tbuckley/cabot-search huggingface dataset:
Cooksey report recommends central coordinating body for research
Authors: Andrew Cole
Journal: BMJ (2006)

The long awaited report by Sir David Cooksey on UK healthcare research has proposed a new model of structured coordination between the NHS, the Medical Research Council (MRC), and the healthcare industry to ensure more research is translated into tangible benefits for patients. 

But the report, commissioned by the chancellor, Gordon Brown, has decided against merging the two main funding bodies, the MRC and the NHS's National Institute for Health Research (NIHR). 

Instead the report proposes a central coordinating body, the Office for Strategic Coordination of Health Research, which will oversee all health research funding, determine strategy, and monitor progress against targets. 

In addition, a joint MRC-NIHR Translational Medicine Funding Board will direct money towards …
Abstract 15778: HNO Enhances SERCA2a Activity and Cardiomyocyte Function by Altering Key Cysteine Residues 41 and 46 in Phospholamban
Authors: Vidhya Sivakumaran, Carlo G Tocchetti, Chevon N Thorpe, Jeff D Ballin, Lufang Zhou, Dong I Lee, Brian O'Rourke, David A Kass, Gerald M Wilson, James E Mahaney, Nazareno Paolocci
Journal: Circulation (2011)

Rationale. Nitroxyl (HNO) exerts positive cardiac inotropy/lusitropy partially via the acceleration of sarcoplasmic reticulum (SR) Ca2+ re-uptake/release. However, the role of phospholamban (PLN) i...
Abstract 2455: BRCA1 and BARD1 expression and localization in breast cell lines
Authors: Cristobal Herrera, Elisa Pérez, Elías Blanco, Patricia Gajardo, Pilar Carvallo
Journal: Cancer Research (2014)

Abstract One of the principal functions of BRCA1 is to keep the integrity of DNA by homologous recombination which repairs DNA double strand breaks, thus its localization is mainly nuclear in a normal cell. BRCA1 nuclear function is enhanced by its interaction with BARD1, which promotes the import and nuclear retention of BRCA1 by masking its nuclear export signal. Therefore, the interaction of these two proteins is relevant in BRCA1 nuclear function. On the other hand, in tumor cell lines, splicing variants of BARD1 lacking the BRCA1 interaction domain have been described. The expression of these splicing variants of BARD1 could contribute to the loss of nuclear localization of BRCA1. Recently, our group found that a high percentage of triple negative breast cancer tumors showed cytoplasmic or no expression of BRCA1 (unpublished data). Our interest is to study the molecular mechanisms that explain the cytoplasmic localization of BRCA1 in breast cancer cells. We studied mRNA expression of BRCA1, BARD1 and BARD1β through RT-PCR and expression of both proteins by western blot, immunocytochemistry and immunofluorescence in two breast cancer cell lines (HCC1937: ER-, mutated in BRCA1, and T47D: ER+) and one non-tumor breast cell line (MCF10A). BRCA1 and BARD1 expression was coherent between immunocytochemistry and immunofluorescence assay. The HCC1937 cell line presented a weak BRCA1 protein expression mainly in the cytoplasm. The other cell lines had a high nuclear and weak cytoplasmic expression. BARD1 protein is expressed in the nucleus and cytoplasm in all cell lines. BARD1 full mRNA had an equal expression in the three cell lines, and its isoform BARD1β, which do not interact with BRCA1, was expressed at higher levels in tumor cell lines than in the non-tumor cell lines. However, T47D cell line showed nuclear localization of BRCA1 despite high levels of BARD1β mRNA. This suggests that BARD1β either does not express at protein level, or that full-length BARD1 levels are enough to keep BRCA1 in the nucleus. The study of molecular causes of BRCA1 localization in cell lines will allow us to better understand subcellular localization of BRCA1 in tumors and its interaction with BARD1. FONDECYT 1120200. Citation Format: Cristobal Herrera, Elisa Pérez, Elías Blanco, Patricia Gajardo, Pilar Carvallo. BRCA1 and BARD1 expression and localization in breast cell lines. [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 2455. doi:10.1158/1538-7445.AM2014-2455
Scottish Adjuvant Tamoxifen Trial: a Randomized Study Updated to 15 Years
Authors: H. J. Stewart, R. J. Prescott, A. P. M. Forrest
Journal: JNCI Journal of the National Cancer Institute (2001)

