tbuckley/cabot-search huggingface dataset:
Allogeneic Stem-Cell Transplantation in Patients With <i>NPM1</i>-Mutated Acute Myeloid Leukemia: Results From a Prospective Donor Versus No-Donor Analysis of Patients After Upfront HLA Typing Within the SAL-AML 2003 Trial
Authors: Christoph Röllig, Martin Bornhäuser, Michael Kramer, Christian Thiede, Anthony D. Ho, Alwin Krämer, Kerstin Schäfer-Eckart, Hannes Wandt, Mathias Hänel, Hermann Einsele, Walter E. Aulitzky, Norbert Schmitz, Wolfgang E. Berdel, Matthias Stelljes, Carsten Müller-Tidow, Utz Krug, Uwe Platzbecker, Martin Wermke, Claudia D. Baldus, Stefan W. Krause, Friedrich Stölzel, Malte von Bonin, Markus Schaich, Hubert Serve, Johannes Schetelig, Gerhard Ehninger
Journal: Journal of Clinical Oncology (2014)

The presence of a mutated nucleophosmin-1 gene (NPM1(mut)) in acute myeloid leukemia (AML) is associated with a favorable prognosis. To assess the predictive value with regard to allogeneic stem-cell transplantation (SCT), we compared the clinical course of patients with NPM1(mut) AML eligible for allogeneic SCT in a donor versus no-donor analysis.Of 1,179 patients with AML (age 18 to 60 years) treated in the Study Alliance Leukemia AML 2003 trial, we identified all NPM1(mut) patients with an intermediate-risk karyotype. According to the trial protocol, patients were intended to receive an allogeneic SCT if an HLA-identical sibling donor was available. Patients with no available donor received consolidation or autologous SCT. We compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor.Of 304 eligible patients, 77 patients had a sibling donor and 227 had no available matched family donor. The 3-year RFS rates in the donor and no-donor groups were 71% and 47%, respectively (P = .005); OS rates were 70% and 60%, respectively (P = .114). In patients with normal karyotype and no FLT3 internal tandem duplication (n = 148), the 3-year RFS rates in the donor and no-donor groups were 83% and 53%, respectively (P = .004); and the 3-year OS rates were 81% and 75%, respectively (P = .300).Allogeneic SCT led to a significantly prolonged RFS in patients with NPM1(mut) AML. The absence of a statistically significant difference in OS is most likely a result of the fact that NPM1(mut) patients who experienced relapse responded well to salvage treatment. Allogeneic SCT in first remission has potent antileukemic efficacy and is a valuable treatment option in patients with NPM1(mut) AML with a sibling donor.
Long-term lifestyle changes after colorectal cancer screening: randomised controlled trial
Authors: Paula Berstad, Magnus Løberg, Inger Kristin Larsen, Mette Kalager, Øyvind Holme, Edoardo Botteri, Michael Bretthauer, Geir Hoff
Journal: Gut (2014)

Objective There is uncertainty whether cancer screening affects participant incentives for favourable lifestyle. The present study investigates long-term effects of colorectal cancer (CRC) screening on lifestyle changes. Design In 1999–2001, men and women drawn from the population registry were randomised to screening for CRC by flexible sigmoidoscopy ('invited-to-screening' arm) or to no-screening (control arm) in the Norwegian Colorectal Cancer Prevention trial. A subgroup of 3043 individuals in the 'invited-to-screening' and 2819 in the control arm, aged 50–55 years, randomised during 2001 had their lifestyle assessed by a questionnaire at inclusion and after 11 years (42% of cohort). The outcome was 11-year changes in lifestyle factors (body weight, smoking status, physical exercise, selected dietary habits) and in total lifestyle score (0–4 points, translating to the number of lifestyle recommendations adhered to). We compared outcomes in the two randomisation arms and attendees with positive versus negative findings. Results Total lifestyle scores improved in both arms. The improvement was smaller in the 'invited-to-screening' arm (score 1.43 at inclusion; 1.58 after 11 years) compared with the control arm (score 1.49 at inclusion; 1.67 after 11 years); adjusted difference −0.05 (95% CI −0.09 to −0.01; p=0.03). The change in the score was less favourable in screening attendees with a positive compared with negative screening result; adjusted difference −0.16 (95% CI −0.25 to −0.08; p<0.001). Conclusions The present study suggests that possible unfavourable lifestyle changes after CRC screening are modest. Lifestyle counselling may be considered as part of cancer screening programmes. Trial registration number NCT00119912.
Domiciliary nebulized terbutaline in severe chronic airways obstruction
Authors: NC Hansen, O May
Journal: European Respiratory Journal (1990)

