tbuckley/cabot-search huggingface dataset:
Biomarker reproducibility in exhaled breath condensate collected with different condensers
Authors: P. P. Rosias, C. M. Robroeks, A. Kester, G. J. den Hartog, W. K. Wodzig, G. T. Rijkers, L. J. Zimmermann, C. P. van Schayck, Q. Jöbsis, E. Dompeling
Journal: European Respiratory Journal (2008)

Optimal collection and analysis of exhaled breath condensate (EBC) are prerequisites for standardisation and reproducibility of assessments. The present study aimed to assess reproducibility of EBC volume, hydrogen peroxide (H 2 O 2 ), 8-isoprostane and cytokine measurements using different condensers, including a newly developed glass condenser. At four points in time, 30 healthy subjects performed sequential EBC collections randomly using the following four condensers: glass, silicone, EcoScreen® (Erich Jaeger GmbH, Hoechberg, Germany) and an optimised glass condenser. In small EBC samples, H 2 O 2 was measured by spectrophotometer, 8-isoprostane by enzyme immunoassay, and cytokines by multiplexed xMAP® technology (Luminex Corporation, Austin, TX, USA). The optimised glass condenser yielded significantly more EBC volume (median 2,025 µL, interquartile range 1,600–2,525). The reproducibility of EBC volume, yielded by the new glass condenser, was comparable with EcoScreen® (19–20 coefficients of variation (CV)%), but was significantly better compared with silicone and glass (29–37 CV%). The new condenser was associated with significantly more detections of H 2 O 2 , 8-isoprostane, interleukin-2, -4, -5 and -13, and tumour necrosis factor-α. Isoprostane concentrations were significantly higher using the new condenser, whereas H 2 O 2 and cytokine concentrations were not. Reproducibility of biomarkers was equally variable for all condenser types. In conclusion, significantly more exhaled breath condensate volume and biomarker detections were found using the optimised glass condenser, including higher 8-isoprostane levels. However, biomarker reproducibility in exhaled breath condensate in healthy adults was not influenced by the type of condenser.
Predicting the Risk for Dialysis or Death in IgA Nephropathy
Authors: François Berthoux, Hesham Mohey, Blandine Laurent, Christophe Mariat, Aida Afiani, Lise Thibaudin
Journal: Journal of the American Society of Nephrology (2011)

For the individual patient with primary IgA nephropathy (IgAN), it remains a challenge to predict long-term outcomes for patients receiving standard treatment. We studied a prospective cohort of 332 patients with biopsy-proven IgAN patients followed over an average of 13 years. We calculated an absolute renal risk (ARR) of dialysis or death by counting the number of risk factors present at diagnosis: hypertension, proteinuria ≥1 g/d, and severe pathologic lesions (global optical score, ≥8). Overall, the ARR score allowed significant risk stratification (P < 0.0001). The cumulative incidence of death or dialysis at 10 and 20 years was 2 and 4%, respectively, for ARR=0; 2 and 9% for ARR=1; 7 and 18% for ARR=2; and 29 and 64% for ARR=3, in adequately treated patients. When achieved, control of hypertension and reduction of proteinuria reduced the risk for death or dialysis. In conclusion, the absolute renal risk score, determined at diagnosis, associates with risk for dialysis or death.
Changing Patterns of Symptom Control and Palliative Care Paper Presentations at the Annual Meeting of the American Society of Clinical Oncology
Authors: Catherine Sweeney, Leaha Beattie-Palmer, J. Lynn Palmer, Eduardo Bruera
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.14.3438 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11454893 Changing Patterns of Symptom Control and Palliative Care Paper Presentations at the Annual Meeting of the American Society of Clinical Oncology Catherine SweeneyxCatherine SweeneySearch for articles by this author , Leaha Beattie-PalmerxLeaha Beattie-PalmerSearch for articles by this author , J. Lynn PalmerxJ. Lynn PalmerSearch for articles by this author , Eduardo BrueraxEduardo BrueraSearch for articles by this author Show More M.D. Anderson Cancer Center, Houston, TX https://doi.org/10.1200/JCO.2001.19.14.3438 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
The usefulness of immunofluorescent tests in pemphigus patients in clinical remission
Authors: M. DAVID, V. WEISSMAN-KATZENELSON, A. BEN-CHETRIT, B. HAZAZ, A. INGBER, M. SANDBANK
Journal: British Journal of Dermatology (1989)

