tbuckley/cabot-search huggingface dataset:
Chronic Uremia Induces Permeability Changes, Increased Nitric Oxide Synthase Expression, and Structural Modifications in the Peritoneum
Authors: SOPHIE COMBET, MARIE-LAURE FERRIER, MIEKE VAN LANDSCHOOT, MARIA STOENOIU, PIERRE MOULIN, TOSHIO MIYATA, NORBERT LAMEIRE, OLIVIER DEVUYST
Journal: Journal of the American Society of Nephrology (2001)

Advanced glycation end products (AGE), growth factors, and nitric oxide contribute to alterations of the peritoneum during peritoneal dialysis (PD). These mediators are also involved in chronic uremia, a condition associated with increased permeability of serosal membranes. It is unknown whether chronic uremia per se modifies the peritoneum before PD initiation. A rat model of subtotal nephrectomy was used to measure peritoneal permeability after 3, 6, and 9 wk, in parallel with peritoneal nitric oxide synthase (NOS) isoform expression and activity and structural changes. Uremic rats were characterized by a higher peritoneal permeability for small solutes and an increased NOS activity due to the up-regulation of endothelial and neuronal NOS. The permeability changes and increased NOS activities correlated with the degree of renal failure. Focal areas of vascular proliferation and fibrosis were detected in uremic rats, in relation with a transient up-regulation of vascular endothelial growth factor and basic fibroblast growth factor, as well as vascular deposits of the AGE carboxymethyllysine and pentosidine. Correction of anemia with erythropoietin did not prevent the permeability or structural changes in uremic rats. Thus, in this rat model, uremia induces permeability and structural changes in the peritoneum, in parallel with AGE deposits and up-regulation of specific NOS isoforms and growth factors. These data suggest an independent contribution of uremia in the peritoneal changes during PD and offer a paradigm to better understand the modifications of serosal membranes in uremia.
Functional neurokinin 1 receptors for substance P are expressed by human vascular endothelium.
Authors: E W Greeno, P Mantyh, G M Vercellotti, C F Moldow
Journal: The Journal of Experimental Medicine (1993)

Substance P (SP), a neurotachykinin, is important in a number of inflammatory processes in which the endothelial cell also plays a critical role. SP receptors have previously been identified only on arterial endothelium, and the scant in vitro evidence for direct effects of SP on human endothelium is based on studies using nonarterial cells. To better understand SP's role in inflammation, we sought to identify functional SP receptors on human endothelium in situ and in culture. Autoradiographic ligand binding to human umbilical cord sections demonstrates the presence of SP binding sites with characteristics of the neurokinin 1 (NK-1) receptor (displacement by GTP analogues and the NK-1 specific antagonist CP-96,345) on human umbilical arterial, but not venous, endothelium. In culture, human umbilical venous endothelial cells (HUVECs) and human aortic endothelial cells express low levels of available SP binding sites. However, HUVECs, which are serum starved and refed, undergo a dramatic increase in SP binding. SP binding to starved/refed HUVECs induces a transient increase in intracellular calcium. This calcium flux is dose dependent over appropriate SP concentrations and can be blocked by NK-1 specific antagonists. The proinflammatory effects of SP may be mediated in part through the NK-1 receptor on endothelium.
Isoaspartate-Glycine-Arginine: A New Tumor Vasculature–Targeting Motif
Authors: Flavio Curnis, Angelina Sacchi, Anna Gasparri, Renato Longhi, Angela Bachi, Claudio Doglioni, Claudio Bordignon, Catia Traversari, Gian-Paolo Rizzardi, Angelo Corti
Journal: Cancer Research (2008)

Abstract Asparagine deamidation in peptides or in fibronectin fragments containing the asparagine-glycine-arginine sequence generates isoaspartate-glycine-arginine (isoDGR), a new αvβ3 integrin-binding motif. Because αvβ3 is expressed in angiogenic vessels, we hypothesized that isoDGR-containing peptides could be exploited as ligands for targeted delivery of drugs to tumor neovasculature. We found that a cyclic CisoDGRC peptide coupled to fluorescent nanoparticles (quantum dots) could bind αvβ3 integrin and colocalize with anti-CD31, anti-αvβ3, and anti-α5β1 antibodies in human renal cell carcinoma tissue sections, indicating that this peptide could efficiently recognize endothelial cells of angiogenic vessels. Using CisoDGRC fused to tumor necrosis factor α (TNF) we observed that ultralow doses (1–10 pg) of this product (called isoDGR-TNF), but not of TNF or CDGRC-TNF fusion protein, were sufficient to induce antitumor effects when administered alone or in combination with chemotherapy to tumor-bearing mice. The antitumor activity of isoDGR-TNF was efficiently inhibited by coadministration with an excess of free CisoDGRC, as expected for ligand-directed targeting mechanisms. These results suggest that isoDGR is a novel tumor vasculature–targeting motif. Peptides containing isoDGR could be exploited as ligands for targeted delivery of drugs, imaging agents, or other compounds to tumor vasculature. [Cancer Res 2008;68(17):7073–82]
Analysis of sputum in COPD
Authors: P MAESTRELLI
Journal: Thorax (2001)

