tbuckley/cabot-search huggingface dataset:
An Alternative Formula to the Cockcroft-Gault and the Modification of Diet in Renal Diseases Formulas in Predicting GFR in Individuals with Type 1 Diabetes
Authors: Hassan Ibrahim, Michael Mondress, Abel Tello, Ying Fan, Joseph Koopmeiners, William Thomas
Journal: Journal of the American Society of Nephrology (2005)

Chronic kidney disease is currently on the rise and not only leads to ESRD necessitating dialysis or transplantation but also increases cardiovascular disease risk. Measurement of the GFR, the gold standard for assessing kidney function, is expensive and cumbersome. Several prediction formulas that are based on serum creatinine are currently used to estimate the GFR, but none has been validated in a large cohort of individuals with diabetes. The performance of two commonly used formulas, the abbreviated Modification of Diet in Renal Disease (MDRD) study formula for the GFR and the Cockcroft-Gault estimate of creatinine clearance, were examined against GFR measured by the renal clearance of iothalamate in 1286 individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT). The performance of these formulas was assessed by computing bias, precision, and accuracy. The DCCT participants had normal serum creatinine, unlike the MDRD patients, and somewhat lower creatinine excretion than subjects in the original cohort Cockcroft Gault, which led to biased and highly variable estimates of GFR when these formulas were applied to the DCCT subjects. The MDRD substantially underestimated iothalamate GFR, whereas the Cockcroft Gault formula underestimated it when it was <120 ml/min per 1.73 m(2) and overestimated it when iothalamate GFR was >130 ml/min per 1.73 m(2). Overall, only one third of the formula's estimates were within +/-10% of iothalamate GFR. By underestimating GFR, these formulas were likely to flag early declines in kidney function. Refitting the MDRD formula to the DCCT data gave a more accurate and unbiased prediction of GFR from serum creatinine; percentage of estimate within 10% of measured GFR increased to 56%. A substantial variability in the estimates, however, remained.
Updates on the Treatment of Lupus Nephritis
Authors: Andrew S. Bomback, Gerald B. Appel
Journal: Journal of the American Society of Nephrology (2010)

The treatment of lupus nephritis has changed significantly over the past decade in large part because of data from well-conducted randomized clinical trials. The concept of two phases of therapy—induction and maintenance—is widely accepted. The histopathologic classification of lupus nephritis continues to guide therapy, and treatment for all major classes of lupus nephritis has seen some shift in management during this time. New regimens using lower doses and shorter treatment durations of intravenous cyclophosphamide have been advanced to reduce toxicity without sacrificing efficacy of therapy. Mycophenolate mofetil has emerged as a viable alternative to cyclophosphamide for induction therapy of both proliferative and membranous lupus nephritis. Combination induction treatment with multiple agents has also been successful. Large controlled trials using mycophenolate mofetil and azathioprine for maintenance therapy have been performed. Here, we review recent additions to the growing body of literature on how to most effectively treat lupus nephritis with the least amount of toxicity. We discuss new treatment strategies currently being explored in clinical trials.
P1009 THE HISTOLOGICAL OR ULTRASONOGRAPHIC DETECTION OF STEATOSIS AFFECTS THE PERFORMANCE OF LIVER STIFFNESS MEASUREMENT FOR FIBROSIS ASSESSMENT IN PATIENTS WITH CHRONIC HCV GENOTYPE 1 INFECTION
Authors: F.S. Macaluso, M. Maida, C. Cammà, G. Cabibbo, D. Cabibi, V. Di Marco, A. Craxì, S. Petta
Journal: Journal of Hepatology (2014)
Pharmacokinetic and demographic markers of 5-fluorouracil toxicity in 181 patients on adjuvant therapy for colorectal cancer
Authors: M. Gusella, G. Crepaldi, C. Barile, A. Bononi, D. Menon, S. Toso, D. Scapoli, L. Stievano, E. Ferrazzi, F. Grigoletto, M. Ferrari, R. Padrini
Journal: Annals of Oncology (2006)
Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure
Authors: Paul M. Heerdt, Jeffrey W. Holmes, Bolin Cai, Alessandro Barbone, John D. Madigan, Steven Reiken, David L. Lee, Mehmet C. Oz, Andrew R. Marks, Daniel Burkhoff
Journal: Circulation (2000)

