tbuckley/cabot-search huggingface dataset:
The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition
Authors: David S. Yee, Yaxiong Tang, Xuesen Li, Zhongbo Liu, Yi Guo, Samia Ghaffar, Peter McQueen, Dash Atreya, Jun Xie, Anne R. Simoneau, Bang H. Hoang, Xiaolin Zi
Journal: Molecular Cancer (2010)

Abstract Background Aberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3. Results The WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues. Conclusion These data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients.
Hirschsprung's disease and idiopathic megacolon in adults and adolescents.
Authors: P R Barnes, J E Lennard-Jones, P R Hawley, I P Todd
Journal: Gut (1986)

The distinction between Hirschsprung9s disease and idiopathic megacolon in childhood dates from the classic clinical, radiological, and histological studies of Bodian, Stephens, and Ward. This article describes clinical experience over 15 years of 94 patients in whom megacolon of these two types was recognised for the first time after the age of 10, to illustrate the problems of diagnosis and treatment in later years. Just as it is now recognised that patients with the clinical characteristics of Hirschsprung9s disease may have one of several abnormalities of the myenteric plexus, including not only absence of ganglion cells, but also patchy or zonal loss, abnormal neurones or neuronal dysplasia, so idiopathic megacolon may also be a heterogeneous group of cases. This paper suggests on clinical grounds that those patients with idiopathic megacolon whose symptoms start in childhood differ from those whose symptoms develop in later years.
Contrasting Diabetes Phenotypes Associated With Hepatocyte Nuclear Factor-1α and -1β Mutations
Authors: Ewan R. Pearson, Michael K. Badman, Christopher R. Lockwood, Penelope M. Clark, Sian Ellard, Coralie Bingham, Andrew T. Hattersley
Journal: Diabetes Care (2004)

OBJECTIVE—Mutations in the highly homologous transcription factors hepatocyte nuclear factor (HNF)-1α and -1β cause maturity-onset diabetes of the young types 3 and 5, respectively. Diabetes due to HNF-1α mutations is well characterized. However, physiological assessment of the HNF-1β phenotype is limited. We aimed to test the hypothesis that the diabetes phenotype due to HNF-1β mutations is similar to that in HNF-1α. RESEARCH DESIGN AND METHODS—Fasting biochemistry and a tolbutamide-modified intravenous glucose tolerance test (IVGTT) were compared in matched HNF-1β, HNF-1α, type 2 diabetic, and control subjects. Homeostasis model assessment indexes were determined from fasting insulin and glucose. The peak measures for the insulin increment after tolbutamide and for the insulin increment after glucose were determined from the IVGTT. RESULTS—The HNF-1β patients showed a 2.4-fold reduction in insulin sensitivity compared with the HNF-1α patients (P = 0.001) with fasting insulin concentrations 2.7-fold higher (P = 0.004). HNF-1β patients had lower HDL cholesterol (1.17 vs. 1.46 mmol/l; P = 0.009) and higher triglyceride (2.2 vs. 1.35 mmol/l; P = 0.015) levels than HNF-1α patients. The HNF-1β patients had similar β-cell responses to tolbutamide and glucose as the type 2 diabetic patients, but in the HNF-1α patients, the tolbutamide response was considerably increased relative to the response to glucose (P = 0.002). CONCLUSIONS—HNF-1β patients have a different diabetes phenotype than HNF-1α patients. Those with HNF-1β mutations have hyperinsulinemia and associated dyslipidemia consistent with insulin resistance and may have a different β-cell defect. This suggests that despite considerable homology and a shared binding site, HNF-1α and HNF-1β have a different role in maintaining normal glucose homeostasis. This result suggests a new etiological pathway for insulin resistance involving HNF-1β.
Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial
Authors: Shumpei Yokota, Tomoyuki Imagawa, Masaaki Mori, Takako Miyamae, Yukoh Aihara, Shuji Takei, Naomi Iwata, Hiroaki Umebayashi, Takuji Murata, Mari Miyoshi, Minako Tomiita, Norihiro Nishimoto, Tadamitsu Kishimoto
Journal: The Lancet (2008)
Ferrochelatase activities in patients with erythropoietic protoporphyria and their families
Authors: G. GOERZ, S. BUNSELMEYER, K. BOLSEN, N.Y. SCHÜRER
Journal: British Journal of Dermatology (1996)

