tbuckley/cabot-search huggingface dataset:
Serum immunoreactive leptin concentration and its relation to the body fat content in chronic renal failure.
Authors: O Heimbürger, F Lönnqvist, A Danielsson, J Nordenström, P Stenvinkel
Journal: Journal of the American Society of Nephrology (1997)

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. The role of leptin in humans has been only partly revealed. However, obese patients have markedly elevated levels of this hormone, and in both normal-weight and obese subjects there is a direct correlation between serum leptin levels and the percentage of body fat. The aim of the present study was to investigate the role of leptin and its relation to body fat content in chronic renal failure (CRF), a disorder associated with decreased appetite. Serum leptin levels and body composition (dual-energy x-ray absorptiometry) were measured in a cohort of 59 patients with terminal CRF (creatinine clearance rate, 8 +/- 1 ml/min). Sixteen of the patients were re-evaluated after 12 mo of peritoneal dialysis treatment, and eight patients were re-evaluated after 12 mo of hemodialysis treatment. The mean serum leptin concentrations were markedly higher (mean +/- SEM) in patients with CRF than in healthy control subjects matched for gender and body mass index (25.7 +/- 5.2 ng/ml versus 8.4 +/- 0.9 ng/ml; P < 0.001). Patients with ongoing signs of inflammation (C-reactive protein > 10 mg/L) demonstrated higher serum leptin levels (41.9 +/- 13.7 ng/ml versus 18.6 +/- 4.2 ng/ml; P < 0.05) than patients with normal C-reactive protein. A strong positive correlation (rho = 0.83; P < 0.0001) was found between serum leptin concentrations and the percentage of body fat. After 12 mo of peritoneal dialysis, the amount of body fat increased markedly (19.0 +/- 1.5 to 25.1 +/- 2.2 kg; P < 0.001), and the changes in serum leptin concentrations correlated significantly (rho = 0.69; P < 0.01) to the changes in the body fat content. In contrast, no significant changes in either body fat content or serum leptin levels were recorded in the eight patients that were re-evaluated after 12 mo of hemodialysis. Serum leptin concentrations are approximately three times higher in patients with CRF compared with healthy control subjects with a similar body mass index. In this study, it is also demonstrated that serum leptin is a good marker for the body fat content in CRF patients and correlates strongly to changes in body fat during 12 mo of peritoneal dialysis. These findings suggest that serum leptin could serve as a valuable clinical marker for the body fat content in patients with CRF. Further studies are needed to verify the hypothesis that increased serum leptin concentrations may contribute to uremic anorexia.
Biomarkers Predict Progression of Acute Kidney Injury after Cardiac Surgery
Authors: Jay L. Koyner, Amit X. Garg, Steven G. Coca, Kyaw Sint, Heather Thiessen-Philbrook, Uptal D. Patel, Michael G. Shlipak, Chirag R. Parikh
Journal: Journal of the American Society of Nephrology (2012)

Being able to predict whether AKI will progress could improve monitoring and care, guide patient counseling, and assist with enrollment into trials of AKI treatment. Using samples from the Translational Research Investigating Biomarker Endpoints in AKI study (TRIBE-AKI), we evaluated whether kidney injury biomarkers measured at the time of first clinical diagnosis of early AKI after cardiac surgery can forecast AKI severity. Biomarkers included urinary IL-18, urinary albumin to creatinine ratio (ACR), and urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL); each measurement was on the day of AKI diagnosis in 380 patients who developed at least AKI Network (AKIN) stage 1 AKI. The primary end point (progression of AKI defined by worsening AKIN stage) occurred in 45 (11.8%) patients. Using multivariable logistic regression, we determined the risk of AKI progression. After adjustment for clinical predictors, compared with biomarker values in the lowest two quintiles, the highest quintiles of three biomarkers remained associated with AKI progression: IL-18 (odds ratio=3.0, 95% confidence interval=1.3-7.3), ACR (odds ratio=3.4, 95% confidence interval=1.3-9.1), and plasma NGAL (odds ratio=7.7, 95% confidence interval=2.6-22.5). Each biomarker improved risk classification compared with the clinical model alone, with plasma NGAL performing the best (category-free net reclassification improvement of 0.69, P<0.0001). In conclusion, biomarkers measured on the day of AKI diagnosis improve risk stratification and identify patients at higher risk for progression of AKI and worse patient outcomes.
Exogenously Regulated Stem Cell-Mediated Gene Therapy for Bone Regeneration
Authors: Ioannis K. Moutsatsos, Gadi Turgeman, Shuanhu Zhou, Basan Gowda Kurkalli, Gadi Pelled, Liat Tzur, Pamela Kelley, Natalie Stumm, Sha Mi, Ralph Müller, Yoram Zilberman, Dan Gazit
Journal: Molecular Therapy (2001)

