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

The importance of adhesion in regulating locomotion and accumulation of polymorphonuclear leukocytes (PMN) has remained vague. We found that the chemotaxis of human PMN resuspended in heat-inactivated plasma was maximal toward 1-10 nM N-formyl-met-leu-phe (f-Met-Leu-Phe), but fell below random motility toward >/= 100 nM. This impressive decrease of motility was paralleled by increased cell adherence on Petri dishes being minimal at 1 nM and maximal at >10 nM f-Met-Leu-Phe (6+/-1 and 37+/-2% [SE] adherent cells, respectively). Checked by phase-contrast microscopy, cells under stimulated adhesion lost the typical bipolar shape of moving PMN and became immobilized and highly flattened. PMN, preexposed to 250 nM f-Met-Leu-Phe and tested after washing, retained increased adhesiveness and showed extremely low random and chemotactic motility. In contrast, preexposure to 1 nM f-Met-Leu-Phe had no effect on chemotaxis. Supporting the concept that immobilizing hyperadhesiveness does not correspond to a general functional hyporesponsiveness of PMN, no depression of the initial ingestion rate was observed in the presence of 250 nM f-Met-Leu-Phe. Moreover, a close correlation was found between the induction of PMN adhesiveness and the stimulation of the hexose monophosphate pathway activity as well as of lysomal enzyme release (r >/= 0.98). Thus, "chemotactic deactivation" and "high-dose inhibition of chemotaxis" by N-formyl peptides is the consequence of increased cell adhesiveness. This phenomenon provides a mechanism for cell trapping at the inflammatory site. Conversely, if operative in circulating blood, e.g., in septicemia, it may impair PMN emigration to such sites.
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PMID:Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function. 44 62

Enhancement of in vitro nitroblue tetrazolium dye reduction by human polymorphonuclear leukocytes may be mediated by a low molecular weight fluid phase component of the complement system. This occurs in the absence of phagocytosis and is associated with an increase in leukocyte hexose monophosphate shunt activity. The stimulatory component may be generated by activating the alternate complement pathway in serum, and shares many of the properties of human C5a. Thus, the enhanced spontaneous reduction of nitroblue tetrazolium by leukocytes from patients with bacterial sepsis may not necessarily be due to the phagocytic activity of these cells, but rather may occur as a consequence of in vivo complement activation by either intact microorganisms or their products.
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PMID:Enhancement of nitroblue tetrazolium dye reduction by leukocytes exposed to a component of complement in the absence of phagocytosis. 109 Jun 64

To understand the molecular mechanisms responsible for the sepsis-induced enhanced glucose uptake, we have examined the levels of GLUT4 and GLUT1 mRNA and protein in the adipose tissue of septic animals. Rats were challenged with a nonlethal septic insult where euglycemia was maintained and hexose uptake in adipose tissue was markedly elevated. Northern blot analysis of total RNA isolated from epididymal fat pads indicated differential regulation of the mRNA content for the two transporters: GLUT1 mRNA was increased 2.6 to 4.6-fold, while GLUT4 mRNA was decreased by 2.5 to 2.9-fold. Despite the difference in mRNA levels, both GLUT1 and GLUT4 protein were down regulated in plasma membranes (40% and 25%, respectively) and microsomal membranes (42% and 25%, respectively) of the septic animals. The increased glucose uptake cannot be explained by the membrane content of GLUT1 and GLUT4 protein. Thus, during hypermetabolic sepsis, increased glucose utilization by adipose tissue is dependent on alternative processes.
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PMID:Differential regulation of glucose transporter gene expression in adipose tissue or septic rats. 155 May 51

Despite numerous reports, the role of tumor necrosis factor (TNF) in polymorphonuclear leukocyte (PMN) function remains controversial. We found TNF to be a potent, pertussis toxin-independent stimulator of PMN adhesion (ED50 2.6 pM). TNF-stimulated PMN under adherent conditions released up to 65% of their transcobalamine content (ED50 3.9 pM) and increased their burst activity 10-fold (ED50 3.2 pM) as measured by the hexose monophosphate shunt, whereas PMN held in suspension hardly degranulated at all and only little burst activity was demonstrable. However, preincubation of PMN with TNF in suspension led to a decrease in cellular adhesiveness, degranulation, and burst activity in response to a secondary stimulus of TNF under adherent conditions, although cells remained fully responsive toward phorbol myristate acetate. A concomitant dose-dependent decline of TNF receptor numbers that correlated well with the inhibition of PMN function (r = 0.91) suggests receptor down-regulation as the mechanism of functional PMN deactivation. Remarkably, preincubation with other PMN stimuli such as N-formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, leukotriene B4, complement component fragment 5a (C5a)/C5a (desarginated), and endotoxin also led to a reduction of TNF-specific PMN responses (cross-deactivation) from 35% (LTB4) to 90% (endotoxin), corresponding with the down-regulation of TNF receptors. Deactivation and receptor down-regulation are independent of pertussis toxin-sensitive G proteins and protein kinase C but seemed to depend on changes in calcium metabolism. Granulocyte hyporesponsiveness towards TNF in sepsis (with elevated blood levels of endotoxin and TNF) might be a mechanism of self-protection or, to the contrary, might impair a possibly central mode of host defense.
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PMID:The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation. 216 42