Ferrochelatase, estimated as zinc chelatase, was measured in the lymphocytes of 30 patients with erythropoietic protoporphyria (EPP), in 35 first- or second-degree relatives of patients with EPP, and in 50 healthy controls. In 30 EPP patients the zinc chelatase level (mean +/- standard deviation, SD) was 0.45 +/- 0.10 nmol of zinc protoporphyrin per hour per milligram of protein, in 14 EPP carriers the zinc chelatase level (mean +/- SD) was 0.42 +/- 0.09 and in 50 healthy controls the zinc chelatase level (mean +/- SD) was 0.84 +/- 0.27. All patients with EPP were also demonstrated to have an elevated protoporphyrin level in their red blood cells: the erythrocyte protoporphyrin levels were as follows EPP patients (mean +/- SD) 1300 +/- 758 nmol protoporphyrin/dl, EPP carriers (mean +/- SD) 60 +/- 24, and healthy controls (mean +/- SD) 50 +/- 25 (P < 0.001 for EPP patients compared to controls and EPP carriers). The families of 12 out of 15 EPP patients were examined with respect to the mode of inheritance of the disorder. Of 35 relatives, 14 were carriers of EPP, as characterized by reduced zinc chelatase activity in lymphocytes and by a normal protoporphyrin level in red blood cells. None of the 14 EPP carriers had presented with clinical symptoms of EPP. The mod of inheritance was autosomal dominant in seven of the 12 examined families, and autosomal recessive in two. In two families only one parent could be investigated, but we nevertheless concluded that the inheritance was autosomal dominant. Inheritance in one EPP family could not be elucidated as both parents showed normal zinc chelatase levels and did not demonstrate abnormal erythrocyte protoporphyrin levels.
Insulin resistance differentially affects the PI 3-kinase– and MAP kinase–mediated signaling in human muscle
Authors: Kenneth Cusi, Katsumi Maezono, Abdullah Osman, Merri Pendergrass, Mary Elizabeth Patti, Thongchai Pratipanawatr, Ralph A. DeFronzo, C. Ronald Kahn, Lawrence J. Mandarino
Journal: Journal of Clinical Investigation (2000)

The broad nature of insulin resistant glucose metabolism in skeletal muscle of patients with type 2 diabetes suggests a defect in the proximal part of the insulin signaling network. We sought to identify the pathways compromised in insulin resistance and to test the effect of moderate exercise on whole-body and cellular insulin action. We conducted euglycemic clamps and muscle biopsies on type 2 diabetic patients, obese nondiabetics and lean controls, with and without a single bout of exercise. Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1–association with PI 3-kinase defines a key step in insulin resistance.
Prognostic role of anti-HCV in liver cirrhosis
Authors: G. D'Amico, L. Pasta, G. Vizzini, F. Politi, M. Traina, M. Caltagirone, S. Hadonia, L. Montalbano, A. Luca, P. Hondello, S. Patti, C. Spanò
Journal: Journal of Hepatology (1991)
Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL
Authors: Lili Wang, Alex K. Shalek, Mike Lawrence, Ruihua Ding, Jellert T. Gaublomme, Nathalie Pochet, Petar Stojanov, Carrie Sougnez, Sachet A. Shukla, Kristen E. Stevenson, Wandi Zhang, Jessica Wong, Quinlan L. Sievers, Bryan T. MacDonald, Alexander R. Vartanov, Natalie R. Goldstein, Donna Neuberg, Xi He, Eric Lander, Nir Hacohen, Aviv Regev, Gad Getz, Jennifer R. Brown, Hongkun Park, Catherine J. Wu
Journal: Blood (2014)
Prognostic factors for outcome in patients with refractory and relapsed acute lymphocytic leukemia treated with inotuzumab ozogamicin, a<scp>CD</scp>22 monoclonal antibody
Authors: Elias Jabbour, Susan O'Brien, Xuelin Huang, Deborah Thomas, Michael Rytting, Koji Sasaki, Jorge Cortes, Guillermo Garcia‐Manero, Tapan Kadia, Farhad Ravandi, Sherry Pierce, Hagop Kantarjian
Journal: American Journal of Hematology (2014)

