UMLS:C0036690 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0036690 (sepsis)
59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a new, specific, and highly sensitive enzyme-linked immunosorbent assay (ELISA) which quantitates activation of the alternative pathway in human serum, plasma, or on the surface of activators. The ELISA detects the third component of complement (C3b), proteolytic fragment of complement Factor B (Bb), and properdin (P) complex or its derivative product, C3b,P. In the method, activator-plasma mixtures, plasma containing an activated alternative pathway, or other samples are added to the wells of microtitration plates precoated with antibody to P. C3b, Bb,P or C3b,P complexes which become bound are quantitated by subsequently added, enzyme-labeled, anti-C3. The resulting hydrolysis of the chromogenic substrate is expressed as nanograms of C3b by reference to a C3 standard curve. In addition to absolute specificity for activation of the pathway because of the nature of the complex detected by the assay, the ELISA is highly sensitive and able to reproducibly detect 10-20 ng/ml of C3b,P complexes in serum. This value corresponds to 0.0015% of the C3 in serum. In a series of studies to validate the parameters of the ELISA, reactivity was found to be dependent on the presence of alternative pathway proteins, the functional integrity of the pathway, and on the presence of magnesium. Sheep erythrocytes were converted to activators by treatment with neuraminidase. By using a variety of activators, the kinetics of activation and the numbers of bound C3b molecules quantitated by the ELISA were very similar to those measured by C3b deposition. The ELISA also detected identical activation kinetics when MgEGTA-serum and a mixture of the purified alternative pathway proteins were used as sources of the pathway. ELISA reaction kinetics also correlated with the restriction index, a measure of alternative pathway-activating ability. These studies cumulatively validate the ELISA as a direct and quantitative assay for alternative pathway activation. The sensitivity of the ELISA has permitted its use to detect direct alternative pathway activation by several viruses. The ELISA has also shown that certain classical pathway activators trigger the amplification loop of the alternative pathway while others do not. In addition, stable ELISA reactive complexes appeared in the supernatant of mixtures of serum with certain, but not other activators. The ability of the ELISA to detect activation which has already occurred and the stability of the reactive complexes permits studies of clinical sera. Normal human sera (20) contained low levels (5-20 ng/ml) of ELISA-reactive complexes. A proportion of sera from individuals with the adult respiratory distress syndrome (9-10), typhoid fever (8-10), malaria (3-5), gram-negative sepsis (9 of 47), acute trauma and shock (6 f 25), and systemic lupus erythematosus (3 of 29) showed elevated levels of complexes reactive in the alternative pathway ELISA. In contrast, nine sera from patients with circulating C3 nephritic factor were not reactive in the ELISA.
...
PMID:Development and application of an enzyme-linked immunosorbent assay for the quantitation of alternative complement pathway activation in human serum. 641 67

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.
...
PMID:Molecular cloning and functional expression of bacteriophage PK1E-encoded endoneuraminidase Endo NE. 756 5

In this study, 91 F165-positive Escherichia coli isolated from calves and piglets with diarrhea or septicemia were characterized with respect to receptor binding specificity, presence of the aerobactin system, production of colicin V, resistance to the bactericidal effects of serum. Although most F165-positive isolates shared similar DNA sequences with pap operon sequences, less than half of these isolates demonstrated MRHA to P antigen of human red blood cells and Forssman antigen of sheep red blood cells recognized by P and F (or Prs) adhesins respectively. Certain F165-positive isolates sharing similar DNA sequences with both pap and sfa operon sequences demonstrated mannose-resistant hemagglutination of sheep erythrocytes, as observed in human uropathogenic E. coli possessing the prs operon. Most isolates caused mannose-resistant, neuraminidase-resistant hemagglutination of human, equine, feline, and bovine erythrocytes. Thus, F165-positive isolates express one or more adhesins with different receptor binding specificities. An association was observed between the various receptor binding specificities and serogroup. Most F165-positive isolates possessed the aerobactin system and were resistant to the bactericidal effects of serum, but only 38.5% isolates produced colicin V.
...
PMID:Virulence factors associated with F165-positive Escherichia coli strains isolated from piglets and calves. 790 50

Most of 82 F165-positive Escherichia coli isolated from calves and piglets with diarrhea or septicemia and possessing pap related sequences caused mannose-resistant, neuraminidase-resistant hemagglutination of human and bovine erythrocytes. Less than half of these isolates demonstrated binding specificity for the alpha-D-galactosyl-(1-4)-beta-D-galactopyranose or galactose-N-acetyl-alpha-(1-3) galactose-N-acetyl moieties recognized by P and F (or Prs) adhesins respectively. Binding specificity for the galactose-N-acetyl-alpha-(1-3) galactose-N-acetyl moiety was associated with isolates causing septicemia in newborn piglets.
...
PMID:Receptor binding specificity and pathogenicity of Escherichia coli F165-positive strains isolated from piglets and calves and possessing pap related sequences. 809 16

