Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue factor (TF), a 46-kD glycoprotein receptor for coagulation factors VII and VIIa, is expressed on the surface of endothelial cells in response to a variety of agonists and is thought to play an important role in initiating the thrombosis associated with inflammation during infection, sepsis, and organ transplant rejection. The induction of TF activity by lipopolysaccharide (LPS) is regulated, at least partially, at a transcriptional level and an LPS response element containing two activator protein-1 sites and a nuclear factor-kappa B (NF kappa B)-like site has been localized to the 5' flanking region of the TF gene by transfection studies of TF promoter/reporter gene constructs. We have examined the effect of pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of the NF kappa B pathway on the expression of the endogenous TF gene in human umbilical vein endothelial cells (HUVEC). Preincubation of HUVEC for 60 minutes with PDTC inhibited LPS induction of TF activity on the cell surface in a dose-dependent manner, with 50% inhibition occurring at 10 mumol/L PDTC and 100% inhibition at higher concentrations (> or = 100 mumol/L). Furthermore, PDTC inhibited TF expression in response to tumor necrosis factor-alpha, interleukin-1 beta, and phorbol 12-myristate 13-acetate. The effect of PDTC was at the mRNA level, as seen by the complete abrogation of the large increase in TF mRNA observed in LPS-treated HUVEC. These results suggest that endothelial cell activation by diverse agonists initiates intracellular signaling events that converge upon a common pathway involving NF kappa B and, furthermore, that NF kappa B activation is an obligatory step induction of TF.
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PMID:Pyrrolidine dithiocarbamate abrogates tissue factor (TF) expression by endothelial cells: evidence implicating nuclear factor-kappa B in TF induction by diverse agonists. 760 83

The receptor for urokinase plasminogen activator (uPA-R, CD87) is a glycosylphosphatidylinositol (GPI)-anchored 50 to 65 kD glycoprotein that, by regulating membrane-associated plasmin activity, may facilitate the invasion of inflammatory and malignant cells. Certain other GPI-anchored glycoproteins are shed from the cell membrane and exist as soluble products in vitro and in vivo. To determine if uPA-R undergoes a similar phenomenon, we have developed a sensitive enzyme-linked immunoabsorbent assay (ELISA) (using a rabbit antiserum as both capture and detection reagents) to measure the quantity of soluble uPA-R (suPA-R) in tissue culture supernatants and biologic fluids. Using this ELISA, we have detected suPA-R in the culture supernatants of U-937 cells and human monocytes stimulated in vitro by certain soluble inflammatory mediators (Sitrin et al, Blood 84:1268, 1994; Mizukami et al., Clin Res 42:115A, 1994). To determine if suPA-R exists in vivo, we have screened the plasma of 20 normal volunteers (mean +/- SD, 3 +/- 3 ng/mL; median, 2 ng/mL; range, 1 to 11 ng/mL [serum values slightly higher]); the plasma of 13 ICU patients with clinical sepsis syndrome (mean +/- SD, 30 +/- 11 ng/mL; median, 11 ng/mL; range, 4 to 221 ng/mL); and the extravascular fluids (pleural, pericardial, and peritoneal) of 84 individuals with presumed inflammatory or malignant conditions (mean +/- SD, 21 +/- 39 ng/mL; median, 10 ng/mL; range, 2 to 253 ng/mL). Among the latter specimens, most were inflammatory exudates (only six were malignant by positive cytology) with the highest quantities of suPA-R associated with neutrophilic exudates. The solubility of suPA-R contained within these fluids was confirmed by reanalysis after ultracentrifugation to remove particulate material. When tested in a uPA ligand capture ELISA, representative specimens of extravascular body fluids and sepsis plasma contained suPA-R capable of binding uPA ligand (generally representing a small fraction of the immunoreactive material). We conclude from these data that suPA-R is immunologically detectable in vitro and in vivo with high concentrations of receptor found under conditions of inflammatory stimulation. The possibility of suPA-R's biologic activity is suggested by its partial retention of ligand binding capacity.
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PMID:Enzyme-linked immunoabsorbent assay detection of a soluble form of urokinase plasminogen activator receptor in vivo. 779 25

Colony-stimulating factors, a complex family of cytokines often referred to as hematopoietic growth factors, are a family of glycoprotein hormones that regulate production and differentiation of hematopoietic cells. The study of colony-stimulating factors was originally confined to stimulation and formation of clonal colonies in in vitro culture systems. The study of hematopoietic growth factors has since evolved into an expanding number of clinical applications in the treatment of patients with hematopoietic and immunologic diseases. Increased occurrence rates of infection have been demonstrated to be associated with both severity and duration of neutropenia. Sepsis has also been associated with phagocytic functional abnormalities. Both neutropenia and neutrophil dysfunction have been shown, in part, to be corrected by granulocyte colony-stimulating factor or granulocyte-monocyte colony-stimulating factor. In clinical trials to date, neither of these growth factors has shown significant toxicity. This article discusses the possible use of these and other growth factors in the treatment of sepsis.
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PMID:Colony-stimulating factors in the modulation of sepsis. 792 98