Forty-eight patients with severe chronic airways obstruction were given 5 mg terbutaline or placebo from a nebulizer twice daily for 2 + 2 weeks. Twenty three patients preferred terbutaline, 9 placebo and 16 had no preference. The baseline lung function and the 6 minute walking distance were not increased after the terbutaline period. The patients who preferred terbutaline indicated less dyspnoea after the terbutaline period as compared to the placebo period, but did not differ with regard to lung function or walking distance after the terbutaline treatment. The physiology behind the subjective relief from the terbutaline inhalations remains unexplained.
Dependence of Cisplatin-Induced Cell Death In Vitro and In Vivo on Cyclin-Dependent Kinase 2
Authors: Peter M. Price, Fang Yu, Philipp Kaldis, Eiman Aleem, Graz[Combining Dot Above]yna Nowak, Robert L. Safirstein, Judit Megyesi
Journal: Journal of the American Society of Nephrology (2006)

Cisplatin is one of the most effective chemotherapeutics, but its usefulness is limited by its toxicity to normal tissues, including cells of the kidney proximal tubule. The purpose of these studies was to determine the mechanism of cisplatin cytotoxicity. It was shown in vivo that cisplatin administration induces upregulation of the gene for the p21 cyclin-dependent kinase (cdk) inhibitor in kidney cells. This protein is a positive effector on the fate of cisplatin-exposed renal tubule cells in vivo and in vitro; adenoviral transduction of p21 completely protected proximal tubule cells from cisplatin toxicity. Herein is reported that cdk2 inhibitory drugs protect kidney cells in vivo and in vitro, that transduction of kidney cells in vitro with dominant-negative cdk2 also protected, and that cdk2 knockout cells were resistant to cisplatin. The cdk2 knockout cells regained cisplatin sensitivity after transduction with wild-type cdk2. It is concluded that cisplatin cytotoxicity depends on cdk2 activation and that the mechanism of p21 protection is by direct inhibition of cdk2. This demonstrated the involvement of a protein that previously was associated with cell-cycle progression with pathways of apoptosis. It also was demonstrated that this pathway of cisplatin-induced cell death can be interceded in vivo to prevent nephrotoxicity.
Putative mechanisms of the impairment of endothelium-dependent relaxation of the aorta with atheromatous plaque in heritable hyperlipidemic rabbits.
Authors: H Tagawa, H Tomoike, M Nakamura
Journal: Circulation Research (1991)

Attenuation of acetylcholine-induced endothelium-dependent relaxation of thoracic aortas excised from Watanabe heritable hyperlipidemic (WHHL) rabbits linearly correlated with the percent area coated with atheromatous plaque. To elucidate mechanisms related to this reduced endothelium-dependent relaxation in the presence of atherosclerosis, the acetylcholine-induced release of endothelium-derived relaxing factor (EDRF) was assessed functionally as a percent relaxation of the precontracted detector strips obtained from the tunica media beneath the intact intima or the atheromatous plaque in the same aortic ring preparation. Relaxations of the normal detectors to effluents containing EDRF of thoracic aortas during stimulation by acetylcholine (3 x 10(-6) M) in heterozygous and homozygous WHHL rabbits were 73 +/- 5% and 59 +/- 9% (p less than 0.01) of the phenylephrine-induced precontraction, respectively. Relaxations of the atherosclerotic detectors to effluents (EDRF) through the aortas during stimulation by acetylcholine (3 x 10(-6) M) in heterozygous and homozygous WHHL rabbits were 16 +/- 4% and 14 +/- 5%, respectively--values significantly smaller than those seen in the normal detectors. When superoxide dismutase was added to the perfusate of the donors from homozygous and heterozygous WHHL rabbits, atherosclerotic detectors relaxed by effluents stimulated by acetylcholine to 73% and 65% (p less than 0.01 versus before the addition of superoxide dismutase) of the normal detector, respectively. Relaxations induced by sodium nitroprusside as well as the contractions by acetylcholine, phenylephrine, and KCl (118 mM) were comparable in detector strips from the normal and atherosclerotic portions. Thus, not only is the amount of EDRF released by acetylcholine reduced in the presence of atherosclerosis, the tunica media beneath the atheromatous plaque is also to some extent responsible for the superoxide-induced inactivation of EDRF.
Prognostic value of exercise testing, coronary angiography and left ventriculography 6--8 weeks after myocardial infarction.
Authors: P J De Feyter, M J van Eenige, D H Dighton, F C Visser, J de Jong, J P Roos
Journal: Circulation (1982)

