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)

Alterations in hepatic function are seen in sepsis or multiple-system organ failure. We have hypothesized that Kupffer cells (KCs) within the liver alter the function of contiguous hepatocytes after exposure to septic stimuli. Using an in vitro coculture system, we have found that lipopolysaccharide (LPS) induced a 40% to 60% decrease in cocultured hepatocyte protein synthesis but had no effect on hepatocytes alone. Coculture in the absence of LPS resulted in enhanced hepatocyte protein synthesis proportional to the number of KCs or macrophages (M0s). Conditioned medium (CM) from LPS-triggered coculture or KC alone decreased protein synthesis of hepatocytes whereas CM from hepatocytes alone had no effect. Gel filtration of active M0-CM showing maximal hepatocyte inhibitory activity was present in fractions between 15,000 and 30,000 daltons. This inhibitory activity was inactivated by exposure to 65 degrees C for 30 minutes. Although CM from untriggered M0 did not inhibit hepatocyte protein synthesis, lysates from both LPS-triggered and control M0 were inhibitory. These results show that M0s/KCs exposed to septic stimuli decrease hepatocyte protein synthesis via heat labile, soluble mediator(s) that may already be synthesized within untriggered cells. We hypothesize that soluble M0/KC mediators normally modulate hepatocyte function and that this normal homeostatic control is profoundly altered during sepsis.
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PMID:Further characterization of Kupffer cell/macrophage-mediated alterations in hepatocyte protein synthesis. 373 62

Endotoxin producing bacteria cause disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in man is still unclear. Impairment of the fibrinolytic system has been suggested as a contributing mechanism. A single injection of Escherichia coli lipopolysaccharide in rabbits resulted in a marked and prolonged increase of the levels of a fast-acting inhibitor of plasminogen activator (PA-inhibitor) in plasma (from 3.9 +/- 0.7 to 41 +/- 13.2 U/ml after 3 h). Gel filtration studies indicated that inhibition of human tissue-type plasminogen activator (t-PA) by rabbit plasma is accompanied by a change in the elution profile of the activator compatible with the formation of an enzyme-inhibitor complex with an apparent molecular weight of 100,000. Injection of human t-PA (1,500 IU/kg body wt) in endotoxin treated animals resulted in very fast inhibition of t-PA and formation of a similar complex. The half-life of circulating PA-inhibitor activity in rabbits was about 7 min as estimated by donor receiver plasma transfusion experiments. Stimulation of cultured human endothelial cells with endotoxin resulted in enhanced rate of accumulation of PA-inhibitor activity in the culture medium (two- to sevenfold increase). In five patients with septicemia, markedly increased levels of PA-inhibitor (14.3 +/- 15.5 U/ml) as compared with control subjects (1.3 +/- 0.7 U/ml) were observed in plasma. A very strong correlation (r = 0.98) was found between inhibition of t-PA and of urokinase in all conditions, suggesting that this fast-acting inhibitor reacts with both plasminogen activators. These data suggest that the appearance of this fast-acting PA-inhibitor is very sensitive to endotoxin stimulation. The marked increase in the level of PA-inhibitor in blood may contribute to the pathogenesis of DIC in septicemia.
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PMID:Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. 392 Feb 45

Phospholipase A2 (PLA2) activity was purified 12,544-fold with a 13% yield from the plasma of patients diagnosed of septic shock by the sequential use of heparin-agarose affinity chromatography, gel filtration, and reverse-phase f.p.l.c. Gel-filtration chromatography of plasma omitting high-ionic-strength buffer revealed a molecular mass different from that of purified PLA2 and co-elution with apolipoprotein A-I peaks, which suggests its association with high-density lipoproteins (HDL). N-terminal analysis of the enzyme activity protein band, electroblotted from a SDS-acrylamide gel and with an assessed molecular mass of 19 kDa, showed an identical sequence to that of alpha-chain of human C3 complement component, suggesting the presence in this band of a complex formed by a complement C3-derived anaphylatoxin (C3a)-related fragment and the PLA2 linked side-by-side. Because the preparation of plasma enzyme showed lower activity than the enzyme obtained from fibroblasts transfected with the coding sequence of human group-II PLA2, and because the addition of C3-derived anaphylatoxins from human serum inhibited the activity of this recombinant PLA2, it was considered that C3a-related peptides behave as inhibitors of group-II PLA2. The enzyme showed optimal activity on [14C]oleate-labelled autoclaved E. coli, on synthetic phosphatidylethanolamine, and on [3H]arachidonate-labelled membranes of the monoblast cell line U937, but it did not show any activity on the release of [3H]arachidonate from pre-labelled human polymorphonuclear leukocytes (PMNs). In short, PLA2 from plasma of sepsis patients shows unique associations with other plasma proteins which may influence its functional properties. The association with C3-related peptides shows an inhibitory effect on the enzyme activity, whereas the association with HDL might influence its environment and/or its interaction with cells. The study of the catalytic properties shows a prominent effect on bacterial phospholipids, synthetic phosphatidylethanolamine, and membranes from U937 monoblasts, but not on synthetic phosphatidylcholine or on PMNs, even when these cells were maintained in culture to allow spontaneous apoptosis and became a good substrate for pancreatic type PLA2.
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PMID:Phospholipase A2 from plasma of patients with septic shock is associated with high-density lipoproteins and C3 anaphylatoxin: some implications for its functional role. 786 6

