tbuckley/cabot-search huggingface dataset:
Germline and somatic JAK2 mutations and susceptibility to chronic myeloproliferative neoplasms
Authors: Lynn R Goldin, Magnus Björkholm, Sigurdur Y Kristinsson, Jan Samuelsson, Ola Landgren
Journal: Genome Medicine (2009)

Myeloproliferative neoplasms (MPNs) are a group of closely related stem-cell-derived clonal proliferative diseases. Most cases are sporadic but first-degree relatives of MPN patients have a five- to seven-fold increased risk for developing an MPN. The tumors of most patients carry a mutation in the Janus kinase 2 gene (JAK2(V617F)). Recently, three groups have described a strong association of JAK2 germline polymorphisms with MPN in patients positive for JAK2(V617F). The somatic mutation occurs primarily on one particular germline JAK2 haplotype, which may account for as much as 50% of the risk to first-degree relatives. This finding provides new directions for unraveling the pathogenesis of MPN.
Synthesis of very low density lipoproteins in the cockerel. Effects of estrogen.
Authors: L Chan, R L Jackson, B W O'Malley, A R Means
Journal: Journal of Clinical Investigation (1976)

The effect of estrogen on the synthesis of plasma very low density lipoproteins (VLDL) in the cockerel was studied both in vivo and in vitro. Synthesis was studied by immunoprecipitation techniques with antisera prepared against VLDL and a major VLDL protein. VLDL were isolated from the plasma of white Leghorn hens and estrogen-treated white Leghorn cockerels by ultracentrifugal flotation at d 1.006 g/ml. After delipidation, the lipid-free proteins (apoproteins) were fractionated on Sephadex G-150 and DEAE-cellulose. Both the hen and the estrogen-treated cockerel VLDL were shown to contain an identical apoprotein with a mol wt of approximately 12,000; the apoprotein is designated fraction B. Reduction and S-carboxy-methylation of fraction B resulted in a reduction of the molecular weight by approximately one-half, indicating a dimer-monomer relationship. Antiserum prepared to the hen VLDL dimer protein gave precipitin lines of complete identity to both the hen and cockerel dimer, monomer, VLDL, apoVLDL, low density lipoproteins, and plasma; no precipitin line was formed with either hen or cockerel high density lipoproteins. After a single subcutaneous injection of diethylstilbestrol into the cockerel, plasma VLDL protein, cholesterol, and triglyceride increased, reaching a maximum 24--48 h after hormone administration. Liver slices from similarly treated animals were incubated in vitro in culture medium in the presence of [3H]lysine for 2 h. Immunoprecipitable radioactivity in VLDL increased within 2 h of diethylstilbestrol treatment and reached a maximum at 24 h; VLDL radioactivity returned to base-line levels by 72 h. At the peak of induction, newly synthesized VLDL represented 11% of the total soluble protein synthesized. When actinomycin-D (5 mg/kg) was administered simultaneously with estrogen, the induction of VLDL synthesis was totally inhibited. To determine whether the effect of estrogen on VLDL synthesis was mediated at the level of transcription, partially-purified cockerel liver mRNA was prepared from estrogen-treated animals and the mRNA activity for fraction B was quantitated in a wheat germ translation system. Fraction B mRNA was found to increase from a low base-line value to a maximum 16-24 h after estrogen treatment, returning towards baseline values at 30 h. At the peak of induction, fraction B constituted 12% of the total protein synthesized. The kinetics of induction of fraction B mRNA activity in the cell-free translation system is very similar to that observed in liver slice experiments. This finding suggests that estrogen stimulates VLDL synthesis, at least partially, by enhancing the accumulation of the mRNA for one of their major apoproteins.
The placebo effect: powerful, powerless or redundant?
Authors: Steven J Kamper, Christopher Michael Williams
Journal: British Journal of Sports Medicine (2012)

Over the last 200 years, the placebo effect has cast a large and persuasive shadow over the medical field. In that time it has been by turn; harmless charade, charlatan's ruse, therapeutic device, methodological tool, ethical dilemma, research theme and source of controversy. Despite popular recognition, pervasive problems underlie conceptualisation of placebos and placebo effects. With medicine now firmly entrenched in the age of evidence-based practice, there is a question as to whether it is time to leave the old placebo behind us. The idea of a magical black box from which unexplained therapeutic effects spring up is archaic and also unhelpful from a scientific point of view. If there really is an effect, surely we are best served by directly investigating what is responsible for it. This knowledge can be used in the clinic to improve treatment effectiveness and in research to inform study design.