This study provides data on a consecutive series of 179 survivors of acute myocardial infarction (MI) who had symptom-limited treadmill exercise testing, coronary angiography and left ventriculography within 6--8 weeks after infarction. No patient died. The prevalence of multivessel disease was higher in the symptomatic survivors (79%) (p less than 0.001). The prevalence of multivessel disease in inferior MI was 63% and in anterior MI 42% (p less than 0.001). Left ventricular impairment was more severe in anterior and preexisting MI than in inferior and nontransmural MI (p less than 0.005). During a mean follow-up of 28 months, 11 cardiac deaths and 12 reinfarctions occurred. The total mortality rate was 22% (10 of 46) in patients with an ejection fraction less than 30% or three-vessel disease and 1% (one of 133) in patients with an ejection fraction greater than or equal to 30% and one- or two-vessel disease (p less than 0.001). A group at high risk of mortality is thus identified by angiography. The total reinfarction rate was 9% (11 of 121) in patients with an exercise tolerance of less than 10 minutes (Bruce protocol) and 2% (one of 58) in patients with an exercise tolerance of 10 minutes or more (p less than 0.1). The 58 patients who had an exercise tolerance of 10 minutes or more had a very low risk for cardiac death or reinfarction.
Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years
Authors: W.-Y. Au, S.-Y. Ma, C.-S. Chim, C. Choy, F. Loong, A.K.W. Lie, C.C.K. Lam, A.Y.H. Leung, E. Tse, C.-C. Yau, R. Liang, Y.-L. Kwong
Journal: Annals of Oncology (2005)
Procainamide-induced systemic lupus erythematosus.
Authors: P J Sheldon, W R Williams
Journal: Annals of the Rheumatic Diseases (1970)

Ladd (1962) described the case of a 49-year-old man who was taking procainamide 1 to 2 g. daily.In the space of 3 months he developed a rash, migrating arthralgia, and pleuritic chest pain.LE-cells and antinuclear factor were present, but disappeared along with the rash and arthralgia within 9 weeks of discontinuing the drug.This case drew attention to the role of procaina- mide in inducing a condition resembling systemic lupus erythematosus (SLE).Other drugs impli- cated include hydrallazine, mephenytoin,
Renal Nerves Drive Interstitial Fibrogenesis in Obstructive Nephropathy
Authors: Jinu Kim, Babu J. Padanilam
Journal: Journal of the American Society of Nephrology (2012)

The signals that drive fibrogenesis after an initiating insult to the kidney are incompletely understood. Here, we report that renal nerve stimulation after ureteral obstruction is the primary profibrotic signal and that renal denervation prevents both fibrogenesis and the inflammatory cascade. Local infusion of neural factors, norepinephrine, and calcitonin gene-related peptide (CGRP) in denervated kidneys mimicked the fibrotic response observed in innervated obstructed kidneys. Norepinephrine and CGRP act through the α2-adrenergic receptor and CGRP receptor, respectively, because blocking these receptors prevented fibrosis, the inflammatory response, and tubular cell death. In tubular epithelial cells, both norepinephrine and CGRP induced apoptosis and the release of profibrotic factors capable of stimulating the differentiation of fibroblasts to myofibroblasts. In conclusion, these data suggest that nerve-derived signaling molecules may drive renal fibrosis and that their suppression may be a therapeutic approach to fibrosis prevention.
Augmentation of DHCR24 expression by hepatitis C virus infection facilitates viral replication in hepatocytes
Authors: Takashi Takano, Kyoko Tsukiyama-Kohara, Masahiro Hayashi, Yuichi Hirata, Masaaki Satoh, Yuko Tokunaga, Chise Tateno, Yukiko Hayashi, Tsunekazu Hishima, Nobuaki Funata, Masayuki Sudoh, Michinori Kohara
Journal: Journal of Hepatology (2010)
Glomerular involution in children with frequently relapsing minimal change nephrotic syndrome: An unrecognized form of glomerulosclerosis?
Authors: H.B.P.M. Dijkman, J.F.M. Wetzels, J.H. Gemmink, J. Baede, E.N. Levtchenko, E.J. Steenbergen
Journal: Kidney International (2006)
Medical Ethics and the Interrogation of Guantanamo 063
Authors: Steven H. Miles
Journal: The American Journal of Bioethics (2007)