Background and Methods: The Scottish Adjuvant Tamoxifen Trial (main trial) was initiated in April 1978 to assess the effect of tamoxifen given to patients with breast cancer immediately after mastectomy (or mastectomy plus radiation therapy) (adjuvant arm) or only after the patients had had a relapse (control arm); 1323 patients were randomly assigned (667 to the adjuvant arm and 656 to the control arm). Results have been reported for the follow-up period from 2.5 through 8 years. In this article, we report updated results after a median follow-up of 15 years. If agreeable and eligible, patients who were disease free at 5 years in the adjuvant arm of the main trial were entered into a duration trial and randomly assigned either to stop taking tamoxifen (169 patients) or to continue taking it indefinitely until relapse or death (173 patients). For this update, we analyzed information on death, recurrence, survival, and other malignancies for all but 21 of the 560 living patients from the original and duration trials to determine the probabilities of total survival, systemic relapse of disease, and death from breast cancer. All statistical tests are two-sided. Results: The beneficial effect of adjuvant tamoxifen given for 5 years on the probability of total survival (P = .006), systemic relapse (P = .007), and death from breast cancer (P = .002) has been maintained through 15 years. No additional benefit was observed in those randomly assigned to continue taking tamoxifen beyond 5 years. Conclusion: Information from this study suggests that, if adjuvant tamoxifen is given to women with operable breast cancer, it need not be for more than 5 years.
The Effect of the Garren-Edwards Gastric Bubble on Solid and Liquid Gastric Emptying
Authors: HARVEY A. ZIESSMAN, MARTIN J. COLLEN, FREDERIC H. FAHEY, CECELIA A. CIARLEGLIO, KATHLEEN A. MAHER, EDWARD L. CATTAU, DAVID E. FLEISCHER, JAMES H. LEWIS, STANLEY B. BENJAMIN
Journal: Clinical Nuclear Medicine (1988)

To determine the effect of the Garren-Edwards Gastric Bubble (GEGB) on gastric emptying, radionuclide solid and liquid gastric emptying in 12 obese patients prior to insertion of the GEGB was studied. Four were restudied at one and seven days and ten patients were restudied at twelve weeks with the GEGB in place. There were no significant differences in liquid gastric emptying at one and seven days nor in solid and liquid gastric emptying at twelve weeks. Solid gastric emptying was significantly decreased from a mean of 63% to 31% after one day (P less than 0.05) and returned to preplacement baseline by seven days. These results indicate that gastric emptying is not significantly changed after twelve weeks with the GEGB in place. Therefore, the mechanism of action for weight reduction with the GEGB is not likely to be mediated by an effect on gastric emptying. However, the solid food-induced dyspeptic symptoms commonly noted 1-3 days after placement of the GEGB, which resolve within seven days, are probably explained by transiently delayed solid gastric emptying.
AIP1 Recruits Phosphatase PP2A to ASK1 in Tumor Necrosis Factor–Induced ASK1-JNK Activation
Authors: Wang Min, Yan Lin, Shibo Tang, Luyang Yu, Haifeng Zhang, Ting Wan, Tricia Luhn, Haian Fu, Hong Chen
Journal: Circulation Research (2008)

