tbuckley/cabot-search huggingface dataset:
Some physical factors in toxicological assessment tests.
Authors: V H Freed, C T Chiou, D Schmedding, R Kohnert
Journal: Environmental Health Perspectives (1979)

Many thousand organic compounds are in common use and new ones introduced daily. With many of these materials, little is known about their toxic hazard. For years scientists have been investigating the relation of structure and properties to biological activity. Among the factors relating to toxicity are bioaccumulation and persistence in the organism. In this study, the relation of partition coefficient and solubility to bioaccumulation of some organochlorine compounds was investigated as was also the reactivity of several organophosphates. The work adds confirmation to the relation of molecular parameters to penetration, accumulation, and persistence in toxic action.
Favourable and sustained response to anakinra in tumour necrosis factor receptor-associated periodic syndrome (TRAPS) with or without AA amyloidosis
Authors: L. Obici, A. Meini, M. Cattalini, S. Chicca, M. Galliani, S. Donadei, A. Plebani, G. Merlini
Journal: Annals of the Rheumatic Diseases (2010)

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) is a dominantly inherited autoinflammatory disease characterised by recurrent episodes of fever, arthritis and serositis. In adulthood, inflammation often becomes persistent1 and AA amyloidosis may occur. Evidence of dysregulated secretion of proinflammatory cytokines, particularly interleukin 1 (IL-1) beta, in autoinflammatory diseases recently supported anakinra, the recombinant IL-1 receptor antagonist, as a target therapy for most of these conditions.2 3 In TRAPS, response to anakinra was reported in two case reports and in one prospective trial, in which five patients were treated for a mean duration of 11.4 months.4,–,6 However, longer follow-up and additional observations are warranted. We report the long-term efficacy and safety of anakinra in seven TRAPS patients with and without …
A Comparison of Bare-Metal and Drug-Eluting Stents for Off-Label Indications
Authors: Oscar C. Marroquin, Faith Selzer, Suresh R. Mulukutla, David O. Williams, Helen A. Vlachos, Robert L. Wilensky, Jean-François Tanguay, Elizabeth M. Holper, J. Dawn Abbott, Joon S. Lee, Conrad Smith, William D. Anderson, Sheryl F. Kelsey, Kevin E. Kip
Journal: New England Journal of Medicine (2008)

Recent reports suggest that off-label use of drug-eluting stents is associated with an increased incidence of adverse events. Whether the use of bare-metal stents would yield different results is unknown.
Propranolol for Prevention of Recurrent Gi Bleeding
Authors: Harvey Licht, Alan Mermelstein, Didier Lebrec, Thierry Poynard, Jacques Bernuau, Eric Bercoff, Olivier Nouel, Jean-Pierre Capron, Raoul Poupon, Mitchel Bouvry, Bernard Rueff, Jean-Pierre Benhamou
Journal: Hepatology (1985)
Estrone Sulfate: Production Rate and Metabolism in Man
Authors: Henry J. Ruder, Lynn Loriaux, M. B. Lipsett
Journal: Journal of Clinical Investigation (1972)

Since estrone sulfate (E1S) is present at high concentration in plasma, we have examined the parameters of the plasma estrone, estradiol, E1S system. The metabolic clearance rate of E1S was 157 liter/day (range 70-292) in men and women. Estimated plasma production rates of E1S were (μgrams per day): men, 77; women, early follicular phase, 95; women, early luteal phase, 182. The conversion of plasma estrone and estradiol to E1S was measured and from these data and the metabolic clearance rates of the estrogens, the transfer factors were ρE1E1S = 0.54 and ρE2E1S = 0.65. Using average production rates, all plasma E1S could be shown to be derived from plasma estrone and estradiol.
Peliosis hepatis induced by 6-thioguanine administration.
Authors: D Larrey, E Freneaux, A Berson, G Babany, C Degott, D Valla, D Pessayre, J P Benhamou
Journal: Gut (1988)

