tbuckley/cabot-search huggingface dataset:
Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo
Authors: Maurizio Bruschi, Renato Alberto Sinico, Gabriella Moroni, Federico Pratesi, Paola Migliorini, Maricla Galetti, Corrado Murtas, Angela Tincani, Michael Madaio, Antonella Radice, Franco Franceschini, Barbara Trezzi, Laura Bianchi, Agata Giallongo, Rita Gatti, Regina Tardanico, Andrea Scaloni, Chiara D’Ambrosio, Maria Luisa Carnevali, Piergiorgio Messa, Pietro Ravani, Giancarlo Barbano, Beatrice Bianco, Alice Bonanni, Francesco Scolari, Alberto Martini, Giovanni Candiano, Landino Allegri, Gian Marco Ghiggeri
Journal: Journal of the American Society of Nephrology (2014)

Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti–α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti–α-enolase/low anti-annexin AI IgG2 and patients with low anti–α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti–α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum.
Tuberculous Infection of an Extrapleural Pneumothorax complicated by Cl. welchii Infection
Authors: M. G. Tate
Journal: BMJ (1944)

adduced to indicate that the parenteral administration of strychnine leads to any improvement in the general condition of the patient.I should like to express my indebtedness to Prof. Noah Morris for his help, and to the Medical Research Council for a grant cowards expenses.
Different Signaling Pathways Induce Apoptosis in Endothelial Cells and Cardiac Myocytes During Ischemia/Reperfusion Injury
Authors: Tiziano M. Scarabelli, Anastasis Stephanou, Evasio Pasini, Laura Comini, Riccardo Raddino, Richard A. Knight, David S. Latchman
Journal: Circulation Research (2002)

Apoptosis contributes, with necrosis, to the cardiac cell loss after ischemia/reperfusion injury. The apoptotic cascade is initiated either by mitochondrial damage and activation of caspase-9 or by death receptor ligation and activation of caspase-8. In the present study, performed in the isolated rat heart exposed either to ischemia alone or ischemia followed by reperfusion, cleavage of caspase-9 was observed primarily in endothelial cells. Conversely, caspase-8 cleavage was only found in cardiomyocytes, where it progressively increased throughout reperfusion. Addition of a specific caspase-9 inhibitor to the perfusate before ischemia prevented endothelial apoptosis, whereas preischemic infusion of a specific caspase-8 inhibitor affected only myocyte apoptosis. Additionally, caspase-8-mediated BID processing was observed only during reperfusion. Production of tBID then sustains mitochondrial injury and perpetuates caspase-9 activation.
InSilico DB: an online platform to collaboratively structure and export publicly available datasets from the Gene Expression Omnibus database
Authors: A Coletta, C Molter, R Duqué, D Steenhoff, J Taminau, V de Schaetzen, C Lazar, S Meganck, A Nowé, H Bersini, D Weiss
Journal: Genome biology (2011)

There are more than 20,000 genomic studies comprising 500,000 samples freely available in the Gene Expression Omnibus (GEO) database [1]. However, accessing these data requires complex computational steps, including structuring and formatting the clinical vocabulary used to annotate the samples. These complex steps hinder the accessibility of genomic datasets through visualization and analysis software platforms, such as GenePattern and R/Bioconductor, therefore hampering the pace of research.

InSilico DB [2] is an online platform that provides a complete collaborative solution for structuring and formatting clinical annotations from GEO, making GenePattern and R datasets one click away for researchers.

InSilico DB has made available powerful and intuitive online curation tools to structure the metadata of GEO datasets. The database is automatically updated daily, through GEO import pipelines. Datasets can have multiple annotations given by different users, and one user can have multiple versions of an annotation to suit different experimental questions.

The InSilico DB platform supports datasets from Affymetrix human gene expression platforms, which account for 2,900 studies comprising 110,000 samples, making InSilico DB the largest public database of manually curated human gene expression samples. In addition to the web interface, InSilico DB offers programmatic access through an R/Bioconductor package [3].