Left ventricular (LV) assist devices (LVADs) can improve contractile strength and normalize characteristics of the Ca(2+) transient in myocytes isolated from failing human hearts. The purpose of the present study was to determine whether LVAD support also improves contractile strength at different frequencies of contraction (the force-frequency relationship [FFR]) of intact myocardium and alters the expression of genes encoding for proteins involved in Ca(2+) handling.The isometric FFRs of LV trabeculae isolated from 15 patients with end-stage heart failure were compared with those of 7 LVAD-supported patients and demonstrated improved contractile force at 1-Hz stimulation, with reversal of a negative FFR after LVAD implantation. In 20 failing hearts, Northern blot analysis for sarcoplasmic endoreticular Ca(2+)-ATPase subtype 2a (SERCA2a), the ryanodine receptor, and the sarcolemmal Na(+)-Ca(2+) exchanger was performed on LV tissue obtained before and after LVAD implantation. These paired data demonstrated an upregulation of all 3 genes after LVAD support. In tissue obtained from subsets of these patients, Western blot analysis was performed, and oxalate-supported Ca(2+) uptake by isolated sarcoplasmic reticular membranes was determined. Despite higher mRNA for all genes after LVAD support, only SERCA2a protein was increased. Functional significance of increased SERCA2a was confirmed by augmented Ca(2+) uptake by sarcoplasmic reticular membranes isolated from LVAD-supported hearts.LVAD support can improve contractile strength of intact myocardium and reverse the negative FFR associated with end-stage heart failure. The expression of genes encoding for proteins involved in Ca(2+) cycling is upregulated (reverse molecular remodeling), but only the protein content of SERCA2a is increased.
Coexpression of gene Oct4 and Nanog initiates stem cell characteristics in hepatocellular carcinoma and promotes epithelial-mesenchymal transition through activation of Stat3/Snail signaling
Authors: Xin Yin, Bo-Heng Zhang, Su-Su Zheng, Dong-Mei Gao, Shuang-Jian Qiu, Wei-Zhong Wu, Zheng-Gang Ren
Journal: Journal of Hematology & Oncology (2015)

Oct4 and Nanog are key regulatory genes that maintain the pluripotency and self-renewal properties of embryonic stem cells. We previously reported that the two stemness markers were tightly associated with cancer progression and poor outcomes of hepatocellular carcinoma. In this study, we demonstrate that coexpression of Oct4/Nanog modulates activation of signal transducer and activator of transcription 3 (Stat3), an oncogenic transcription factor that is activated in many human malignancies including hepatocellular carcinoma (HCC), as well as the expression of Snail, a key regulator implicated in epithelial-mesenchymal transition and tumor metastasis. Oct4 and Nanog were ectopic expressed in MHCC97-L cell lines via lentiviral gene transfection. The stemness characteristics including self-renewal, proliferation, chemoresistance, and tumorigenicity were assessed. The effect of coexpression of Oct4 and Nanog on epithelial-mesenchymal transition change, and the underlying molecular signaling was investigated. Ectopic coexpression of Oct4 and Nanog empowered MHCC97-L cells with cancer stem cell (CSC) properties, including self-renewal, extensive proliferation, drug resistance, and high tumorigenic capacity. Significantly, Oct4 and Nanog encouraged epithelial-mesenchymal transition change contributing to tumor migration, invasion/metastasis in vitro and in vivo. Following molecular mechanism investigation indicated Oct4/Nanog-regulated epithelial-mesenchymal transition change through Stat3-dependent Snail activation. Moreover, silencing Stat3 abrogates Oct4/Nanog-mediated epithelial-mesenchymal transition (EMT) change and invasion/metastasis in HCC. We delineate Oct4 and Nanog initiate stem cell characteristics in hepatocellular carcinoma and promote epithelial-mesenchymal transition through activation of Stat3/Snail signaling. Our findings propose Stat3/Snail pathway as a novel therapeutic target for the treatment of progression and metastasis of HCC with CSC-like signatures and epithelial-mesenchymal transition phenotype.
The role of extracellular vesicles in phenotypic alteration of lung cells in pulmonary fibrosis
Authors: Mateja Cernelc-Kohan, Simon Wong, Celia Espinoza, Carmen Taype de Roberts, James Hagood
Journal: European Respiratory Journal (2013)