Direct and indirect immunofluorescent studies (DIF, IIF) were performed on 24 pemphigus vulgaris patients who were in a state of clinical remission. The tests were repeated after an interval of 6 months. All the patients were on maintenance therapy with oral prednisone. The DIF in eight patients showed negative results among whom seven remained negative. Six patients out of 24 showed weakly positive fluorescence and ten patients showed strong positive fluorescence. The IIF was negative in 17 patients and positive in seven patients who also showed positive DIF. During a follow-up period of 20 months, one of eight patients with negative DIF relapsed compared with two of six patients with weak positive DIF and five of 10 patients with strong DIF. Five patients with strong DIF for IgG also had C3, of whom three relapsed, compared with five of 19 patients who were negative for C3. Four of seven patients with positive IIF relapsed compared with four of 17 with negative IIF. It is suggested that repeated DIF tests in pemphigus patients, who are in clinical remission, may serve as an indicator for the immunological activity and be of help in the management of these cases.
Exchange Protein Directly Activated by cAMP Mediates Slow Delayed-Rectifier Current Remodeling by Sustained β-Adrenergic Activation in Guinea Pig Hearts
Authors: Mona Aflaki, Xiao-Yan Qi, Ling Xiao, Balazs Ordog, Artavazd Tadevosyan, Xiaobin Luo, Ange Maguy, Yanfen Shi, Jean-Claude Tardif, Stanley Nattel
Journal: Circulation Research (2014)

Rationale: β-Adrenoceptor activation contributes to sudden death risk in heart failure. Chronic β-adrenergic stimulation, as occurs in patients with heart failure, causes potentially arrhythmogenic reductions in slow delayed-rectifier K + current (I Ks ). Objective: To assess the molecular mechanisms of I Ks downregulation caused by chronic β-adrenergic activation, particularly the role of exchange protein directly activated by cAMP (Epac). Methods and Results: Isolated guinea pig left ventricular cardiomyocytes were incubated in primary culture and exposed to isoproterenol (1 μmol/L) or vehicle for 30 hours. Sustained isoproterenol exposure decreased I Ks density (whole cell patch clamp) by 58% ( P &lt;0.0001), with corresponding decreases in potassium voltage-gated channel subfamily E member 1 (KCNE1) mRNA and membrane protein expression (by 45% and 51%, respectively). Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) mRNA expression was unchanged. The β1-adrenoceptor antagonist 1-[2-((3-Carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol dihydrochloride (CGP-20712A) prevented isoproterenol-induced I Ks downregulation, whereas the β 2 -antagonist ICI-118551 had no effect. The selective Epac activator 8-pCPT-2′-O-Me-cAMP decreased I Ks density to an extent similar to isoproterenol exposure, and adenoviral-mediated knockdown of Epac1 prevented isoproterenol-induced I Ks /KCNE1 downregulation. In contrast, protein kinase A inhibition with a cell-permeable highly selective peptide blocker did not affect I Ks downregulation. 1,2-Bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetate-AM acetoxymethyl ester (BAPTA-AM), cyclosporine, and inhibitor of nuclear factor of activated T cell (NFAT)-calcineurin association-6 (INCA6) prevented I Ks reduction by isoproterenol and INCA6 suppressed isoproterenol-induced KCNE1 downregulation, consistent with signal-transduction via the Ca 2+ /calcineurin/NFAT pathway. Isoproterenol induced nuclear NFATc3/c4 translocation (immunofluorescence), which was suppressed by Epac1 knockdown. Chronic in vivo administration of isoproterenol to guinea pigs reduced I Ks density and KCNE1 mRNA and protein expression while inducing cardiac dysfunction and action potential prolongation. Selective in vivo activation of Epac via sp-8-pCPT-2′-O-Me-cAMP infusion decreased I Ks density and KCNE1 mRNA/protein expression. Conclusions: Prolonged β 1 -adrenoceptor stimulation suppresses I Ks by downregulating KCNE1 mRNA and protein via Epac-mediated Ca 2+ /calcineurin/NFAT signaling. These results provide new insights into the molecular basis of K + channel remodeling under sustained adrenergic stimulation.
Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes
Authors: Gino JE Baart, Bert Zomer, Alex de Haan, Leo A van der Pol, E Coen Beuvery, Johannes Tramper, Dirk E Martens
Journal: Genome biology (2007)

Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years.Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested successfully in batch and chemostat cultures.The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature.
Weight Change in Diabetes and Glycemic and Blood Pressure Control
Authors: Adrianne C. Feldstein, Gregory A. Nichols, David H. Smith, Victor J. Stevens, Keith Bachman, A. Gabriela Rosales, Nancy Perrin
Journal: Diabetes Care (2008)

Weight loss in type 2 diabetes is undisputedly important, and data from community settings are limited. We evaluated weight change and resulting glycemic and blood pressure control in type 2 diabetic patients at an HMO.Using electronic medical records, this retrospective cohort study identified 2,574 patients aged 21-75 years who received a new diagnosis of type 2 diabetes between 1997 and 2002. We estimated 3-year weight trajectories using growth curve analyses, grouped similar trajectories into four categories using cluster analysis, compared category characteristics, and predicted year-4 above-goal A1C and blood pressure by group.The weight-trajectory groups were defined as higher stable weight (n = 418; 16.2%), lower stable weight (n = 1,542; 59.9%), weight gain (n = 300; 11.7%), and weight loss (n = 314; 12.2%). The latter had a mean weight loss of 10.7 kg (-9.8%; P < 0.001) by 18 months, with near-complete regain by 36 months. After adjusting for age, sex, baseline control, and related medication use, those with higher stable weight, lower stable weight, or weight-gain patterns were more likely than those who lost weight to have above-goal A1C (odds ratio [OR] 1.66 [95% CI 1.12-2.47], 1.52 [1.08-2.14], and 1.77 [1.15-2.72], respectively). Those with higher stable weight or weight-gain patterns were more likely than those who lost weight to have above-goal blood pressure (1.83 [1.31-2.57] and 1.47 [1.03-2.10], respectively).A weight-loss pattern after new diagnosis of type 2 diabetes predicted improved glycemic and blood pressure control despite weight regain. The initial period postdiagnosis may be a critical time to apply weight-loss treatments to improve risk factor control.
Cyclophosphamide Synergizes with Type I Interferons through Systemic Dendritic Cell Reactivation and Induction of Immunogenic Tumor Apoptosis
Authors: Giovanna Schiavoni, Antonella Sistigu, Mara Valentini, Fabrizio Mattei, Paola Sestili, Francesca Spadaro, Massimo Sanchez, Silvia Lorenzi, Maria Teresa D'Urso, Filippo Belardelli, Lucia Gabriele, Enrico Proietti, Laura Bracci
Journal: Cancer Research (2010)

Successful chemotherapy accounts for both tumor-related factors and host immune response. Compelling evidence suggests that some chemotherapeutic agents can induce an immunogenic type of cell death stimulating tumor-specific immunity. Here, we show that cyclophosphamide (CTX) exerts two types of actions relevant for the induction of antitumor immunity in vivo: (i) effect on dendritic cell (DC) homeostasis, mediated by endogenous type I interferons (IFN-I), leading to the preferential expansion of CD8α(+) DC, the main subset involved in the cross-presentation of cell-derived antigens; and (ii) induction of tumor cell death with clear-cut immunogenic features capable of stimulating tumor infiltration, engulfment of tumor apoptotic material, and CD8 T-cell cross-priming by CD8α(+) DC. Notably, the antitumor effects of CTX were efficiently amplified by IFN-I, the former providing a source of antigen and a "resetting" of the DC compartment and the latter supplying optimal costimulation for T-cell cross-priming, resulting in the induction of a strong antitumor response and tumor rejection. These results disclose new perspectives for the development of targeted and more effective chemoimmunotherapy treatments of cancer patients.
Remarks on the Treatment of Gunshot-Wounds of the Abdomen in Relation to Modern Peritoneal Surgery
Authors: J. M. Sims
Journal: BMJ (1881)