Massive hemolysis is a rare, usually fatal complication of Clostridium perfringens septicemia. Of all toxins produced by the bacterium, phospholipase C (PLC) is believed to be the most likely cause of hemolysis. An influence of neuraminidase has often been suspected. In the present study, a case of C. perfringens septicemia with acute massive intravascular hemolysis is described. It led to death within 4 h of admission to the hospital. While the course of events was comparable to previously reported cases, we succeeded in gaining deeper insight into the pathogenesis by monitoring serum anti-T titer and quantifying serum PLC activity during the course of the disease. We excluded an effect of neuraminidase by a negative direct antiglobulin test, a negative anti-T lectin test, and a steady serum anti-T titer of 1 in 32. Serum PLC activity, on the other hand, showed a nearly fivefold increase (6.0 to 27.3 U/l), which is consistent with the hypothesized dominant role of this enzyme.
...
PMID:Investigation of the pathogenesis of massive hemolysis in a case of Clostridium perfringens septicemia. 837 4

A 4 month old girl developed a severe hemolytic uremic syndrome (HUS) following pneumococcal sepsis and meningitis. As a result of the hemolytic anemia and thrombocytopenia with associated gastrointestinal bleeding several red blood cell and thrombocyte transfusions became necessary. No plasma was transfused to the patient and all cellular blood components to be transfused were washed thoroughly in order to avoid the administration of eventually dangerous donor anti-T antibodies. Continuous peritoneal dialysis was performed for 23 days until sufficient spontaneous urine production was resumed. From the start of increased hemolysis T-transformation of the patient's red blood cells could be shown; bacterial neuraminidase was proven in the patient's serum, which could be neutralized in vitro by a commercial intravenous IgG preparation. The direct Coombs-Test was negative and no significant amounts of anti-T antibodies were detectable in the patient's serum at any stage of the disease. Our observation suggest that the T-transformation itself has caused the increased hemolysis and not an antigen-antibody (T-anti-T) reaction. In cases of HUS und proven T-transformation, intravenous IgG preparations should be tried therapeutically to inhibit the bacterial neuraminidase.
...
PMID:[Hemolytic-uremic syndrome in pneumococcal meningitis and infection. Importance of T-transformation]. 847 69

The type VIII capsular polysaccharide has been isolated and purified from a newly described strain of group B Streptococcus which is a leading cause of sepsis and neonatal meningitis in Japan. The polysaccharide contains D-glucose, D-galactose, L-rhamnose, and sialic acid in the molar ratio 1:1:1:1. By means of high resolution 1H nuclear magnetic resonance (1H NMR), 13C NMR, and homo- and heterocorrelated NMR, the repeating unit structure of the type VIII polysaccharide was delineated as the following, [formula: see text] Enzymatic studies established this polysaccharide as the first from which sialic acid, linked to a branched beta-D-galactopyranosyl residue, is known to be removed by bacterial neuraminidase.
...
PMID:Structural and immunochemical characterization of the type VIII group B Streptococcus capsular polysaccharide. 862 15

Streptococcus pneumoniae is an uncommon etiological organism in hemolytic uremic syndrome (HUS). Production of neuraminidase by S. pneumoniae results in exposure of red blood cell T-antigen, resulting in hemolysis, thrombocytopenia, and acute renal failure. Hepatic involvement in this form of HUS has not been described in the literature. We report in three children with S. pneumoniae-associated HUS the presence of severely elevated transaminases and conjugated hyperbilirubinemia. Increases in asparagine transaminase ranged from 11 to 46 times normal values and an increase in alanine transaminase ranged from 1.6 to 8 times normal. In all patients the rise in total bilirubin was 7-15 times normal. Biliary tree obstruction and viral causes for liver dysfunction were absent. Hepatocellular injury in S. pneumoniae-associated HUS likely results from mechanisms involved in sepsis and pneumonia-induced jaundice, combined with severely increased bilirubin production following massive hemolysis. The hepatic injury in all three patients resolved within 9, 5, and 10 days. Our experience suggests that an extensive evaluation including liver biopsy is not indicated.
...
PMID:Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic syndrome in children. 874 6