INTRODUCTION: Idiopathic pulmonary fibrosis is a disease of altered fibroblast-epithelial interaction. In response to stress lung fibroblast shed Thy-1 in the form of extracellular vesicles (EV). Exosomes are nano-sized vesicles that can be released from mesenchymal stem cells (MSC) as well. Supernatants from MSC, which contain EV have been shown to promote repair of neonatal lung injury. In this study we aimed to determine the role of EV in phenotypic modification of lung cells.  METHODS: Exosomes were isolated from conditioned media of Thy-1(+) and Thy-1(-) rat lung fibroblasts (rfEV), respectively and human mesenchymal stem cells (hmEV) at baseline and after stimulation with Il-1-β and TNF-α. MSC were co-cultured with Thy-1(+) rfEV and Thy-1(-) rfEV. Rat lung fibroblasts (RLF) were cultured with hmEV. RNA was isolated from recipient cells. Species-specific primers were used to evaluate for the expression of myofibroblastic genes in hMSC and RLF.  RESULTS: Cytokine-stimulated rfEV induced expression of α-smooth muscle actin, collagen 1, TGF-β and fibronectin-1 in hMSC. This process was independent of whether vesicles were Thy-1 (+) or (-). However, cytokine-stimulated hmEV suppressed expression of myofibroblastic genes by real time PCR in Thy-1(+) RLF. Nevertheless, in Thy-1(-) RLF cytokine-stimulated hmEV promoted myofibroblastic phenotype. Pretreatment of hmEV with RNase did not abolish in vitro effect of EV on target cell gene expression.  CONCLUSIONS: RfEV promote acquisition of myofibroblastic genes in MSC in vitro. Effects of stimulated hmEV, released during inflammation can be either protective or detrimental, depending on Thy-1 characteristics of target lung fibroblast.
DST and TRH stimulation test in mood disorder subtypes
Authors: A B Levy, S L Stern
Journal: American Journal of Psychiatry (1987)

Both the dexamethasone suppression test (DST) and the thyrotropin-releasing hormone (TRH) stimulation test have been reported to be useful in subtyping some depression diagnoses. Whether the DST discriminates delusional from nondelusional depression remains controversial, but this possibility has not been studied for the TRH test. The authors evaluated DST and TRH test results in 29 depressed hospitalized patients; both tests significantly discriminated patients with nonendogenous depression from those with endogenous depression. Furthermore, postdexamethasone cortisol levels but not the change in thyroid-stimulating hormone discriminated the patients with endogenous delusional depression from those with endogenous nondelusional depression.
miR-30b/30d Regulation of GalNAc Transferases Enhances Invasion and Immunosuppression during Metastasis
Authors: Avital Gaziel-Sovran, Miguel F. Segura, Raffaella Di Micco, Mary K. Collins, Douglas Hanniford, Eleazar Vega-Saenz de Miera, John F. Rakus, John F. Dankert, Shulian Shang, Robert S. Kerbel, Nina Bhardwaj, Yongzhao Shao, Farbod Darvishian, Jiri Zavadil, Adrian Erlebacher, Lara K. Mahal, Iman Osman, Eva Hernando
Journal: Cancer Cell (2011)
Cell and Tissue Imaging with Molecularly Imprinted Polymers as Plastic Antibody Mimics
Authors: Stephanie Kunath, Maria Panagiotopoulou, Jacqueline Maximilien, Nataliya Marchyk, Jörg Sänger, Karsten Haupt
Journal: Advanced Healthcare Materials (2015)

Molecularly imprinted polymers can be used as "plastic antibodies" for cell and tissue imaging, as demonstrated using hyaluronan on cell surfaces as a model target. Fluorescent nanoparticles binding a hyaluronan substructure, glucuronic acid, are used to image fixated and living cells and tissues. Plastic antibodies can be tailored to specific targets and easily labeled, and are physically and chemically stable. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Mechanisms of Activation of Cardiac Glycogen Phosphorylase in Ischemia and Anoxia
Authors: JAMES G. DOBSON, STEVEN E. MAYER
Journal: Circulation Research (1973)

