tbuckley/cabot-search huggingface dataset:
Abstract A52: Mechanisms of 1,25-dihdyroxyvitamin D-mediated growth arrest and apoptosis in transformed mammary cells
Authors: Meggan E. Keith, Erika LaPorta, JoEllen Welsh
Journal: Cancer Research (2009)

Abstract 1,25-Dihdyroxyvitamin D (1,25D), the biologically active form of vitamin D, exerts pro-differentiating and anti-proliferative actions on epithelial cells, but the exact role of the vitamin D receptor (VDR) in mediating these effects remains to be defined. The goal of this project is to link specific functional domains of the VDR with regulation of cancer cell proliferation, invasion, and apoptosis. Epithelial cell lines derived from DMBA induced mammary tumors generated in VDR knock-out (KO) mice and their wild-type (WT) littermates were characterized for growth arrest and apoptosis following 1,25D treatment. Cells derived from WT tumors expressed VDR and exhibited growth arrest and apoptosis in response to 1,25D. In VDR positive cells, 1,25D mediated apoptosis was associated with activation of multiple caspases and calpain, resulting in PARP cleavage. In contrast, cells derived from KO tumors lacked VDR and failed to undergo growth arrest and apoptosis upon 1,25D treatment. To recreate VDR signaling in KO cells, human VDR was stably expressed in the KO240 cell line, generating the KOhVDR cell line. KOhVDR cells expressed transcriptionally active VDR protein at levels comparable to that of WT cells. Re-introduction of VDR did not affect doubling time of KOhVDR cells in the absence of ligand, but did sensitize cells to growth arrest and apoptosis in response to VDR agonists. PCR screening arrays and independent qPCR validation were used to identify VDR target genes in this model system. In WT cells, 6-24h treatment with 100nM 1,25D induced PDGF-B (up to 10 fold) and VEGF-A (up to 5 fold). No changes in PDGF-B or VEGF-A expression were observed in KO cells treated with 1,25D, but both genes were inducible by 1,25D in KOhVDR cells stably expressing hVDR. Thus, 1,25D can activate either human or murine VDR to induce endogenous PDGF-B and VEGF-A gene expression in these murine cells. In summary, these data indicate that VDR does not exert ligand-independent effects on mammary cell growth, but is essential to trigger gene expression, growth arrest and apoptosis in response to 1,25D. Supported by NIH CA69700. Citation Information: Cancer Res 2009;69(23 Suppl):A52.
Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance
Authors: Volker Adams, Hong Jiang, Jiangtao Yu, Sven Möbius-Winkler, Eduard Fiehn, Axel Linke, Claudia Weigl, Gerhard Schuler, Rainer Hambrecht
Journal: Journal of the American College of Cardiology (1999)
implications for memetics
Authors: susan blackmore
Journal: Behavioral and Brain Sciences (2005)

the implications that steels &amp; belpaeme's (s&amp;b's) models have for memetics are discussed. the results demonstrate the power of memes (in this case colour words) to influence both concept formation, and the creation of innate concepts. they provide further evidence for the memetic drive hypothesis, with implications for the evolution of the human brain and for group differences in categorisation.
Abstract 3179: Targeted re-sequencing of cancer-related genes from matched FFPE and fresh-frozen tumor samples using the Illumina sequencing platform
Authors: Marina Bibikova, Jeremy Chien, Vincent Ho, Craig April, Sarah Munchel, Erich Jaeger, Samantha Cooper, Russell Grocock, Fiona Nielsen, Yaman Tarabishy, Daniel Visscher, Megan Manion, Jonathan Liu, Eric Wieben, Lynn Hartmann, Kimberly Kalli, Viji Shridhar, Jian-Bing Fan
Journal: Cancer Research (2012)