Previously we have shown that AIP1 (apoptosis signal-regulating kinase [ASK]1-interacting protein 1), a novel member of the Ras-GAP protein family, facilitates dephosphorylation of ASK1 at pSer967 and subsequently 14-3-3 release from ASK1, leading to enhanced ASK1-JNK signaling. However, the phosphatase(s) responsible for ASK1 dephosphorylation at pSer967 has not been identified. In the present study, we identified protein phosphatase (PP)2A as a potential phosphatase in vascular endothelial cells (ECs). Tumor necrosis factor (TNF)-induced dephosphorylation of ASK1 pSer967 in ECs was blocked by PP2A inhibitor okadaic acid. Overexpression of PP2A catalytic subunit induced dephosphorylation of ASK1 pSer967 and activation of c-Jun N-terminal kinase (JNK). In contrast, a catalytic inactive form of PP2A or PP2A small interfering RNA blunted TNF-induced dephosphorylation of ASK1 pSer967 and activation of JNK without effects on NF-κB activation. Whereas AIP1, via its C2 domain, binds to ASK1, PP2A binds to the GAP domain of AIP1. Endogenous AIP1-PP2A complex can be detected in the resting state, and TNF induces a complex formation of AIP1-PP2A with ASK1. Furthermore, TNF-induced association of PP2A with ASK1 was diminished in AIP1-knockdown ECs, suggesting a critical role of AIP1 in recruiting PP2A to ASK1. TNF-signaling molecules TRAF2 and RIP1, known to be in complex with AIP1 and activate AIP1 by phosphorylating AIP1 at Ser604, are critical for TNF-induced ASK1 dephosphorylation. Finally, PP2A and AIP1 cooperatively induce activation of ASK1-JNK signaling and EC apoptosis, as demonstrated by both overexpression and small interfering RNA knockdown approaches. Taken together, our data support a critical role of PP2A-AIP1 complex in TNF-induced activation of ASK1-JNK apoptotic signaling.
Nontransmission of T-Cell Subset Abnormalities From Hemophiliacs to Their Spouses
Authors: Joan K. Kreiss
Journal: JAMA (1984)

Hemophiliacs who are exposed to pooled clotting factor concentrate constitute one group at increased risk for development of acquired immune deficiency syndrome. To determine the prevalence of cellular immune aberrations in asymptomatic hemophiliacs, we studied a group of 65 adult hemophiliacs for T-cell subset abnormalities. Sixty-five percent of concentrate recipients had an abnormal T-helper to T-suppressor cell ratio, 40% had a depressed absolute T-helper cell level, and 29% had an elevated absolute T-suppressor cell count. To determine whether horizontal transmission of T-cell subset abnormalities from hemophiliacs to their female sexual partners occurred, we studied 41 spouses. We found no correlation between paired husband and wife values for T-cell ratio or any other immune parameter studied. There were no significant differences found between wives of hemophiliacs with reversed T-cell ratios and wives of hemophiliacs with T-cell ratios of 1.0 or greater, with respect to immunologic tests. We conclude that there is no evidence to date for heterosexual or household-contact transmission of T-cell subset abnormalities from hemophiliacs to their spouses in our study population.
Regulation of survivin expression through Bcr-Abl/MAPK cascade: targeting survivin overcomes imatinib resistance and increases imatinib sensitivity in imatinib-responsive CML cells
Authors: Bing Z. Carter, Duncan H. Mak, Wendy D. Schober, Maria Cabreira-Hansen, Miloslav Beran, Teresa McQueen, Wenjing Chen, Michael Andreeff
Journal: Blood (2005)
Free radical generation coupled with arachidonate lipoxygenase reaction relates to reoxygenation induced myocardial cell injury
Authors: T. Kuzuya, S. Hoshida, Y. Kim, H. Oe, M. Hori, T. Kamada, M. Tada
Journal: Cardiovascular Research (1993)

