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)

The possession of any of eight different plasmids by Staphylococcus aureus strain 649--either singly or simultaneously (in no. 649MR)--caused changes in growth kinetics. Six of the plasmids caused an increase in exponential doubling time (by 8-25%), and most also altered the duration of the lag period. Strain 649MR was significantly less virulent for 10-day chick embryos than the corresponding plasmid-negative culture (no. 649N). The avirulence persisted even after loss of the plasmids from no. 649MR. The presence of a single plasmid specifying tetracycline resistance produced a moderate reduction in virulence, but chromosomal tetracycline resistance had an insignificant effect on it. The decrease in virulence could not be attributed to reduced formation of soluble products. It probably resulted from alterations in the cell surface, but membrane-polypeptide profiles of virulent and avirulent cells lacking plasmids were similar. Survival of strains 649MR and 649N on glass was identical. Therefore, reduction in the incidence of staphylococcal sepsis may be due in part to loss of virulence that has resulted from plasmid carriage.
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PMID:Effect of plasmid carriage on the virulence of staphylococcus aureus. 103 30

An extracellular toxin produced by Aeromonas hydrophila from cultured crucian carp with septicemia was detected. The toxin was purified by ammonium sulfate precipitation, DEAE-cellulose chromatography and Sephadex G-100 gel filtration. The factor was a single polypeptide with a molecular weight of 52.5kd determined by SDS-PAGE. The heat-stable toxin possesses hemolytic, enterotoxic and cytolytic activities. The hemolytic activity on human erythrocytes was 3.81 x 10(3) HU/mg, CD50 for Vero cell was 0.26 microgram. The LD50 for crucian carp and mice was 4.44 micrograms and 3.58 micrograms respectively. The toxin was neutralized py homologous antibodies. The toxin shows unique characteristics as compared with other known bacterial toxins therefore the authors propose to name the toxin "hec" toxin.
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PMID:[Purification and characterization of hec toxin produced by Aeromonas hydrophila]. 129 32

The polypeptide cytokine interleukin-1 (IL-1) affects nearly every tissue and organ system. IL-1 is the prototype of the pro-inflammatory cytokines in that it induces the expression of a variety of genes and synthesis of several proteins which, in turn, induce acute and chronic inflammatory changes. Most studies on the biology of IL-1 have been carried out in animals, but human subjects have recently been injected with recombinant IL-1 and the results confirm IL-1 as being a mediator of disease as well as host defense. However, overproduction of IL-1 leads to debilitation of normal host functions; therefore, reduction of IL-1 synthesis or blockade of IL-1 activity becomes a target of therapy in many diseases. Agents for reducing the synthesis or antagonizing the effects of IL-1 have been sought, but the naturally occurring IL-1 receptor antagonist (IL-1Ra) has opened new experimental and clinical approaches. The ability of IL-1Ra to block IL-1 receptors without agonist activities has reduced the severity of diseases such as septic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.
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PMID:The role of interleukin-1 in host responses to infectious diseases. 134 62

A steroid binding capacity assay and a radioimmunoassay were both used to measure corticosteroid binding globulin (CBG) in serum samples from 22 patients with sepsis. An approximately 50% discordancy between the two values in one patient suggested the presence of a CBG variant with reduced affinity for cortisol, and this was confirmed by Scatchard analysis. We therefore used the polymerase chain reaction to amplify exons that encode for human CBG from the genomic DNA of this patient. This revealed two mutations within the coding sequences: one of which results in a Leu----His substitution at residue 93 and another which encodes a Ser----Ala substitution at residue 224 of the human CBG polypeptide. To assess the impact of each substitution on the steroid binding affinity of CBG, each mutation was introduced separately into a normal human CBG cDNA, and the normal and mutated cDNAs were expressed in Chinese hamster ovary cells. Scatchard analysis of the CBG produced in culture indicated that the His93 mutation (Kd = 2.24 +/- 1.75 nM) reduced the cortisol binding affinity of CBG (mean +/- SD) significantly (P less than 0.024) when compared to normal CBG (Kd = 0.64 +/- 0.31 nM), while the Ala224 mutation (Kd = 0.63 +/- 0.33 nM) did not influence cortisol binding affinity. We therefore conclude that residue 93 may play an important role in determining the structure of the CBG steroid binding site.
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PMID:A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. 150 7

Despite antibiotic therapy, the septic shock syndrome continues to have a high mortality. Tumor necrosis factor (TNF) and interleukin 1 (IL 1), two polypeptide cytokines produced during sepsis, are thought to mediate the hypotension and tissue damage of shock. In the present studies, rabbits were infused with Escherichia coli organisms to produce shock. The IL 1 receptor antagonist (IL 1ra), which competes with IL 1 for occupancy of the IL 1 cell-surface receptors without agonist properties, was given 15 min before the bacterial infusion and during the subsequent 4 h. In saline-treated controls, hypotension was sustained for 4 h and death occurred for two of five rabbits; in rabbits treated with the IL 1ra, however, blood pressure was only transiently decreased, returned to pre-E. coli levels, and no deaths occurred. The associated leukopenia was also reduced by treatment with the antagonist (P less than 0.05). Histological examination of lung tissues showed reduced infiltrating neutrophils in the IL 1ra treatment group. Despite the attenuated responses in animals treated with the IL 1ra, circulating TNF and IL 1 levels were nearly identical in both groups. We conclude that specific blockade of IL 1 at the receptor level demonstrates an essential role for this cytokine in the pathogenesis of septic shock.
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PMID:A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits. 182 16

