.J. A. BOYLE (Glasgow) I am a little unhappy about the effect of obesity on your results.Please could you explain what you did to assess this effect?D R. D ARLI NG TO N We decided to match gouty patients and controls for the Ponderal Index, which correlated well with the serum uric acid, and we accepted that the gouty patients were significantly heavier than the controls.We then divided both the gouty patients and the controls into two groups, i.e. obese and non-obese (according to whether they were more than 10 per cent.heavier than their average weight-obtained from Tables taking age and height into consideration-or not).A Student's t-test was applied to each group of lipid results.The only significant result was a marginal effect upon unesterified fatty acids and we were satisfied that obesity was not significantly affecting our findings.
Cryoanalgesia for relief of pain after thoracotomy.
Authors: O Maiwand, A R Makey
Journal: BMJ (1981)

One hundred patients undergoing thoracotomy had their intercostal nerves blocked by cryoanalgesia before closure and the effect of this on their postoperative pain was evaluated. Of the 100 patients, 79 were free of pain, 12 had some discomfort, and nine reported severe pain necessitating narcotic analgesia (mean 1.5 injections per patient). Only five patients needed assisted removal of sputum, though eight showed retention of sputum or subsegmental collapse of lung radiographically. Overall, lack of pain and greater alertness much enhanced the value of physiotherapy, which resulted in a low incidence of complications and a smooth recovery. The technique of cryoanalgesia is simple, extremely effective, and apparently offers benefits not conferred by other methods of preventing pain after thoracotomy.
TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts
Authors: Diana L. Bernstein, John E. Le Lay, Elena G. Ruano, Klaus H. Kaestner
Journal: Journal of Clinical Investigation (2015)

Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.
Shaping the synaptic signal: molecular mobility inside and outside the cleft
Authors: Dmitri A. Rusakov, Leonid P. Savtchenko, Kaiyu Zheng, Jeremy M. Henley
Journal: Trends in Neurosciences (2011)

Rapid communication in the brain relies on the release and diffusion of small transmitter molecules across the synaptic cleft. How these diffuse signals are transformed into cellular responses is determined by the scatter of target postsynaptic receptors, which in turn depends on receptor movement in cell membranes. Thus, by shaping information transfer in neural circuits, mechanisms that regulate molecular mobility affect nearly every aspect of brain function and dysfunction. Here we review two facets of molecular mobility that have traditionally been considered separately, namely extracellular and intra-membrane diffusion. By focusing on the interplay between these processes we illustrate the remarkable versatility of signal formation in synapses and highlight areas of emerging understanding in the molecular physiology and biophysics of synaptic transmission. Rapid communication in the brain relies on the release and diffusion of small transmitter molecules across the synaptic cleft. How these diffuse signals are transformed into cellular responses is determined by the scatter of target postsynaptic receptors, which in turn depends on receptor movement in cell membranes. Thus, by shaping information transfer in neural circuits, mechanisms that regulate molecular mobility affect nearly every aspect of brain function and dysfunction. Here we review two facets of molecular mobility that have traditionally been considered separately, namely extracellular and intra-membrane diffusion. By focusing on the interplay between these processes we illustrate the remarkable versatility of signal formation in synapses and highlight areas of emerging understanding in the molecular physiology and biophysics of synaptic transmission.
Optimal Management of Acute Coronary Syndromes
Authors: L. David Hillis, Richard A. Lange
Journal: New England Journal of Medicine (2009)

In the United States, more than a million people are hospitalized annually with unstable angina or myocardial infarction without ST-segment elevation, so-called acute coronary syndromes. For these patients, several treatments have proved to be effective in reducing the incidence of death, infarction or reinfarction, and recurrent ischemia. These treatments include intensive medical therapy and coronary angiography followed by revascularization, if indicated.1,2 Given the sheer number of medical interventions that are now available for these conditions, knowing which therapy to administer and when to do so is confusing for many physicians. The studies by Giugliano et al.3 and Mehta et . . .
Racial discrimination against doctors
Authors: F B Beswick
Journal: BMJ (1993)

EDITOR,-We sympathise with A Esmail and S Everington over the medicolegal problems resulting from their study but were sorry to note their observation on the "comparative unpopularity" of psychiatry.'We recently published a study of predictors of shortlisting and appoint- ments for training posts in psychiatry.2Not having an English name was associated with not being shortlisted at senior registrar level (4/18 v 8/14; p < 0 05).In our "real life" study, however, having an English name was significantly associated with having obtained a British undergraduate education (p < 0-001).This in turn was associated with achieving a publication containing data (p<0005), which emerged as the strongest predictor (p<0-001) of shortlisting for a senior registrar post.Our results show the artificiality of comparing curricula vitae identical in all but name and the promotional value (for better or worse) of achieving publication.Our paper nevertheless echoes Esmail and Everington's in concluding that "members of appointments committees should . .become still more aware of their commitment to equal opportunities and their vulnerability to prejudice."
Innovation in general practice
Authors: J F Forbes
Journal: BMJ (1988)

gresses more rapidly in this group is in dispute.Although we are unlikely to find premalignant disease in the sexually active girls under 16, we think that cytological screening is useful to educate them about the need for regular cervical smears.These patients are likely to have many sexual partners, have a high prevalence of sexually trans- mitted diseases (770/o-A J Robinson, unpublished data), and be at high risk of developing cervical intraepithelial neoplasia.
Federal Spending for Illness Caused by the Human Immunodeficiency Virus
Authors: William Winkenwerder, Austin R. Kessler, Rhonda M. Stolec
Journal: New England Journal of Medicine (1989)

Is the federal government devoting sufficient resources to fighting the epidemic of human immunodeficiency virus (HIV) infection, and are these resources being spent appropriately? Some observers contend that the amounts have been inadequate, but until now there has been no overall accounting of federal activities and spending to combat the epidemic. We report expenditure data collected from federal agencies for the years 1982 to 1989. In all, $5.5 billion will have been spent on HIV-related illness during this period by the federal government, nearly 60 percent of it by the U.S. Public Health Service. Federal spending on HIV-related illness in 1989 will reach $2.2 billion, representing over one third of all estimated national (public and private) HIV expenditures, and tripling state expenditures. In 1992, federal spending on the epidemic will reach an estimated $4.3 billion. Although sizable, this will be just 1.8 percent of all 1992 federal health dollars. Similarly, in 1992, national (public and private) spending on HIV-related illness will consume roughly 1.6 percent of all health-related costs in the United States. Federal spending for HIV research and prevention is similar to funding for other major diseases, including some conditions, such as cancer and heart disease, that now have a greater impact on mortality.
Lipid-Based Nutrient Supplements: How Can They Combat Child Malnutrition?
Authors: Kathryn G. Dewey, Mary Arimond
Journal: PLoS Medicine (2012)

Kathryn Dewey and Mary Arimond discuss new research in PLOS Medicine that assesses the effect of blanket provision of ready-to-use supplementary food to children at high risk of malnutrition in Chad, and highlight some of the challenges of investigating the efficacy of supplementary foods for malnourished children.