Regulated expression of transgene production and function is of great importance for gene therapy. Such regulation can potentially be used to monitor and control complex biological processes. We report here a regulated stem cell-based system for controlling bone regeneration, utilizing genetically engineered mesenchymal stem cells (MSCs) harboring a tetracycline-regulated expression vector encoding the osteogenic growth factor human BMP-2. We show that doxycycline (a tetracycline analogue) is able to control hBMP-2 expression and thus control MSC osteogenic differentiation both in vitro and in vivo. Following in vivo transplantation of genetically engineered MSCs, doxycycline administration controlled both bone formation and bone regeneration. Moreover, our findings showed increased angiogenesis accompanied by bone formation whenever genetically engineered MSCs were induced to express hBMP-2 in vivo. Thus, our results demonstrate that regulated gene expression in mesenchymal stem cells can be used as a means to control bone healing.
Integrin-Mediated Transcriptional Activation of Inhibitor of Apoptosis Proteins Protects Smooth Muscle Cells Against Apoptosis Induced by Degraded Collagen
Authors: Karin von Wnuck Lipinski, Petra Keul, Nicola Ferri, Susann Lucke, Gerd Heusch, Jens W. Fischer, Bodo Levkau
Journal: Circulation Research (2006)

Apoptosis of smooth muscle cells (SMC) and degradation of the extracellular matrix (ECM) have both been implicated in atherosclerotic plaque rupture. We have previously reported that degraded type I collagen fragments induce a rapid but transient apoptotic burst initiated by calpains in SMC. The aim of the current study was to identify the pathway responsible for consecutive SMC survival. We show that exposure of SMC to collagen fragments resulted in a sustained activation of nuclear factor (NF)-kappaB via phosphorylation and degradation of IkappaBalpha. Its prevention through retroviral expression of superrepressor IkappaBalpha or proteasome inhibition potently induced apoptosis. In the presence of blocking antibodies to alpha(v)beta(3) integrin and RGD peptides, collagen fragments no longer activated NF-kappaB and apoptosis was enhanced. The mechanism by which NF-kappaB was protecting SMC against collagen fragment-induced apoptosis was a transcriptional activation of several endogenous caspase inhibitors of the inhibitor of apoptosis protein (IAP) family as: (1) the expression of xIAP, c-IAP2, and survivin was potently induced by collagen fragments; (2) IAP expression was abrogated by superrepressor IkappaBalpha; and (3) knockdown of each of the 3 IAPs by small interfering RNA (siRNA) resulted in enhanced apoptosis after collagen fragment treatment. Our data suggest that SMC exposed to degraded collagen are protected against apoptosis by a mechanism involving alpha(v)beta(3)-dependent NF-kappaB activation with consequent activation of IAPs. This may constitute a novel antiapoptotic pathway ensuring SMC survival in settings of enhanced ECM degradation such as cell migration, vascular remodeling, and atherosclerotic plaque rupture.
Eosinophils generate brominating oxidants in allergen-induced asthma
Authors: Weijia Wu, Michael K. Samoszuk, Suzy A.A. Comhair, Mary Jane Thomassen, Carol F. Farver, Raed A. Dweik, Mani S. Kavuru, Serpil C. Erzurum, Stanley L. Hazen
Journal: Journal of Clinical Investigation (2000)

Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific "molecular fingerprint" for proteins modified through the eosinophil peroxidase-H2O2 system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase. Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans.
Protein C inhibitor regulates hepatocyte growth factor activator-mediated liver regeneration in mice
Authors: T Hamada, H Kamada, T Hayashi, J Nishioka, E C Gabazza, S Isaji, S Uemoto, K Suzuki
Journal: Gut (2007)