Inotuzumab ozogamicin was found to be highly active in patients with refractory-relapsed acute lymphocytic leukemia (ALL), with an overall response rate of 58% and a median survival of 6.3 months. Identifying factors associated with different outcomes on inotuzumab therapy may help select patients for this treatment and advice of prognosis. A total of 89 patients treated with inotuzumab on previous studies were analyzed. Inotuzumab was given at 1.3-1.8 mg/m(2) intravenously (IV) × 1 every 3-4 weeks or weekly (0.8 mg/m(2) day 1, 0.5 mg/m(2) days 8 and 15) every 3-4 weeks. Pretreatment factors associated with achieving marrow complete response (CR) and with survival were analyzed using standard statistical methods. The median survival of patients with at least marrow CR was 9.2 months versus 3.4 months for those without marrow CR (P < 0.001). By multivariate analysis, a high peripheral blood absolute blast count and low platelet count were independently associated with a lower likelihood of achieving at least marrow CR. Baseline characteristics independently associated with worse survival included adverse cytogenetics [complex karyotype, translocation (4;11), translocation (9;22), abnormal chromosome 17], disease beyond first salvage, and high peripheral blood absolute count. Patients with 0, 1-2, or 3 adverse factors had a median survival of 39+, 7.5, and 2.4 months, respectively. Our current analyses identified a subset of adult patients with ALL in whom outcome of therapy with inotuzumab ozogamicin can be differentially predicted.
Role of TRPM2 Channel in Mediating H <sub>2</sub> O <sub>2</sub> -Induced Ca <sup>2+</sup> Entry and Endothelial Hyperpermeability
Authors: Claudie M. Hecquet, Gias U. Ahmmed, Stephen M. Vogel, Asrar B. Malik
Journal: Circulation Research (2007)

Oxidative stress through the production of oxygen metabolites such as hydrogen peroxide (H2O2) increases vascular endothelial permeability. H2O2 stimulates ADP-ribose formation, which in turn opens transient receptor potential melastatin (TRPM)2 channels. Here, in endothelial cells, we demonstrate transcript and protein expression of TRPM2, a Ca2+-permeable, nonselective cation channel. We further show the importance of TRPM2 expression in signaling of increased endothelial permeability by oxidative stress. Exposure of endothelial cell monolayers to sublytic concentrations of H2O2 induced a cationic current measured by patch-clamp recording and Ca2+ entry detected by intracellular fura-2 fluorescence. H2O2 in a concentration-dependent manner also decreased trans-monolayer transendothelial electrical resistance for 3 hours (with maximal effect seen at 300 micromol/L H2O2), indicating opening of interendothelial junctions. The cationic current, Ca2+ entry, and transendothelial electrical resistance decrease elicited by H2O2 were inhibited by siRNA depleting TRPM2 or antibody blocking of TRPM2. H2O2 responses were attenuated by overexpression of the dominant-negative splice variant of TRPM2 or inhibition of ADP-ribose formation. Overexpression of the full-length TRPM2 enhanced H2O2-mediated Ca2+ entry, cationic current, and the transendothelial electrical resistance decrease. Thus, TRPM2 mediates H2O2-induced increase in endothelial permeability through the activation of Ca2+ entry via TRPM2. TRPM2 represents a novel therapeutic target directed against oxidant-induced endothelial barrier disruption.
Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study
Authors: Mark J Cook, Terence J O'Brien, Samuel F Berkovic, Michael Murphy, Andrew Morokoff, Gavin Fabinyi, Wendyl D'Souza, Raju Yerra, John Archer, Lucas Litewka, Sean Hosking, Paul Lightfoot, Vanessa Ruedebusch, W Douglas Sheffield, David Snyder, Kent Leyde, David Himes
Journal: The Lancet Neurology (2013)
Community Cardiopulmonary Resuscitation
Authors: L A Cobb, A P Hallstrom, R G Thompson, L P Mandel, M K Copass
Journal: Annual Review of Medicine (1980)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Percutaneous coronary intervention versus coronary bypass graft surgery for diabetic patients with unstable angina and risk factors for adverse outcomes with bypass
Authors: Steven P Sedlis, Douglass A Morrison, Jeffrey D Lorin, Rick Esposito, Gulshan Sethi, Jerome Sacks, William Henderson, Frederick Grover, K.B Ramanathan, Darryl Weiman, Jorge Saucedo, Tamim Antakli, Venki Paramesh, Stuart Pett, Sarah Vernon, Vladimir Birjiniuk, Frederick Welt, Mitchell Krucoff, Walter Wolfe, John C Lucke, Sundeep Mediratta, David Booth, Edward Murphy, Herbert Ward, LaWayne Miller, Stefan Kiesz, Charles Barbiere, Dan Lewis
Journal: Journal of the American College of Cardiology (2002)
Support for the Coelomata Clade of Animals from a Rigorous Analysis of the Pattern of Intron Conservation
Authors: Jie Zheng, Igor B. Rogozin, Eugene V. Koonin, Teresa M. Przytycka
Journal: Molecular Biology and Evolution (2007)