The Thomsen-Friedenreich cryptantigen (TCA) is located on the surface of all red cells, but is concealed by a layer of neuraminic acid. When bacteria that produce neuraminidase disrupt this coating, the TCA can be exposed and activated. If blood products containing antibody to the TCA are subsequently administered, haemolysis can result. While the relationship between TCA and necrotising enterocolitis (NEC) is well described, the incidence of TCA activation in other forms of sepsis in surgical neonates is not known. In a prospective study, 117 patients admitted to the Surgical Neonatal Nursery were examined for evidence of TCA activation. Of the 117 babies, 69 were clinically non-septic and only 1 had weak TCA activation (1.4%). Forty-eight were clinically or bacteriologically septic; 8 of these demonstrated TCA activation (17%), 3 of whom died. Forty of the septic group showed no evidence of TCA activation although 27 grew organisms on culture; 17 in this group died. Two of the TCA-activated babies received unwashed red cells, and both haemolysed; 4 TCA-activated babies received washed red cells and none haemolysed. Although 1 of the well babies in this study demonstrated TCA activation, we would not recommend routine TCA testing on clinically well babies. We would, however, recommend routine testing in all clinically septic infants, as 17% showed signs of TCA activation in this study. We would also suggest the adoption of a selective transfusion policy in TCA-activated patients to avoid the risk of haemolysis. This may help to reduce unnecessary morbidity and mortality in a high-risk group of neonates.
...
PMID:T-cryptantigen (TCA) activation in surgical neonates: a hidden problem. 988 Jul 50

Streptococcus pneumoniae infection and disease have been modeled in several animal species including infant and adult mice, infant and adult rats, infant Rhesus monkeys, and adolescent and adult chinchillas. Most are models of sepsis arising from intravenous or intraperitoneal inoculation of bacteria, and a few were designed to study disease arising from intranasal infection. Chinchillas provide the only animal model of middle ear pneumococcal infection in which the disease can be produced by very small inocula injected into the middle ear (ME) or intranasally, and in which the disease remains localized to the ME in most cases. This model, developed at the University of Minnesota in 1975, has been used to study pneumococcal pathogenesis at a mucosal site, immunogenicity and efficacy of pneumococcal capsular polysaccharide (PS) vaccine antigens, and the kinetics and efficacy of antimicrobial drugs. Pathogenesis experiments in the chinchilla model have revealed variation in ME virulence among different pneumococcal serotypes, enhancement of ME infection during concurrent intranasal influenza A virus infections, and natural resolution of pneumococcal otitis media (OM) without intervention. Research has explored the relative contribution of pneumococcal and host products to ME inflammation. Pneumococcal cell wall components and pneumolysin have been studied in the model. Host inflammatory responses studied in the chinchilla ME include polymorphonuclear leukocyte oxidative products, hydrolytic enzymes, cytokine and eicosanoid metabolites, and ME epithelial cell adhesion and mucous glycoprotein production. Both clinical (tympanic membrane appearance) and histopathology (ME, Eustachian tube, inner ear) endpoints can be quantified. Immunologic and inflammatory studies have been facilitated by the production of affinity-purified antichinchilla immunoglobulin G (IgG), IgM, and secretory IgA polyclonal antibody reagents, and the identification of cross-reactivity between human and chinchilla cytokines, and between guinea pig and chinchilla C3. Alteration of ME mucosa by pneumococcal neuraminidase and alteration of ME epithelial cell (MEEC) surface carbohydrates during intranasal pneumococcal infection have been demonstrated. Pathogenesis studies have been aided by cultured chinchilla MEEC systems, in which the ability of platelet activating factor and interleukin (IL)-1 beta to stimulate epithelial mucous glycoprotein synthesis has recently been demonstrated. Because chronic OM with effusion is characterized by presence of large amounts of mucous glycoprotein in the ME, pneumococcus may have an important role in both acute and chronic ME disease. Both unconjugated PS and PS-protein-conjugated vaccines are immunogenic after intramuscular administration without adjuvant in chinchillas. Passive protection studies with human hyperimmune immunoglobulin demonstrated that anti-PS IgG alone is capable of protecting the chinchilla ME from direct ME challenge with pneumococci. Active PS immunization studies demonstrated protection following direct ME and intranasal pneumococcal challenge with and without concurrent influenza A virus infection. An attenuated influenza A virus vaccine also showed protection for pneumococcal OM. Antimicrobial treatment of acute OM has been based almost exclusively on empirical drug use and clinical trials without a foundation of ME pharmacokinetics. Studies in the chinchilla model have started to bring a rational basis to drug selection and dosing. Microassays have been developed using high-pressure liquid chromatography for many relevant drugs. Studies have explored the in vivo ME response in pneumococcal OM to antimicrobial drugs at supra- and sub-minimum inhibitory concentration (MIC), the effect of concurrent influenza A virus infection on ME drug penetration, and the effect of treatment on sensorineural hearing loss produced by pneumococcal OM.
...
PMID:Otitis media: the chinchilla model. 1033 23

<< Previous 1 2 3 4 5 Next >>