A patient with acute myeloblastic leukaemia developed jaundice revealing peliosis hepatis after receiving 6-thioguanine for two months. Peliosis hepatis was severe and was associated with mild lesions of centrilobular veins. Withdrawal of 6-thioguanine was followed by a progressive improvement of liver dysfunction. This report shows that 6-thioguanine, a thiopurine already reported to be responsible for veno-occlusive disease of the liver, can induce peliosis hepatis. This suggests that some liver vascular disorders caused by thiopurines (6-thioguanine, azathioprine and 6-mercaptopurine), particularly peliosis hepatis, veno-occlusive disease, sinusoidal dilatation and perisinusoidal fibrosis, might be related syndromes caused by similar lesions at different sites.
SGLT2 Mediates Glucose Reabsorption in the Early Proximal Tubule
Authors: Volker Vallon, Kenneth A. Platt, Robyn Cunard, Jana Schroth, Jean Whaley, Scott C. Thomson, Hermann Koepsell, Timo Rieg
Journal: Journal of the American Society of Nephrology (2010)

Mutations in the gene encoding for the Na(+)-glucose co-transporter SGLT2 (SLC5A2) associate with familial renal glucosuria, but the role of SGLT2 in the kidney is incompletely understood. Here, we determined the localization of SGLT2 in the mouse kidney and generated and characterized SGLT2-deficient mice. In wild-type (WT) mice, immunohistochemistry localized SGLT2 to the brush border membrane of the early proximal tubule. Sglt2(-/-) mice had glucosuria, polyuria, and increased food and fluid intake without differences in plasma glucose concentrations, GFR, or urinary excretion of other proximal tubular substrates (including amino acids) compared with WT mice. SGLT2 deficiency did not associate with volume depletion, suggested by similar body weight, BP, and hematocrit; however, plasma renin concentrations were modestly higher and plasma aldosterone levels were lower in Sglt2(-/-) mice. Whole-kidney clearance studies showed that fractional glucose reabsorption was significantly lower in Sglt2(-/-) mice compared with WT mice and varied in Sglt2(-/-) mice between 10 and 60%, inversely with the amount of filtered glucose. Free-flow micropuncture revealed that for early proximal collections, 78 ± 6% of the filtered glucose was reabsorbed in WT mice compared with no reabsorption in Sglt2(-/-) mice. For late proximal collections, fractional glucose reabsorption was 93 ± 1% in WT and 21 ± 6% in Sglt2(-/-) mice, respectively. These results demonstrate that SGLT2 mediates glucose reabsorption in the early proximal tubule and most of the glucose reabsorption by the kidney, overall. This mouse model mimics and explains the glucosuric phenotype of individuals carrying SLC5A2 mutations.
Interferon-γ Augments Acute Macrophage-Mediated Renal Injury Via a Glucocorticoid-Sensitive Mechanism
Authors: Yohei Ikezumi, Robert C. Atkins, David J. Nikolic-Paterson
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Macrophages have been implicated in causing renal injury in both human and experimental kidney disease. The aim of the current study was to determine whether modulating the state of macrophage activation directly affects the capacity of these cells to cause renal injury. This was investigated using an adoptive transfer model in which macrophage activation can be manipulated <i>in vitro</i>, using interferon-γ (IFN-γ) or dexamethasone (Dex), and then macrophage-mediated renal injury determined <i>in vivo</i>. In this model, rats were made leukopenic by administration of cyclophosphamide (CyPh). Two days later (day 0), animals were injected with sheep anti-GBM serum followed by a single injection of rat NR8383 macrophages on day 1 and then killed 3 or 24 h after cell transfer. NR8383 macrophages were incubated IFN-γ and/or Dex before adoptive transfer into animals. Induction of proteinuria and glomerular cell proliferation (PCNA+ cells) in this model was dependent on transfer of NR8383 macrophages. Exposure of macrophages to IFN-γ for 18 h (but not 3 h) before transfer caused a twofold increase in the degree of proteinuria and glomerular cell proliferation compared with unstimulated cells (Nil <i>versus</i> IFN-γ; <i>P</i> &lt; 0.001). This was due to an increase in the number of transferred macrophages within the glomerulus and a significant increase in degree of renal injury per transferred glomerular macrophage. IFN-γ increased iNOS and PDGF-B gene expression and upregulated adhesion molecule expression in NR8383 macrophages. In contrast, exposure of NR8383 cells to Dex for 18 h (but not 1 h) abrogated renal injury due to a failure of transferred macrophages to accumulate within the glomerulus. In addition, Dex abrogated renal injury caused by IFN-γ–stimulated macrophages. In conclusion, activation of macrophages by IFN-γ, independent of any effect on other leukocytes or renal cells, can substantially augment macrophage-mediated renal injury. This IFN-γ augmentation of renal injury is sensitive to the action of glucocorticoids, which act directly on macrophages to prevent their recruitment to the inflamed glomerulus. This study provides the first evidence that it is possible to directly modulate macrophage-mediated renal injury. E-mail: David.Nikolic-Paterson@med.monash.edu.au
E-Cadherin Regulates Human Nanos1, which Interacts with p120ctn and Induces Tumor Cell Migration and Invasion
Authors: Kristin Strumane, Arnaud Bonnomet, Christophe Stove, Roosmarijn Vandenbroucke, Beatrice Nawrocki-Raby, Erik Bruyneel, Marc Mareel, Philippe Birembaut, Geert Berx, Frans van Roy
Journal: Cancer Research (2006)