Many intron positions are conserved in varying subsets of eukaryotic genomes and, consequently, comprise a potentially informative class of phylogenetic characters. Roy and Gilbert developed a method of phylogenetic reconstruction using the patterns of intron presence–absence in eukaryotic genes and, applying this method to the analysis of animal phylogeny, obtained support for an Ecdysozoa clade (Roy SW, Gilbert W. 2005. Resolution of a deep animal divergence by the pattern of intron conservation. Proc Natl Acad Sci USA. 102:4403–4408). The critical assumption in the method was the independence of intron loss in different branches of the phylogenetic tree. Here, this assumption is refuted by showing that the branch-specific intron loss rates are strongly correlated. We show that different tree topologies are obtained, in each case with a significant statistical support, when different subsets of intron positions are analyzed. The analysis of the conserved intron positions supports the Coelomata topology, that is, a clade comprised of arthropods and chordates, whereas the analysis of more variable intron positions favors the Ecdysozoa topology, that is, a clade of arthropods and nematodes. We show, however, that the support for Ecdysozoa is fully explained by parallel loss of introns in nematodes and arthropods, a factor that does not contribute to the analysis of the conserved introns. The developed procedure for the identification and analysis of conserved introns and other characters with minimal or no homoplasy is expected to be useful for resolving many hard phylogenetic problems.
Identification and upregulation of galactose/N-acetylgalactosamine macrophage lectin in rat cardiac allografts with arteriosclerosis.
Authors: M E Russell, U Utans, A F Wallace, P Liang, R J Arceci, M J Karnovsky, L R Wyner, Y Yamashita, C Tarn
Journal: Journal of Clinical Investigation (1994)

Using differential mRNA display to uncover potential mediators associated with chronic rejection, we identified a cDNA fragment induced in Lewis to F344 rat cardiac allografts with arteriosclerosis but not Lewis syngrafts. The full-length cDNA (1.4 kb) isolated from a rat cardiac allograft cDNA library was 99% identical to galactose/N-acetylgalactosamine (Gal/GalNAc) macrophage lectin, a cell-surface receptor. This cDNA hybridized in Northern analysis with total RNA from eight cardiac allografts but not with host hearts, syngrafts, or other organs. There was a significant allograft-specific increase in transcript levels measured by reverse transcriptase PCR at days 7, 14, 28, and 75 in comparison with paired F344 host hearts (subject to same circulation but histologically normal), day-0 hearts, and syngrafts (P < 0.008, n = 4 at each time). Transcript levels in cardiac allografts were higher than those in paired host spleens (a major source of inflammatory cells) (P < 0.0001), indicating the localized nature of Gal/GalNAc lectin induction. By in situ hybridization and immunostaining, Gal/GalNAc lectin expression localized to a subset of inflammatory cells in cardiac allografts. These findings link Gal/GalNAc macrophage lectin to the chronic rejection process, as a possible mediator of macrophage infiltration.
Flow-volume loop: window to a smooth diagnosis?
Authors: C. Orton, S. Ward, S. Jordan, A. Menzies-Gow, J. H. Hull
Journal: Thorax (2015)