Abstract High throughput sequencing technologies open up a new dimension in cancer genomics by enabling the characterization of cancer genomes at base-pair resolution. To date, the majority of large-scale genomics projects rely on fresh-frozen biospecimens in their studies, which are difficult to obtain and often lack long-term clinical data. Unlike fresh-frozen samples, archived formalin-fixed paraffin-embedded (FFPE) tissues are more readily accessible, and are often associated with known clinical outcomes and more complete clinical annotations. However, sequencing library preparation methods need to be further optimized with regard to applicability to FFPE samples. To test whether next-generation sequencing technologies could overcome previously reported artifacts associated with formalin fixation and report accurate sequencing results, we compared whole-genome and targeted enrichment DNA sequencing data obtained from five FFPE tumor samples for which matching frozen tissues were available. We successfully generated sequencing libraries using 1 µg of genomic DNA as input material and a modified TruSeq™ sample preparation protocol. We designed a custom enrichment pool targeting exons from 215 cancer-related genes and utilized this pool to pull-down and sequence approximately 1.3 Mb region of the genome with an average 400x coverage depth to test if deep sequencing would improve validation of tumor-specific somatic mutations. We used the Illumina sequence analysis pipeline and the Windows-based second generation DNA sequencing software NextGENe® to analyze the data and identify sequence variations that are different from the human reference genome. CNV detection was overall higher among FFPE samples compared with fresh-frozen samples, demonstrating that tissue processing impacts sequencing data quality. We obtained good concordance in variant calls between matched FFPE and fresh-frozen samples. Discordant variant calls were mainly due to low depth of coverage in the regions where variant calls were made. Improvements to DNA sequencing methods for archived samples will significantly enhance cancer research and will result in more reliable prediction of individual cancer therapies. 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 3179. doi:1538-7445.AM2012-3179
Left Ventricular Mass and Systolic Performance in Pediatric Patients With Chronic Renal Failure
Authors: Mark M. Mitsnefes, Thomas R. Kimball, Sandra A. Witt, Betty J. Glascock, Philip R. Khoury, Stephen R. Daniels
Journal: Circulation (2003)

Background— Children with chronic renal disease have a high prevalence of left ventricular hypertrophy (LVH), which is thought to be adaptive to improve contractility and lower wall stress in the face of increased afterload and preload. The aim of this study was to determine the association between LV mass, LV performance, and LV contractility in children with chronic renal insufficiency (CRI) and children undergoing chronic dialysis. Methods and Results— Twenty-five children with CRI, 12 undergoing chronic dialysis, and 24 controls had echocardiographic evaluation during rest and peak exercise. LV performance was assessed by calculation of shortening fraction and heart rate–corrected velocity of circumferential fiber shortening (VCF). Contractility (VCF difference) was determined based on the relation between VCF and end-systolic wall stress. Contractile reserve was assessed by the difference between contractility at rest and peak exercise. The dialysis group had higher LVM index than the group with CRI (42.9±10.3 versus 29.9±9.4 g/m 2.7 , P &lt;0.001). Both groups had higher LVM index compared with controls (22.2±6.1 g/m 2.7 , P &lt;0.001). At rest, the CRI and dialysis groups had significantly higher VCF c ( P &lt;0.001) and VCF difference ( P &lt;0.05) and significantly lower wall stress ( P &lt;0.01) compared with the control group. Dialysis patients had significantly lower contractile reserve compared with the control group ( P &lt;0.03). Conclusions— These results indicate that children with CRI and undergoing chronic dialysis have increased LVM, LV performance, and contractility at rest. However, dialysis patients have diminished contractile reserve during exercise, which might be an indicator for the development of more severe systolic dysfunction over time.
Cutting Into Cholesterol
Authors: Joseph R. Evans
Journal: JAMA (1988)

To the Editor.—  In reference to the article entitled Cutting Into Cholesterol: Cost-Effective Alternatives for Treating Hypercholesterolemia in the April 15 issue, 1 it seems to me that the authors are comparing apples and oranges in their comparison of anion-exchange resins with oat bran. None of the cholesterol-lowering agents have been compared with each other in terms of efficacy and, except for the anion-exchange resin agents and gemfibrozil, I have not seen proof of decreased morbidity or mortality.
Limb Salvage Surgery for Sarcomas: A Good Idea Receives Formal Blessing
Authors: Robert S. Benjamin
Journal: JAMA (1985)

