Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hairy cells from eight patients with hairy cell leukemia were evaluated with both light and transmission electron microscopy for their capacity to phagocytose zymosan, latex, staphylococcus aureus, and pseudomonas aeruginosa. In two patients, there was no phagocytosis of any of these substances; cells from three patients phagocytosed only latex; two, all except pseudomonas; and one, all 4 substances. Hairy cells became relatively smooth while in culture with staphylococcus, but no surface changes were noted during incubation with the other substances. Of the eight patients studied, one died of pseudomonas pneumonia and sepsis; pseudomonas was the only substance which her hairy cells did not phagocytose. The one patient whose hairy cells phagocytosed all 4 test substances developed a disseminated Mycobacterium intracellulare infection; culture of his hairy cells with this atypical myocbacterium showed no phagocytosis. Hairy cells have different phagocytic capabilities from patient to patient, and the evaluation of these capabilities in vitro might provide early identification of potential infectious complications.
Virchows Arch B Cell Pathol Incl Mol Pathol 1979 May 04
PMID:Hairy cell leukemia: differences in phagocytic capacity of cells in vitro. 3 38

1. Hepatic carbohydrate metabolism was studied by an intravenous galactose test in control patients, malnourished non-septic patients, patients with prolonged severe sepsis and patients after recovery from sepsis. 2. Blood galactose half-life was not significantly increased in the septic group despite abnormal liver-function tests, whereas it was approximately doubled in the malnourished patients. 3. The rise in blood glucose after galactose injection was less in both the septic and malnourished groups, as compared with that in the control subjects. 4. Fasting blood glucose, lactate and pyruvate concentrations were similar in all groups, whereas blood ketone bodies were increased in the malnourished and septic groups, and blood alanine was decreased only in the septic group. 5. The changes in hepatic metabolism and function were reversible on recovery from sepsis. 6. It is suggested that alterations in hepatic blood flow and the metabolic fate of galactose within the liver may explain the changes in the metabolic response to galactose observed in malnourished or septic patients.
Clin Sci Mol Med 1978 Aug
PMID:Galactose and hepatic metabolism in malnutrition and sepsis in man. 67 28

The most common predisposing factor for development of the adult respiratory distress syndrome is gram-negative sepsis. Our previous studies have shown that a single infusion of Escherichia coli endotoxin into sheep causes early sequestration of lymphocytes in the lungs' microcirculation. In this report, we examined the effects of endotoxin on sheep lymphocyte adherence to sheep pulmonary microvascular endothelial cells in vitro. Endothelial cells were exposed to endotoxin, and subsequent adherence of 51Cr-labeled lymphocytes was measured in a monolayer adhesion assay. Endotoxin enhanced adherence of lymphocytes isolated from blood and caudal mediastinal node (CMN) lymph in a time- and dose-dependent manner. Adherence of CMN lymphocytes increased from a control value of 13.6 +/- 1.6% to 29.9 +/- 3.1% after 4 h of treatment with 1 microgram/ml endotoxin. Both B and T lymphocytes contributed to the increased adherence. Pretreatment of the endothelial cells with cycloheximide revealed that the endotoxin-enhanced adherence was partially dependent upon protein synthesis. Morphologic studies revealed that enhanced adherence was accompanied by a 5-fold increase in migration of lymphocytes between endothelial cells. In contrast to human umbilical vein endothelial cells, antibodies to the known lymphocyte adherence molecules, lymphocyte function-associated antigen (LFA-1), CD-44, and the lymphocyte homing receptor (LECAM-1), were ineffective in blocking adherence to the sheep pulmonary endothelial cells. We conclude that the acute sequestration of lymphocytes in the pulmonary microcirculation of sheep after endotoxin administration is due to increased adhesive properties of the endothelial cells. Our data suggest that this adherence is mediated by as yet undescribed mechanisms that may be unique to pulmonary microvascular endothelium.
Am J Respir Cell Mol Biol 1992 Jul
PMID:Endotoxin enhancement of lymphocyte adherence to cultured sheep lung microvascular endothelial cells. 137 87

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.
J Steroid Biochem Mol Biol 1992 Aug
PMID:A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. 150 7

Tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) are inflammatory cytokines produced by alveolar macrophages (AMs) and implicated in sepsis-related adult respiratory distress syndrome (ARDS). Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS. The purpose of the present study was to examine the effect of Exosurf on inflammatory cytokine secretion from AMs in vitro. AMs were obtained from normal nonsmoking adult volunteers. Secreted TNF, IL-1, IL-6, and IL-8 were measured by enzyme-linked immunoassays in 24 h culture fluids of AMs. Exosurf inhibited LPS-stimulated TNF, IL-1, and IL-6 secretion in a dose-dependent fashion. IL-8 secretion was not affected by Exosurf under these conditions. However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf. Regulation of IL-8 production may differ from TNF, IL-1, and IL-6. Unstimulated cytokine secretion was not affected by any of the tested concentrations of Exosurf. The inhibitory effect of Exosurf on endotoxin-induced cytokine secretion by human AMs suggests that Exosurf may modulate inflammatory cytokine production in the lung.
Am J Respir Cell Mol Biol 1992 Sep
PMID:Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages. 152 Apr 90

Sequestration of activated polymorphonuclear leukocytes (PMN) within the lung microcirculation may contribute to pulmonary vascular injury following trauma, sepsis, or disseminated intravascular coagulation. In this study cultured rat endothelial cells were utilized to evaluate the effect of PMN activation on endothelial cell attachment. The concept that disruption of the extracellular fibronectin matrix is associated with altered endothelial cell adhesion was also tested. Rat endothelial cells were grown in culture and identified by morphological techniques as well as immunofluorescent staining of Factor VIII R:Ag. Endothelial cells were labeled with 51Cr in order to establish a cell injury assay based on release of free 51Cr or cell-associated 51Cr. PMN activation was verified microscopically and by chemiluminescence activity following phorbol myristate acetate (PMA) or opsonized zymosan exposure. Following incubation with PMA, the leukocytes aggregated, chemiluminesced vigorously, and caused endothelial cell injury and detachment as determined by release of 51Cr-labeled endothelial cells. PMNs exposed to serum-treated zymosan exhibited a more modest chemiluminescence burst which was consistent with their decreased activity to injure the endothelial monolayer. With PMA activation the degree of endothelial detachment from the monolayer increased as a function of time with a plateau observed by 3 hr. Microscopic immunofluorescent analysis of extracellular fibronectin in endothelial cell cultures revealed disruption of the fibrillar matrix fibronectin after incubation with PMA-activated neutrophils in association with endothelial cell disadhesion. Thus, exposure of activated rat PMN to rat endothelial cells in culture induces endothelial damage and an associated disruption of the fibronectin matrix which may contribute to endothelial cell detachment.
Exp Mol Pathol 1986 Aug
PMID:Matrix fibronectin disruption in association with altered endothelial cell adhesion induced by activated polymorphonuclear leukocytes. 309 67

Hyperoxia impairs cytoskeleton-dependent phagocytic functions in polymorphonuclear leukocytes (PMNs) and alveolar macrophages (AMs). To investigate the effect of different oxygen concentrations on the cytoskeleton, in particular the microtubule (MT) and microfilament (MF) system, the fluorescence pattern of Concanavalin A (Con A) receptors in AMs and PMNs was observed. Cells were obtained from guinea-pigs exposed to different oxygen concentrations. The exposure of guinea-pigs to oxygen concentrations of up to 50% induced in AMs and PMNs mainly spontaneous Con A capping, demonstrating an altered MT system. Oxygen tensions above 50% lead to an increased number of AMs and PMNs exhibiting a patchy Con A fluorescence distribution. Even in the presence of the microtubule-disrupting agent colchicine most AMs and PMNs were unable to form a Con A cap fluorescence distribution under these high oxygen tensions. This study demonstrates that the exposure of guinea-pigs to an oxygen concentration greater than 50% increases the relative number of AMs and PMNs demonstrating a patchy distribution of Con A. This patchy fluorescence pattern is associated with a severe cytoskeletal defect, i.e. MT and MF disruption. The various leukocyte function defects induced by hyperoxia, demonstrated in previous studies, are based on this MT and MF alteration in AMs and PMNs, representing an additional sepsis-promoting factor during hyperoxia.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:Concanavalin A distribution in polymorphonuclear leukocytes and alveolar macrophages during hyperoxia. 613 6