Abstract Down-regulation of the epithelial cell-cell adhesion molecule E-cadherin is frequently associated with tumor formation and progression. Besides its role in physical cell-cell adhesion, E-cadherin is also thought to be involved in intracellular signaling in normal epithelial cells. In these cells, the Armadillo catenin p120ctn binds to the cytoplasmic domain of E-cadherin and stabilizes the adhesion complexes. On loss of E-cadherin, cytoplasmic p120ctn might accumulate and contribute to tumor malignancy. We used suppression subtractive hybridization to search for genes regulated by E-cadherin expression. We isolated human Nanos1 as a transcript of which levels decrease on E-cadherin reexpression in a human breast cancer cell line. The hNanos1 protein bears a COOH-terminal (CCHC)2 zinc finger domain and belongs to an evolutionarily conserved protein family sharing functions in germ cell development in both vertebrates and invertebrates. We found an inverse correlation between E-cadherin and hNanos1 expression in various cell lines and under diverse conditions. Conditional expression of hNanos1 in human colorectal DLD1 cancer cells functionally abolished cell-cell adhesion. It induced cytoplasmic translocation of p120ctn, as well as strong migratory and invasive properties. We also found that the NH2-terminal domain of hNanos1, which is conserved only among mammals, interacts with p120ctn. hNanos1 counteracted the stimulatory effect of p120ctn on cell protrusion formation. Together, these findings describe a new function for hNanos1 as a downstream effector of E-cadherin loss contributing to tumor progression. Targeting hNanos1 might be a promising strategy in the treatment of E-cadherin–negative tumors in particular. (Cancer Res 2006; 12(20): 10007-15)
A Novel Method of Transcriptional Response Analysis to Facilitate Drug Repositioning for Cancer Therapy
Authors: Guangxu Jin, Changhe Fu, Hong Zhao, Kemi Cui, Jenny Chang, Stephen T.C. Wong
Journal: Cancer Research (2011)

Little research has been done to address the huge opportunities that may exist to reposition existing approved or generic drugs for alternate uses in cancer therapy. In addition, there has been little work on strategies to reposition experimental cancer agents for testing in alternate settings that could shorten their clinical development time. Progress in each area has lagged, in part, because of the lack of systematic methods to define drug off-target effects (OTE) that might affect important cancer cell signaling pathways. In this study, we addressed this critical gap by developing an OTE-based method to repurpose drugs for cancer therapeutics, based on transcriptional responses made in cells before and after drug treatment. Specifically, we defined a new network component called cancer-signaling bridges (CSB) and integrated it with a Bayesian factor regression model (BFRM) to form a new hybrid method termed CSB-BFRM. Proof-of-concept studies were conducted in breast and prostate cancer cells and in promyelocytic leukemia cells. In each system, CSB-BFRM analysis could accurately predict clinical responses to more than 90% of drugs approved by the U.S. Food and Drug Administration and more than 75% of experimental clinical drugs that were tested. Mechanistic investigation of OTEs for several high-ranking drug-dose pairs suggested repositioning opportunities for cancer therapy, based on the ability to enforce retinoblastoma-dependent repression of important E2F-dependent cell-cycle genes. Together, our findings establish new methods to identify opportunities for drug repositioning or to elucidate the mechanisms of action of repositioned drugs.
Necrotizing sarcoid granulomatosis in a 14-yr-old female
Authors: E Tauber, C Wojnarowski, E Horcher, G Dekan, T Frischer
Journal: European Respiratory Journal (1999)