A number of studies have suggested a pathogenetic role for airway inflammation in the induction of both chronic sputum production and chronic airflow obstruction in smokers.1 It is therefore important to characterise and quantify inflammatory changes in the assessment of subjects with chronic obstructive pulmonary disease (COPD). Assessment of inflammation may be achieved by different means including invasive methods such as bronchial biopsies, bronchoalveolar lavage (BAL) or examination of surgical specimens and non-invasive methods such as spontaneous or induced sputum.

The induction of sputum by inhalation of hypertonic saline is a safe, reliable, and relatively non-invasive method in COPD, provided the technique is performed in a standardised way and measures are used to prevent adverse reactions.2-4 Induced sputum differs from spontaneous sputum by having a higher number of viable cells and less squamous cell contamination.3 There are no differences between spontaneous and induced samples from patients with COPD or asthma in the total and differential cell counts, but there is poor agreement in the fluid phase components.5 6 

Bronchial biopsies and BAL can be performed in COPD for investigative use according to the published recommendations.7 8 When the different methods of assessing airway inflammation are compared in the same subjects, a different profile of inflammatory cells is obtained depending on the compartment of the lung examined by each technique—that is, the lumen of the central airways using sputum analysis,9 the airway wall using bronchial biopsies, and the peripheral airways using BAL.10 By combining these techniques, integrated and comprehensive information on cell traffic and inflammatory processes in COPD at different levels of the airway can be obtained. Analysis of induced or spontaneous sputum has contributed to the identification of smokers susceptible to developing COPD, to the characterisation of the inflammatory process during exacerbations, and …
Adenovirus-specific immunoglobulin G maturation in acute exacerbations of COPD
Authors: Lucas Boeck, Mikael Gencay, Michael Roth, Hans Hirsch, Mirjam Christ-Crain, Beat Müller, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2013)

Background: B-cells in airways and lung parenchyma gained importance in COPD pathogenesis. So far, responsible antigenic epitopes remain unknown. Pathogens may drive a beneficial as well as a harmful antibody response.  Objectives: To investigate maturation of adenovirus-specific immunoglobulins in COPD patients in respect to clinical outcome.  Methods: The presence of adenovirus-specific immunoglobulins during acutely exacerbated COPD (AECOPD) was analyzed at exacerbation and 2-3 weeks later. Patients with detectable adenovirus-specific IgM and low IgG avidity were grouped into fast and delayed IgG maturation, depending on IgG avidity 2-3 weeks after AECOPD.  Results: Out of 208 patients, 43 patients (20.7%) had serologic evidence of recent adenovirus infection and were sub-grouped into 26 patients with fast IgG maturation and 17 patients with delayed IgG maturation. Baseline characteristics, AECOPD therapy, and duration of hospitalization were similar in both groups. However, the AECOPD recurrence rate within six months was significantly higher in patients with delayed IgG maturation (p = 0.003, figure), whereas the AECOPD related re-hospitalization rate did not differ (p = 0.061). The time to re-hospitalization or death within two years was significantly shorter in patients with delayed IgG maturation (p = 0.003).  Conclusions: Delayed immunoglobulin avidity maturation, following COPD exacerbation, is associated with poor outcome.
How “healthy” should children be when selecting reference samples for spirometry?
Authors: Sooky Lum, Vassiliki Bountziouka, Samatha Sonnappa, Tim J. Cole, Rachel Bonner, Janet Stocks
Journal: European Respiratory Journal (2015)

How “healthy” do children need to be when selecting reference samples for spirometry? Anthropometry and spirometry were measured in an unselected, multi-ethnic population of school children aged 5–11 years in London, UK, with follow-up assessments 12 months later. Parents provided information on children's birth data and health status. Forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were adjusted for sex, age, height and ethnicity using the 2012 Global Lungs Initiative equations, and the effects of potential exclusion criteria on the z-score distributions were examined. After exclusions for current and chronic lung disease, acceptable data were available for 1901 children on 2767 occasions. Healthy children were defined as those without prior asthma or hospitalisation for respiratory problems, who were born at full-term with a birthweight ≥2.5 kg and who were asymptomatic at testing. Mean± sd z-scores for FEV 1 and FVC approximated 0±1, indicating the 2012 Global Lungs Initiative equations were appropriate for this healthy population. However, if children born preterm or with low birthweight, children with prior asthma or children mildly symptomatic at testing were included in the reference, overall results were similar to those for healthy children, while increasing the sample size by 25%. With the exception of clear-cut factors, such as current and chronic respiratory disease, paediatric reference samples for spirometry can be relatively inclusive and hence more generalisable to the target population.
Expression of the splicing regulator polypyrimidine tract-binding protein in normal and neoplastic brain
Authors: Ian E. McCutcheon, Stephen J. Hentschel, Gregory N. Fuller, Wei Jin, Gilbert J. Cote
Journal: Neuro-Oncology (2004)