Journal Article Free radical generation coupled with arachidonate lipoxygenase reaction relates to reoxygenation induced myocardial cell injury Get access Tsunehiko Kuzuya, Tsunehiko Kuzuya Department of Pathophysiology and the First Department of Medicine, Osaka University School of Medicine, Osaka, Japan: T Kuzuya, S Hoshida, Y Kim, H Oe, M Hori, T Kamada, M Tada. Correspondence to Dr Kuzuya. Search for other works by this author on: Oxford Academic PubMed Google Scholar Shiro Hoshida, Shiro Hoshida Department of Pathophysiology and the First Department of Medicine, Osaka University School of Medicine, Osaka, Japan: T Kuzuya, S Hoshida, Y Kim, H Oe, M Hori, T Kamada, M Tada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Youngjoon Kim, Youngjoon Kim Department of Pathophysiology and the First Department of Medicine, Osaka University School of Medicine, Osaka, Japan: T Kuzuya, S Hoshida, Y Kim, H Oe, M Hori, T Kamada, M Tada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hiroshi Oe, Hiroshi Oe Department of Pathophysiology and the First Department of Medicine, Osaka University School of Medicine, Osaka, Japan: T Kuzuya, S Hoshida, Y Kim, H Oe, M Hori, T Kamada, M Tada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Masatsugu Hori, Masatsugu Hori Department of Pathophysiology and the First Department of Medicine, Osaka University School of Medicine, Osaka, Japan: T Kuzuya, S Hoshida, Y Kim, H Oe, M Hori, T Kamada, M Tada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Takenobu Kamada, Takenobu Kamada Department of Pathophysiology and the First Department of Medicine, Osaka University School of Medicine, Osaka, Japan: T Kuzuya, S Hoshida, Y Kim, H Oe, M Hori, T Kamada, M Tada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Michihiko Tada Michihiko Tada Department of Pathophysiology and the First Department of Medicine, Osaka University School of Medicine, Osaka, Japan: T Kuzuya, S Hoshida, Y Kim, H Oe, M Hori, T Kamada, M Tada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 6, June 1993, Pages 1056–1060, https://doi.org/10.1093/cvr/27.6.1056 Published: 01 June 1993 Article history Received: 18 June 1992 Accepted: 23 November 1992 Published: 01 June 1993
Alcoholism as Willful Misconduct
Authors: Jeffrey A. Schaler
Journal: JAMA (1989)

To the Editor.—  I oppose the suggestion by Mr Seessel 1 that JAMA readers write to their senators and representatives requesting that the willful misconduct label be removed from alcoholism as I believe the Supreme Court's decision on April 20 was a good one.  The fact that the Court relied heavily on the writings of University of California philosophy professor Herbert Fingarette's book Heavy Drinking: The Myth of Alcoholism as a Disease is a strength, not the weakness intimated by Mr Seessel. Simply calling alcoholism a disease does not make it one, even if it assists in creating sobriety.  Advocates of the disease model of alcoholism love to use diabetes as a metaphor to describe the behavior of an alcoholic. The analogy is not reciprocal. A diabetic is not like an alcoholic.  A person does not will the onset of diabetes, essential hypertension, or the presence or absence of a
Meningiomas Involving the Temporal Bone: Clinical and Pathological Aspects
Authors: Oscar Sugar
Journal: JAMA (1964)

There are four sites of predilection for meningiomas within the temporal bone, and these are precisely the four areas which arachnoidal cell clusters are normally encountered: within the internal acoustic meatus, within the jugular foramen, in the region of the geniculate ganglion, and in the sulcus of the greater and lesser superficial petrosal nerves. Meningiomas invading the temporal bone may also arise from the anterior and posterior surfaces of the petrous bone. Although these last sites give rise to 1.5% of all brain tumors, invasion is relatively rare, so that Nager was able to find only 30 literature references to meningiomas invading the temporal bone. He adds seven cases (three surviving patients, four instances from serially sectioned temporal bones). The importance of these rare tumors is manifold: they have been mistaken for glomus tumors when they have spread into the neck or into the middle ear, they may seem to
Inaccuracies in Measurement of Dried Milk Powders
Authors: P. W. Wilkinson, T. C. Noble, G. Gray, O. Spence
Journal: BMJ (1973)

Infant feeds made up from dried milk are known to be hazardous if the mixture is too concentrated. Tests with five commercial brands of dried milk showed that nurses, midwives, and mothers often made up feeds incorrectly; in most cases the amount of powder used was excessive. Fewer mistakes would be made if scoops were standardized or, better, if the milk was made up in small, accurately weighed packets.
Pulmonary hypertension and NO in sickle cell
Authors: Mark T. Gladwin, Robyn J. Barst, Oswaldo L. Castro, Victor R. Gordeuk, Cheryl A. Hillery, Gregory J. Kato, Daniel B. Kim-Shapiro, Roberto Machado, Claudia R. Morris, Martin H. Steinberg, Elliott P. Vichinsky
Journal: Blood (2010)
New Surveys Show Use of Mammography Rising
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1990)

New Surveys Show Use of Mammography Rising Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 18, 19 September 1990, Pages 1451–1453, https://doi.org/10.1093/jnci/82.18.1451 Published: 19 September 1990
Early prenatal diagnosis.
Authors: H. B. Valman
Journal: BMJ (1989)