Elsewhere in this issue of<i>JAMA</i>is a consensus development conference statement entitled "Limb-Sparing Treatment of Adult Soft-Tissue Sarcomas and Osteosarcomas,"1 prepared by a panel of 14 "drawn from the medical professions and the general public." As might be expected from the fact that every major center specializing in sarcoma treatment is already actively carrying out limb salvage surgery, the panel recommends its use in appropriately selected patients with sarcomas of soft tissue and bone. Obviously, any attempt at limb salvage surgery must not sacrifice the chances of cure, and there are some patients whose tumor size and/or location unfortunately prohibits adequate resection without sacrificing the extremity. Luckily, among those who have achieved full growth, such patients are in the minority. The benefits of limb salvage surgery are so obvious that one might question the rationale for convening such a panel in the first place, and so the organizers broadened
Thyroid Hormonelike Actions of 3,3′,5′-l-Triiodothyronine and 3,3′-Diiodothyronine
Authors: Stathis S. Papavasiliou, Joseph A. Martial, Keith R. Latham, John D. Baxter
Journal: Journal of Clinical Investigation (1977)

l-Thyroxine is converted to 3,5,3'-l-triiodothyronine (T(3)) as well as to 3,3',5'-l-triiodothyronine (reverse T(3)). One product of further deiodination is 3,3'-diiodothyronine (3,3'T(2)). The serum levels of reverse T(3) and 3,3'T(2) change considerably in various physiological and disease states. We previously found that reverse T(3) and 3,3'T(2) bind to the solubilized hepatic nuclear "receptors" for thyroid hormones. This led us to study binding and actions of these metabolites in cultured rat pituitary cells in which glucose consumption and growth hormone production are regulated by T(3) and l-thyroxine. Reverse T(3) and 3,3'T(2) stimulated growth hormone production and glucose consumption and inhibited nuclear binding of radioactive T(3). Either metabolite produced maximal effects that equaled those of T(3), and neither inhibited the T(3) response. Further, additive effects were observed when reverse T(3) was combined with submaximal concentrations of T(3). In serum-free and serum-containing media, concentrations of 3,3'T(2) 50- to 70- and 10- to 100-fold greater, respectively, than those of T(3) were required for equivalent stimulations and for inhibition of nuclear binding by T(3). The relative activity differences under the two conditions can be attributed to weaker serum protein binding of 3,3'T(2) than T(3). With cells in serum-free media, reverse T(3) was a less avid competitor than 3,3'T(2) for T(3) binding by the nuclear receptors, and was less potent than 3,3'T(2) (0.001 the potency of T(3)) in inducing growth hormone production or glucose oxidation. In incubations with serum-containing media, reverse T(3) was an ineffective competitor for T(3) binding, and had only 0.1 the inducing potency of 3,3'T(2) (0.001 the potency of T(3)). The weaker activity of reverse T(3) relative to 3,3'T(2) in serum-containing media could be explained by stronger serum binding of reverse T(3) than 3,3'T(2). In addition, after long-term incubation of cells with radioactive reverse T(3), much of the cell-associated radioactivity was recovered as 3,3'T(2). These studies suggest that reverse T(3) and 3,3'T(2) can stimulate thyroid hormone-regulated functions as weak agonists by acting via the same receptors that mediate T(3) actions. Moreover, some of the effects of reverse T(3) may be due to 3,3'T(2) produced by deiodination of reverse T(3).
Medical and Hospital Negligence
Authors: Vincent A. Maressa
Journal: JAMA (1990)

This publication is a comprehensive treatise on<i>Medical and Hospital Negligence</i>. It is currently a four-volume, loose-leaf edition. The editors (Goldstein and Zaremski) are well-recognized and respected litigators. Goldstein specializes in plaintiff representation, while Zaremski's practice focuses on defendants. They have organized a complex and voluminous amount of material in a readable—but, more important, easily usable—format. In addition to themselves, there are 76 other contributors, a veritable<i>Who's Who</i>of medical-legal experts. This work is an outstanding reference source and may be the best of its type presently available. It is a welcome addition to every complete health law library and, with its unusual scope, provides practical, useful, and detailed material for both plaintiff and defense counsel. Additionally, there are sections that will be helpful to physicians, administrators, and other nonattorneys in the health care field. One of the more frequent drawbacks to this type of treatise is the failure
Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?
Authors: Elias Zintzaras, Ioannis Stefanidis, Mauro Santos, Francesc Vidal
Journal: Hepatology (2006)

