tbuckley/cabot-search huggingface dataset:
Acceleration of Blood Coagulation in Acute Myocardial Infarction as Demonstrated by the Heparin Clotting Time; Effect of Dicumarol Therapy
Authors: ROBERT L. ROSENTHAL, JOHN C. WEAVER, AGNES BENEDEK
Journal: Circulation (1952)

A study of blood coagulation was made on cardiac patients with and without acute myocardial infarction, prior to anticoagulant therapy. The heparin clotting time, an in vitro modification of the heparin tolerance test, was accelerated in 74 per cent (14 out of 19) of the patients with acute myocardial infarction studied within three weeks after the attack. One out of 14 patients without acute myocardial infarction had an accelerated heparin clotting time below 20 minutes, the lower limit of the "normal" range established on the basis of study of over 100 control subjects. The clotting time and platelet count revealed no significant variations. Serial coagulation studies, performed on patients receiving Dicumarol therapy, revealed that the heparin clotting time, which provides a sensitive measure of over-all coagulability, is prolonged as the prothrombin concentration is diminished. The significance of these findings in relation to thromboembolic complications of acute myocardial infarction and anticoagulant therapy is discussed.
GSK faces fresh allegations of bribery in Syria
Authors: N. Hawkes
Journal: BMJ (2014)

GlaxoSmithKline, already under siege in China over charges of corruption that are likely to be aired in a Beijing courtroom on 7 August, faces fresh allegations of similar behaviour made by a whistleblower in Syria.

The new claims, reported by Reuters, bring to six the countries in which GSK has been accused of various malpractices: China, Poland, Iraq, Jordan, Lebanon, and now Syria. The Syrian charges relate to non-prescription products, including the painkiller Panadol, and allege that GSK used bribes, speakers’ fees, trips, and free samples to promote its business, in breach of corruption laws. The offences are alleged to have taken place between 2010 and 2012, when the worsening security situation in …
Sphingosine contributes to tumor necrosis factor-a-mediated contractile dysfunction in response to coronary microembolization
Authors: Matthias Thielmann, Claus Martin, Hilmar Dörge, Sergej Belosjorow, Uwe Schwanke, Arne Krüger, Anita van de Sand, Ina Konietzka, Rainer Schulz, Gerd Heusch
Journal: Journal of the American College of Cardiology (2002)
THE CRYSTALLIZATION AND SEROLOGICAL DIFFERENTIATION OF A STREPTOCOCCAL PROTEINASE AND ITS PRECURSOR
Authors: S. D. Elliott
Journal: The Journal of Experimental Medicine (1950)

Grown in dialysate broth at a pH between 5.5 and 6.5, some strains of group A streptococci elaborate the precursor of a proteolytic enzyme. Within this range of hydrogen concentration the precursor is also produced when the streptococci are suspended in a peptone dialysate containing glucose and incubated at 37 degrees C. The precursor does not appear to be produced at a neutral or alkaline reaction. Methods are described whereby the precursor and proteinase have been isolated in crystalline form. The precursor crystallizes from half-saturated ammonium sulfate at pH 8.0 and a temperature of 22 degrees C. or higher; the proteinase crystallizes from 0.15 saturated ammonium sulfate at pH 8.0 but does so most readily at refrigerator temperature. The degree of purification achieved by these procedures is discussed. The activity of purified preparations of the precursor and of proteinase has been tested against alpha-benzoyl-l-arginineamide and, with this as a substrate, the conversion of precursor to proteinase by autocatalysis or by trypsin has been confirmed. Immunological experiments are described, the results of which provide evidence of the distinct antigenic specificity of the precursor and proteinase; the conversion of precursor to proteinase has been followed by means of serological tests.
Unresponsiveness of Pial Precapillary Vessels to Catecholamines and Sympathetic Nerve Stimulation
Authors: A. Jarrell Raper, Hermes A. Kontos, Enoch P. Wei, John L. Patterson
Journal: Circulation Research (1972)

A systematic analysis of the possible existence of neurogenic control of precapillary pial vessels was made in three species (cat, dog, and rabbit). In all of these animals, pial vessels failed to respond to externally applied isoproterenol or norepinephrine in high concentrations (up to 100 µg/ml), although the vessels did dilate in response to externally applied histamine. Adrenergic nerve endings on the pial vessels were demonstrated by fluorescent histochemical techniques specific for catecholamines. However, in the absence of changes in arterial blood pressure and arterial blood carbon dioxide tension, pial precapillary vessels showed no change in caliber in response to stimulation of the ipsilateral superior cervical ganglion. These results show that pial precapillary vessels are not subject to vasoconstriction probably because they lack sufficient receptors for the catecholamine neurotransmitter.
Subdural haematoma in the elderly
Authors: E. A. Teale, S. Iliffe, J. B. Young
Journal: BMJ (2014)