Con lz-tded fromz jSage 926 of lav!t memwber.]LAPAROTOMY and cystorraphy were advocated by Vincent of Lyons, at the International Medical Congress.The bladder has been wounded in ovariotomy and in extirpation of uterine
PI3K signaling and miRNA expression during the response of quiescent human fibroblasts to distinct proliferative stimuli.
Authors: Jian Gu, Vishwanath R Iyer
Journal: Genome biology (2006)

Abstract Background Serum treatment of quiescent human dermal fibroblasts induces proliferation, coupled with a complex physiological response that is indicative of their normal role in wound-healing. However, it is not known to what extent such complex transcriptional events are specific to a given cell type and signal, and how these global changes are coordinately regulated. We have profiled the global transcriptional program of human fibroblasts from two different tissue sources to distinct growth stimuli, and identified a striking conservation in their gene-expression signatures. Results We found that the wound-healing program of gene expression was not specific to the response of dermal fibroblasts to serum but was regulated more broadly. However, there were specific differences among different stimuli with regard to signaling pathways that mediate these transcriptional programs. Our data suggest that the PI3-kinase pathway is differentially involved in mediating the responses of cells to serum as compared with individual peptide growth factors. Expression profiling indicated that let7 and other miRNAs with similar expression profiles may be involved in regulating the transcriptional program in response to proliferative signals. Conclusion This study provides insights into how different stimuli use distinct as well as conserved signaling and regulatory mechanisms to mediate genome-wide transcriptional reprogramming during cell proliferation. Our results indicate that conservation of transcriptional programs and their regulation among different cell types may be much broader than previously appreciated.
Native type II collagen-induced arthritis in the rat. I. Incidence and humoral response to collagen.
Authors: K Morgan, R B Clague, M J Shaw, P J Holt
Journal: Annals of the Rheumatic Diseases (1980)

An acute inflammatory arthritis has been induced in 76% of rats injected intradermally with native bovine type II collagen emulsified in Freund's complete (CFA) or incomplete (ICFA) adjuvant. The arthritis became chronic in 14 out of 31 rats, and ear and tail lesions were noted in some rats. No arthritis was induced by native type I collagen, denatured type II collagen, rabbit IgG, or buffer alone injected intradermally with adjuvant. Using a solid-phase radioimmunoassay for serum antibodies we have shown that IgM and IgG levels to native bovine type II collagen were significantly higher in arthritic than nonarthritic rats. Antiglobulin antibody levels were not raised in arthritic rats. Equivalent antibody levels to native type II collgen were obtained whether this antigen was emulsified in ICFA or CFA. However, native type I collagen produced high antibody levels only when emulsified in CFA, indicating a difference in the immunogenicity of these collagens. These studies suggest that native type II collagen possesses arthritogenic properties in the rat and that humoral immunity may play a role in the induction of this arthritis.
Impact of Diabetes on Cardiac Sympathetic Innervation in Patients With Heart Failure
Authors: Stefania Paolillo, Giuseppe Rengo, Gennaro Pagano, Teresa Pellegrino, Gianluigi Savarese, Grazia D. Femminella, Marianna Tuccillo, Antonio Boemio, Emilio Attena, Roberto Formisano, Laura Petraglia, Francesco Scopacasa, Gennaro Galasso, Dario Leosco, Bruno Trimarco, Alberto Cuocolo, Pasquale Perrone-Filardi
Journal: Diabetes Care (2013)