The view and role of placebos have developed over time. Modern medical understanding of placebos dates back to the late 1700s1, and since then, placebo interventions appear to have been used fairly commonly in medical practice alongside other treatments.2 Up until midway through the 20th century, the prevailing opinion appears to have been that placebo interventions had no effect on pathophysiology. Placebos were used only to bring comfort to the patient, ‘a camouflage behind which to watch nature takes its course’1 (p. 512).

From the 1950s onwards, there was a shift towards regarding placebos as having genuine effects of their own. Beecher's well-known article ‘The Powerful Placebo’3 apparently confirmed the claims of widespread and important therapeutic effectiveness of placebo interventions. This period also saw the start of rapid growth in the use of placebos as a control intervention for testing the efficacy of other treatments. Thus, as research generally, and …
Can Hysterectomy Be Considered a Risk Factor for Cardiovascular Disease?
Authors: Kate M. Brett
Journal: Circulation (2005)

n this issue of Circulation, Howard and colleagues 1 present a study on the risk of cardiovascular disease (CVD) by hysterectomy status using data from the Women's Health Initiative Observational Study.The purpose of this editorial is to put their work and its findings into context by reviewing the literature both on the epidemiology of hysterectomy, as well as on menopause, sex hormones, and blood loss, and their impact on the risk of CVD.
556 SVR AND TACROLIMUS WITH AZATHIOPRINE IN HCV POST LT PATIENTS WERE ASSOCIATED WITH FIBROSIS REGRESSION BASED ON COLLAGEN PROPORTIONATE AREA
Authors: P. Manousou, A. Dhillon, E. Cholongitas, D. Samonakis, G. Isgro, V. Calvaruso, T.V. Luong, E. Tsochatzis, D. Patch, D. Thorburn, J. O'Beirne, A. Buroughs
Journal: Journal of Hepatology (2011)
A NOTE ON THE EFFECT OF THE ANGLE OF INCIDENCE UPON THE DOSE OF X-RAYS ABSORBED BY THE SKIN
Authors: JOHN KINNEAR
Journal: British Journal of Dermatology (1935)

British Journal of DermatologyVolume 47, Issue 5 p. 202-203 A NOTE ON THE EFFECT OF THE ANGLE OF INCIDENCE UPON THE DOSE OF X-RAYS ABSORBED BY THE SKIN JOHN KINNEAR M.D., M.R.C.P.Ed., JOHN KINNEAR M.D., M.R.C.P.Ed. Physician for Diseases of the Skin, Dundee Royal InfirmarySearch for more papers by this author JOHN KINNEAR M.D., M.R.C.P.Ed., JOHN KINNEAR M.D., M.R.C.P.Ed. Physician for Diseases of the Skin, Dundee Royal InfirmarySearch for more papers by this author First published: May 1935 https://doi.org/10.1111/j.1365-2133.1935.tb09855.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume47, Issue5May 1935Pages 202-203 RelatedInformation
Influence of coronary occlusion during PTCA on end-systolic and end-diastolic pressure-volume relations in humans.
Authors: D A Kass, M Midei, J Brinker, W L Maughan
Journal: Circulation (1990)

The influence of acute coronary occlusion on systolic and diastolic left ventricular pressure-volume relations was studied in 10 patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Pressure-volume relations were obtained by conductance catheter and micromanometer techniques and with volume load altered by transient inferior vena caval occlusion. End-systolic and end-diastolic pressure-volume relations were obtained at baseline, during 60-90 seconds of ischemia, and at return to baseline after angioplasty balloon deflation. Coronary occlusion significantly altered systolic and diastolic chamber function. Systolic dysfunction was characterized by a reproducible rightward shift of the end-systolic pressure-volume relation (+25.4 +/- 18.4 ml) that was greater for proximal left anterior descending and circumflex coronary artery occlusions (+41 ml) than for distal or right coronary artery occlusions (+15.4 ml, p less than 0.05). Occlusion also lowered chamber systolic function indexes, such as the end-systolic pressure-volume relation slope (from 4.2 to 2.8 mm Hg/ml) and preload recruitable stroke work (from 97 to 78.6 mm Hg). All systolic (and diastolic) changes were resolved with successful angioplasty. Diastolic abnormalities during angioplasty were characterized by prolonged pressure relaxation and an upward shift of the resting diastolic pressure-volume data and by an apparent increase in chamber elastic stiffness. However, when end-diastolic data from multiple beats during inferior vena caval occlusion were compared, control and ischemic end-diastolic pressure-volume relations displayed little or no difference. Thus, elevations in resting diastolic pressure-volume relations and apparent increase in chamber elastic stiffness during coronary occlusion in humans appear dominated by altered right ventricular or pericardial loading. These data indicate that pressure-volume analysis is useful in assessing the functional significance of coronary lesions and reperfusion.
Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin According to Thymidylate Synthase Expression in Nonsquamous Non–Small-Cell Lung Cancer: A Biomarker-Stratified Randomized Phase II Trial
Authors: Jong-Mu Sun, Jin Seok Ahn, Sin-Ho Jung, Jiyu Sun, Sang Yun Ha, Joungho Han, Keunchil Park, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2015)