The insulin stimulatory effect of 7 mM glucose on isolated perifused rat islets is dramatically potentiated by the monokine interleukin 1 (IL-1). At levels (10(-10) -10(-8) M) noted in vivo during sepsis, it reversibly amplifies peak second phase insulin release to the hexose. At 2.75 mM glucose, however, IL-1 has no effect on insulin secretion. IL-1 also potentiates glyceraldehyde (2 mM)- and alpha-ketoisocaproate (5 mM)-induced insulin secretion. In islets whose phosphoinositides were prelabeled with myo-[2-3H]inositol, 2.0-5.0 nM IL-1 increases the efflux of [3H]inositol from subsequently perifused islets, the parallel accumulation of labeled inositol phosphates, and insulin secretion in the simultaneous presence of 7 mM glucose but not 2.75 mM glucose. In support of these in vitro observations, the in vivo infusion of IL-1 (40 micrograms/kg body wt) elevated circulating plasma insulin levels two-to fourfold. These results establish IL-1 as a potent, readily reversible, glucose-dependent modulator of stimulated insulin secretion and further suggest that its positive impact on insulin release is mediated, at least in part, by phosphoinositide-derived second messenger molecules. IL-1-induced insulin secretion may participate in the multiple metabolic and immunologic adaptations occurring during sepsis.
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PMID:Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis. 253 31

Aged individuals have diminished resistance to severe sepsis and septic shock. Previous studies in young animals showed that the liver's gluconeogenic capacity was an important determinant of survival in shock states. This study compared hepatic carbohydrate intermediates from young rats and old rats to correlate changes during peritonitis septic shock with known differences in survival times. Old control rats had glucose 6-phosphate (G6P) concentrations two-fold higher than young controls, 354 +/- 49 nanomole/g wet liver vs 180 +/- 41, suggesting a reduced ability to convert hexose monophosphate precursor into blood sugar. There was a 53% increase in G6P levels in the peritonitis livers, to 540 +/- 155 nanomole/g liver while in young septic rats the G6P decreased 33 per cent. These opposite, highly significant changes in shock (P = 0.01) show the reduced ability of old animals to mobilize gluconeogenic precursors. Fructose 1,6-biphosphate (FBP) in old control liver was 14 +/- 3 nanomole/g liver and did not change in shock; in young rats, FBP was 7.0 +/- 3 nanomole and increased 230 per cent in shock, showing a different metabolic response in young and old animals. These data suggest older animals may be more vulnerable to shock because of lower gluconeogenic potential.
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PMID:Liver gluconeogenic metabolites in young and old rats during septic shock. 338 97

A 52 yr old Caucasian female (F. E.) had hemolytic anemia, a leukemoid reaction, and fatal sepsis due to Escherichia coli. Her leukocytes ingested bacteria normally but did not kill catalase positive Staphylococcus aureus, Escherichia coli, and Serratia marcescens. An H(2)O(2)-producing bacterium, Streptococcus faecalis, was killed normally. Granule myeloperoxidase, acid and alkaline phosphatase, and beta glucuronidase activities were normal, and these enzymes shifted normally to the phagocyte vacuole (light and electron microscopy). Intravacuolar reduction of nitroblue tetrazolium did not occur. Moreover, only minimal quantities of H(2)O(2) were generated, and the hexose monophosphate shunt (HMPS) was not stimulated during phagocytosis. These observations suggested the diagnosis of chronic granulomatous disease. However, in contrast to control and chronic granulomatous disease leukocytes, glucose-6-phosphate dehydrogenase activity was completely absent in F. E. leukocytes whereas NADH oxidase and NADPH oxidase activities were both normal. Unlike chronic granulomatous disease, methylene blue did not stimulate the hexose monophosphate shunt in F. E. cells. Thus, F. E. and chronic granulomatous disease leukocytes appear to share certain metabolic and bactericidal defects, but the metabolic basis of the abnormality differs. Chronic granulomatous disease cells lack oxidase activity which produces H(2)O(2); F. E. cells had normal levels of oxidase activity but failed to produce NADPH due to complete glucose-6-phosphate dehydrogenase deficiency. These data indicate that a complete absence of leukocyte glucose-6-phosphate dehydrogenase with defective hexose monophosphate shunt activity is associated with low H(2)O(2) production and inadequate bactericidal activity, and further suggest an important role for NADPH in the production of H(2)O(2) in human granulocytes.
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PMID:Complete deficiency of leukocyte glucose-6-phosphate dehydrogenase with defective bactericidal activity. 440 Dec 71