Impaired parasympathetic and sympathetic nervous system activity have been demonstrated in patients with diabetes mellitus (DM) and correlated with worse prognosis. Few data are available on the effect of DM on cardiac neuropathy in heart failure (HF). The aim of the current study was to assess cardiac sympathetic activity in HF patients with and without DM.Patients with severe HF (n = 75), with (n = 37) and without DM (n = 38), and 14 diabetic patients with normal cardiac function underwent (123)I meta-iodobenzylguanidine scintigraphy from which early and late heart-to-mediastinum (H/M) ratios were calculated. Clinical, echocardiographic, and biochemical data were measured.DM compared with non-DM patients showed significantly lower early (1.65 ± 0.21 vs. 1.75 ± 0.21; P < 0.05) and late H/M ratios (1.46 ± 0.22 vs. 1.58 ± 0.24; P < 0.03). Early and late H/M were significantly higher in DM patients without HF (2.22 ± 0.35 and 1.99 ± 0.24, respectively) than HF patients with (P < 0.0001) and without (P < 0.0001) DM. In HF patients, an inverse correlation between early or late H/M ratio and hemoglobin A1c (HbA1c) (Pearson = -0.473, P = 0.001; Pearson = -0.382, P = 0.001, respectively) was observed. In DM, in multivariate analysis, HbA1c and ejection fraction remained significant predictors of early H/M; HbA1c remained the only significant predictor of late H/M. No correlation between early or late H/M and HbA1c was found in non-DM patients.Diabetic patients with HF show lower cardiac sympathetic activity than HF patients not having DM or than DM patients with a similar degree of autonomic dysfunction not having HF. HbA1c correlated with the degree of reduction in cardiac sympathetic activity.
Immunobiological Characterization of Cancer Stem Cells Isolated from Glioblastoma Patients
Authors: Tiziano Di Tomaso, Stefania Mazzoleni, Ena Wang, Gloria Sovena, Daniela Clavenna, Alberto Franzin, Pietro Mortini, Soldano Ferrone, Claudio Doglioni, Francesco M. Marincola, Rossella Galli, Giorgio Parmiani, Cristina Maccalli
Journal: Clinical Cancer Research (2010)

Cancer stem cells (CSC) have been isolated from human tumors, including glioblastoma multiforme (GBM). The aims of this study were the immunobiological characterization of GBM CSCs and the assessment of whether these cells represent suitable targets for immunotherapy.GBM CSC lines and their fetal bovine serum (FBS)-cultured non-CSC pair lines were generated and examined by flow cytometry for expression of known tumor antigens, MHC-I and MHC-II molecules, antigen-processing machinery components, and NKG2D ligands. In addition, immunogenicity and immunosuppression of such cell lines for autologous or allogeneic T lymphocytes were tested by cytokine secretion (ELISPOT) or proliferation (carboxyfluorescein diacetate succinimidyl ester) assays, respectively.Both GBM CSC and FBS lines were weakly positive and negative for MHC-I, MHC-II, and NKG2D ligand molecules, respectively. Antigen-processing machinery molecules were also defective in both cell types. Upregulation of most molecules was induced by IFNs or 5-Aza deoxycytidine, although more efficiently in FBS than in CSCs. Patient T-cell responses, mediated by both TH1 and the TH2 subsets, against autologous CSC could be induced in vitro. In addition, CSC but not their paired FBS tumor lines inhibited T-cell proliferation of healthy donors. Notably, a differential gene signature that was confirmed at the protein levels for some immunologic-related molecules was also found between CSC and FBS lines.These results indicate lower immunogenicity and higher suppressive activity of GBM CSC compared with FBS lines. The immunogenicity, however, could be rescued by immune modulation leading to anti-GBM T cell-mediated immune response.
An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode
Authors: Andrea Doni, Tiziana Musso, Diego Morone, Antonio Bastone, Vanessa Zambelli, Marina Sironi, Carlotta Castagnoli, Irene Cambieri, Matteo Stravalaci, Fabio Pasqualini, Ilaria Laface, Sonia Valentino, Silvia Tartari, Andrea Ponzetta, Virginia Maina, Silvia S. Barbieri, Elena Tremoli, Alberico L. Catapano, Giuseppe D. Norata, Barbara Bottazzi, Cecilia Garlanda, Alberto Mantovani
Journal: The Journal of Experimental Medicine (2015)

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.