We recently reported that human protein C inhibitor (PCI), a major inhibitor of activated protein C (APC), inhibits hepatocyte growth factor activator (HGFA) by forming HGFA-PCI complexes in vitro. In this study, we evaluated whether PCI regulates HGFA-mediated liver regeneration in a human PCI gene transgenic (hPCI-Tg) mouse model.After partial hepatectomy in hPCI-Tg and wild-type (WT) mice, the degree of liver regeneration, protein and mRNA expression of HGFA, proHGF activation, plasma levels of PCI and HGFA-PCI complex, and other markers were evaluated in the remnant liver. We also evaluated the effect of anti-human PCI antibody on liver regeneration, which significantly decreased in hPCI-Tg mice compared to WT mice. HGFA mRNA levels in naive and remnant livers after hepatectomy were the same in both WT and hPCI-Tg mice; however, plasma HGFA levels and HGF activation in the liver were lower in hPCI-Tg than in WT mice. There was no difference in plasma levels of transaminases and inflammatory cytokines. However, sinusoidal congestion and bleeding were detected and the serum hyaluronic acid level was elevated in hPCI-Tg mice, indicating that human PCI aggravates sinusoidal injury by inhibiting the cytoprotective effect of APC. APC decreased thrombin-induced IL-6 production in isolated hepatic nonparenchymal cells (NPCs) in vitro. This impaired liver regeneration was reversed by anti-human PCI antibody treatment in vivo.PCI regulates liver regeneration after hepatectomy by forming an HGFA-PCI complex and aggravates hepatic NPC injury by inhibiting the cytoprotective effect of APC. Anti-PCI antibody treatment may be a novel therapy for improving liver regeneration.
Wnt/frizzled signalling modulates the migration and differentiation of immortalized cardiac fibroblasts
Authors: Hilde Laeremans, Sander S. Rensen, Harry C.J. Ottenheijm, Jos F.M. Smits, W. Matthijs Blankesteijn
Journal: Cardiovascular Research (2010)

The Wnt/frizzled (Fzd) signal transduction cascade has been implicated in the proliferation, differentiation, and migration of many cell types, but the role of this pathway in cardiac fibroblast differentiation is not known. Our lab previously showed an up-regulation of Fzd-1 and -2 expression in myofibroblasts after myocardial infarction (MI), indicating a potential role for the Fzd receptor in fibroblast–myofibroblast differentiation. The present study was performed to further define the role of specific Wnt and Fzd proteins in the proliferation, migration, and differentiation of cardiac fibroblasts. Because primary fibroblasts become senescent after a few passages and are difficult to transfect, we immortalized rat cardiac fibroblasts with telomerase [cardiac fibroblasts immortalized with telomerase (CFIT)]. Proliferation of CFIT was not significantly influenced by Wnt/Fzd signalling. The migration, however, was attenuated by all Wnt/Fzd combinations tested. Also, specific Wnt/Fzd combinations modulated the expression of the following myofibroblast markers: collagen Iα1, collagen III, fibronectin and its splice variants, and α-smooth muscle actin. The results indicate that myofibroblast migration and differentiation, but not proliferation, can be modulated by interventions in Wnt/Fzd signalling. Therefore, Wnt/Fzd signalling may serve as a novel therapeutic target to ameliorate wound healing after MI.
A review of pleural fluid TB culture at a large acute UK hospital
Authors: Samal Gunatilake, Suresh Babu, Nuala Whitehead, Michaela Reichmann, Anoop Chauhan
Journal: European Respiratory Journal (2014)

