UMLS:C0243026 - FACTA Search

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Query: UMLS:C0243026 (sepsis)
52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 100 patient-years' experience has been acquired in the treatment of 133 patients with ambulatory home total parenteral nutrition (TPN) between May 1974 and December 1983. Indications for chronic or permanent home TPN include short bowel syndrome, malabsorption, scleroderma, and vasoactive intestinal polypeptide syndrome. Indications for acute or temporary home TPN include Crohn's disease, malignancies, gastrointestinal fistulas, ulcerative colitis, anorexia nervosa, and numerous other disorders. Eighty-two patients in the acute group were treated primarily with percutaneously placed standard subclavian catheters and 51 patients in the chronic group have been treated thus far with implanted silicone rubber, Dacron-cuffed catheters for a cumulative total of 38,939 patient days. Of the 125 implanted catheters, 115 were placed in the superior vena cava and ten in the inferior vena cava for an average duration of 250 catheter-days, the longest single catheter remaining in situ for more than 8 1/2 years. Catheter-related sepsis occurred 33 times with the implanted catheters, or once every 2.6 catheter-years. One hundred and fourteen temporary catheters were placed percutaneously in the superior vena cava via a subclavian vein for an average duration of 68 days, the longest single catheter remaining in situ for 213 days. Catheter-related sepsis occurred seven times, equivalent to one episode per 3 catheter-years. Total catheter-related complications were quite infrequent and were directly related to duration of catheterization. They included venous thrombosis (12), clotted catheter (11), catheter failure or rupture (8), catheter compression (5) and inadvertent catheter removal (4). Twenty-six catheters were repaired or spliced in situ when the external segment was accidentally damaged or deteriorated secondary to long-term material fatigue. One remarkable patient has been maintained exclusively by TPN originally as an inpatient and subsequently as an outpatient for the entire 13 years of his life.
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PMID:100 patient-years of ambulatory home total parenteral nutrition. 642 31

CD14, a glycolipid-anchored membrane glycoprotein, acts as a high affinity lipopolysaccharide receptor on leukocytes. We previously reported that the Mono-Mac-6 cell line releases two different soluble forms of CD14 (sCD14) (Labeta et al., Eur. J. Immunol. 1993. 23: 2144). Here we show that the two sCD14, which we now refer to as sCD14 alpha (low M(r)) and sCD14 beta (high M(r)), are also synthesized and released by normal human monocytes and present in normal plasma. Their mechanism of release was examined by using the Mono-Mac-6 cell line, chinese hamster ovary cell (CHO)/CD14+ transfectants and plasma from paroxysmal nocturnal hemoglobinuria (PNH) patients. It was found that: (1) sCD14 beta is released faster than sCD14 alpha and that the release of the latter is a lengthy process. (2) Monensin blocked the biosynthesis of membrane-bound CD14 (mCD14) and sCD14, additionally, a 50-kDa CD14 polypeptide accumulated in the cell lysate, suggesting that the different forms of CD14 may have a common precursor. (3) Monensin also blocked the release of sCD14 alpha from surface-labeled cells, suggesting that conversion of mCD14 to sCD14 alpha involves a mechanism of endocytosis followed by exocytosis. Interestingly, (4) sCD14 alpha and sCD14 beta were detected in PNH plasma, indicating that sCD14 alpha may also derive from an endogenous pathway. (5) Phospholipase C-released CD14 was identical in size to mCD14, thus differed from sCD14 beta by approximately 2000, indicating that release of sCD14 beta involves further processing. (6) CHO cells transfected with a CD14 cDNA coding for an eight C-terminal amino acids shorter product released an sCD14 beta-like form; thus absence of the eight C-terminal amino acids prevented mCD14 expression but not the secretion of sCD14 beta. The characterization of sCD14 alpha and sCD14 beta reported here may be useful for better understanding of variations in sCD14 levels in pathological conditions and the contribution of each sCD14 in sepsis and other, as yet unknown functions.
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PMID:The two soluble forms of the lipopolysaccharide receptor, CD14: characterization and release by normal human monocytes. 752 57

Homopolymeric alpha-2,8-linked sialic acid (PSA) has been found as a capsular component of sepsis- and meningitis-causing bacterial pathogens, and on eukaryotic cells as a post-translational modification of the neural cell adhesion molecule (NCAM). The polysaccharide is specifically recognized and degraded by a phage-encoded enzyme, the endo-N-acetylneuraminidase E (Endo NE). Endo NE therefore has become a valuable tool in the study of bacterial pathogenesis and eukaryotic morphogenesis. In this report we describe the molecular cloning of Endo NE and the expression of a functionally active recombinant enzyme. The cloned DNA sequence (2436 bp) encodes a polypeptide of 811 amino acids, which at the 5' end contains a totally conserved neuraminidase motif. Expressed in Escherichia coli, the enzyme migrates as a single band of approximately 74 kDa in SDS-PAGE. A central domain of 669 amino acid residues is about 90% homologous to the recently cloned Endo NF. Both phage-induced lysis of bacteria and the catalysis of PSA degradation by the recombinant enzyme are efficiently inhibited by a polyclonal antiserum raised against the intact phage particle. The C-terminal region seems to be essential to enzymatic functions, as truncation of 32 amino acids outside the homology domain completely abolishes Endo NE activity. Our data also indicate that the 38 kDa protein, previously assumed to be a subunit of the Endo NE holoenzyme, is the product of a separate gene locus and is not necessary for in vitro depolymerase activity.
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PMID:Molecular cloning and functional expression of bacteriophage PK1E-encoded endoneuraminidase Endo NE. 756 5

