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)

Fatal infections in severely burned patients are often preceded by a decline in the production of colony-stimulating factor (CSF) and the proliferation of granulocyte-macrophage stem cells (CFU-GM), and overwhelming sepsis is often associated with leukopenia. The underlying mechanisms accounting for these granulopoietic defects are poorly understood, but the fact that postburn serum has been shown to inhibit CSF production suggests that a humoral factor or factors may play a role. Previous work has demonstrated that plasma levels of lactoferrin (LF), a known inhibitor of CSF production, are elevated following burn injury. To determine if LF is responsible for serum-mediated inhibition of CSF production, serial plasma levels of LF were measured in 18 burn patients using an enzyme-linked immunoabsorbent assay (ELISA). LF was elevated within 24 hours of injury and was associated with an absolute granulocytosis which rapidly declined, reaching a nadir at postburn days 3 through 5. Postburn serum, especially when collected during the first 24 hours following burn injury, inhibited in vitro CSF production by normal human peripheral blood mononuclear cells. Pre-incubation of postburn serum with an LF antibody restored normal CSF production. These data suggest that LF may play an important role in the regulation of postburn granulopoiesis.
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PMID:Inhibition of colony-stimulating factor (CSF) production by postburn serum: negative feedback inhibition mediated by lactoferrin. 326 9

Cerebrospinal fluid measurements of lactoferrin and alpha-1-antitrypsin showed significant elevation in bacterial meningitis in children. 8 of 10 lactoferrin values and 6 of 11 alpha-1-antitrypsin values were above the upper range of controls. Both proteins correlated well with the total number of leukocytes in the cerebrospinal fluid. C-reactive protein, measured by either agglutination or radial immunodiffusion in the cerebrospinal fluid, failed to demonstrate any usefulness in diagnosing bacterial meningitis. Neither elevated serum C-reactive protein in cases of bacterial meningitis, nor sepsis, gave detectable concentrations of C-reactive protein in the cerebrospinal fluid.
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PMID:Lactoferrin, C-reactive protein, alpha-1-antitrypsin and immunoglobulin GA in cerebrospinal fluid in meningitis. 348 45

Degradation of structural elements and excessive consumption of humoral factors, especially of plasma proteinase inhibitors, by proteolysis and/or oxidation is a major cause of multiple organ failure in sepsis or septic shock. Such pathobiochemical reactions seem to be induced primarily by extracellularly liberated lysosomal proteins from PMN granulocytes (e.g. elastase, cathepsin G, myeloperoxidase, lactoferrin) as well as oxygen radicals produced during extensive phagocytosis. In clinical studies on septicemia and septic shock the consumption of plasma proteins including proteinase inhibitors was inversely correlated to the liberation of lysosomal factors, especially the granulocytic elastase. Administration of relatively specific elastase-cathepsin G-inhibitors (Bowman-Birk inhibitor, eglin) in experimental septicemia proved to be a promising therapeutic approach to reduce consumption of plasma proteinase inhibitors and development of interstitial lung edema in severe inflammation.
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PMID:Pathobiochemistry of sepsis: role of proteinases, proteinase inhibitors and oxidizing agents. 352 75

The interrelationships between various components of the non-immune inflammatory response (white cell count, plasma lactoferrin, C-reactive protein, ferritin, iron and iron-binding capacity), were studied serially in a variety of inflammatory conditions including acute lobar pneumonia, active pulmonary tuberculosis, rheumatoid arthritis on gold therapy and sepsis in the face of marrow hypoplasia induced by chemotherapy. Lactoferrin concentrations paralleled the white count in all groups. They were highest in pneumonia and tuberculosis, mildly elevated in rheumatoid arthritis and markedly decreased in neutropenic sepsis. Very high initial lactoferrin concentrations were associated with a poor prognosis in acute pneumonia. C-reactive protein and ferritin concentrations remained elevated through the period of study in acute pneumonia and neutropenic sepsis, while they gradually normalised over weeks in subjects with tuberculosis or rheumatoid arthritis on therapy. In pneumonia and tuberculosis moderate hypoferraemia and a reduced iron-binding capacity were evident. In contrast, a raised percentage saturation was present in neutropenic sepsis, probably related to erythroid marrow suppression. Comparisons between ferritin, lactoferrin and C-reactive protein in the various groups supported the concept that ferritin behaves in part as an acute phase reactant and that hypoferraemia in inflammation is due to deviation of iron into ferritin stores. The suggestion that lactoferrin is responsible for the hypoferraemia and hyperferritinaemia was not supported by the present data. Iron deficiency appeared to limit the hyperferritinaemic response in rheumatoid arthritis, while erythropoietic inhibition by chemotherapy dampened the hypoferraemic response in neutropenic sepsis.
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PMID:The non-immune inflammatory response: serial changes in plasma iron, iron-binding capacity, lactoferrin, ferritin and C-reactive protein. 378 68

Twenty burned patients were studied (with mean body surface area burned 46.5%, mean age 25.4 years, and mean survival probability 78%), and lactoferrin, white-cells count and blood cultures were determined. Lactoferrin was detected more frequently (P less than 0.01) in the samples of patients with positive blood cultures. The role of lactoferrin in host defense mechanism and its possible function in sepsis is considered.
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PMID:Lactoferrin serum levels in burned patients. 315 85