Twenty isolates of Pasteurella (Moraxella) anatipestifer from ducks with serositis and septicemia in Thailand between 1988 and 1989 were characterized by various tests. Eighteen isolates fermented glucose and maltose, 3 fructose and 1 each mannose, arabinose, trehalose or sorbitol. All isolates produced gelatinase but not urease, while 2, 3, 5 and 6 produced indole, were CAMP positive, and were proteolytic for milk and coagulated serum respectively. Seven enzymes, phosphatase alkaline, esterase (C4), esterase lipase (C8), leucine arylamidase, valine arylamidase, phosphatase acid and phosphoamidase were detected from all the isolates. The isolates were highly susceptible to ampicillin, erythromycin, penicillin G and tylosin. Gel-diffusion precipitin tests demonstrated that serotype 1 was most prevalent (60%) and serotype 6 followed (5%). Seven isolates (35%) were untypable. These results indicated that P. anatipestifer of serotype 1 played an important role in recent outbreaks of the disease in Thailand.
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PMID:Physiological characteristics, antimicrobial susceptibility and serotypes of Pasteurella anatipestifer isolated from ducks in Thailand. 820 23

Acute-phase reactants (APRs) are proteins synthesized in the liver following induction by interleukin-1 (IL-1), IL-6, and glucocorticoids, involving transcriptional gene activation. Lipopolysaccharide-binding protein (LBP) is a recently identified hepatic secretory protein potentially involved in the pathogenesis of sepsis, capable of binding the bacterial cell wall product endotoxin and directing it to its cellular receptor, CD14. In order to examine the transcriptional induction mechanisms by which the LBP gene is activated, we have investigated the regulation of expression of its mRNA in vitro and in vivo as well as the organization of 5' upstream regulatory DNA sequences. We show that induction of LBP expression is transcriptionally regulated and is dependent on stimulation with IL-1beta, IL-6, and dexamethasone. By definition, LBP thus has to be viewed as a class 1 acute-phase protein and represents the first APR identified which is capable of detecting pathogenic bacteria. Furthermore, cloning of the LBP promoter revealed the presence of regulatory elements, including the common APR promoter motif APRE/STAT-3 (acute-phase response element/signal transducer and activator of transcription 3). Luciferase reporter gene assays utilizing LBP promoter truncation and point mutation variants indicated that transcriptional activation of the LBP gene required a functional APRE/STAT-3 binding site downstream of the transcription start site, as well as an AP-1 and a C/EBP (CCAAT enhancer-binding protein) binding site. Gel retardation and supershift assays confirmed that upon cytokine stimulation APRF/STAT-3 binds to its recognition site, leading to strong activation of the LBP gene. Unraveling of the mechanism of transcriptional activation of the LBP gene, involving three known transcription factors, may contribute to our understanding of the acute-phase response and the pathophysiology of sepsis and septic shock.
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PMID:The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins. 866 65

Elevated serum levels of the prohormone of calcitonin (CT), procalcitonin (ProCT), have been documented in illnesses such as inhalational burn injury, in several sepsis syndromes, and in endotoxemia. In this study, we measured and characterized the circulating precursor forms of CT during the course of infectious pneumonitis. The initial (mean +/- SEM) serum total multiform CT level in 12 patients with acute infectious pneumonia was 1,019 +/- 430 pg/mL. In comparison, the mean level of total CT for 19 age-matched control patients without lung disease was 32 +/- 6 pg/mL (P < 0.001). The mean serum total CT level on initial examination was greater in the 6 patients with bacterial isolates, at 1,793 +/- 752 pg/mL, than in those with nonbacterial infectious pneumonia, at 242 +/- 109 pg/mL (P = 0.018). After admission to the hospital, patients' serum total CT progressively declined concomitantly with the clinical resolution of the pneumonia; at discharge, mean serum level was 121 +/- 34 pg/mL. On discharge, the patients who had persistent radiographic abnormalities had significantly higher levels than did those who had complete resolution. Both the mean serum calcium and phosphate were significantly lower at the initial time of study than at discharge (P < 0.002 and P < 0.0004, respectively). Gel filtration chromatography of sera obtained during the acute pneumonitis phase revealed increased levels of precursor forms of CT, including ProCT; these levels diminished with clinical resolution. In an additional three patients, the serum total CT increased very rapidly after aspiration (within 6 to 12 hours); the peak levels were several times greater than the upper limits of normal. In these patients, the principal serum CT components were ProCT and other precursor forms. These results show that both infectious and aspiration pneumonitis are associated with a rapid increase in circulating ProCT and other precursor forms of CT.
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PMID:Pneumonitis-associated hyperprocalcitoninemia. 868 24