The controversy over abusive interrogations of prisoners during the war against terrorism spotlights the need for clear ethics norms requiring physicians and other clinicians to prevent the mistreatment of prisoners. Although policies and general descriptions pertaining to clinical oversight of interrogations in United States' war on terror prisons have come to light, there are few public records detailing the clinical oversight of an interrogation. A complaint by the Federal Bureau of Investigation (FBI) led to an Army investigation of an interrogation at the United States prison at Guantanamo Bay. The declassified Army investigation and the corresponding interrogation log show clinical supervision, monitoring and treatment during an interrogation that employed dogs, prolonged sleep deprivation, humiliation, restraint, hypothermia and compulsory intravenous infusions. The interrogation and the involvement of a psychologist, physician and medics violate international and medical norms for the treatment of prisoners.
Analysis of autosomal genes reveals gene–sex interactions and higher total genetic risk in men with systemic lupus erythematosus
Authors: Travis Hughes, Adam Adler, Joan T Merrill, Jennifer A Kelly, Kenneth M Kaufman, Adrienne Williams, Carl D Langefeld, Gary S Gilkeson, Elena Sanchez, Javier Martin, Susan A Boackle, Anne M Stevens, Graciela S Alarcón, Timothy B Niewold, Elizabeth E Brown, Robert P Kimberly, Jeffrey C Edberg, Rosalind Ramsey-Goldman, Michelle Petri, John D Reveille, Lindsey A Criswell, Luis M Vilá, Chaim O Jacob, Patrick M Gaffney, Kathy L Moser, Timothy J Vyse, Marta E Alarcón-Riquelme, Judith A James, Betty P Tsao, R Hal Scofield, John B Harley, Bruce C Richardson, Amr H Sawalha
Journal: Annals of the Rheumatic Diseases (2011)

Objectives Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci. Methods A total of 18 autosomal genetic susceptibility loci for SLE were genotyped in a large set of patients with SLE and controls of European descent, consisting of 5932 female and 1495 male samples. Sex-specific genetic association analyses were performed. The sex–gene interaction was further validated using parametric and non-parametric methods. Aggregate differences in sex-specific genetic risk were examined by calculating a cumulative genetic risk score for SLE in each individual and comparing the average genetic risk between male and female patients. Results A significantly higher cumulative genetic risk for SLE was observed in men than in women. (P=4.52x10-8) A significant sex–gene interaction was seen primarily in the human leucocyte antigen (HLA) region but also in IRF5 , whereby men with SLE possess a significantly higher frequency of risk alleles than women. The genetic effect observed in KIAA1542 is specific to women with SLE and does not seem to have a role in men. Conclusions The data indicate that men require a higher cumulative genetic load than women to develop SLE. These observations suggest that sex bias in autoimmunity could be influenced by autosomal genetic susceptibility loci.
Effects of Diets Enriched in Saturated (Palmitic), Monounsaturated (Oleic), or <i>trans</i> (Elaidic) Fatty Acids on Insulin Sensitivity and Substrate Oxidation in Healthy Adults
Authors: Jennifer C. Lovejoy, Steven R. Smith, Catherine M. Champagne, Marlene M. Most, Michael Lefevre, James P. DeLany, Yvonne M. Denkins, Jennifer C. Rood, Johannes Veldhuis, George A. Bray
Journal: Diabetes Care (2002)