An 84 year old woman with a history of postural hypotension and frequent falls presented with a two week history of confusion and wandering. Her general practitioner diagnosed delirium secondary to a urinary tract infection on the basis of a positive urinary dipstick test for white blood cells and nitrites. She failed to improve with oral antibiotics and was admitted to hospital for further assessment. Clinical examination showed a lack of focal neurological signs but cranial computed tomography revealed a left sided chronic subdural haematoma. A subdural haematoma results from tearing of the veins linking the cerebral cortex and the dural sinuses, causing blood to accumulate between the dura and arachnoid maters. Brain atrophy associated with ageing or dementia stretches these fragile veins such that they are more prone to tearing after relatively trivial (and often forgotten) head injury1; in up to half of cases there is a history of fall without head trauma.1 2 3 Over time, there is fibrin deposition and organisation of the haematoma, resulting in a chronic subdural haematoma. Neovascularisation processes within the subdural haematoma increase the propensity for acute or chronic bleeding.4 Anticoagulation increases the risk of subdural haematoma and the likelihood of fresh bleeding into an established haematoma.4 #### How common is subdural haematoma?
An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: A randomized, controlled trial
Authors: Douglas L. Seidner, Bret A. Lashner, Aaron Brzezinski, Phillip L.C. Banks, John Goldblum, Claudio Fiocchi, Jeffry Katz, Gary R. Lichtenstein, Peter A. Anton, Lori Y. Kam, Keith A. Garleb, Stephen J. Demichele
Journal: Clinical Gastroenterology and Hepatology (2005)
Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy.
Authors: J D Conger, S A Falk
Journal: Journal of Clinical Investigation (1977)

Tubular fluid flow, urine osmolality, and pH were selectively altered to determine the relative protective roles of these factors in a rat model of acute urate nephrophathy. Various prehyper uricemic conditions were established in five groups of animals: (a) normopenic Wistar rats given no pretreatment (Group I); (b) Wistar rats given acetazolamide, 20 mg/kg, and isotonic NaHCO3 to produce urine alkalinization (Group II); (c) Wistar rats in which a moderate diuresis, similar to that observed in Group II but without urine alkalinization, was induced with furosemide, 2 mg/kg (Group III); (d) Wistar rats in which a high-flow solute diuresis was induced with furosemide, 15 mg/kg (Group IV); (e) Brattleboro rats, homozygous for pituitary diabetes insipidus, that had a spontaneous high-flow water diuresis (Group V). A comparable level of hyperuricemia (19.4+/-2.2 mg/100 ml) was achieved in all animals with intravenous urate infusion. Clearance and micropuncture studies were performed before and 1 h after induction of hyperuicemia. Group I rats had mean falls in renal plasma flow and glomerular filtration rate of 83 and 86%, respectively; nephron filtration rate decreased 66%, and tubular and microvascular pressures increased twofold. In Group II there were 45 and 47% declines in renal plasma flow and glomerular filtration rate, respectively, a 66% fall in nephron filtration rate, and a 30% increase in tubular and vascular pressures. Moderate amounts of urate were seen in the kidneys. Group III had changes in renal function identical to Group II suggesting that the moderate prehyperuricemic diuresis in the latter group and not urine alkalinization produced the partial protection observed. Groups IV and V were completely and comparably protected with renal function studies unchanged from controls. It is concluded that high tubular fluid flow, whether induced by a solute or water diuresis, is the primary mechanism of protection in acute urate nephropathy. At most, urine alkalinization plays a minor preventive role.
Abstract 5718: Convergence of vitamin D and PPARγ signaling in human breast cancer cell lines
Authors: Fatouma Alimirah, Rajendra G. Mehta, Xinjian Peng
Journal: Cancer Research (2010)