We isolated a cDNA clone, kan-1, from a rat liver cDNA library using a reverse transcriptase PCR cloning method. The kan-1 cDNA encoded a polypeptide of 420 amino acids, and was 70 and 69% identical in nucleotide and amino acid sequences respectively with human liver bile acid-CoA-amino acid N-acyltransferase (BAT). Thus Kan-1 is probably a rat homologue of human BAT (rBAT). Kan-1/rBAT mRNA was mainly expressed in the livers of adult rats and rats immediately after, but not before, birth. It was expressed in the hepatocytes, the sinusoidal endothelial cells and the Kupffer cells of the liver. An anti-Kan-1/rBAT polyclonal antibody detected a protein of molecular mass 46 kDa in the liver. After partial hepatectomy, the levels of Kan-1/rBAT mRNA decreased at 6 and 12 h in the regenerating liver. In a sepsis model, hepatic expression of Kan-1/rBAT mRNA decreased at 6 and 12 h after caecal ligation and puncture. The kinetics of Kan-1/rBAT mRNA expression suggests that it may play a role in acute-phase reactions.
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PMID:Reduced expression of kan-1 (encoding putative bile acid-CoA-amino acid N-acyltransferase) mRNA in livers of rats after partial hepatectomy and during sepsis. 757 55

The vascular endothelium plays a central role in the regulation of extrinsic fibrinolysis and thus maintains vascular patency through clot dissolution. Plasminogen activation provides an important source of localized proteolytic activity not only during fibrinolysis but also during a variety of other physiological and pathological processes. Numerous studies have indicated that human endothelial cells can directly synthesize and secrete plasminogen activators (PA) and inhibitors of these activators. PAs specifically hydrolyse a single arginine-valine bond in plasminogen, an abundant and widely distributed plasma zymogen, to form the broad spectrum serine protease, plasmin. Tissue type-PA (t-PA) and urokinase type PA (u-PA) forms of PA have been described in endothelial cells, although t-PA production and secretion is elevated most frequently. The tPA form of PA functions predominantly in endothelial cell mediated fibrinolysis, while uPA is involved in tissue remodeling. During inflammatory reactions activated mononuclear phagocytes produce a variety of cytokines which may influence the phenotype of the endothelium through a process termed "endothelial cell activation". Tumor necrosis factor alpha (TNF alpha), a mononuclear cytokine, is a distinct polypeptide of Mr 17,000 and has been implicated as a mediator of gram negative induced sepsis as well as angiogenesis. TNF alpha is known to interact with specific endothelial cell receptors and to alter endothelial coagulant and anticoagulant properties implying that cytokines may be potent modulators of hemostasis. Recent observations have indicated that TNF alpha and lymphotoxin (TNF beta) can promote the expression, synthesis and secretion of urokinase plasminogen activator (uPA) in human endothelial cells. The upregulation of uPA results in an alteration in the fibrinolytic capacity of endothelial cells and allows cells the selective ability to degrade and invade underlying subendothelial extracellular matrix (ECM). Endothelial cells treated with TNF alpha also display, in an in vitro angiogenic assay, the ability to invade Matrigel and reorganize into tube-like structures, unlike control cultures. The effects of TNF alpha on the PA proteolytic system of endothelial cells, the biological significance of this event and potential in vivo consequences will be discussed. In addition, the influence of cytokine regulatory control systems will be described, since it is becoming increasingly clear that cytokines do not act in isolation. The vascular endothelium serves as a widely distributed anatomical interface between the blood and tissue with diverse capabilities, performing distinctive biologic functions at different sites and within specific organs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytokine regulation of endothelial cell extracellular proteolysis. 835 23