Background  The British Thoracic Society (BTS) recommend pleural fluid TB culture (TBC) should only be requested where there is clinical suspicion of TB pleuritis. Many clinicians request TBC when investigating pleural effusions regardless of clinical suspicion.  Objectives  To examine the sensitivity of pleural fluid TBC in TB patients.  To audit the appropriateness of pleural fluid TBC requests.  To determine if enhanced clinical information increased the utility of TBC.  Method  We assessed pleural fluid from TB patients and clinical information accompanying all pleural fluid TBC requests at our hospital between Jan 2008 and Dec 2012. Clinical information suspecting TB on the request form was considered a high level of suspicion. Absence of information was considered a low level of suspicion.  Results  The prevalence of pleural effusion in TB was low 6/120 (5%). The sensitivity of pleural fluid TBC in cases of TB presenting with a pleural effusion was 33%.  Of 918 pleural fluid samples, 67 (7.3%) had a high clinical suspicion. The positive predictive value (PPV) of pleural fluid TBC with high clinical suspicion was 3% (table 1). The remaining 851 had low clinical suspicion with a negative predictive value of 100%.  Discussion  The prevalence of TB diagnosed by pleural fluid TBC is low (2/918). Clinical suspicion of TB did not significantly improve the PPV. No patients with a low clinical suspicion cultured TB. Our data supports BTS recommendations that pleural fluid TBC should only be requested when TB pleuritis is suspected.
Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma
Authors: Elon H C van Dijk, Carla M L van Herpen, Marina Marinkovic, John B A G Haanen, Drake Amundson, Gré P M Luyten, Martine J Jager, Ellen H W Kapiteijn, Jan E E Keunen, Grazyna Adamus, Camiel J F Boon
Journal: Ophthalmology (2015)
Abnormalities of T lymphocyte subsets in systemic sclerosis demonstrated with anti-CD45RA and anti-CD29 monoclonal antibodies.
Authors: A Kahan, A Kahan, F Picard, C.J Menkès, B Amor
Journal: Annals of the Rheumatic Diseases (1991)

T cell subpopulations were assessed by two colour flow cytometry with phycoerythrin conjugated anti-CD45RA and anti-CD29 and fluorescein conjugated anti-CD4 and anti-CD8 monoclonal antibodies, on peripheral blood lymphocytes from 12 patients with systemic sclerosis and from nine control subjects. The percentage of CD4+CD29+ cells was significantly higher in patients with systemic sclerosis than in controls (mean (SEM) 68.8 (3.1) v 47.9 (4.1) respectively). CD4+CD45RA+ cells were not significantly different in patients and controls. CD8+CD29+ and CD8+CD45RA+ subpopulations were significantly higher in patients with systemic sclerosis than in controls (83.0 (3.2) v 58.7 (6.8) and 80.2 (3.0) v 66.9 (3.2) respectively). The increase in the percentage of CD29+ cells suggests an activation of memory cells in patients with systemic sclerosis, which may play an important part in the pathogenesis of the disease.
Isolation of Human Colon Carcinoma Cells for Resistance to a Single Interferon Associated With Cross-Resistance to Multiple Recombinant Interferons: , beta, and 
Authors: K. Morikawa, R. Morikawa, J. J. Killion, D. Fan, I. J. Fidler
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Isolation of Human Colon Carcinoma Cells for Resistance to a Single Interferon Associated With Cross-Resistance to Multiple Recombinant Interferons: α, β, and γ Get access Kiyoshi Morikawa, Kiyoshi Morikawa Department of Internal Medicine, Iwamizawa Rosai HospitalIwamizawa, Hokkaido, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Reiko Morikawa, Reiko Morikawa Department of Dermatology, Hokkaido School of MedicineSapporo, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Jerald J. Killion, Jerald J. Killion Department of Cell Biology, The University of Texas M. D. Anderson Cancer CenterHouston, TX Search for other works by this author on: Oxford Academic PubMed Google Scholar Dominic Fan, Dominic Fan Department of Cell Biology, The University of Texas M. D. Anderson Cancer CenterHouston, TX Search for other works by this author on: Oxford Academic PubMed Google Scholar Isaiah J. Fidler Isaiah J. Fidler * Department of Cell Biology, The University of Texas M. D. Anderson Cancer CenterHouston, TX *Correspondence to : Isaiah J. Fidler, DVM, Ph.D., Department of Cell Biology (Box 173), The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 6, 21 March 1990, Pages 517–522, https://doi.org/10.1093/jnci/82.6.517 Published: 21 March 1990 Article history Received: 16 October 1989 Revision received: 12 December 1989 Accepted: 19 December 1989 Published: 21 March 1990
Successful treatment with oral alitretinoin in women of childbearing potential with Darier's disease
Authors: M. Zamiri, C.S. Munro
Journal: British Journal of Dermatology (2013)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Alitretinoin (9‐cis‐retinoic acid) is a synthetic vitamin A derivative with immunomodulatory and anti‐inflammatory activity recently licensed as a treatment for refractory chronic hand eczema.1 Here, we report the successful use of oral alitretinoin in two women of childbearing age with Darier's disease (DD). DD (OMIM 124200) is an autosomal dominant disorder of keratinization characterized by multiple discrete or confluent warty papules and plaques in seborrhoeic areas, palmoplantar pits, and distinctive nail dystrophy2 of teenage or adult onset. Histologically, DD lesions show suprabasal acantholysis and dyskeratosis, and ultrastructurally lesions show reduced numbers of desmosomes, disruption of desmosomal complexes and perinuclear aggregates of keratin filaments.3 4 A large spectrum of heterozygous mutations in ATP2A2, encoding the sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2) are responsible for DD. Calcium pumps of the SERCA family have a key role in intracellular signalling by regulating cell–cell adhesion and epidermal differentiation.3 5 6
Membrane attack complex of complement: a structural analysis of its assembly.
Authors: E R Podack, A F Esser, G Biesecker, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1980)