Purpose We investigated whether thymidylate synthase (TS) expression is a predictive marker for the clinical outcome of pemetrexed/cisplatin in patients with nonsquamous non–small-cell lung cancer. Patients and Methods Eligible patients were tested for TS expression by immunohistochemistry and stratified into either a TS-negative or a TS-positive group. After stratification, patients in each group were randomly assigned (1:1 ratio) to receive either pemetrexed/cisplatin or gemcitabine/cisplatin for a maximum of six cycles until disease progression. The primary end point was evaluation of the interaction between TS groups and treatment allocation for objective response rate. Results Of 321 enrolled patients with nonsquamous non–small-cell lung cancer, 315 received at least one dose of study chemotherapy and were analyzed. By investigator assessment, response rates were 47% for the pemetrexed/cisplatin arm and 21% for the gemcitabine/cisplatin arm in the TS-negative group and 40% and 39%, respectively, for the TS-positive group (interaction P = .0084). By independent reviewers, response rates of pemetrexed/cisplatin and gemcitabine/cisplatin were 39% and 21%, respectively, in the TS-negative group and 40% and 48% in the TS-positive group (interaction P = .0077). The median progression-free survival times for the pemetrexed/cisplatin and the gemcitabine/cisplatin arms were 6.4 and 5.5 months, respectively, in the TS-negative group and 5.9 and 5.3 months in the TS-positive group (interaction P = .07). Conclusion With regard to response rate and progression-free survival, pemetrexed/cisplatin was superior to gemcitabine/cisplatin in the TS-negative group but not in the TS-positive group, indicative of TS expression as a potential predictive marker. Additional prospective studies involving larger cohorts are warranted to confirm the predictive role of TS expression.
A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates
Authors: Guillaume Blin, David Nury, Sonia Stefanovic, Tui Neri, Oriane Guillevic, Benjamin Brinon, Valérie Bellamy, Catherine Rücker-Martin, Pascal Barbry, Alain Bel, Patrick Bruneval, Chad Cowan, Julia Pouly, Shoukhrat Mitalipov, Elodie Gouadon, Patrice Binder, Albert Hagège, Michel Desnos, Jean-François Renaud, Philippe Menasché, Michel Pucéat
Journal: Journal of Clinical Investigation (2010)