Future releases of InSilico DB will include Illumina RNA-Seq platform data and Affymetrix mouse gene expression data.
Mutation of the RAD51C gene in a Fanconi anemia–like disorder
Authors: Fiona Vaz, Helmut Hanenberg, Beatrice Schuster, Karen Barker, Constanze Wiek, Verena Erven, Kornelia Neveling, Daniela Endt, Ian Kesterton, Flavia Autore, Franca Fraternali, Marcel Freund, Linda Hartmann, David Grimwade, Roland G Roberts, Heiner Schaal, Shehla Mohammed, Nazneen Rahman, Detlev Schindler, Christopher G Mathew
Journal: Nature Genetics (2010)
Hepatitis C virus recurrence after liver transplantation
Authors: T BIZOLLON, C DUCERF, C TREPO, D MUTIMER
Journal: Gut (1999)

Cirrhosis due to hepatitis C virus (HCV) is now the most common indication of liver transplantation in Western Europe and the United States. In the absence of effective prophylaxis, recurrent HCV infection is almost inevitable. Though the natural history and intermediate term outcome of recurrent HCV are now better documented, those factors which may influence the recurrence of hepatitis and consequent progression of graft disease remain unclear. Interferon (IFN) as a sole agent for the treatment of recurrent infection has proved unsatisfactory. Early intervention with a combination of IFN and ribavirin seems promising, and this approach may prevent or delay progression of HCV related graft disease after liver transplantation.
Collagen content of alveolar wall tissue in emphysematous and non-emphysematous lungs.
Authors: M R Lang, G W Fiaux, M Gillooly, J A Stewart, D J Hulmes, D Lamb
Journal: Thorax (1994)

BACKGROUND--Emphysema is currently defined as "a condition of the lung characterised by abnormal, permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, and without obvious fibrosis." The functional and morphological changes that occur in emphysema have largely been attributed to changes in alveolar elastin rather than in collagen. A study was performed to determine whether the amount of collagen in the alveolar wall changes with age in the lungs of non-smokers and of smokers with different types of macroscopically defined emphysema in relation to a microscopic measurement of lung structure. METHODS--Total alveolar wall collagen was measured (as hydroxyproline) in known volumes of distended lung tissue (by reverse phase high pressure liquid chromatography) in the lungs of non-smokers (n = 23) and in regions sampled away from emphysematous lesions in the lungs of 36 smokers (four with no emphysema, 13 with centriacinar emphysema (CAE), nine with panacinar emphysema (PAE), and 10 with a mixture (MIX) of both PAE and CAE). Mean lung airspace wall surface area per unit volume (AWUV) was calculated from at least six random blocks per lung and on histological sections immediately adjacent to those prepared for collagen measurement with a rapid scanning device (fast interval processor). RESULTS--In non-smokers there was no significant correlation between the amount of collagen in the alveolar wall tissue and either mean lung AWUV or increasing patient age when amounts of collagen were expressed either per unit volume of distended lung (40 mm3 sample) or per unit surface area of airspace wall tissue. Smokers without emphysema had similar amounts of collagen to non-smokers. Lungs with PAE and MIX, but not CAE alone, contained significantly more collagen than normal when expressed per unit volume of airspace wall tissue whereas all groups, including CAE, contained significantly raised amounts of collagen when expressed per unit surface area. CONCLUSIONS--There is no significant age related change in the collagen content of the lungs of non-smokers which suggests that, as AWUV is lost with age, the main collagenous framework is maintained. However, in smokers with emphysema there is a loss of airspace wall tissue in regions remote from the macroscopic lesions that is accompanied by a net increase in collagen mass. The greater accumulation of collagen in MIX lungs than in CAE lungs suggests a greater degree of structural damage, indicative of an alternative pathogenetic mechanism operating between the different types of emphysema. Our results suggest an active alveolar wall fibrosis in emphysema as a consequence of cigarette smoking. It is suggested that the definition of emphysema may require further revision to include such change.
An overview of benefit/risk of disease modifying treatment of rheumatoid arthritis as of today
Authors: H. E Paulus
Journal: Annals of the Rheumatic Diseases (1982)

