tbuckley/cabot-search huggingface dataset:
The Prognostic Significance of Vasohibin-1 Expression in Patients with Upper Urinary Tract Urothelial Carcinoma
Authors: Yasumasa Miyazaki, Takeo Kosaka, Shuji Mikami, Eiji Kikuchi, Nobuyuki Tanaka, Takahiro Maeda, Masaru Ishida, Akira Miyajima, Ken Nakagawa, Yasunori Okada, Yasufumi Sato, Mototsugu Oya
Journal: Clinical Cancer Research (2012)

Vasohibin-1 (VASH1) is a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells, and the status of VASH1 expression has been documented in cancer angiogenesis. The aim of this study was to address the prognostic value of VASH1 expression in upper urinary tract urothelial carcinomas (UTUC).We retrospectively analyzed the clinical records of 171 patients with locally advanced UTUC (Ta-3N0M0). The median follow-up period was 3.8 years. We immunohistochemically examined the accomplished microvessels with anti-CD34 as microvessel density (MVD) and the microvessels with activated endothelial cells as VASH1 density. Then, we analyzed the association between immunohistochemical expression and clinical outcomes.Forty-two patients experienced tumor recurrence and of these 34 died of the disease during follow-up. VASH1 density was significantly associated with tumor grade, pathologic T stage, and MVD. The 5-year recurrence-free and cancer-specific survival rates were 66.1% and 72.8% in patients with VASH1 density (≥ 40/mm(2)) and 81.0% and 86.5% in their counterparts, respectively (P < 0.05). MVD was not an independent predictor of tumor recurrence or cancer-specific survival. Multivariate analyses revealed that high VASH1 density was an independent prognostic indicator of both tumor recurrence (P = 0.024, HR = 2.10) and cancer-specific survival (P = 0.031, HR = 2.23) as well as other standard prognostic factors including high tumor grade and lymphovascular invasion.VASH1 density represents a clinically relevant predictor of patient prognosis in UTUC. The results suggest that VASH1 density could become a new biomarker and provide additional prognostic information in patients with UTUC.
Disease progression in patients with thin cutaneous melanomas: reply from authors
Authors: M-H. Schmid-Wendtner, C.A. Sander
Journal: British Journal of Dermatology (2004)

Journal Article Disease progression in patients with thin cutaneous melanomas: reply from authors Get access M‐H. Schmid‐Wendtner, M‐H. Schmid‐Wendtner Department of Dermatology and Allergology, Ludwig‐Maximilians University, Frauenlobstr. 9–11, D‐80337 Munich, Germany, and *Department of Dermatology, Allgemeines Krankenhaus St Georg, Lohmühlenstr. 5, D‐20099 Hamburg, Germany E‐mail: m.schmid‐wendtner@lrz.uni‐muenchen.de Search for other works by this author on: Oxford Academic Google Scholar C.A. Sander C.A. Sander Department of Dermatology and Allergology, Ludwig‐Maximilians University, Frauenlobstr. 9–11, D‐80337 Munich, Germany, and *Department of Dermatology, Allgemeines Krankenhaus St Georg, Lohmühlenstr. 5, D‐20099 Hamburg, Germany E‐mail: m.schmid‐wendtner@lrz.uni‐muenchen.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 150, Issue 6, 1 June 2004, Page 1224, https://doi.org/10.1111/j.1365-2133.2004.05990.x Published: 01 June 2004
The International Registry of Acute Aortic Dissection (IRAD)
Authors: Peter G. Hagan, Christoph A. Nienaber, Eric M. Isselbacher, David Bruckman, Dean J. Karavite, Pamela L. Russman, Arturo Evangelista, Rossella Fattori, Toru Suzuki, Jae K. Oh, Andrew G. Moore, Joseph F. Malouf, Linda A. Pape, Charlene Gaca, Udo Sechtem, Suzanne Lenferink, Hans Josef Deutsch, Holger Diedrichs, Jose Marcos y Robles, Alfredo Llovet, Dan Gilon, Sugata K. Das, William F. Armstrong, G. Michael Deeb, Kim A. Eagle
Journal: JAMA (2000)