Cell therapy holds promise for tissue regeneration, including in individuals with advanced heart failure. However, treatment of heart disease with bone marrow cells and skeletal muscle progenitors has had only marginal positive benefits in clinical trials, perhaps because adult stem cells have limited plasticity. The identification, among human pluripotent stem cells, of early cardiovascular cell progenitors required for the development of the first cardiac lineage would shed light on human cardiogenesis and might pave the way for cell therapy for cardiac degenerative diseases. Here, we report the isolation of an early population of cardiovascular progenitors, characterized by expression of OCT4, stage-specific embryonic antigen 1 (SSEA-1), and mesoderm posterior 1 (MESP1), derived from human pluripotent stem cells treated with the cardiogenic morphogen BMP2. This progenitor population was multipotential and able to generate cardiomyocytes as well as smooth muscle and endothelial cells. When transplanted into the infarcted myocardium of immunosuppressed nonhuman primates, an SSEA-1+ progenitor population derived from Rhesus embryonic stem cells differentiated into ventricular myocytes and reconstituted 20% of the scar tissue. Notably, primates transplanted with an unpurified population of cardiac-committed cells, which included SSEA-1- cells, developed teratomas in the scar tissue, whereas those transplanted with purified SSEA-1+ cells did not. We therefore believe that the SSEA-1+ progenitors that we have described here have the potential to be used in cardiac regenerative medicine.
Tagging Single Nucleotide Polymorphisms in Phosphoinositide-3-Kinase–Related Protein Kinase Genes Involved in DNA Damage “Checkpoints” and Lung Cancer Susceptibility
Authors: Zhibin Hu, Hongliang Liu, Haifeng Wang, Ruifen Miao, Weiwei Sun, Guangfu Jin, Ying Wang, Hongxia Ma, Li Jin, Qingyi Wei, Daru Lu, Wei Huang, Hongbing Shen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: DNA damage checkpoints are initiated by its sensor proteins of the phosphoinositide-3-kinase–related protein kinase family, including ataxia-telangiectasia mutated, ataxia-telangiectasia and Rad3-related, and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). We hypothesized that polymorphisms in these genes may alter the regulation of DNA repair and the risk of lung cancer. Experimental Design: We genotyped 12 tagging single nucleotide polymorphisms (tSNP) in these three phosphoinositide-3-kinase–related protein kinase genes in 500 incident lung cancer cases and 517 controls in a Chinese population by using the Illumina SNP genotyping BeadLab platform. Results: Single locus analyses revealed that some of the heterozygotes or variant homozygotes of DNA-PKcs tSNPs were associated with decreased risks of lung cancer compared with their wild-type homozygotes. In the combined analyses of two tSNPs (rs8178085 and rs12334811) with approaching dose-dependent effect on lung cancer predisposition, subjects carrying two to four risk genotypes were associated with a 43% decreased lung cancer risk compared with subjects carrying zero to one risk genotypes (adjusted odds ratio, 0.53; 95% confidence interval, 0.35-0.80). Moreover, the decreased risk associated with the combined genotypes of rs8178085 and rs12334811 was slightly more pronounced in nonsmokers and in carriers with ataxia-telangiectasia mutated rs228591 variant allele or ataxia-telangiectasia and Rad3-related rs6782400 wild-type homozygous genotype. Conclusion: These results indicate, for the first time, that tSNPs in DNA-PKcs may play a protective role in lung cancer development.
A CASE OF RETROPERITONEAL HAEMATOCELE PRODUCING ACUTE INTESTINAL OBSTRUCTION
Authors: H. T. Mursell
Journal: BMJ (1907)

IN the BRflISH MEDICAL JOURNAL of December 2nd, 1905, I reported a case of retroperitoneal lipoma weighing 21 lb., sittated in intimate relation to the right kidney and ireter, which I removed with ease, the tumour shelling out of its bed apparently completely.The pationt a woman aged 40, rapidly recovered from the operation, and put on flesh.She remained in perfect health for about two years, but at the end of that time, eight-inonths before I saw her again, she began to suffer from stbmach troubles, and from slight pain in. the back and sides.Two months.later the abdomen began to swell, and these symptoms went on for six months, when she consulted Dr. KirkhopeQf Belfast, who sent her to me.She came into hospital on Xarch 2td, 1907.Her appearance on admission was much better than when she first came under my care, she was much fatter andmore healthy looking.I found the abdomen distended and filled with a lobulated tumour ; the individual massea -were firm in consistence, one in the epigastrium in particular was so hard that I was led to fear tbat the recurrence which was evidently present was of a malignant type.During the four days which she passed in hospital before operation she.Wil quite free from symptoms of any kind.It is interesting to note that, the sear of the first operation, which measured over 9 in. in length, showed no signs of yielding.On March 6th I opened the abdomen by an incision of about 9 in. in length, and fou-nd the following state of affairs: The tumour consisted of a number of lobes varying in size from that of a goose-egg up to that of a Rugby football, more or less pedunculated, and only united at their common site of origin, which was in the right flank in the anigle between the outer border of the kidnay and the iliac creat.The right colon lay internal to.this, an1 everal large vessels ran from its outer border into the pedicle.One small mass, burrowing benaeath the caecum, had opened up the layers of the meso appendix,
Bystander Activation of Cytotoxic T Cells: Studies on the Mechanism and Evaluation of In Vivo Significance in a Transgenic Mouse Model
Authors: Stephan Ehl, Joachim Hombach, Peter Aichele, Hans Hengartner, Rolf M. Zinkernagel
Journal: The Journal of Experimental Medicine (1997)