The effects of ischemia and anoxia on cardiac adenosine 3', 5'-monophosphate (cyclic AMP) concentration, glycogen phosphorylase activity ratio (-5'-AMP: +5'-AMP), phosphorylase kinase activity ratio (pH 6.8:8.2), and myocardial contractility (left ventricular dP/dt) were studied in an open-chest rat heart preparation. Ischemia produced by termination of coronary blood flow increased cyclic AMP from 0.55 to 0.77 µmoles/kg in 5 seconds and phosphorylase from 0.14 to 0.57 in 20 seconds. Anoxia induced by breathing N 2 increased cyclic AMP from 0.50 to 0.62 µmoles/kg in 10 seconds and phosphorylase from 0.14 to 0.65 in 30 seconds. Phosphorylase kinase increased with ischemia but did not change with anoxia. Beta-receptor blockade with practolol prevented the rise in cyclic AMP and phosphorylase kinase but blocked the increase in phosphorylase only in ischemia. Myocardial contractility declined precipitously during the first 20 seconds of anoxia. Epinephrine (0.1 µg/kg) caused an increase in cyclic AMP comparable to that elicited by anoxia, and it produced an increase in dP/dt during N 2 breathing. These results suggest that in the intact working heart ischemia induces phosphorylase a formation through a cyclic AMP-dependent transformation of phosphorylase kinase; however, in anoxia phosphorylase a formation depends only on the regulation of the catalytic activity of phosphorylase kinase without conversion of this enzyme to its activated form. An increase in cyclic AMP during anoxia is not associated with a positive inotropic response even though such a response is obtained with epinephrine. Factors other than the elevation of myocardial cyclic AMP may be limiting in the control of both cardiac glycogenolysis and inotropic state.
Effects of endurance training on the isocapnic buffering and hypocapnic hyperventilation phases in professional cyclists
Authors: José L Chicharro, Jesús Hoyos, Alejandro Lucía
Journal: British Journal of Sports Medicine (2000)

Objectives —To evaluate the changes produced in both the isocapnic buffering and hypocapnic hyperventilation (HHV) phases of professional cyclists (n = 11) in response to endurance training, and to compare the results with those of amateur cyclists (n = 11). Methods —Each professional cyclist performed three laboratory exercise tests to exhaustion during the active rest (autumn: November), precompetition (winter: January), and competition (spring: May) periods of the sports season. Amateur cyclists only performed one exercise test during the competition period. The isocapnic buffering and HHV ranges were calculated during each test and defined as V o 2 and power output (W). Results —No significant differences were found in the isocapnic buffering range in each of the periods of the sports season in professional cyclists. In contrast, there was a significant reduction in the HHV range (expressed in W) during both the competition (p&lt;0.01) and precompetition(p&lt;0.05) periods compared with the rest period. On the other hand, a longer HHV range (p&lt;0.01) was observed in amateur cyclists than in professional cyclists (whether this was expressed in terms of V o 2 or W). Conclusions —No change is observed in the isocapnic buffering range of professional cyclists throughout a sports season despite a considerable increase in training loads and a significant reduction in HHV range expressed in terms of power output.
SOCIAL STRUCTURE AND PSYCHIATRIC DISORDERS
Authors: F. C. REDLICH, A. B. HOLLINGSHEAD, B. H. ROBERTS, H. A. ROBINSON, L. Z. FREEDMAN, J. K. MYERS
Journal: American Journal of Psychiatry (1953)

The relationship between social level and psychiatric disorders has been explored by a a demographic study of patients (i. e., patients in professional contact with psychiatrists) in metropolitan New Haven, and by a background study of the stratification of a sample of the general population in the same community. Significant relationships have been found between social level and (1) prevalence of psychiatric patients according to our definition, (2) types of psychiatric disorders in the patient population, and (3) types of therapy. Our data throw some light on social stratification in current psychiatric practice; they suggest the existence of an uneven social class distribution of psychoses in the general population. The project will continue, by sociological, psychiatric, and psychological techniques, to gather facts and to explore the meaning of the preliminary findings reported in this paper. Only a study of incidence and prevalence of psychiatric disorders in the general population will solve some of the basic problems posed.
Sleep quality and duration in patients with chronic heart failure and sleep disordered breathing
Authors: Anke Türoff, Henrik Fox, Jens Spießhöfer, Thomas Bitter, Dieter Horstkotte, Olaf Oldenburg
Journal: European Respiratory Journal (2014)

Sleep disordered breathing (SDB) represents a highly prevalent comorbidity in chronic heart failure (HF). SDB in non-HF leads to typical daytime symptoms including sleepiness whereas these symptoms in HF are usually missing. This study aimed to investigate sleep quality in HF patients with and without obstructive (OSA) or central sleep apnea (CSA).  Retrospectively we examined the sleep structure und duration on 350 patients (307 male and 43 female, mean age 67 ± 11 years) with stable heart failure (NYHA ≥ 2, left ventricular ejection fraction [LVEF] ≤ 45 %) by analyzing polysomnographic data.  Results are presented in table 1. Besides of limited data on HF patients without SDB, there were no obvious differences in sleep duration or quality.  HF patients without SDB or with OSA or CSA show no obvious differences in sleep-duration and sleep-quality when investigated by cardiorespiratory polysomnography. These data need to be compared to a matched-cohort of non-HF patients.
Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis
Authors: M Yonemaru, I Kasuga, H Kusumoto, A Kunisawa, H Kiyokawa, S Kuwabara, Y Ichinose, K Toyama
Journal: European Respiratory Journal (1997)