Case–control studies that have investigated the association between alcoholism and alcohol-induced liver damage and the ADH2 , ADH3 , CYP2E1 , and ADLH2 polymorphisms have reported controversial or inconclusive results. Thus, we conducted a meta-analysis of 50 association studies of the above polymorphisms. We explored potential sources of heterogeneity and bias, performed subgroup analyses by racial background and sex, performed sensitivity analyses for studies not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases that met strict criteria for alcoholism. The present meta-analysis underscores significant associations of ADH2 * 1 , ADH3 * 2 , and ALDH2 * 1 alleles and the risk of alcoholism (OR = 1.89 [95% CI 1.56–2.28], 1.32 [95% CI 1.12–1.57], and 4.35 [95% CI 3.04–6.23], respectively). The subsequent subgroup analyses showed association for ADH2*1 and ADH3*2 only in East Asians (OR = 2.23 [95% CI 1.81–2.74] and 1.91 [95% CI 1.45–2.53], respectively) and East Asian males (OR = 2.21 [95% CI 1.57–3.10], 1.69 [95% CI 1.10–2.59], respectively). In East Asian males, the OR for ALDH2*1 was 3.66 (95% CI 1.68–7.96). In Caucasians, sensitivity analysis revealed an association for ADH2*1 in alcoholism (OR = 1.62 [95% CI 1.22–1.89]). When strict criteria were imposed, the pattern of results remained unaltered. For liver disease, there were no significant associations for ADH2*1, ADH3*2, or ALDH2*1 in all subpopulations. The CYP2E1 polymorphism showed no association whatsoever. There is evidence that alleles are mainly dominant. In conclusion , there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2, and lack of bias in all polymorphisms. The above findings reinforce the need for more rigorous studies, and for regular synthesis of studies' results. Supplementary material for this article can be found on the HEPATOLOGY website ( http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html ). (Hepatology 2006;43:352–361.)
Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903
Authors: Ruben A. Mesa, Xiaopan Yao, Larry D. Cripe, Chin Yang Li, Mark Litzow, Elisabeth Paietta, Jacob M. Rowe, Ayalew Tefferi, Martin S. Tallman
Journal: Blood (2010)
Plans for new hospitals should focus on ensuring low running costs
Authors: R. Watson
Journal: BMJ (2009)

Hospitals must move away from the static concept of bed numbers and become far better able to meet future healthcare needs, participants at the annual European Health Forum in Gastein, Austria, were told last week.

Urging planners to show greater imagination, Martin McKee, research director at the European Observatory on Health Systems and Policies, said, “We are concerned that hospitals are still being built to reflect the needs of patients from the 19th and 20th centuries, not the 21st.”

He added: “There is a necessity …
Children and sport
Authors: H. Trippe
Journal: BMJ (1996)

Links between exercise and health are well established,1 yet levels of activity among adults are at best moderate and in many cases low.2 3 4 Concerns about the decline in provision of physical activity for children at school have been raised at various times during the past decade.5 6 Against this background the British government's new policy statement on sport, “Raising the Game,” aims to help schools to re-establish sport as “one of the great pillars of education,” to achieve “the wider social and health benefits of sport,” and to assist children to make “informed decisions about adopting healthy and active lifestyles.”7 Although this comes at a time when schools have weathered a great deal of change, much of which has affected the teaching of sport,5 cynics might still observe that there is a lot of ground to be made up before all pupils play sport in the sunlit uplands described in the report. The main thrust of the publication is about raising standards and levels …
The relationship between plasma levels of immunoreactive atrial natriuretic hormone and hemodynamic function in man.
Authors: E R Bates, Y Shenker, R J Grekin
Journal: Circulation (1986)