A case of a 14-yr-old female with necrotizing sarcoid granulomatosis (NSG) is presented. She was referred because of chest pain and malaise, and radiography revealed multiple pulmonary nodules. Her history showed seasonal sensitization to aeroallergens and hay fever. Infectious agents or malignancies did not characterize these nodules. However, she was treated with macrolide antibiotics because of suspected infection with Chlamydia pneumoniae. Open lung biopsy showed histological findings of NSG, with epithelioid granulomatous inflammation, including giant cells, and vasculitis. No further treatment was performed, and symptoms disappeared within a few weeks. The chest radiograph showed gradual improvement. The aetiology of NSG is poorly understood, and is postulated to represent either sarcoidosis or rare forms of pulmonary vasculitis such as Wegener's granulomatosis or the Churg-Strauss syndrome. In the case presented, a coincidence of infection with Chlamydia pneumoniae suggests an involvement of infectious agents in the pattern of formation of immune complexes in the aetiology of NSG.
Pretreatment Nomogram for Predicting the Outcome of Three-Dimensional Conformal Radiotherapy in Prostate Cancer
Authors: Michael W. Kattan, Michael J. Zelefsky, Patrick A. Kupelian, Peter T. Scardino, Zvi Fuks, Steven A. Leibel
Journal: Journal of Clinical Oncology (2000)

Several studies have defined risk groups for predicting the outcome after external-beam radiotherapy of localized prostate cancer. However, most models formed patient risk groups, and none of these models considers radiation dose as a predictor variable. The purpose of this study was to develop a nomogram to improve the accuracy of predicting outcome after three-dimensional conformal radiotherapy.This study was a retrospective, nonrandomized analysis of patients treated at the Memorial Sloan-Kettering Cancer Center between 1988 and 1998. Clinical parameters of the 1,042 patients included stage, biopsy Gleason score, pretreatment serum prostate-specific antigen (PSA) level, whether neoadjuvant androgen deprivation therapy was administered, and the radiation dose delivered. Biochemical (PSA) treatment failure was scored when three consecutive rises of serum PSA occurred. A nomogram, which predicts the probability of remaining free from biochemical recurrence for 5 years, was validated internally on this data set using a bootstrapping method and externally using a cohort of patients treated at the Cleveland Clinic, Cleveland, OH.When predicting outcomes for patients in the validation data set from the Cleveland Clinic, the nomogram had a Somers' D rank correlation between predicted and observed failure times of 0.52. Predictions from this nomogram were more accurate (P<.0001) than the best of seven published risk stratification systems, which achieved a Somers' D coefficient of 0.47.The development process illustrated here produced a nomogram that seems to predict more accurately than other available systems and may be useful for treatment selection by both physicians and patients.
Visual art in hospitals: case studies and review of the evidence
Authors: Louise Lankston, Pearce Cusack, Chris Fremantle, Chris Isles
Journal: Journal of the Royal Society of Medicine (2010)