A 50-year-old woman was referred with a three-year history of cough, difficulty clearing secretions and intermittent wheeze. Examination revealed normal breath sounds and a chest radiograph was normal.

Clinic spirometry revealed a normal volume–time spirogram (figure 1A) with supra-normal indices: FEV1 3.4 L (119% predicted) and FVC 4.1 L (123% predicted).



Figure 1 
(A) Volume–time spirograph. (B) Reproducible early expiratory notch (red arrow) on flow–volume loops.



Full lung function testing was arranged and the flow–volume loop was immediately flagged as abnormal; demonstrating a reproducible notch in the early forced expiratory phase of the manoeuvre (figure 1B).

What …
Improving Diabetic Retinopathy Screening Ratios Using Telemedicine-Based Digital Retinal Imaging Technology
Authors: Cathy R. Taylor, Lawrence M. Merin, Amy M. Salunga, Joseph T. Hepworth, Terri D. Crutcher, Denis M. O’Day, Bonita A. Pilon
Journal: Diabetes Care (2007)

To evaluate the impact of a telemedicine, digital retinal imaging strategy on diabetic retinopathy screening rates in an inner-city primary care clinic.This retrospective cohort study included all diabetic patients aged > or = 18 years (n = 495) seen at Vine Hill Community Clinic between 1 September 2003 and 31 August 2004. Patients were offered ophthalmology referral or digital screening. Patients choosing referral received the next available (within 3 months) appointment at the Vanderbilt Eye Clinic; patients choosing digital screening were screened during the visit.Retinal screening was documented for 293 (59.2%) patients, a significant improvement compared with the 23% baseline rate. Of 293 patients screened, 92 (31.4%) were screened in ophthalmology, and 201 (68.6%) were digitally screened. Among the 201 digitally screened patients, 104 (51.7%) screened negative and were advised to rescreen in 1 year, 75 (37.3%) screened positive and were nonurgently referred to ophthalmology, and 22 (11.0%) screened positive for sight-threatening eye disease and were urgently referred for ophthalmological follow-up. Digital imaging technical failure rate was 0.5%. Referral status was associated with race/ethnicity (chi2 = 7.9, P < 0.02) with whites more likely to screen negative than non-whites (62.4 vs. 47.8%, respectively). Sight-threatening disease among non-whites (14.7%) was more than double that observed for whites (5.9%).Digital imaging technology in the primary care visit can significantly improve screening rates over conventional methods, increase access to recommended diabetic eye care, and focus specialty care on medically indigent patients with greatest need.
CEREBRAL HEMODYNAMICS IN PATIENTS WITH HEART FAILURE ASSOCIATED WITH HYPERTENSION AND THE RESPONSE TO TREATMENT 1
Authors: John H. Moyer, Sam I. Miller, Harvey Snyder
Journal: Journal of Clinical Investigation (1955)

C-Control.D-After treatment for heart failure.Mean Blood Presure CVR-Cerebrovascular resistance -Cerebral Blood Flow' °-Cerebral blood flow in ml. per 100 grams of brain times Arterial-Venous Oxygen difference.P COr-Partial pressure of carbon dioxide in mm.Hg.A-V Or-Arterial-Venous Os.. Received NH4C1 before and during studies.Azotemia-Patient 2-BUN -34 mg. per cent 5/15 and 16 mg.per cent 5/29.Patient 4-BUN -27 mg. per cent during control study. 14mg.per cent after treatment.Hemoglobin -10 gm.Poor reulta with treatment.Mentally confused.+ «Standard Error -Standard Error N This is the standard error for patients 1 to 20.S.E.-Standard