The aim of this study was to determine whether latent viral infection is associated with idiopathic pulmonary fibrosis (IPF), an interstitial lung disease whose aetiology remains to be elucidated. Cytomegalovirus (CMV) immunoglobulin G (IgG) and complement fixation (CF), Epstein-Barr (EB) viral capsid antigen (VCA) IgG, herpes simplex virus (HSV) IgG, adenovirus CF, and parainfluenza 3 virus haemagglutinin inhibition (HI) titres were measured in the serum from patients with pulmonary diseases. The study included five subject groups: 35 normal controls (aged (mean +/- SD) 38 +/- 17 yrs); 43 IPF (63 +/- 10 yrs), seven collagen vascular disease-related interstitial pneumonitis (CVD-IP) (62 +/- 12 yrs); 22 sarcoidosis (36 +/- 14 yrs); and 17 emphysema (66 +/- 11 yrs). Levels of CMV IgG in IPF (87.6 +/- 51.7) and CVD-IP (101.2 +/- 69.9) were significantly elevated compared to those in the control (30.9 +/- 24.1), sarcoidosis (34.4 +/- 38.3) and emphysema groups (40.3 +/- 24.6), whereas CMV immunoglobulin M (IgM) was generally below the limit of detection. Similarly, CMV CF titres in IPF and CVD-IP were elevated compared to those in other diseases. EB VCA IgG titres in IPF, CVD-IP and emphysema and HSV IgG in IPF were also elevated. In contrast, adenovirus CF and parainfluenza 3 HI titres demonstrated no significant difference among all of the groups investigated. Increases in cytomegalovirus immunoglobulin G and complement fixation titres with negative cytomegalovirus immunoglobulin M suggest that latent cytomegalovirus infection may be more prominent in idiopathic pulmonary fibrosis or collagen vascular disease-related interstitial pneumonitis. Together with the elevation of Epstein-Barr virus viral capsid antigen and herpes simplex virus immunoglobulin G in idiopathic pulmonary fibrosis and/or collagen vascular disease-related interstitial pneumonitis, it is rational to assume that these viruses may be implicated in the development of pulmonary fibrosis. Further study is necessary to investigate the relationship between latent viral infection and pulmonary fibrosis.
Phosphoproteomic analysis reveals Smarcb1 dependent EGFR signaling in Malignant Rhabdoid tumor cells
Authors: Jonatan Darr, Agnes Klochendler, Sara Isaac, Tami Geiger, Amir Eden
Journal: Molecular Cancer (2015)

The SWI/SNF ATP dependent chromatin remodeling complex is a multi-subunit complex, conserved in eukaryotic evolution that facilitates nucleosomal re-positioning relative to the DNA sequence. In recent years the SWI/SNF complex has emerged to play a role in cancer development as various sub-units of the complex are found to be mutated in a variety of tumors. One core-subunit of the complex, which has been well established as a tumor suppressor gene is SMARCB1 (SNF5/INI1/BAF47). Mutation and inactivation of SMARCB1 have been identified as the underlying mechanism leading to Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. We present a phosphoproteomic study of Smarcb1 dependent changes in signaling networks. The SILAC (Stable Isotopic Labeling of Amino Acids in Cell Culture) protocol was used to quantify in an unbiased manner any changes in the phosphoproteomic profile of Smarcb1 deficient murine rhabdoid tumor cell lines following Smarcb1 stable re-expression and under different serum conditions. This study illustrates broad changes in the regulation of multiple biological networks including cell cycle progression, chromatin remodeling, cytoskeletal regulation and focal adhesion. Specifically, we identify Smarcb1 dependent changes in phosphorylation and expression of the EGF receptor, demonstrate downstream signaling and show that inhibition of EGFR signaling specifically hinders the proliferation of Smarcb1 deficient cells. These results support recent findings regarding the effectivity of EGFR inhibitors in hindering the proliferation of human MRT cells and demonstrate that activation of EGFR signaling in Rhabdoid tumors is SMARCB1 dependent.