Abstract Previous studies have demonstrated a positive interaction between vitamin D and peroxisome proliferator- activated receptor γ (PPARγ) mediated signaling while other studies have shown an inverse relationship between these two pathways. Therefore, we sought to determine the functional interaction between the vitamin D receptor (VDR) and PPARγ in human breast cancer cells. We report the physical interaction and nuclear colocalization of VDR and PPARγ in the T47D human breast cancer cell line as determined by co-immunoprecipitation and immunofluorescence respectively. Furthermore, 1alpha,25-dihydroxyvitamin D3 (1,25D3) treatment of MCF-7 and T47D cells significantly upregulated PPARγ protein expression in a dose and time dependent manner. Conversely, knockdown of unliganded VDR also upregulated PPARγ protein expression, suggesting that it is a potential VDR target gene. Thus, VDR itself in the absence of ligand, can suppress PPARγ basal expression. This paradoxical effect may be due to the differential binding of VDR to its coactivators or corepressors during the liganded and unliganded state. Consistent with this, the basal expression of PPARγ mRNA was inversely correlated with VDR mRNA expression in several human breast cancer cell lines. Reciprocally, a PPARγ agonist attenuated vitamin D mediated upregulation of vitamin D target genes CYP24 and p21. Similarly, the activity of VDRE, a vitamin D responsive reporter was decreased by 2 fold in the presence of the PPARγ agonist. Together, these observations infer that VDR and PPARγ protein interactions negatively influence their respective pathways. (This work was supported by NCI predoctoral fellowship 1F31CA132619 (F.A.) and NCI R03 CA121365 (X.P). 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 5718.
Left-Right Symmetry Breaking in Tissue Morphogenesis via Cytoskeletal Mechanics
Authors: Ting-Hsuan Chen, Jeffrey J. Hsu, Xin Zhao, Chunyan Guo, Margaret N. Wong, Yi Huang, Zongwei Li, Alan Garfinkel, Chih-Ming Ho, Yin Tintut, Linda L. Demer
Journal: Circulation Research (2012)

Left-right (LR) asymmetry is ubiquitous in animal development. Cytoskeletal chirality was recently reported to specify LR asymmetry in embryogenesis, suggesting that LR asymmetry in tissue morphogenesis is coordinated by single- or multi-cell organizers. Thus, to organize LR asymmetry at multiscale levels of morphogenesis, cells with chirality must also be present in adequate numbers. However, observation of LR asymmetry is rarely reported in cultured cells.
Role of Macrophage Inhibitory Cytokine-1 in Tumorigenesis and Diagnosis of Cancer
Authors: Asne R. Bauskin, David A. Brown, Tamara Kuffner, Heiko Johnen, X. Wei Luo, Mark Hunter, Samuel N. Breit
Journal: Cancer Research (2006)

Abstract Macrophage inhibitory cytokine-1 (MIC-1), a transforming growth factor-β superfamily cytokine, is involved in tumor pathogenesis, and its measurement can be used as a clinical tool for the diagnosis and management of a wide range of cancers. Although generally considered to be part of the cell's antitumorigenic repertoire, MIC-1 secretion, processing, and latent storage suggest a complex, dynamic variability in MIC-1 bioavailability in the tumor microenvironment, potentially modulating tumor progression and invasiveness. (Cancer Res 2006; 66(10): 4983-5)
67Ga Uptake After Cosmetic Augmentation With Silicone in HIV-Infected Patient With Unexplained Hypercalcemia
Authors: Aron Gould-Simon, William Erdman, Orhan K. Öz
Journal: Clinical Nuclear Medicine (2012)

A 56-year-old HIV-infected man underwent 67Ga scintigraphy because of unexplained hypercalcemia, elevated calcitriol, and concern for chronic granulomatous disease, including tuberculosis. Although no abnormalities were identified to indicate sarcoidosis or tuberculosis, increased radiotracer accumulation in the face and gluteal region was observed. On questioning, the patient revealed a 3-year history of liquid silicone use for soft-tissue augmentation of the face and buttocks. After SPECT/CT imaging, the etiology of the patient's hypercalcemia was attributable to silicone-induced granulomatosis. We present this case to highlight the appearance of 67Ga uptake on SPECT/CT after cosmetic augmentation with liquid silicone in the face and buttocks and silicone-induced granulomatosis as a cause of unexplained elevated vitamin D and hypercalcemia.
Abstract P1-07-02: Acceptability of Breast Cancer Medical Prevention by Letrozole in Post-Menopausal Women with a BRCA1/2 Mutation in the LIBER Trial
Authors: P Pujol, S Mijonnet, C Dugast, P Berthet, C Lasset, J-P Fricker, S Delaloge, P This, K Baudry, C Nogues, A-L. Martin
Journal: Cancer Research (2010)