In chronic rheumatoid arthritis (RA), disease modifying drugs are used in an attempt to suppress the progressive damage to tissues and joints that is associated with active disease. Their success in achieving this goal is variable; responses vary from complete suppression of all signs and symptoms of RA to continued active disease, with progressive disability, despite prolonged therapy. Because disease activity almost always recurs after the therapy is stopped, early interruption of an effective therapy for any reason will make its benefit insignificant in a lifelong disease such as RA. Similarly, short-term sequential use of multiple disease modifying therapies is unlikely to be beneficial. The immediate problems with these therapies are substantial. In general, fewer than 50% of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months or longer to achieve maximum effects, those patients who are unable to continue the drug receive little benefit from it. Inevitable delayed side-effects, such as those associated with chronic corticosteroid therapy, may make the benefit/risk ratio unacceptable. Potential late lethal adverse effects, such as malignancy, weight the benefit/risk ratio to varying extents for individual patients, depending on the relative probability that the adverse effect will occur during the remainder of the patient9s anticipated life span, and are of greater importance in younger patients. In that minority of patients who achieve remission or near remission and are able to tolerate a disease modifying treatment for many years, it is of truly significant benefit. We are still searching for a therapy that will reliably achieve this goal for most patients with RA.
Effect of Danaparoid Sodium on Proteinuria, von Willebrand Factor, and Hard Exudates in Patients with Diabetes Mellitus Type 2
Authors: JOHAN W. VAN DER PIJL, HERMAN H. P. J. LEMKES, MARIJKE FRÖLICH, FOKKO J. VAN DER WOUDE, FELIX J. M. VAN DER MEER, LEENDERT A. VAN ES
Journal: Journal of the American Society of Nephrology (1999)

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.
Endoglin (CD105) Contributes to Platinum Resistance and Is A Target for Tumor-Specific Therapy in Epithelial Ovarian Cancer
Authors: Angela J. Ziebarth, Somaira Nowsheen, Adam D. Steg, Monjri M. Shah, Ashwini A. Katre, Zachary C. Dobbin, Hee-Dong Han, Gabriel Lopez-Berestein, Anil K. Sood, Michael Conner, Eddy S. Yang, Charles N. Landen
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Endoglin (CD105) is a membranous protein overexpressed in tumor-associated endothelial cells, chemoresistant populations of ovarian cancer cells, and potentially stem cells. Our objective was to evaluate the effects and mechanisms of targeting endoglin in ovarian cancer. Experimental Design: Global and membranous endoglin expression was evaluated in multiple ovarian cancer lines. In vitro, the effects of siRNA-mediated endoglin knockdown with and without chemotherapy were evaluated by MTT assay, cell-cycle analysis, alkaline comet assay, γ-H2AX foci formation, and quantitative PCR. In an orthotopic mouse model, endoglin was targeted with chitosan-encapsulated siRNA with and without carboplatin. Results: Endoglin expression was surprisingly predominantly cytoplasmic, with a small population of surface-positive cells. Endoglin inhibition decreased cell viability, increased apoptosis, induced double-stranded DNA damage, and increased cisplatin sensitivity. Targeting endoglin downregulates expression of numerous DNA repair genes, including BARD1, H2AFX, NBN, NTHL1, and SIRT1. BARD1 was also associated with platinum resistance, and was induced by platinum exposure. In vivo, antiendoglin treatment decreased tumor weight in both ES2 and HeyA8MDR models when compared with control (35%–41% reduction, P &amp;lt; 0.05). Endoglin inhibition with carboplatin was associated with even greater inhibitory effect when compared with control (58%–62% reduction, P &amp;lt; 0.001). Conclusions: Endoglin downregulation promotes apoptosis, induces significant DNA damage through modulation of numerous DNA repair genes, and improves platinum sensitivity both in vivo and in vitro. Antiendoglin therapy would allow dual treatment of both tumor angiogenesis and a subset of aggressive tumor cells expressing endoglin and is being actively pursued as therapy in ovarian cancer. Clin Cancer Res; 19(1); 170–82. ©2012 AACR.
Kawasaki Disease: Novel Insights into Etiology and Genetic Susceptibility
Authors: Anne H. Rowley
Journal: Annual Review of Medicine (2010)