Polypyrimidine tract-binding protein (PTB) is a nuclear factor that binds to the polypyrimidine tract of premRNA introns, where it is associated with negative regulation of RNA splicing and with exon silencing. We have previously demonstrated that PTB expression is increased during glial cell transformation and that this increase correlates with changes in the RNA splicing of the fibroblast growth factor receptor 1. In this paper we examine the specific cellular distribution of PTB expression in normal brain and in glial and neuronal tumors. Paraffin sections were stained by using a primary monoclonal antibody against PTB. Tissues that were analyzed included normal brain (n = 2) and tumors of various types (low-grade astrocytoma, n = 2; anaplastic astrocytoma, n = 2; glioblastoma, n = 4; medulloblastoma, n = 4; central neurocytoma, n = 2; dysplastic gangliocytoma, n = 1; ganglioglioma, n = 1; paraganglioma, n = 1). In glial cell populations the majority of astrocytes and oligodendrocytes were negative, but occasional positively staining cells were observed. Strongly positive PTB staining was observed in ependymocytes, choroid plexus epithelium, microglia, arachnoid membrane, and adenohypophysis, and weak staining was found in the neurohypophysis. In all cases vascular endothelium and smooth muscle stained strongly. In tumor samples, intense positive nuclear staining was observed in transformed cells of low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, medulloblastoma, paraganglioma, and the glial population of both ganglioglioma and dysplastic gangliocytoma (the neuronal cells of both were negative). In medulloblastoma, neoplastic neuronal cells were positive, as were other cell lineages. In normal brain, all neuron populations and pineocytes were negative for PTB. We conclude that although glial cells show derepression of PTB expression, a similar mechanism is absent in both nonneoplastic neurons and in most neuronally derived tumor cells. Strong upregulation of PTB expression in tumor cells of glial or primitive neuroectodermal origin suggests involvement of this protein in cellular transformation. Whether PTB affects splicing of RNAs critical to cellular transformation or proliferation is an important question for future research.
Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus
Authors: Peter A Banks, Thomas L Bollen, Christos Dervenis, Hein G Gooszen, Colin D Johnson, Michael G Sarr, Gregory G Tsiotos, Santhi Swaroop Vege
Journal: Gut (2012)

<h3>Background and objective</h3> The Atlanta classification of acute pancreatitis enabled standardised reporting of research and aided communication between clinicians. Deficiencies identified and improved understanding of the disease make a revision necessary. <h3>Methods</h3> A web-based consultation was undertaken in 2007 to ensure wide participation of pancreatologists. After an initial meeting, the Working Group sent a draft document to 11 national and international pancreatic associations. This working draft was forwarded to all members. Revisions were made in response to comments, and the web-based consultation was repeated three times. The final consensus was reviewed, and only statements based on published evidence were retained. <h3>Results</h3> The revised classification of acute pancreatitis identified two phases of the disease: early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis, the most common form, has no organ failure, local or systemic complications and usually resolves in the first week. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ failure &gt;48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). We present a standardised template for reporting CT images. <h3>Conclusions</h3> This international, web-based consensus provides clear definitions to classify acute pancreatitis using easily identified clinical and radiologic criteria. The wide consultation among pancreatologists to reach this consensus should encourage widespread adoption.
Identification of a Soluble Form of B7-H1 That Retains Immunosuppressive Activity and Is Associated with Aggressive Renal Cell Carcinoma
Authors: Xavier Frigola, Brant A. Inman, Christine M. Lohse, Christopher J. Krco, John C. Cheville, R. Houston Thompson, Bradley Leibovich, Michael L. Blute, Haidong Dong, Eugene D. Kwon
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Release of inhibitory coregulatory proteins into the circulation may represent one mechanism by which tumors thwart immune responses. Our objective was to determine whether soluble B7-H1 (sB7-H1) levels in patients with clear cell renal cell carcinoma (ccRCC) are associated with pathologic features and patient outcome. Experimental Design: We developed an ELISA for quantification of sB7-H1 in biological fluids. Biochemical confirmation of the measured analyte as sB7-H1 was done by protein microsequencing using supernates from tumor cell lines. Biological activity of sB7-H1 was assessed in vitro utilizing T-cell apoptosis assays. We tested sB7-H1 levels in the sera from 172 ccRCC patients and correlated sB7-H1 levels with pathologic features and patient outcome. Results: sB7-H1 was detected in the cell supernatants of some B7-H1–positive tumor cell lines. Protein sequencing established that the measured sB7-H1 retained its receptor-binding domain and could deliver proapoptotic signals to T cells. Higher preoperative sB7-H1 levels were associated with larger tumors (P &amp;lt; 0.001), tumors of advanced stage (P = 0.017) and grade (P = 0.044), and tumors with necrosis (P = 0.003). A doubling of sB7-H1 levels was associated with a 41% increased risk of death (P = 0.010). Conclusion: Our observations suggest that sB7-H1 may be detected in the sera of ccRCC patients and that sB7-H1 may systemically impair host immunity, thereby fostering cancer progression and subsequent poor clinical outcome. Clin Cancer Res; 17(7); 1915–23. ©2011 AACR.
Applications of Proteomics to Lab Diagnosis
Authors: Raghothama Chaerkady, Akhilesh Pandey
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Detailed and comprehensive characterization of proteins is a major goal of proteomics. This goal has become more realistic today with the latest high-resolution mass spectrometers capable of faster sequencing in a high-throughput fashion and with the emergence of new techniques such as protein and peptide microarrays. A promising area for discovery is the application of these advanced mass spectrometric and other quantitative proteomic methodologies to laboratory diagnosis. This review focuses on the role of proteomics in the development of new laboratory diagnostics and the implications for routine diagnosis and monitoring of diseases.
The Role and Regulation of Adenosine in the Central Nervous System
Authors: Thomas V. Dunwiddie, Susan A. Masino
Journal: Annual Review of Neuroscience (2001)