Summary In 2006 a Department of Health Working Group on Arts and Health reported that the arts have ‘a clear contribution to make and offer major opportunities in the delivery of better health, wellbeing and improved experience for patients, service users and staff alike’. In this review we examine the evidence underpinning this statement and evaluate the visual art of three of Scotland's newest hospitals: the Royal Infirmary of Edinburgh, the new Stobhill Hospital, and the new Victoria Infirmary in Glasgow. We conclude that art in hospitals is generally viewed positively by both patients and staff, but that the quality of the evidence is not uniformly high. Effects may be mediated by psychological responses to colour hue, brightness and saturation. Colours that elicit high levels of pleasure with low levels of arousal are most likely to induce a state of calm, while those causing displeasure and high levels of arousal may provoke anxiety. The fact that patients frequently express a preference for landscape and nature scenes is consistent with this observation and with evolutionary psychological theories which predict positive emotional responses to flourishing natural environments. Contrary to a view which may prevail among some contemporary artists, patients who are ill or stressed about their health may not always be comforted by abstract art, preferring the positive distraction and state of calm created by the blues and greens of landscape and nature scenes instead.
Paclitaxel Encapsulated in Cationic Liposomes Increases Tumor Microvessel Leakiness and Improves Therapeutic Efficacy in Combination with Cisplatin
Authors: Sebastian Strieth, Martin E. Eichhorn, Alexander Werner, Birgitta Sauer, Michael Teifel, Uwe Michaelis, Alexander Berghaus, Marc Dellian
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Paclitaxel encapsulated in cationic liposomes (EndoTAG-1) is a vascular targeting formulation for the treatment of solid tumors. It triggers intratumoral microthrombosis, causing significant inhibition of tumor perfusion and tumor growth associated with endothelial cell apoptosis. Here, we quantified the effects of repeated EndoTAG-1 therapy on tumor microvascular leakiness with respect to leukocyte-endothelial cell interactions, the targeting property of cationic liposomes, and the therapeutic combination with conventional cisplatin chemotherapy. Experimental Design: Using dorsal skinfold chamber preparations in Syrian Golden hamsters, in vivo fluorescence microscopy experiments were done after repeated EndoTAG-1 treatment of A-Mel-3 tumors. Controls received glucose, paclitaxel alone, or cationic liposomes devoid of paclitaxel. Extravasation of rhodamine-labeled albumin was measured to calculate microvessel permeability, and intratumoral leukocyte-endothelial cell interactions were quantified. Subcutaneous tumor growth was evaluated after combination therapy followed by histologic analysis. Results: Microvascular permeability was significantly increased only after treatment with EndoTAG-1, whereas intratumoral leukocyte-endothelial cell interactions were not affected by any treatment. In separate skinfold chamber experiments, fluorescently labeled cationic liposomes kept their targeting property for tumor endothelial cells after repeated EndoTAG-1 treatment and no signs of extravasation were observed. Subcutaneous A-Mel-3 tumor growth was significantly inhibited by the combination of cisplatin and EndoTAG-1. Conclusions: These data show that vascular targeting with EndoTAG-1 increases tumor microvessel leakiness probably due to vascular damage. This mechanism is not mediated by inflammatory leukocyte-endothelial cell interactions. Manipulating the blood-tumor barrier by repeated tumor microvessel targeting using EndoTAG-1 can effectively be combined with tumor cell–directed conventional cisplatin chemotherapy.
Association of Heart Failure in Homozygous β-Thalassemia With the Major Histocompatibility Complex
Authors: Dimitrios T. Kremastinos, Panagiota Flevari, Maria Spyropoulou, Helen Vrettou, Dimitrios Tsiapras, Catherine G. Stavropoulos-Giokas
Journal: Circulation (1999)

In beta-thalassemia major, heart failure primarily affecting left ventricular systolic function is the most common complication and cause of death. Apart from iron deposition, it has been recently reported that myocarditis might be another contributing factor in the pathogenesis of acute or chronic heart failure, acting possibly through an autoimmune mechanism. In an attempt to assess the role of immunogenetic factors in the development of heart failure associated with beta-thalassemia major, we studied the frequency of major histocompatibility antigens/alleles A, B, DR, and DQ in homozygous beta-thalassemic patients with and without heart failure primarily affecting the left ventricle.Forty-five consecutive unrelated Greek patients with homozygous beta-thalassemia and left-sided chronic heart failure were studied. Fifty-eight unrelated Greek patients with homozygous beta-thalassemia without heart failure and 130 unrelated Greek healthy controls were also studied. In all subjects, class I HLA-A and -B typing was performed by the complement-mediated lymphocytotoxicity assay, whereas class II HLA-DR and -DQ typing was performed by polymerase chain reaction. HLA-DRB1*1401 allele frequency was significantly increased in patients with beta-thalassemia major without left-sided heart failure compared with those with heart failure (corrected P [P(c)]=0. 02, odds ratio 0.1) and healthy controls (P(c)=0.001). HLA-DQA1*0501 allele frequency was increased in patients with heart failure compared with patients without heart failure (P(c)=0.04, odds ratio 14) and healthy controls (P(c)=0.004).Differences exist in the immunogenetic profile between homozygous beta-thalassemic patients with and without left-sided heart failure, raising the possibility that genetically defined immune mechanisms may play an important role in the pathogenesis of heart failure in beta-thalassemia.