ContextAcute aortic dissection is a life-threatening medical emergency associated with high rates of morbidity and mortality. Data are limited regarding the effect of recent imaging and therapeutic advances on patient care and outcomes in this setting.ObjectiveTo assess the presentation, management, and outcomes of acute aortic dissection.DesignCase series with patients enrolled between January 1996 and December 1998. Data were collected at presentation and by physician review of hospital records.SettingThe International Registry of Acute Aortic Dissection, consisting of 12 international referral centers.ParticipantsA total of 464 patients (mean age, 63 years; 65.3% male), 62.3% of whom had type A dissection.Main Outcome MeasuresPresenting history, physical findings, management, and mortality, as assessed by history and physician review of hospital records.ResultsWhile sudden onset of severe sharp pain was the single most common presenting complaint, the clinical presentation was diverse. Classic physical findings such as aortic regurgitation and pulse deficit were noted in only 31.6% and 15.1% of patients, respectively, and initial chest radiograph and electrocardiogram were frequently not helpful (no abnormalities were noted in 12.4% and 31.3% of patients, respectively). Computed tomography was the initial imaging modality used in 61.1%. Overall in-hospital mortality was 27.4%. Mortality of patients with type A dissection managed surgically was 26%; among those not receiving surgery (typically because of advanced age and comorbidity), mortality was 58%. Mortality of patients with type B dissection treated medically was 10.7%. Surgery was performed in 20% of patients with type B dissection; mortality in this group was 31.4%.ConclusionsAcute aortic dissection presents with a wide range of manifestations, and classic findings are often absent. A high clinical index of suspicion is necessary. Despite recent advances, in-hospital mortality rates remain high. Our data support the need for continued improvement in prevention, diagnosis, and management of acute aortic dissection.
Toll-like receptor 2–dependent induction of vitamin A–metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity
Authors: Santhakumar Manicassamy, Rajesh Ravindran, Jiusheng Deng, Herold Oluoch, Timothy L Denning, Sudhir Pai Kasturi, Kristen M Rosenthal, Brian D Evavold, Bali Pulendran
Journal: Nature Medicine (2009)
c-Myc Interacts with Hypoxia to Induce Angiogenesis <b> <i>In vivo</i> </b> by a Vascular Endothelial Growth Factor-Dependent Mechanism
Authors: Ulrike E. Knies-Bamforth, Stephen B. Fox, Richard Poulsom, Gerard I. Evan, Adrian L. Harris
Journal: Cancer Research (2004)

Abstract The proto-oncogene c-myc is involved in the regulation of cell proliferation, differentiation, and apoptosis. In this study, we used an inducible transgenic mouse model in which c-Myc was targeted to the epidermis and, after activation, gave rise to hyperplastic and dysplastic skin lesions and to dermal angiogenesis, involving both vascular endothelial growth factor (VEGF) receptor-1 and VEGF receptor-2. After c-Myc activation, VEGF mRNA was expressed in postmitotic keratinocytes where it colocalized with transgene expression and areas of tissue hypoxia, suggesting a role of hypoxia in VEGF induction. In vitro, c-Myc activation alone was able to induce VEGF protein release and in conjunction with hypoxia, c-Myc activation further increased VEGF protein. Blocking VEGF signaling in vivo significantly reduced dermal angiogenesis, demonstrating the importance of VEGF as a mediating factor for the c-Myc–induced angiogenic phenotype.
Toll-like receptor 3 and 4 signalling through the TRIF and TRAM adaptors in haematopoietic cells promotes atherosclerosis
Authors: Anna M. Lundberg, Daniel F.J. Ketelhuth, Maria E. Johansson, Norbert Gerdes, Sang Liu, Masahiro Yamamoto, Shizuo Akira, Göran K. Hansson
Journal: Cardiovascular Research (2013)

Members of the Toll-like receptor (TLR) family initiate innate immune responses and were recently shown to play a role in atherosclerosis. However, the mechanisms that link TLR ligation to vascular inflammation and atherogenesis remain unclear. To identify which signalling pathways downstream of TLRs in immune cells are pro-atherogenic, we analysed the role of the TLR-specific adaptors MyD88 adaptor-like (MAL), TRIF-related adaptor molecule (TRAM), and TIR-domain-containing adaptor-inducing interferon-β (TRIF) in atherosclerosis. Using a bone-marrow transplantation strategy into low-density lipoprotein receptor-deficient (Ldlr−/−) mice, we could specifically study the absence of the TLR adaptors in immune cells. We showed that haematopoietic deficiency of TRAM and TRIF, but not MAL, reduces atherosclerosis without affecting cholesterol metabolism. This was mediated by decreased aortic inflammation, indicated by lower aortic levels of pro-inflammatory mediators, and reduced influx of macrophages and T cells. Furthermore, by studying Tlr3−/− chimeric Ldlr−/− mice, we found that deleting TLR3 in immune cells significantly reduced both aortic inflammation and atherosclerotic burden. By studying hypercholesterolaemic mice with defects in TLR-signalling adaptors, we demonstrated that deleting either TRAM or TRIF in immune cells is sufficient to attenuate vessel inflammation and protect against atherosclerosis. In addition, these adaptors elicit partly different sets of inflammatory mediators and can independently inhibit the disease process. Furthermore, we identify TLR3 as a pro-atherogenic receptor in haematopoietic immune cells. The identification of these pro-atherogenic pathways downstream of TLR3 and TLR4 contributes to a better understanding of TLRs and their signalling pathways in the pathogenesis of atherosclerosis.
Deregulated Akt3 Activity Promotes Development of Malignant Melanoma
Authors: Jill M. Stahl, Arati Sharma, Mitchell Cheung, Melissa Zimmerman, Jin Q. Cheng, Marcus W. Bosenberg, Mark Kester, Lakshman Sandirasegarane, Gavin P. Robertson
Journal: Cancer Research (2004)