Kawasaki disease (KD) is a vasculitis of young childhood that particularly affects the coronary arteries. Molecular analysis of the oligoclonal IgA response in acute KD led to production of synthetic KD antibodies. These antibodies identify intracytoplasmic inclusion bodies in acute KD tissues. Light and electron microscopic studies indicate that the inclusion bodies are consistent with aggregates of viral proteins and RNA. Advances in molecular genetic analysis and completion of the Human Genome Project have sparked a worldwide effort to identify genes associated with KD. A polymorphism of one such gene, ITPKC, a negative regulator of T cell activation, confers susceptibility to KD in Japanese populations and increases the risk of developing coronary artery abnormalities in both Japanese and U.S. children. Identification of the etiologic agent and of genes conferring KD susceptibility are the best means of improving diagnosis and therapy and enabling prevention of this important disorder of childhood.
Does food affect acute inflammatory bowel disease? The role of parenteral nutrition, elemental and exclusion diets.
Authors: J Rhodes, J Rose
Journal: Gut (1986)

Revue de publications sur ce probleme tres discute. La plupart des malades reussissent a exclure de leur regime les aliments declenchant les crises, mais les explorations systematiques semblent trop longues, trop couteuses et trop peu efficaces dans l'etat actuel des connaissances
Towards a Definition and Classification of Acute Kidney Injury
Authors: David G. Warnock
Journal: Journal of the American Society of Nephrology (2005)

Chertow and colleagues ([1][1]) have an interesting and provocative paper in this issue of JASN that brings a pragmatic approach to bear on the issue of defining acute renal failure. This area is rapidly gaining prominence and was the theme of one of the American Society of Nephrology's research
The Outcome of Neutrophil Gelatinase-Associated Lipocalin-Positive Subclinical Acute Kidney Injury
Authors: Michael Haase, Prasad Devarajan, Anja Haase-Fielitz, Rinaldo Bellomo, Dinna N. Cruz, Gebhard Wagener, Catherine D. Krawczeski, Jay L. Koyner, Patrick Murray, Michael Zappitelli, Stuart L. Goldstein, Konstantinos Makris, Claudio Ronco, Johan Martensson, Claes-Roland Martling, Per Venge, Edward Siew, Lorraine B. Ware, T. Alp Ikizler, Peter R. Mertens
Journal: Journal of the American College of Cardiology (2011)
Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study
Authors: P. Rich, B. Sigurgeirsson, D. Thaci, J.-P. Ortonne, C. Paul, R.E. Schopf, A. Morita, K. Roseau, E. Harfst, A. Guettner, M. Machacek, C. Papavassilis
Journal: British Journal of Dermatology (2013)

Background Interleukin (IL)-17A has major proinflammatory activity in psoriatic lesional skin. Objectives To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-IL-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment-at-start-of-relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). Results At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start-of-relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection-site reactions were reported. Reported cases of neutropenia were mild-to-moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. Conclusions Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis.
Revisiting the Total Contact Cast
Authors: Marc Petre, Paul Tokar, Debra Kostar, Peter R. Cavanagh
Journal: Diabetes Care (2005)

Although the benefits of total contact casting for healing plantar neuropathic ulcers are consistent throughout a large body of available literature, the method of cast application varies (1–17). Cast structure at the ulcer site provides one major variance, i.e., should the cast create total contact with the entire plantar surface of the foot or should the wound be isolated? This article aims to resolve this issue by examining the differences in plantar pressure at the wound site between total contact casting using full contact with the plantar aspect of the foot and wound isolation.

A total of 10 healthy adult subjects (aged 28 ± 13 years, height 1.81 ± 0.1 m, and weight 92.6 ± 18 kg) with focal areas of pressure (but no history of ulceration) under their metatarsal heads were recruited. For each subject, a region of interest (ROI) was selected to encompass areas of particularly high pressure. This study was approved by the Institutional Review Board of the Cleveland Clinic Foundation, and all subjects signed informed consent forms. A Pliance pressure-sensitive array (Novel) was fixed directly to the subject’s foot covering the ROI. The 16 × 16 sensor array had a sensor size of 19.36 mm2 and a sampling rate of 50 …