The interleukin-1 receptor antagonist (IL-1ra or IRAP) is a small, acidic glycoprotein that competitively inhibits the biological activities of interleukin-1 (IL-1). Alternative splicing gives rise to secreted and intracellular forms of IL-1ra. Both forms block cellular responses to IL-1 by occupying IL-1 receptors without triggering an agonist response. The affinity of IL-1ra for the type I IL-1 receptor is approximately that of IL-1. However, because of IL-1's pronounced "spare receptor" effect, IL-1ra is a weak inhibitor of biological responses to IL-1. The value for the affinity constant of IL-1ra's binding to the type II IL-1 receptor has been the subject of disagreement. However, recent data suggest that human IL-1ra has only weak affinity for the human type II receptor. This is consistent with the likelihood that the type II receptor plays no role in signal transduction, instead being a "decoy" that can be shed as a soluble receptor with the ability bind, and thus inhibit, IL-1. Under the name Antril, IL-1ra is being tested in clinical trials of a number of human diseases where IL-1 plays a major pathophysiologic role. These diseases include sepsis, rheumatoid arthritis, chronic myelogenous leukemia, and asthma, among others. Although IL-1ra has clear pharmacologic potential in such conditions, its application in chronic diseases is limited by difficulties associated with delivering proteins as drugs. As an alternative, we have suggested transfer of the gene coding for IL-1ra; strategies for both local and systemic gene delivery are being developed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The interleukin-1 receptor antagonist and its delivery by gene transfer. 803 9

Expression of S-fimbriae is frequent in Escherichia coli strains causing sepsis and meningitis in the newborn period. We analysed the ability of human skim milk to inhibit adhesion of S-fimbriated E. coli to human buccal epithelia. Adhesion was inhibited by up to 90% using colostrum (5%) and up to 50% with mature milk (5%), indicating that this anti-infective mechanism depends on the period of lactation. Elimination of up to 99% of immunoglobulins and 91% of lactoferrin by affinity chromatography had no effect on the inhibition of adhesion. After separation of high- (> 10 kD) and low-molecular-weight fractions of skim milk, only the fraction > 10 kD was found to be able to inhibit bacterial adhesion. In order to further characterize receptor molecules for bacteria, we investigated binding of isolated S-fimbriae to glycoprotein bands on Western blot strips. Fimbriae mainly bound to a high-molecular-weight band (> 200 kD). According to molecular weight and staining behaviour, this band most likely represents mucins. We conclude that carbohydrate residues on secreted mucins of human skim milk are able to inhibit bacterial adhesion to mucosal surfaces. This could provide protection against neonatal sepsis and meningitis caused by E. coli.
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PMID:Inhibition of adhesion of S-fimbriated E. coli to buccal epithelial cells by human skim milk is predominantly mediated by mucins and depends on the period of lactation. 809 30

The prophylactic and therapeutic efficacies of the immunomodulating agent RU 41.740 (a glycoprotein extract from Klebsiella pneumoniae) were studied in a murine model of intra-abdominal abscess formation with Bacteroides fragilis, Escherichia coli, and bran as an abscess-potentiating agent. Parenteral injection of RU 41.740, either before or after injection of an abscess-inducing mixture (AIM), was associated with significantly diminished incidence and size of abscesses. Abscess incidence and size were significantly decreased by oral administration of RU 41.740 after, but not before, AIM injection. Abscess formation and resolution are the results of complex interactions of host defence mechanisms with bacteria and potentiating agent, and RU 41.740 has been shown previously to activate both macrophage and neutrophil function. These results indicate that activation of non-specific defences may protect against abscess development in chronic sepsis.
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PMID:The effects of RU 41.740, a glycoprotein immunomodulating agent derived from Klebsiella pneumoniae, on intra-abdominal abscess formation in mice. 851 Jan 39

Reverse transcriptase-dependent polymerase chain reaction (RT-PCR) was applied to the detection and differentiation of viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV) using primer pairs designed for the amplification of glycoprotein G-specific gene fragments of the two viruses. The products of 443 bp (VHS) and 548 bp (IHN), respectively, were amplified from the total RNA extracts of RTG-2 cells infected with a total of 9 different strains of either VHS virus or IHN virus. Restriction analysis using FokI, and DNA sequencing of the PCR products demonstrated specificity of the amplification. The RT-PCR amplification of VHSV or IHNV G-genes was found to be a simple, highly specific and sensitive method allowing differential diagnosis of VHS and IHN within 8 h.
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PMID:Differential diagnosis of fish pathogenic rhabdoviruses by reverse transcriptase-dependent polymerase chain reaction. 857 1