Pseudomonas pseudomallei is a causative agent of melioidosis. The disease manifestations range from fulminant sepsis to asymptomatic seroconversion. In septicemic cases, a mortality rate of 80-90% is reported. Rapid and specific diagnosis has become important to the clinical microbiology laboratory. We have developed a P. pseudomallei-specific DNA probe. The cloned fragment, herein designated pKKU-S23L, contained 1.5 kb of P. pseudomallei chromosomal DNA. A radioactively labelled pKKU-S23L insert could detect 1.5 ng of its genomic DNA or 40,000 P. pseudomallei cells. The probe was highly specific for P. pseudomallei DNA and did not cross-hybridize with DNAs prepared from other related bacteria. Using pKKU-S23L as a probe in total cellular DNA digestions and Southern blot hybridization, we were able to classify 60 P. pseudomallei clinical isolates obtained from individual melioidosis patients into eight categories. Therefore, this probe has a potential not only for use in development of specific detection of bacterial DNA in clinical specimens but also for application in epidemiological studies of P. pseudomallei.
Mol Cell Probes 1994 Feb
PMID:Construction of a specific DNA probe for diagnosis of melioidosis and use as an epidemiological marker of Pseudomonas pseudomallei. 751 36

A major determinant of survival in patients with advanced viral or bacterial infection, or following severe trauma or burns complicated by multiple organ failure, is the combination of clinical signs termed the systemic inflammatory response syndrome (SIRS). SIRS is characterized by hypotension, tachypnea, hypo- or hyperthermia and leukocytosis as well as other clinical signs and symptoms, including a depression in myocardial contractile function. Heart failure complicating systemic sepsis or other causes of SIRS is usually not accompanied by coronary artery ischemia due to hypotension, myocardial necrosis, or marked cardiac interstitial inflammatory infiltrates, and thus the cause of cardiac contractile dysfunction in this syndrome has remained unclear. However, recent evidence has implicated an endogenous nitric oxide (NO) signalling pathway within cardiac myocytes and other cellular constituents of cardiac muscle, including the microvascular endothelium, as a possible contributor to the pathogenesis of heart failure in this syndrome. Cardiac myocytes are now known to express both constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) activities. Activation of cNOS appears to modulate cardiac myocyte responsiveness to muscarinic cholinergic and beta-adrenergic receptor stimulation. Induction of iNOS by soluble inflammatory mediators, including cytokines, causes a marked depression in myocyte contractile responsiveness to beta-adrenergic agonists. Thus, inappropriate activation of cNOS or excessive or prolonged induction of iNOS in the myocardium may contribute to cardiac dysfunction complicating SIRS.
J Mol Cell Cardiol 1995 Jan
PMID:Myocardial contractile dysfunction in the systemic inflammatory response syndrome: role of a cytokine-inducible nitric oxide synthase in cardiac myocytes. 753 82

Gram-negative sepsis is the most common cause of the adult respiratory distress syndrome (ARDS). Lipopolysaccharide (LPS) when administered in vivo produces pathophysiologic changes similar to those seen in ARDS. The pathogenesis of these changes is mediated in part by oxidative stress. We demonstrate that LPS induces high mRNA levels of the stress-inducible gene heme oxygenase-1 (HO-1) in the rat lung. Increased HO-1 mRNA levels correlate with increased HO-1 protein and enzyme activity. Immunohistochemical analyses of lung tissues from rats treated with LPS reveal abundant HO-1 expression in inflammatory and bronchoalveolar epithelial cells. We further examined the molecular regulation of HO-1 gene expression after exposure of RAW 264.7 macrophage cells to LPS in vitro. These cells respond to LPS with increased HO-1 mRNA expression and HO-1 gene transcription. Transcriptional activation of the mouse HO-1 gene by LPS is mediated by a 5' distal enhancer fragment located approximately 4 kbp upstream from the transcription site. Electrophoretic mobility shift assays show increased activator protein-1 (AP-1) binding activity in RAW 264.7 cells after LPS treatment. Mutation of the AP-1 binding site in this enhancer fragment completely abolishes HO-1 gene activation while mutation of CCAAT/enhancer-binding protein (C/EBP) binding site exerts negligible effect, suggesting that the AP-1 family of transcription factors plays a critical role in regulating HO-1 gene activation following LPS treatment. Furthermore, upstream phosphorylation events modulate this AP-1-dependent expression of the HO-1 gene after LPS treatment.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Induction of heme oxygenase-1 gene expression by lipopolysaccharide is mediated by AP-1 activation. 754 68


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