Two challenges (intraperitoneal lipopolysaccharide (LPS) administration and cecal ligation and puncture (CLP)) and two strains of mice (LPS-normoresponder (C3H/HeN) and LPS-hyporesponder (C3H/HeJ)) were used to investigate pathways of cell injury. After intraperitoneal administration of LPS, endotoxin was absorbed into the bloodstream (HeN, 10.4 +/- 9.4 x 10(4) EU/mL; HeJ, 14.7 +/- 6.0 x 10(4) EU/mL), but as expected, only C3H/HeN mice produced serum tumor necrosis factor (TNF) (HeN, 2.5 +/- 2.0 x 10(3)pg/mL; HeJ, 87.0 +/- 38.7 pg/mL). Gel electrophoretic analysis of DNA extracted from six organs demonstrated the apoptotic "ladder" only in the thymus and only in the HeN mice. When the mice were challenged with CLP, both HeN and HeJ produced a small amount of serum TNF (HeN, 5.8 +/- 3.5 x 10(2) pg/mL; HeJ, 2.2 +/- 2.5 x 10(2) pg/mL) and both strains had very mild endotoxemia (HeN, 23.4 +/- 3.8 EU/mL; HeJ, 27.9 +/- 10.1 EU/mL). The DNA fragmentation pattern characteristic of apoptosis was observed not only in thymus but also in spleen, lung, and Peyer's patch of gut of both strains. This organ-specific pattern was more pronounced in the thymus of HeN mice; otherwise, the organ-specific patterns were similar for HeN and HeJ mice challenged by CLP but absent in those same organs when those same mice were challenged with LPS. The data suggest the existence not only of an endotoxin-driven activation for thymic apoptosis, but also of an endotoxin-independent, TNF-independent pathway activating widespread apoptosis in the murine CLP model of sepsis.
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PMID:Cecal ligation and puncture (CLP) induces apoptosis in thymus, spleen, lung, and gut by an endotoxin and TNF-independent pathway. 911 Apr 9

Patients severely neutropenic, when hospitalized, occasionally receive selective digestive decontamination, and the risk of vancomycin-resistant strain selection is a drawback since glycopeptide resistance is often associated with betalactam and aminoglycosid resistance. Bacterial translocation can lead to multiresistant bacterial sepsis. Eighteen Enterococcus faecium strains were collected from patients hospitalized in the leukemia unit of the Universitary Hospital of Lille (CHRU, Pr Bauters) between October 1992 and July 1997 and were studied. Nosocomial acquisition or endogenous origin were investigated to choose well-adapted prevention. All the vancomycin-resistant strains were shown by Polymerase Chain Reaction having the van A gene. The clonality of these strains was investigated by Pulsed-Field-Gel-Electrophoresis after Sma I restriction. Pulsotype analysis showed variable homology (52%-100%). Our results do not show evidence of patient-to-patient E. faecium transmission and suggest vancomycin-resistant strains were independently selected by antibiotic therapy from individual fecal flora. Except when epidemic events or happen, this strain isolation is more related to antibiotic prescription than misuse of isolation techniques.
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PMID:[Determination of the nosocomial origin of vancomycin-resistance strains of Enterococcus isolated from stool of patients in a hematology department]. 1041 13

BACKGROUND: Increased serum levels of procalcitonin (ProCT) and its component peptides have been reported in humans with sepsis. Using a hamster model of bacterial peritonitis, we investigated whether serum ProCT levels are elevated and correlate with mortality and hypocalcemia. RESULTS: Incremental increases in doses of bacteria resulted in proportional increases in 72h mortality rates (0, 20, 70, and 100%) as well as increases in serum total immunoreactive calcitonin (iCT) levels at 12 h (250, 380, 1960, and 4020 pg/ml, respectively, vs control levels of 21 pg/ml). Gel filtration studies revealed that ProCT was the predominant (> 90%) molecular form of serum iCT secreted. In the metabolic experiments, total iCT peaked at 12 h concurrent with the maximal decrease in serum calcium. CONCLUSIONS: In this animal model, hyper-procalcitoninemia was an early systemic marker of sepsis which correlated closely with mortality and had an inverse correlation with serum calcium levels.
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PMID:Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis. 1105 17

Intravisceral bleeding is a life-threatening situation demanding fast and active steps to control, unless it stops spontaneously as in a few lucky patients. A surgical approach is a major intervention with its associated procedural risks when the site is in organs other than the spleen. The transcatheter approach helps in precise location and embolization of the bleeding site; it is a more practical approach that has been known for the past 2 decades to be effective and provide good long-term results. However, the transcatheter approach has been reported in fewer than 200 cases in the literature. Our small series of 43 cases shows initial success of 95% and a fatal early recurrence of only 2.4%. Non-hemorrhagic etiology (sepsis, head injury, etc.) was the major cause of early death (14.6%) among the successfully embolized cases. Long-term follow-up shows recurrence (4.8%) only in the group of chronic etiology. Transcatheter embolization of intravisceral bleeding with Gel-Foam and/or poly-vinyl alcohol particles is a swift, effective and precise method of treatment without major operational hazards.
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PMID:Transcatheter therapy of intravisceral bleeding. 1117 23


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