Abstract Malignant melanoma is the skin cancer with the most significant impact on man, carrying the highest risk of death from metastasis. Both incidence and mortality rates continue to rise each year, with no effective long-term treatment on the horizon. In part, this reflects lack of identification of critical genes involved and specific therapies targeted to correct these defects. We report that selective activation of the Akt3 protein promotes cell survival and tumor development in 43 to 60% of nonfamilial melanomas. The predominant Akt isoform active in melanomas was identified by showing that small interfering RNA (siRNA) against only Akt3, and not Akt1 or Akt2, lowered the amount of phosphorylated (active) Akt in melanoma cells. The amount of active Akt3 increased progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Mechanisms of Akt3 deregulation occurred through a combination of overexpression of Akt3 accompanying copy number increases of the gene and decreased PTEN protein function occurring through loss or haploinsufficiency of the PTEN gene. Targeted reduction of Akt3 activity with siRNA or by expressing active PTEN protein stimulated apoptotic signaling, which reduced cell survival by increasing apoptosis rates thereby inhibiting melanoma tumor development. Identifying Akt3 as a selective target in melanoma cells provides new therapeutic opportunities for patients in the advanced stages of this disease.
Folotyn (Pralatrexate Injection) for the Treatment of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma: U.S. Food and Drug Administration Drug Approval Summary
Authors: Shakun M. Malik, Ke Liu, Xu Qiang, Rajeshwari Sridhara, Shenghui Tang, W. David McGuinn, S. Leigh Verbois, Anshu Marathe, Gene M. Williams, Julie Bullock, Christoffer Tornoe, Sue Ching Lin, Terrance Ocheltree, Milinda Vialpando, Alice Kacuba, Robert Justice, Richard Pazdur
Journal: Clinical Cancer Research (2010)

On September 24, 2009, the U.S. Food and Drug Administration granted accelerated approval for Folotyn (pralatrexate injection, Allos Therapeutics, Inc.) as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL); it is the first drug approved for this indication.This review was based on study PDX-008, a phase II, single-arm, nonrandomized, open-label, international, multicenter trial, designed to evaluate the safety and efficacy of pralatrexate when administered concurrently with vitamin B(12) and folic acid supplementation in patients with relapsed or refractory PTCL.The overall response rate was 27% in 109 evaluable patients [95% confidence interval (CI), 19-36%]. Twelve percent of 109 evaluable patients (95% CI, 7-20%)] had a response duration of ≥14 weeks. Six of these 13 patients achieved a complete response, and one patient had complete response unconfirmed. The most common grade 3 and 4 toxicities were thrombocytopenia, mucositis, and neutropenia.This accelerated approval was based on a response rate that is reasonably likely to predict clinical benefit in this heavily pretreated patient population with this rare disease. The applicant has committed to conducting postmarketing clinical trials to assess clinical benefit. The recommended starting dose of pralatrexate in patients with relapsed or refractory PTCL is 30 mg/m(2) via intravenous push over 3 to 5 min weekly for 6 weeks followed by a one-week rest (one cycle). Intramuscular injection of 1 mg vitamin B(12) should be administered every 8 to 10 weeks along with 1.0 mg folic acid given orally once a day.
Randomized controlled trial of exercise training in patients with congestive heart failure (EXERT)
Authors: R.S. McKelvie, K.K. Teo, N. McCartney, R.S. Roberts, L.A. Costantini, T.J. Montague, D.P. Humen, G.H. Guyatt, S. Yusuf
Journal: Journal of the American College of Cardiology (1998)
Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome
Authors: Florence Roufosse, Aurore de Lavareille, Liliane Schandené, Elie Cogan, Ann Georgelas, Lori Wagner, Liqiang Xi, Mark Raffeld, Michel Goldman, Gerald J. Gleich, Amy Klion
Journal: Journal of Allergy and Clinical Immunology (2010)
Parkinsonism with a bovine cough: an unusual presentation.
Authors: M J Bendall
Journal: BMJ (1976)