Group B Streptococcus (GBS) is a major cause of neonatal sepsis, meningitis in early infancy, postpartum endometritis, and serious invasive infections in adults in the United States. We previously cloned, sequenced, and characterized the alpha antigen gene, bca, and showed that the alpha C protein of GBS is a trypsin-resistant, surface-associated polypeptide that contains a signal sequence, a unique N terminus, nine identical tandem repeats, and a C-terminal membrane anchor structure. Polyclonal antiserum raised to the recombinant alpha C protein and an opsonic monoclonal antibody, 4G8, raised to the native protein from GBS have been shown to be protective in a mouse model. The binding site of 4G8 has now been localized to the tandem repeat region of the alpha C protein. To determine whether the N terminus of the alpha C protein contains additional opsonic and/or protective epitopes, the sequence corresponding to the alpha C protein N terminus was subcloned into a pET vector, the expressed peptide from Escherichia coli was purified by Ni2+ affinity chromatography, and rabbit polyclonal antibodies were raised to the purified recombinant peptide. Antibodies to the alpha C protein N terminus were shown to be opsonic by an in vitro opsonophagocytosis assay. In addition, 69% of newborn mouse pups from mothers passively immunized with the antiserum to the recombinant N-terminal polypeptide of the alpha C protein were protected against lethal challenge with GBS A909. These data indicate that at least two distinct regions of the alpha C protein, the N terminus and the tandem repeat region, contain opsonic and protective epitopes.
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PMID:Characterization of two distinct opsonic and protective epitopes within the alpha C protein of the group B Streptococcus. 911 88

The primary structure of human macrophage receptor with collagenous structure (MARCO) was determined from cDNA clones and shown to be highly similar to that of mouse (Elomaa, O., Kangas, M., Sahlberg, C. , Tuukkanen, J., Sormunen, R., Liakka, A., Thesleff, I., Kraal, G., and Tryggvason, K. (1995) Cell 80, 603-609). Features such as potential carbohydrate attachment sites in the extracellular spacer domain III and the interruption of Gly-Xaa-Yaa repeats in the collagenous domain IV were conserved between the two species. However, the human MARCO polypeptide chain lacked the intracellular cysteine present in mouse, as well as two extracellular cysteines that form interchain disulfide bonds in the murine protein. In situ hybridization showed MARCO to be strongly expressed in macrophages of several tissues of human individuals with sepsis. No expression was observed in other cell types. The bacteria-binding region of MARCO was determined in binding studies with full-length and truncated variants of MARCO, and localized to a region proximal to the cysteine-rich part of the COOH-terminal domain V. The intrachain disulfide bond pattern of domain V was established showing that these bonds are between cysteine pairs C1-C5, C2-C6, and C3-C4.
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PMID:Structure of the human macrophage MARCO receptor and characterization of its bacteria-binding region. 946 8

Macrophage migration inhibitory factor (MIF) is a secreted protein that activates macrophages, neutrophils and T cells, and is implicated in sepsis, adult respiratory distress syndrome and rheumatoid arthritis. The mechanism of MIF function, however, is unknown. The three-dimensional structure of MIF is unlike that of any other cytokine, but bears striking resemblance to three microbial enzymes, two of which possess an N-terminal proline that serves as a catalytic base. Human MIF also possesses an N-terminal proline (Pro-1) that is invariant among all known homologues. Multiple sequence alignment of these MIF homologues reveals additional invariant residues that span the entire polypeptide but are in close proximity to the N-terminal proline in the folded protein. We find that p-hydroxyphenylpyruvate, a catalytic substrate of MIF, binds to the N-terminal region and interacts with Pro-1. Mutation of Pro-1 to a glycine substantially reduces the catalytic and cytokine activity of MIF. We suggest that the underlying biological activity of MIF may be based on an enzymatic reaction. The identification of the active site should facilitate the development of structure-based inhibitors.
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PMID:Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor. 964 24

Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lpsd allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-like receptor-4 gene (Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous for a null mutation of Tlr4. Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact.
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PMID:Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. 985 30

Group B streptococcus (GBS) is the leading cause of bacterial sepsis and meningitis in neonates. N-terminal sequencing of major proteins in the culture supernatant of a clinical isolate of GBS identified a protein of about 50 kDa which could be detected in all of 27 clinical isolates tested. The corresponding gene, designated pcsB, was isolated from a GBS cosmid library and subsequently sequenced. The deduced PcsB polypeptide consists of 447 amino acid residues (M(r), 46,754), carries a potential N-terminal signal peptide sequence of 25 amino acids, and shows significant similarity to open reading frames of unknown function from different organisms and to the murein hydrolase P45 from Listeria monocytogenes. Northern blot analysis revealed a monocistronic transcriptional organization for pcsB in GBS. Insertional inactivation of pcsB in the genome of GBS resulted in mutant strain Sep1 exhibiting a drastically reduced growth rate compared to the parental GBS strain and showing an increased susceptibility to osmotic pressure and to various antibiotics. Electron microscopic analysis of GBS mutant Sep1 revealed growth in clumps, cell separation in several planes, and multiple division septa within single cells. These data suggest a pivotal role of PcsB for cell division and antibiotic tolerance of GBS.
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PMID:Identification and molecular analysis of PcsB, a protein required for cell wall separation of group B streptococcus. 1115 29

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