The polypeptide cytokine interleukin-1 (IL-1) affects nearly every tissue and organ system. IL-1 is the prototype of the pro-inflammatory cytokines in that it induces the expression of a variety of genes and the synthesis of several proteins that, in turn, induce acute and chronic inflammatory changes. IL-1 is also the prototypic "alarm" cytokine in that it brings about increases in a variety of defense mechanisms, particularly immunologic and hematologic responses. Most studies on the biology of IL-1 have been performed in animals, but human subjects have recently been injected with recombinant IL-1 and the results confirm the two fundamental properties of IL-1 as being both a mediator of disease as well as of host defense. However, in either situation, over or continued production of IL-1 leads to debilitation of normal host functions; therefore, reduction of IL-1 synthesis or its effects becomes a target of therapy in many diseases. In this review, the structure, gene expression, synthesis, and secretion of IL-1 are described. In addition, the two IL-1 surface receptors, possible signal transduction mechanisms, various biologic activities, and production of IL-1 during disease states are discussed. Similarities and differences between IL-1, tumor necrosis factor, and IL-6 are presented. Although various agents for reducing the synthesis and/or for antagonizing the effects of IL-1 have been proposed, the recent cloning of a naturally occurring IL-1 receptor antagonist (IL-1ra) has opened new experimental and clinical approaches. The ability of this IL-1ra to block the triggering of IL-1 receptors in animals without agonist effects has reduced the severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.
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PMID:Interleukin-1 and interleukin-1 antagonism. 182 16

Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study.
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PMID:The effects of tumor necrosis factor on intestinal structure and metabolism. 225 57

In human blood, cortisol is transported by a plasma protein known as corticosteroid-binding globulin (CBG). As anticipated from primary structure comparisons of CBG and alpha 1-proteinase inhibitor (A1-PI), CBG acts as a substrate for neutrophil elastase. However, unlike A1-PI, CBG does not alter the activity of this enzyme, but is cleaved by it at a single location close to its carboxy-terminus, and this reduces its molecular size by 5 kDa with the concomitant release of more than 80% of CBG-bound cortisol. Three small molecular size fragments are detected after elastase cleavage, and carbohydrate analysis of these fragments suggests that they represent the same polypeptide fragment which has been differentially glycosylated. To assess the biological significance of these observations, CBG was incubated with either mononuclear cells or granulocytes obtained from patients with acute inflammation (sepsis) and from a normal volunteer. Only granulocytes from septic patients reduced the mol wt of CBG by about 5 kDa and destroyed its steroid-binding activity. Preincubation with A1-PI prevented this, which demonstrates that neutrophil elastase plays a key role in this event. These results suggest a physiological role for CBG in the delivery of cortisol to sites of inflammation.
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PMID:A role for corticosteroid-binding globulin in delivery of cortisol to activated neutrophils. 237 Feb 99

Vitronectin, also known as serum-spreading factor or S-protein, mediates cell adhesion and inhibits formation of the membrane-lytic complex of complement and the rapid inactivation of thrombin by antithrombin III in the presence of heparin. Vitronectin is normally present in plasma at a concentration of approximately 300 micrograms/mL. The investigators quantified plasma vitronectin with an enzyme-linked immunosorbent assay and visualized reduced and nonreduced vitronectin by immunoblotting after separation of plasma or serum by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The concentration of plasma vitronectin was markedly reduced in some patients with disseminated intravascular coagulation, especially in those with liver failure; it was near normal in patients with metastatic cancer and acute leukemia. Patients with vitronectin levels less than 40% normal invariably had low fibrinogen and antithrombin III and a prolonged prothrombin time. In both normal and patient plasmas there was heterogeneity in the ratio of the 75,000- and 65,000-mol wt polypeptides of reduced vitronectin: 18% had mostly the 75,000-mol wt polypeptide, 59% had roughly equal amounts of the two polypeptides, and 22% had mostly the 65,000-mol wt polypeptide. This polymorphism is inherited and appears to be due to two alleles that are present with approximately equal frequency. The blotting patterns of vitronectin in reduced and nonreduced plasmas were largely unaltered in plasma of patients with defibrination syndrome, fibrinolysis, liver failure, sepsis, metastatic cancer, and acute leukemia. There was no evidence of fragmentation of vitronectin or formation of the disulfide-bonded complex of vitronectin and thrombin-antithrombin III that is found when blood is clotted. Thus these results corroborate in vitro observations that the liver is the major source of plasma vitronectin, suggest that vitronectin may become depleted during disseminated intravascular coagulation, and define a genetic polymorphism of vitronectin.
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PMID:Plasma vitronectin polymorphism in normal subjects and patients with disseminated intravascular coagulation. 245 67

The growth potential and the polypeptide composition of Yersinia enterocolitica serotype 0:3 isolated from patients with uncomplicated diarrhoea, reactive arthritis or septicemia were evaluated under different culture conditions. The expression of polypeptides varied with presence of the virulence-associated 40-48 Mdal plasmid, growth medium, growth temperature and gas composition of the culture (air, carbon dioxide, oxygen). Also the initial growth medium at 26 degrees C, before temperature shift to 37 degrees C, influenced the subsequent growth potential and expression of polypeptides. The plasmid encoded at least 7 polypeptides. This plasmid also inhibited the multiplication of bacteria under defined culture conditions. The dominating plasmid-encoded polypeptides were optimally expressed in air or oxygen-supplemented growth medium. The majority of the chromosomally encoded polypeptides were expressed independently of presence of the plasmid, whereas the expression of at least 8 were repressed by the plasmid. Five chromosomally encoded polypeptides were expressed only in carbon dioxide and five only in oxygen environment. These results indicate that Y. enterocolitica may express different molecules in different environments in vivo. This may be of importance for host-parasite relationship and immune response.
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PMID:Structural variations and growth potential of Yersinia enterocolitica under different culture conditions. 271 34


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