Sodium valproate and thrombocytopeniaPublished reports on the value of sodium valproate (Epilim) as an anticonvulsant drug have been encouraging.'Acquired platelet function defects ofdoubtful significance have been found and attributed to this drug,2 and there have been two reports of haemorrhages, prolonged bleeding times, and thrombocytopenia in patients on sodium valproate with other anticonvulsant drugs.3 4 The patient we report here developed thrombocytopenia when taking sodium valproate alone, and the investigations are recorded. Case reportA 6-year-old boy weighing 20 kg had been having major and minor seizures for two years and had failed to respond to other anticonvulsant drugs.On treatment with sodium valproate 400 mg four times a day, all other drugs having been stopped, he was rendered fit-free for eight months.His mother then reported that he had developed hair loss and multiple spon- taneous bruises.The bleeding time was prolonged and the platelet count was 15 x 109/1, but other tests of coagulation were normal.Sodium valproate was immediately discontinued.The serum level at this time was very high (244 .tg/ml).At the time of the peripheral thrombocytopenia aspiration of bone marrow
Identification of a human splenic marginal zone B cell precursor with NOTCH2-dependent differentiation properties
Authors: Marc Descatoire, Sandra Weller, Sabine Irtan, Sabine Sarnacki, Jean Feuillard, Sébastien Storck, Anne Guiochon-Mantel, Jérôme Bouligand, Alain Morali, Joseph Cohen, Emmanuel Jacquemin, Maria Iascone, Christine Bole-Feysot, Nicolas Cagnard, Jean-Claude Weill, Claude-Agnès Reynaud
Journal: The Journal of Experimental Medicine (2014)

Mouse splenic marginal zone precursors (MZPs) differentiate into marginal zone B (MZB) cells under a signaling pathway involving Notch2 and its ligand, delta-like 1 ligand (Dll1). We report the identification of an MZP subset in the spleen of young children. These MZPs differentiate into MZ-like B cells in vitro in the presence of OP9 cells expressing human DLL1, as demonstrated by the up-regulation of classical MZB cell markers. A set of diagnostic genes discriminating IgM(+)IgD(+)CD27(+) blood and splenic MZB cells from switched B cells was identified (up-regulation of SOX7, down-regulation of TOX, COCH, and HOPX), and their expression during the induction assay mirrored the one of MZB cells. Moreover, Alagille patients with a NOTCH2 haploinsufficiency display a marked reduction of IgM(+)IgD(+)CD27(+) B cells in blood, whereas their switched memory B cells are not affected. Altogether, these results argue in favor of the existence of a rodent-like MZB cell lineage in humans.
Selective abdominal angiography.
Authors: M J Laurijssens, J T Galambos
Journal: Gut (1965)

EDITORIAL SYNOPSIS This paper illustrates the value of carefully siting the tip of the intra-aortic catheter adjacent to the artery supplying the organ about which more information is required.Cancers in the liver were consistently identified correctly, and useful information has been obtained con- tributing to the diagnosis of pancreatic tumours, chronic pancreatitis, cirrhosis of the liver, cancer of the colon, and visceral vascular disease.
A Mixed Branch Length Model of Heterotachy Improves Phylogenetic Accuracy
Authors: Bryan Kolaczkowski, Joseph W. Thornton
Journal: Molecular Biology and Evolution (2008)