Bystander activation, i.e., activation of T cells specific for an antigen X during an immune response against antigen Y may occur during viral infections. However, the low frequency of bystander-activated T cells has rendered it difficult to define the mechanisms and possible in vivo relevance of this nonspecific activation. This study uses transgenic mice expressing a major histocompatibility complex class I–restricted TCR specific for glycoprotein peptide 33-41 of lymphocytic choriomeningitis virus (LCMV) to overcome this limitation. CD8+ T cells from specific pathogen-free maintained, unimmunized “naive” TCR transgenic mice can differentiate into LCMV-specific cytolytic effector CTL during infections with vaccinia virus or Listeria monocytogenes in vivo or mixed lymphocyte culture in vitro. We show that in these model situations (a) nonspecifically activated CTL are able to confer antiviral protection in vivo, (b) bystander activation is largely independent of the expression of a second T cell receptor of different specificity, (c) bystander activation is not mediated by a broadly cross-reactive TCR, but rather by cytokines, (d) bystander activation can be mediated by cytokines such as IL-2, but not α/β-IFN in vitro; (e) bystander activation is, overall, a rare event, occuring in vivo in roughly 1 in 200 of the LCMV-specific CTL during infection of TCR transgenic mice with vaccinia virus; (f) bystander activation does not have a significant functional impact on nontransgenic CTL memory under the conditions tested; and (g) even in the TCR transgenic situation, where unphysiologically high numbers of T cells of a single specificity are present, bystander activation is not sufficient to cause clinically manifest autoimmune disease in a transgenic mouse model of diabetes. We conclude that although bystander activation via cytokines may generate cytolytically active CTL from naive precursors, quantitative considerations suggest that this is usually not of major biological consequence.
Comparisons of metabolism of apolipoprotein B in normal subjects, obese patients, and patients with coronary heart disease.
Authors: Y A Kesäniemi, W F Beltz, S M Grundy
Journal: Journal of Clinical Investigation (1985)

This study was designed to examine the integrated metabolism of apolipoprotein B (apo B) in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) in normal subjects, obese patients, and a group of patients with coronary heart disease (CHD). Turnover rates of 131I-VLDL-B, 131I-IDL-B, 125I-LDL-B, and [3H]VLDL-triglycerides (TG) were determined by the multicompartmental analysis that used the model described in the preceding article (Beltz, W.F., et al. 1985. J. Clin. Invest. 76: 575-585). Compared with five normal subjects, four obese subjects had increased synthesis rates of both VLDL-B and VLDL-TG. Production of LDL-B was inconsistently raised in these same patients. Five patients with CHD had enhanced production of both VLDL-B and LDL-B, but secretion rates of VLDL-TG were not increased. Thus, in patients with obesity and in those with CHD, synthesis rates of VLDL particles may be abnormally high. In the obese patients, the VLDL appeared to be of normal composition, but in patients with CHD, the VLDL were relatively poor in TG. The study also showed that a significant fraction of VLDL-B is removed directly from the circulation and never reaches LDL regardless of the type of patients. The fraction that does reach LDL is one factor that determines LDL concentrations.
Effect of Recommendations from Reviewers Suggested or Excluded by Authors
Authors: Jessica L. Moore, Eric G. Neilson, Vivian Siegel
Journal: Journal of the American Society of Nephrology (2011)

The Journal of the American Society of Nephrology (JASN) gives authors submitting original research the option of suggesting qualified reviewers or those they wish to exclude. This historical habit often leaves us wondering whether author preferences correlate with reviewer recommendations and whether differences related to reviewer selection affect decisions by editors. In a self-study presented here, we found that author-suggested reviewers, as a group, make more positive recommendations than editor-suggested reviewers (P = 0.01), although the difference disappears when recommendations are compared with those of editor-suggested reviewers of the same manuscript (P = 0.081). The distribution of recommendations by author-excluded reviewers, as a group, did not differ from those by editor-suggested reviewers; however, author-excluded reviewers impart significantly more negative recommendations than other reviewers of the same manuscript (P = 0.029). We further explored whether such differences result from individual reviewer tendencies to give generally more positive or more negative recommendations than editor-suggested reviewers and found no such tendency. Finally, editorial decisions on manuscripts reviewed by author-suggested or author-excluded reviewers do not differ from those decisions on manuscripts assigned but not reviewed by them. JASN's policy of editors making decisions independent from individual reviewer recommendations minimizes the effect of selection bias on publication decisions.