Diets high in total and saturated fat are associated with insulin resistance. This study examined the effects of feeding monounsaturated, saturated, and trans fatty acids on insulin action in healthy adults.A randomized, double-blind, crossover study was conducted comparing three controlled 4-week diets (57% carbohydrate, 28% fat, and 15% protein) enriched with different fatty acids in 25 healthy men and women. The monounsaturated fat diet (M) had 9% of energy as C18:1cis (oleic acid). The saturated fat diet (S) had 9% of energy as palmitic acid, and the trans fatty acid diet (T) had 9% as C18:1trans. Body weight was kept constant throughout the study. After each diet period, insulin pulsatile secretion, insulin sensitivity index (S(I)) by the minimal model method, serum lipids, and fat oxidation by indirect calorimetry were measured.Mean S(I) for the M, S, and T diets was 3.44 +/- 0.26, 3.20 +/- 0.26, and 3.40 +/- 0.26 x 10(-4) min(-1). microU(-1). ml(-1), respectively (NS). S(I) decreased by 24% on the S versus M diet in overweight subjects but was unchanged in lean subjects (NS). Insulin secretion was unaffected by diet, whereas total and HDL cholesterol increased significantly on the S diet. Subjects oxidized the least fat on the M diet (26.0 +/- 1.5 g/day) and the most fat on the T diet (31.4 +/- 1.5 g/day) (P = 0.02).Dietary fatty acid composition significantly influenced fat oxidation but did not impact insulin sensitivity or secretion in lean individuals. Overweight individuals were more susceptible to developing insulin resistance on high-saturated fat diets.
First case of Elizabethkingia anophelis meningitis in the Central African Republic
Authors: Thierry Frank, Jean Chrysostome Gody, Liem Binh Luong Nguyen, Nicolas Berthet, Anne Le Fleche-Mateos, Petula Bata, Clotaire Rafaï, Mirdad Kazanji, Sebastien Breurec
Journal: The Lancet (2013)
Doctors revise Declaration of Helsinki
Authors: B. Christie
Journal: BMJ (2000)

<h3>ABSTRACT</h3> Platinum-based chemotherapeutics are used in many combination regimens in cancer. Despite extensive use across diverse cancer types, there is room for improved efficacy and patient selection for treatment. Here, we use bladder cancer to address both issues. A multi-omic assessment of five human bladder cancer cell lines and their chemotherapy resistant derivatives, coupled with <i>in vitro</i> whole-genome CRISPR screens were used to define functional drivers of treatment resistance. We identified 46 genes that sensitized the resistant cell lines to cisplatin plus gemcitabine (GemCis), a standard combination therapy in bladder cancer. Most genes were involved with DNA damage and repair pathways, which have previously been associated with enhanced sensitivity to cisplatin. Evaluating expression of the 46 genes in the whole transcriptome and proteome data in parental and resistant lines identified the puromycin sensitive aminopeptidase, NPEPPS, as a novel hit. Depletion of NPEPPS resulted in sensitizing resistant bladder cancer cells to cisplatin <i>in vitro</i> and in xenograft experiments. Pharmacologic inhibition of NPEPPS with tosedostat in cells and in chemoresistant, bladder cancer patient tumor-derived organoids improved response to cisplatin. Prior work found NPEPPS in a protein complex with volume regulated anion channels (VRACs) in several cell line models. Interestingly, depletion of two VRAC subunits, LRRC8A and LRRC8D, known importers of intracellular cisplatin, enhanced resistance to cisplatin. Our findings support NPEPPS as a novel and druggable driver of cisplatin resistance with the potential for rapid translation to clinical investigation. <h3>HIGHLIGHTS</h3> CRISPR screens with multi-omics identify NPEPPS as a driver of cisplatin resistance NPEPPS depletion in multiple bladder cancer models enhances cisplatin sensitivity LRRC8A and LRRC8D loss increase resistance to cisplatin in CRISPR screens Unique resource of functional and multi-omic data is provided to the community
Melanocytic agminated naevus on the sole
Authors: M.D. Marrero, E. Nagore, J.A. Ramos-Ñíguez, P. Castejón
Journal: British Journal of Dermatology (2002)

Journal Article Melanocytic agminated naevus on the sole Get access M.D. Marrero, M.D. Marrero Departments of Dermatology and M. D. Marrero. E‐mail: castejon_pil@gva.es Search for other works by this author on: Oxford Academic Google Scholar E. Nagore, E. Nagore Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain Search for other works by this author on: Oxford Academic Google Scholar J.A. Ramos‐Ñíguez, J.A. Ramos‐Ñíguez Pathology, Hospital Francesc de Borja, Passeig de les Germanies 71, 46700 Gandia, Spain Search for other works by this author on: Oxford Academic Google Scholar P. Castejón P. Castejón Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 1, 1 January 2002, Page 154, https://doi.org/10.1046/j.0007-0963.2001.04562.x Published: 01 January 2002 Article history Accepted: 26 August 2001 Published: 01 January 2002
BIOCHEMICAL DIAGNOSIS OF PROLACTINOMA
Authors: TheodoreB. Schwartz, E.A. Cowden, J.G. Ratcliffe, J.A. Thomson, P. Macpherson, D. Doyle, G.M. Teasdale, EugenioE. Müller, Andrea Genazzani, Franco Camanni, Fernando Massara, GianMichele Molinatti, Daniela Cocchi
Journal: The Lancet (1979)