Abstract Background: Women carrying a germline BRCA1/2 mutation have a lifetime risk of developing breast cancer of 56 to 80%. Prophylactic bilateral mastectomy provides a valid option to reduce breast cancer incidence, but considerably affects the quality of life. There is therefore an urgent need to evaluate medical preventive alternative. The major breast cancer prevention trials using tamoxifen showed an approximately 50% incidence reduction in high risk women. Adjuvant trials comparing aromatase inhibitors (AI) to tamoxifen revealed a higher preventive efficacy of AI for contra-lateral cancer with fewer thrombo-embolic side effects. Patients and Methods: The French federation of cancer centres (“FNCLCC”) has designed a randomized phase III trial to determine the efficacy of letrozole to prevent breast cancer in postmenopausal BRCA1/2 carriers. The “LIBER” study is a double-blind, letrozole versus placebo study involving 32 centers among with 20 are actives. The study opened for recruitment in march 2008. Results: Here we present data reflecting the acceptability of this preventive trial. Twenty-one centers replied to an inquiry. 690 women were eligible. Out of 485 women informed by letter, 217 (44%) came to consultation and 62 (13%) entered the study. The main concerns of women while considering to enter the trial were: the potential side effects, the probability to receive the placebo and the lack of support from other practitioners. Out of 78 enrolled women, 48 (62%) were BRCA1 mutation carriers, 30 (38%) were BRCA2 mutation carriers, 73 (93%) were oophorectomized, 38 (49%) had a previous unilateral cancer, 40 (52%) did not have cancer. 30 (38%) women were less than 50 years old, and 48 (62%) were 50 or over 50 years old. Discussion: For post-menopausal women bearing a BRCA1/2 genetic predisposition, prevention of breast cancer risk by letrozole could provide a precious alternative when bilateral mastectomy is not retained. Among women who received oral information, the acceptability of this randomized double-blind letrozole versus placebo trial is 28%. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-07-02.
Copper toxicity in Wilson disease explained in a new way
Authors: Uta Merle, Wolfgang Stremmel, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2011)

Wilson disease (WD) is a rare hereditary condition that is caused by a genetic defect in the copper-transporting ATPase ATP7B that results in hepatic copper accumulation and lethal liver failure. The present study focuses on the structural mitochondrial alterations that precede clinical symptoms in the livers of rats lacking Atp7b, an animal model for WD. Liver mitochondria from these Atp7b-/- rats contained enlarged cristae and widened intermembrane spaces, which coincided with a massive mitochondrial accumulation of copper. These changes, however, preceded detectable deficits in oxidative phosphorylation and biochemical signs of oxidative damage, suggesting that the ultrastructural modifications were not the result of oxidative stress imposed by copper-dependent Fenton chemistry. In a cell-free system containing a reducing dithiol agent, isolated mitochondria exposed to copper underwent modifications that were closely related to those observed in vivo. In this cell-free system, copper induced thiol modifications of three abundant mitochondrial membrane proteins, and this correlated with reversible intramitochondrial membrane crosslinking, which was also observed in liver mitochondria from Atp7b-/- rats. In vivo, copper-chelating agents reversed mitochondrial accumulation of copper, as well as signs of intramitochondrial membrane crosslinking, thereby preserving the functional and structural integrity of mitochondria. Together, these findings suggest that the mitochondrion constitutes a pivotal target of copper in WD.
To Protect Those Who Serve
Authors: Jeffrey M. Drazen, Greg Koski
Journal: New England Journal of Medicine (2000)

Any clinical investigator will tell you that the success of a clinical trial is limited by the ability to recruit patients to become research subjects. Altruism aside, many patients who make this transition reach a conscious and informed decision to forgo standard care or even forgo treatment altogether for the chance, but only a chance, that they may benefit from an as yet unproved drug, device, or procedure. The decision takes special courage, and medical science is grateful to the people who display this courage.The investigational treatment received under a research protocol may be no better than the standard . . .
PDZ Proteins Interacting with C-Terminal GluR2/3 Are Involved in a PKC-Dependent Regulation of AMPA Receptors at Hippocampal Synapses
Authors: Michael I. Daw, Ramesh Chittajallu, Zuner A. Bortolotto, Kumlesh K. Dev, Fabrice Duprat, Jeremy M. Henley, Graham L. Collingridge, John T.R. Isaac
Journal: Neuron (2000)
Restructure for Federal AIDS Research
Authors: Rebecca Voelker
Journal: JAMA (1996)