To evaluate the relationship between plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH) and different hemodynamic parameters in man, we studied 34 patients undergoing right heart catheterization. Plasma levels of IR-ANH in blood samples withdrawn from the femoral vein (n = 28), right ventricle (n = 27), and left ventricle (n = 17) were determined by radioimmunoassay. Right atrial pressure, pulmonary arterial wedge pressure, heart rate, and mean arterial pressure were found to be independent and significant predictors of IR-ANH plasma levels. The closest correlations were between right atrial pressure and either right ventricular IR-ANH levels (r = .78, p greater than .001) or femoral vein IR-ANH levels (r = .52, p less than .006). Five patients with isolated left ventricular failure had elevated IR-ANH levels out of proportion to their right atrial pressure levels. Pulmonary arterial wedge pressure also correlated with right ventricular IR-ANH levels (r = .46, p less than .002) and with femoral vein IR-ANH levels (r = .58, p less than .002). A single patient with isolated right heart failure had markedly elevated IR-ANH levels despite normal pulmonary arterial wedge pressure. Right ventricular levels were twice femoral vein levels and were closely correlated (181 +/- 40 vs 90 +/- 20 pmol/liter; r = .90, p less than .001). Right ventricular and left ventricular levels were almost identical (155 +/- 46 vs 146 +/- 43 pmol/liter; r = .99, p less than .001). Patients with volume overload states had elevated IR-ANH levels.(ABSTRACT TRUNCATED AT 250 WORDS)
The Multiple Organ Donor: Identification and Management
Authors: B Soifer, A W Gelb
Journal: Annals of Internal Medicine (1989)

Advances in surgical and immunosuppressive techniques as well as increased public awareness have made organ transplantation a well-accepted therapy. To meet the increased need for transplantable organs, medical staff need to recognize which dying patients may be suitable organ donors and how to optimally maintain that donor. We present an overview of the absolute and relative contraindications to organ donation as well as a review of the problems that may be encountered when managing organ donors and how they can best be solved. These guidelines will help increase the number of suitable organ donors and optimize the condition of the transplanted organs.
Plasma Metanephrines in the Diagnosis of Pheochromocytoma
Authors: Fernando Elijovich
Journal: Annals of Internal Medicine (1996)

Letters1 April 1996Plasma Metanephrines in the Diagnosis of PheochromocytomaFernando Elijovich, MDFernando Elijovich, MDUniversity of Texas Medical Branch at Galveston; Galveston, TX 77555Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-7-199604010-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Lenders and colleagues [1] accurately concluded that free plasma levels of metanephrines are better than plasma levels of catecholamines or urine levels of metanephrines in diagnosing pheochromocytoma, despite some problems with their study design (such as different centers and different assays). The important issue, however, is whether free plasma levels of metanephrines are a useful screening test. The positive and negative predictive values of 64% and 100%, respectively, reported by Lenders and colleagues are misleading. Emphasis on the negative predictive value of a test is unwarranted when the disease is rare. A clinician answering "no" to the ...REFERENCE1. Lenders JW, Keiser HR, Goldstein DS, Willemsen JJ, Friberg P, Jacobs MC, et al. Plasma metanephrines in the diagnosis of pheochromocytoma. Ann Intern Med. 1995; 123:101-9. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Medical Branch at Galveston; Galveston, TX 77555 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma 1 April 1996Volume 124, Issue 7Page: 694-695KeywordsBlood plasmaCatecholaminesGlucagonImaging techniquesMetabolitesNegative predictive valuePheochromocytomaPositive predictive valueSpecificityUrine ePublished: 15 August 2000 Issue Published: 1 April 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Single- vs Multiple-Fraction Radiotherapy for Bone Metastases From Prostate Cancer
Authors: Justin E. Bekelman, Andrew J. Epstein, Ezekiel J. Emanuel
Journal: JAMA (2013)

Palliative radiotherapy, comprising 1 or more fractions (ie, treatments) of daily radiation, is the mainstay of treatment for painful bone metastases. In 2005, a US-based randomized trial demonstrated no difference in pain relief between single- and multiple-fraction radiotherapy for uncomplicated bone metastases, confirming results from international trials.1,2

The Choosing Wisely campaign advocates single-fraction treatment for bone metastases.3 We examined whether single-fraction treatment has been incorporated into routine clinical practice for Medicare beneficiaries with prostate cancer and at what cost savings.
Dutch law defines patients' rights
Authors: T Sheldon
Journal: BMJ (1994)

The Netherlands has become the first country in Europe to pass a law defining the responsibilities of doctors to their patients. The patients' rights law will set out current practice already established by case law. It will cover informed consent, access to medical files, privacy of information, and the representation of minors and people with learning disabilities.

Government legal advisers say that it will strengthen the position of patients. But some members of parliament warn that a strict legal framework could weaken the relationship between doctors and patients. Patients' …