The possible role of inhibited gluconeogenic enzymes in rat liver during preterminal peritonitis septic shock was investigated. There was no difference in maximal activity of the enzymes phosphofructokinase and fructose biphosphatase in septic and control, fasted rats. Rats with sepsis showed a decrease in hexose monophosphates and an increase in fructose biphosphate. There was an unexpected increase in fructose 2,6-bisphosphate despite the hyperglucagonemic state of sepsis. This suggested a dissociation in the coordination of extracellular hormonal and intracellular effector mechanisms in the control of glucose metabolism during the preterminal phase of septic shock. This dissociation may be responsible for the metabolic dyshomeostasis in septic shock.
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PMID:Hepatic fructose 2,6-bisphosphate in rats with peritonitis and septic shock. 609 Dec 86

Previous work demonstrated that glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) levels declined early in endotoxemic and septic livers. Since glucocorticoids are known to support hepatic gluconeogenesis in endotoxemia, these agents were tested in a peritonitis model produced by cecal incision in fasted adult male rats. Dexamethasone sodium phosphate (DMS) and methylprednisolone sodium succinate (MPS) were given in doses of 1 mg and 3 mg, respectively, per 100 gm rat weight at time of incision. Freeze-clamp biopsy samples obtained at 5 hr were enzymatically assayed. G6P and F6P in sepsis (N = 12) decreased 50% and 36%, respectively, below sham-operated control values (N = 15) of 236 and 61 nmole/gm wet tissue. The decrease with DMS was 20% and 16% and with MPS was 22% and 23%, showing partial restoration to normal levels. Phosphoenolpyruvate (PEP) did not decline in the moderate, non-terminal stage of peritonitis when compared to the control value (N = 19) of 209 nmole/gm. Treatment with glucocorticoids raised PEP to supernormal levels: DMS (N = 19) a 63% elevation, MPS (N = 12) a 51% elevation above controls in peritonitis rats. The glucocorticoid effect was similar in both rapid endotoxic and the slow peritonitis shock models. It is concluded that hexose monophosphate (HMP) increase is secondary to the support of PEP synthesis with glucocorticoid treatment. Changes in sham-operated control rat livers treated with glucocorticoids did not reach statistical significance.
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PMID:Glucocorticoid action on rat hepatic glycolytic intermediates during experimental peritonitis. 730 24

An analysis of the in vitro characteristics of Staphylococcus epidermidis strains isolated from patients with true S. epidermidis septicemia was undertaken. From a potential population of 921 cultures from adult patients with coagulase-negative bacteremia, highly defined selective criteria limited the population to 20 patients with S. epidermidis sepsis, from whose blood cultures the study organisms were isolated. Another population of 11 S. epidermidis blood isolates, clinically determined to be contaminants, were tested as a control group. In vitro assays performed on all isolates included slime quantification, hydrophobicity, surface hexoses, and capsule presence. Murine spleen phagocytosis of intravenously administered isolates was measured in vivo. The assayed quantity of cell-associated bacterial hexose sugars positively correlated with organism virulence to the host (p = 0.02). This bacterial population was also low in slime but varied as to the presence of capsule and ease of phagocytosis. Permanent catheter-bearing patients' bacteria were somewhat more hydrophobic (p = 0.07). We conclude that in vitro assays can differentiate bacteremic cultures from contaminants and that the characteristic that best relates to host toxicity in these S. epidermidis isolates was bacterial cell surface-associated carbohydrate.
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PMID:Bacterial characterization in Staphylococcus epidermidis septicemia. 779 93


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