FEDERAL AIDS RESEARCH faces a major overhaul after a new report called for an infusion of scientific talent, strengthened coordination among research programs, consolidation of clinical trials, and a revamped vaccine research initiative. In an unprecedented review of the $1.4 billion AIDS research effort at the National Institutes of Health (NIH), 114 scientists, academics, pharmaceutical representatives, and community advocates have issued a sometimes unflattering report with dozens of recommendations intended as a blueprint for restructuring federal AIDS research. "Mainly I'm looking at those recommendations that alter the direction we're taking in research, and the mechanisms by which we do the research," said NIH Director Harold Varmus, MD, in explaining plans for implementation. "This really is an extraordinary effort," added William Paul, MD, director of the Office of AIDS Research (OAR) at the NIH. "We've reached a turning point in AIDS research. We've made a major effort and attained a lot
Appropriate Use of Artificial Nutrition and Hydration — Fundamental Principles and Recommendations
Authors: David Casarett, Jennifer Kapo, Arthur Caplan
Journal: New England Journal of Medicine (2005)

Recent events — including the Terri Schiavo case —have involved public questioning of the commonly held belief that decisions about artificial nutrition and hydration should be made in the same way in which decisions about other treatments are made. This article reviews the principles that have guided decisions about the use of artificial nutrition and hydration over the past 20 years. The authors outline their own recommendations for improving decision making about artificial nutrition and hydration.
Ethics of rationing health care services
Authors: D. Cox
Journal: BMJ (1995)

EDITOR,—Unlike Raanon Gillon,1 I find myself agreeing with the King's Fund when it advocates the formation of a Oregon-like commission modelled on the Nuffield Council of Bioethics to start the process of rationing of specific services.2

Gillon doubts whether it is morally safe to use, as he sees it, “populist solutions in distributive justice such as have occurred in Oregon … and technical and simplistic economic solutions such as the system of costed quality adjusted life years (QALYs).”1 Instead he favours seeking ways of “muddling through elegantly” as advocated by Hunter in Rationing Dilemmas in Health Care.3 Gillon is offended by …
CAMPYLOBACTER PYLORI AND RECURRENCE OF DUODENAL ULCERS— A 12-MONTH FOLLOW-UP STUDY
Authors: J.G. Coghlan, H. Humphries, C. Dooley, C. Keane, D. Gilligan, D. Mckenna, E. Sweeney, C. O'Morain
Journal: The Lancet (1987)
Abstract 3530: The parathyroid hormone-related peptide region likely features seven discrete breast cancer susceptibility loci
Authors: Adam N. Freeman, Terence ‘Jack’ Martin, Michael Henderson, Enes Makalic, Daniel F. Schmidt, Miroslaw K. Kapinski, Melissa C. Southey, Graham G. Giles, John L. Hopper
Journal: Cancer Research (2014)

Abstract Parathyroid hormone-related protein (PTHrP), the product of the PTHLH gene, has long been implicated in the mechanism by which breast cancers establish and grow as metastases in bone. Paradoxically, a prospective clinical study clinical suggests that its production early in breast cancer in a cancer is actually protective. Multiple recent Genome-Wide Association Studies (GWAS) have confirmed a single susceptibility locus immediately upstream of the PTHLH gene to be associated with breast cancer. In this study we compare the findings of two GWAS, the ABCFS and the MCCS, along with a large imputed meta-analysis combining the ABCFS, BBCS, DFBBCS, MARIE, SASBAC, HEBCS, GC-HBOC, UK2, BPC3, BCFR and SardiNIA data. To better discern the signals of association with common variant Single Nucleotide Polymorphisms (SNPs) in the PTHLH gene region, we compare results from a conventional marginal analysis performed by plink with those from DepTH, a novel bootstrap permutation-based method that considers multiple contiguous SNPs. These are plotted on the genome and analysed in conjunction with hapmap, encode expression and regulation, genome-wide epistasis, eQTLs, and genetic data. Whereas the classic approach identifies only one SNP (“top hit”), our analysis suggests there are at least 7 discrete regions in and around PTHLH in which there are susceptibility variants, rare or common, with potentially independent functions on disease risk. In addition, exhaustive genome-wide epistasis demonstrates statistical interactions between PTHLH and multiple other gene regions including calcitonin and the vitamin D receptor in breast cancer. Citation Format: Adam N. Freeman, Terence ‘Jack’ Martin, Michael Henderson, Enes Makalic, Daniel F. Schmidt, Miroslaw K. Kapinski, Melissa C. Southey, Graham G. Giles, John L. Hopper. The parathyroid hormone-related peptide region likely features seven discrete breast cancer susceptibility loci. [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 3530. doi:10.1158/1538-7445.AM2014-3530