Infectious hematopoietic necrosis virus (IHNV), a member of the family Rhabdoviridae, causes a severe disease with high mortality in salmonid fish. The nucleotide sequence (11,131 bases) of the entire genome was determined for the pathogenic WRAC strain of IHNV from southern Idaho. This allowed detailed analysis of all 6 genes, the deduced amino acid sequences of their encoded proteins, and important control motifs including leader, trailer and gene junction regions. Sequence analysis revealed that the 6 virus genes are located along the genome in the 3' to 5' order: nucleocapsid (N), polymerase-associated phosphoprotein (P or M1), matrix protein (M or M2), surface glycoprotein (G), a unique non-virion protein (NV) and virus polymerase (L). The IHNV genome RNA was found to have highly complementary termini (15 of 16 nucleotides). The gene junction regions display the highly conserved sequence UCURUC(U)7RCCGUG(N)4CACR (in the vRNA sense), which includes the typical rhabdovirus transcription termination/polyadenylation signal and a novel putative transcription initiation signal. Phylogenetic analysis of M, G and L protein sequences allowed insights into the evolutionary and taxonomic relationship of rhabdoviruses of fish relative to those of insects or mammals, and a broader sense of the relationship of non-segmented negative-strand RNA viruses. Based on these data, a new genus, piscivirus, is proposed which will initially contain IHNV, viral hemorrhagic septicemia virus and Hirame rhabdovirus.
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PMID:The complete genome structure and phylogenetic relationship of infectious hematopoietic necrosis virus. 857 57

The binding of labeled phosphatidylserine (PS) to a collection of synthetic 15-mer peptides covering full-length glycoprotein G (G) of viral hemorrhagic septicemia virus (VHSV), a salmonid rhabdovirus, showed three dominant overlapping reactive peptides. This major PS-binding region was contained in a 28-mer peptide (p2; aa 82-109) with consecutive hydrophobic amino acid a-d heptad repeats (putative amphipathic alpha-helix) and 2 carboxy-terminal arginines. This 28-mer peptide showed a 10-fold higher apparent specific activity for PS binding than the 15-mer peptides. Binding to PS was also detected with virion-purified protein G but was not detected with other viral proteins. The highest apparent specific activity for PS binding was found with purified VHSV particles by both solid-phase and liquid assays. In contrast to the pH-independent PS binding to peptide p2, binding to virions was optimal at pH 5.6. PS binding to purified VHSV was greatly reduced by protease or detergent treatments that removed protein G, by treatment at pH 7.6, or by anti-p2 mouse antibodies at pH 5.6. The PS-binding region seems to be related to viral-host cell fusion since anti-p2 mouse antibodies inhibited VHSV-infected cell to cell fusion (fusion from within) and the pH profile of the VHSV-infected cell to cell fusion was similar to the pH profile of PS binding to VHSV. Comparative analysis showed that sequences similar to the major PS-binding domain of VHSV were also present in other fish rhabdoviruses and in rabies and vesicular stomatitis viruses.
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PMID:Pepscan mapping and fusion-related properties of the major phosphatidylserine-binding domain of the glycoprotein of viral hemorrhagic septicemia virus, a salmonid rhabdovirus. 861 7

Plasma fibronectic (pFN) is a high molecular weight multifunction glycoprotein, which augments neutrophil and macrofage phagocytosis and acts as a nonspecific opsonin for the reticuloendothelial system. In this study we have determined pFN concentrations in fifty eight preterm infants to discriminate infected from non infected ones. Concentrations of pFN decreased from baselin in babies with early or late onset infections. The changes in pFN concentrations were not found before sepsis, but on day 1. By day 5 pFN concentrations have increased and have been no longer different from controls. We have calculated sensitivity (73.68%), specificity (74.36%), positive (58.35%) and negative (85.29%) predictive values of pFN and of other markers of infections (C-reactive protein--CRP-, Immature/Mature neutrophil ratio--I/M n. ratio-). Adding these tests to pFN, provided equal specificity and positive predictive value, but increased sensitivity (94.73%) and negative predictive value (96.43%). Thus, low concentrations of pFN may be a valuable but not early marker for neonatal infections. The combination of pFN, CRP and I/M n. ratio increase the precision of diagnostic testing.
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PMID:[Decreased plasma fibronectin (pFN) level in preterm infants with infections]. 866 94


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