Screening* Ultrasound: 16-18 weeks Recent advances in ultrasound techniques and molecular biology have increased the range of antenatal diagnoses.Some methods are available * Serum a fetoprotein: 16-18 weeks only at specialised centres.This chapter will give a background to the successful techniques.An anomaly may be detected during routine * Mother over 37 years examination of the fetus which is carried out by ultrasound in most (a) Chorionic villus biopsy: 8-12 weeks pregnancies at 16-18 weeks of gestation.In some districts all mothers have a serum a fetoprotein estimation as a screening test for neural tube or or other defects and in all districts mothers of more than a certain age, usually 37 years, are offered a chorionic villus biopsy or amniocentesis (b) Amniocentesis.: 16 weeks to exclude Down's syndrome.After the birth of an abnormal baby or the detection of genetic disease in an older child, a paediatrician or geneticist may recommend a specific test at a particular week in the subsequent pregnancy.Some tests are at a early stage in development and the false positive and negative rates have not been assessed.Some genetic tests are not yet sufficiently precise,to enable an accurate * Full blood count prognosis to be given to every family with that disease.At the first antenatal visit it is still important to carry out a full blood * Group count, blood grouping, rhesus antibody titre, rubella antibody titre, and * Rh antibody titre a test for syphilis.Where indicated haemoglobin electrophoresis may indicate that the mother has a haemoglobinopathy and the father's red * Rubella antibody titre cell investigations may suggest that further studies of the fetus are * Test for syphilis needed. Chorionic villus biopsyChorion sampling may be carried out by the transvaginal or, less commonly, by the transabdominal route under ultrasound guidance.* ~~~~~~~The main indications have been maternal age, previous chromosomal anomaly, fetal sexing, enzyme assay, and gene probe assessment.Gene probes have been developed for several diseases including cystic fibrosis, Duchenne~muscular dy strophy., and the haemoglobinopathies.Deoxyribonucleic acid (DNA) is extracted fr'om the chorion sample and the probe is used to determine whether a spec"ific part of a particular gene is present or absent.,
Remarks ON ANAEMIA IN GENERAL PRACTICE
Authors: L. J. Witts
Journal: BMJ (1933)

malady, which progresses unfavourably while time is lost Remarks during symptomatic treatment.0OMy third axiom, therefore, is that if the haemoglobin is below 75 per cent., a complete blood count should be ANAEMIA IN GENERAL PRACTICE * performed.An accurate-blood count may at once BY elucidate the diagnosis, " showing perhaps leukaemia or frank pernicious anaemia.More commonly a banal L. J. WITTS, M.D., F.R
Thallium poisoning. Diagnosis may be elusive but alopecia is the clue.
Authors: D Moore, I House, A Dixon
Journal: BMJ (1993)

Thallium is a heavy metal whose salts are used in some rodent poisons and in the manufacture of optical lenses, semiconductors, scintillation counters, low temperature thermometers, and switching devices, green coloured fireworks, and imitation jewelery, and as chemical catalysts. In clinical practice thallium isotopes are used in cardiac scanning, but the use of thallium salts to treat scalp ringworm was abandoned earlier this century because of their toxicity. The sale of thallium in Britain is strictly licensed because of its toxicity and potential for use in murder, which is helped by the fact that thallous salts are colourless, tasteless, and odorless. The more water soluble salts (such as thallium sulphate, acetate, or carbonate) have higher toxicity, and although the toxic dose is variable most deaths occur after the ingestion of 10-15 mg/kg of soluble salt. Most cases of thallium toxicity occur after oral ingestion but severe toxicity has been reported after inhalation of contaminated dust from pyrite burners, in zinc and lead smelting, and in the manufacture of cadmium, after dermal absorption through protective rubber gloves, and after snorting what was thought to be cocaine. The elimination half time of thallium is between 1.7 and 30 days depending on the time since, and chronicity of, ingestion. The elimination time phases are apparent and because of the long terminal elimination half time thallium may act as a cumulative poison. We present two cases of thallium poisoning with intent to kill.