Adenosine is a modulator that has a pervasive and generally inhibitory effect on neuronal activity. Tonic activation of adenosine receptors by adenosine that is normally present in the extracellular space in brain tissue leads to inhibitory effects that appear to be mediated by both adenosine A1 and A2A receptors. Relief from this tonic inhibition by receptor antagonists such as caffeine accounts for the excitatory actions of these agents. Characterization of the effects of adenosine receptor agonists and antagonists has led to numerous hypotheses concerning the role of this nucleoside. Previous work has established a role for adenosine in a diverse array of neural phenomena, which include regulation of sleep and the level of arousal, neuroprotection, regulation of seizure susceptibility, locomotor effects, analgesia, mediation of the effects of ethanol, and chronic drug use.
Phlegmonous gastritis: an unusual presenting symptom of Sjogren's syndrome.
Authors: M L van Leeuwen, H L Tjiong, M van Blankenstein, A H Mulder, C M Bakker
Journal: Gut (1993)

This case report describes the histological and macroscopic changes seen within a few months in the gastric mucosa of a 28 year old woman patient with upper abdominal symptoms. With hindsight these changes were the first signs of Sjögren9s syndrome.
Nifuratel Compared with Metronidazole in the Treatment of Trichomonal Vaginitis
Authors: B. A. Evans, R. D. Catterall
Journal: BMJ (1970)

Nifuratel (Magmilor) was compared with metronidazole (Flagyl) in the treatment of trichomonal vaginitis by a randomized double-blind trial. Only 18 out of 47 patients (38%) treated with nifuratel were found to be cured, whereas 42 out of 49 patients (85%) treated with metronidazole were cured. Severe reactions, necessitating withdrawal of treatment, occurred in three patients treated with nifuratel. There were no serious side-effects with metronidazole. The results of this trial indicate that nifuratel is not a satisfactory substitute for metronidazole in the treatment of trichomoniasis.
Accessing Complexity: The Dynamics of Virus-Specific T Cell Responses
Authors: Peter C. Doherty, Jan P. Christensen
Journal: Annual Review of Immunology (2000)

The cellular dynamics of the immune system are complex and difficult to measure. Access to this problematic area has been greatly enhanced by the recent development of tetrameric complexes of MHC class I glycoprotein + peptide (tetramers) for the direct staining of freshly isolated, antigen-specific CD8 + T cells. Analysis to date with both naturally acquired and experimentally induced infections has established that the numbers of virus-specific CD8 + T cells present during both the acute and memory phases of the host response are more than tenfold in excess of previously suspected values. The levels are such that the virus-specific CD8 + set is readily detected in the human peripheral blood lymphocyte compartment, particularly during persistent infections. Experimentally, it is now possible to measure the extent of cycling for tetramer + CD8 + T cells during the acute and memory phases of the host response to viruses. Dissection of the phenotypic, functional, and molecular diversity of CD8 + T cell populations has been greatly facilitated. It is hoped it will also soon be possible to analyze CD4 + T cell populations in this way. Though these are early days and there is an enormous amount to be done, our perceptions of the shape of virus-specific cell-mediated immunity are changing rapidly.