Evolutionary relationships are typically inferred from molecular sequence data using a statistical model of the evolutionary process. When the model accurately reflects the underlying process, probabilistic phylogenetic methods recover the correct relationships with high accuracy. There is ample evidence, however, that models commonly used today do not adequately reflect real-world evolutionary dynamics. Virtually all contemporary models assume that relatively fast-evolving sites are fast across the entire tree, whereas slower sites always evolve at relatively slower rates. Many molecular sequences, however, exhibit site-specific changes in evolutionary rates, called "heterotachy." Here we examine the accuracy of 2 phylogenetic methods for incorporating heterotachy, the mixed branch length model—which incorporates site-specific rate changes by summing likelihoods over multiple sets of branch lengths on the same tree—and the covarion model, which uses a hidden Markov process to allow sites to switch between variable and invariable as they evolve. Under a variety of simple heterogeneous simulation conditions, the mixed model was dramatically more accurate than homotachous models, which were subject to topological biases as well as biases in branch length estimates. When data were simulated with strong versions of the types of heterotachy observed in real molecular sequences, the mixed branch length model was more accurate than homotachous techniques. Analyses of empirical data sets confirmed that the mixed branch length model can improve phylogenetic accuracy under conditions that cause homotachous models to fail. In contrast, the covarion model did not improve phylogenetic accuracy compared with homotachous models and was sometimes substantially less accurate. We conclude that a mixed branch length approach, although not the solution to all phylogenetic errors, is a valuable strategy for improving the accuracy of inferred trees.
Gazing into a crystal ball to predict kidney transplant outcome
Authors: Bernd Schröppel, Peter S. Heeger
Journal: Journal of Clinical Investigation (2010)

Kidney transplantation is the optimal therapy for end-stage kidney disease but requires lifelong immunosuppression. Despite improvements in immunosuppression regimens that have reduced rates of acute transplant rejection, long-term allograft survival remains suboptimal. More than 50% of transplanted kidneys from deceased donors fail within 10 years. In order to improve long-term outcomes, physicians need to better understand mechanisms underlying transplant rejection and tolerance in humans. They also need biomarkers that differentiate patients likely to maintain excellent and stable allograft function from recipients at risk of losing their transplants. By studying kidney transplant recipients at high risk for graft loss and rare, spontaneously tolerant kidney transplant recipients, researchers reporting in 3 papers in this issue of the JCI shed new light on these topics.
Major Depressive Disorder With Subthreshold Bipolarity in the National Comorbidity Survey Replication
Authors: Jules Angst, Lihong Cui, Joel Swendsen, Stéphane Rothen, Anibal Cravchik, Ronald C. Kessler, Kathleen R. Merikangas
Journal: American Journal of Psychiatry (2010)

There is growing clinical and epidemiologic evidence that major mood disorders form a spectrum from major depressive disorder to pure mania. The authors examined the prevalence and clinical correlates of major depressive disorder with subthreshold bipolarity compared with pure major depressive disorder in the National Comorbidity Survey Replication (NCS-R).The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February 2001, and April 2003. Lifetime history of mood disorders, symptoms, and clinical indicators of severity were collected using version 3.0 of the World Health Organization's Composite International Diagnostic Interview.Nearly 40% of study participants with a history of major depressive disorder had a history of subthreshold hypo-mania. This subgroup had a younger age at onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania and lower levels of clinical severity than those with bipolar II disorder.These findings demonstrate heterogeneity in major depressive disorder and support the validity of inclusion of subthreshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice.
Informed consent Consent requires a flexible approach
Authors: R L Souhami, J S Tobias
Journal: BMJ (1994)

Mortality from coronary heart disease has been declining steadily over the past 20 years in Auckland. The possibility that improved survival contributed to this decline was examined in patients who survived four weeks after myocardial infarction, changes in the severity of the disease being controlled for. Patients who had had myocardial infarction in 1966-7 (191 patients) or 1981-2 (203) were compared to determine whether three year survival rates had changed and the severity of the disease altered. With a coronary prognostic index taken as the measure of severity the 1981-2 group had significantly more severe myocardial infarctions than the 1966-7 group, but despite this the three year survival was significantly better (86% in the 1981-2 group v 75% in the 1966-7 group). These findings suggest that improved survival after myocardial infarction contributed to the decline in mortality.
Effects of Smoking Marihuana on Left Ventricular Performance and Plasma Norepinephrine
Authors: ARNOLD GASH
Journal: Annals of Internal Medicine (1978)

In 14 healthy men we assessed the effects of smoking marihuana cigarettes containing 6 mg of delta-9-tetrahydrocannabinol on ultrasound measures of left ventricular function. Four of this group and four additional subjects also had measurements of plasma norepinephrine. Both heart rate and left ventricular performance (mean rate of internal diameter shortening [mean Vcf]) were significantly increased for at least 1 h after drug exposure compared with these values after placebo cigarettes. The immediate tachycardia and increase in mean Vcf were not accompanied by raised plasma norepinephrine levels. However, by 30 min after marihuana exposure, sympathetic neurotransmitter levels were significantly greater than both control values and those after placebo cigarettes, and they remained elevated for at least 2 h. Excessive sympathoadrenal discharge, as evidenced by augmented left ventricular function and prolonged catecholamine release, could adversely affect patients with heart disease.