This study was conducted to gain insight into the process of assembly of the membrane attack complex (MAC) of complement through structural analysis. Four intermediate complexes and the MAC were examined by electron microscopy and by sucrose density-gradient ultracentrifugation. The C5b-6 complex has a sedimentation rate of 11S, an elongated, slightly curved shape and dimensions of 160 x 60 x 60 A. At protein concentrattions greater than 1 mg/ml, and physiologic ionic strength and pH, the complex forms paracrystals that have the appearance of parallel strands. Equimolar quantities of C5b-6 and C7 mixed in the absence of lipids or detergents give rise to C5b-7 protein micelles which are soluble in aqueous media and have a sedimentation rate of 36S, suggesting a tetrameric composition. Ultrastructurally, C5b-7 protein micelles consist of four half-rings, each measuring 200 x 50 A, which are connected to one another by short stalks extending from the convex side of the half-rings. C5b-7 bound to dioleoyl lecithin (DOL) vesicles has a similar ultrastructural appearance. After extraction with deoxycholate (DOC), C5b-7 has a sedimentation velocity of 36S which further suggests the occurrence of C5b-7 in the form of tetrameric protein micelles. Attachment of C8 to vesicle-bound C5b-7 results in dissociation of the protein micelles. An individual C5b-8 complex appears as a half-ring attached to the DOL-vesicle via a 100-A-long and 30-A-wide stalk. After extraction from the DOL-vesicles with DOC, C5b-8 has a sedimentation velocity of approximately 18S. Binding of C9 to DOL-vesicle bound C5b-8 induces the formation of the typical ultrastructural complement lesions. C5b-9 extracted from the vesicles with DOC has a sedimentation rate of 33S, which is characteristic of the C5b-9 dimer. It is concluded that dimerization is a function of C9. C5b-9 monomers are visualized when a single C5b-9 complex or an odd number of complexes were bound per DOL-vesicle. The C5b-9 monomer has an ultrastructural appearance that is theoretically expected of a half-dimer: a 200- x 50-A half-ring which is attached to the DOL-vesicle by a 100- x 80-A appendage. Extracted with DOC, the C5b-9 monomer has a sedimentation rate of 23S. At a higher multiplicity of MAC per DOL-vesicle, large structural defects in the lipid bilayer are seen which are attributed to direct physical destruction of membranes by the known lipid-binding capacity of the MAC. It is proposed that protein micelle formation at the C5b-7 stage of MAC assembly and dissociation of these micelles upon binding of C8 are events that facilitate dimerization of C5b-9 and thus MAC formation.
Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction
Authors: Margherita Massa, Vittorio Rosti, Maurizio Ferrario, Rita Campanelli, Isabella Ramajoli, Roberta Rosso, Gaetano M. De Ferrari, Marco Ferlini, Lucio Goffredo, Alessandra Bertoletti, Catherine Klersy, Alessandro Pecci, Remigio Moratti, Luigi Tavazzi
Journal: Blood (2004)