Burns wound sepsis is not only the most common but also the most severe complication following extensive thermal injury. One conceivable explanation of this problem is a reduced capacity of the polymorphonuclear neutrophil leucocytes of these patients to combat the invading microbes. Fifty patients (42 male and 8 female) with deep dermal burns, covering 20-90 per cent of the total body surface area, were investigated from immediately after the injury until death or until healing of the wounds. The following functions of the neutrophil granulocytes were studied: chemotaxis and random migration utilizing a modified Boyden chamber technique, phagocytosis of Staph. aureus and IgG-coated latex particles, bactericidal capacity, e.g. killing of Staph. aureus and the neutrophil granulocyte content of: myeloperoxidase, lactoferrin, and chymotrypsin-like cationic protein. The presence of stimulators and inhibitors of the granulocyte functions was studied using gel filtration of the patient's serum on Sephacryl gel columns. Sera from all patients obtained within the first 1-3 days post-burn contained significantly increased amounts of heat-labile chemokinetic stimulating activity. Sera obtained between days 4 and 10 after injury contained significantly decreased amounts of heat-stable chemokinetic stimulating activity. Reduced chemokinetic activity was found during the third and fourth weeks following major burns (greater than or equal to 40 per cent) due to the presence of one or both heat-stable chemokinetic inhibitory activities. During the second week post-burn patients with burns larger than 40 per cent of the body surface area who showed an inhibition of chemotaxis, also had defects in phagocytosis, and often impaired bactericidal capacity concomitant with lower contents than normal of the granular enzymes. A hyaluronic acid preparation in low concentrations was found to counteract the migration inhibitory effect demonstrated in vitro in sera from patients with severe burns. Based upon these results a series of patients with severe burns and impaired functions of the neutrophil granulocytes have been treated with small amounts of this hyaluronic acid preparation subcutaneously. Very promising results have been noticed, similar to those found in vitro.
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PMID:Neutrophil granulocyte functions in severely burned patients. 402 46

Serum lactoferrin concentrations were elevated in 22 out of 49 newborn infants with suspected and verified severe bacterial as well as viral infections, suggesting that this protein resembled an acute phase reactant. In the infants suspected of having septicemia, high concentrations of C-reactive protein appeared to indicate a severe bacterial infection. Like lactoferrin, however, haptoglobin, orosomucoid, alpha 1-antitrypsin and alpha 1-antichymotrypsin discriminated only poorly or not at all between infants with severe bacterial infections and those in which such infections were unlikely. Thus, serum CRP concentrations remained the most valuable of the acute phase reactants tested as an aid in ruling out septicemia in the neonatal period.
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PMID:Lactoferrin in relation to acute phase proteins in sera from newborn infants with severe infections. 620 65

The transferrins are iron-binding proteins with molecular weights of around 80,000, which interact with a maximum of two ferric atoms per each protein molecule. The best known transferrins are the serotransferrins from animal sera, lactoferrins from milk, and conalbumin from egg-white. The iron-deficient transferrins will inhibit the growth of certain bacteria and fungi by making iron unavailable for bacterial metabolism. Such activity is abolished if the transferrin is saturated with iron. Many organisms can produce small molecular-weight iron-binding compounds called siderophores that can successfully utilize the iron sequestered by the transferrins. Such organisms are very virulent. Overwhelming evidence is now available to indicate that the transferrins play an important role in mammalian host-defense mechanisms. Thus, iron injections into animals infected with virulent bacteria result in increased death rates, and parenteral iron administration to human infants predisposes them to fatal septicemia. On the other hand, in cases of systemic infection, the organism responds by lowering its total serum iron, so as to make the serotransferrin present less saturated with iron. This phenomenon is called nutritional immunity. The iron apparently moves into the storage tissues from the circulation, and furthermore, it is withheld from circulation by the reticuloendothelial system. Laboratory results in such cases indicate low total serum iron levels and high unsaturated iron-binding activity values, thus increasing the bacteriostatic effects of the serotransferrins. Increased lactoferrin levels are observed in the milks of mastitic cattle.
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PMID:Antimicrobial properties of iron-binding proteins. 645 38

The effects of season and variations in the prevalence of infectious disease on the concentrations and daily production of breast-milk immunoproteins were studied in 152 rural Gambian mothers and their children up to 26 months post-partum. IgA, IgG, IgM, C3, C4, lactoferrin, lysozyme and secretory component concentrations and breast-milk volumes were measured longitudinally over a six month period which encompassed dry and rainy seasons. No increase in the production of any immunoprotein was observed at the time of maximum prevalence of serious infectious diseases, especially diarrhoea, in the children. Enhanced secretion of certain immunoproteins was noted in mothers of children aged 9-18 months at the beginning of the rainy season. There was some evidence that this may have been associated with skin sepsis, particularly impetigo, in the children. The production of most immunoproteins fell during the rainy season. This was not the result of declining maternal food intakes as similar decreases were seen for women receiving a dietary supplement.
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PMID:Breast-milk antimicrobial factors of rural Gambian mothers. II. Influence of season and prevalence of infection. 654 89

Serum lactoferrin concentrations were elevated in almost all children with meningococcal septicemia, in whom the disease had been clinically apparent for less than 18 hours, while the concentrations were normal or only moderately elevated in patients who had had the disease longer before being admitted. Concentrations of C-reactive protein (CRP) were markedly elevated, even with a time lapse of less than six hours, making this the most suitable parameter for the early diagnosis of severe meningococcal infection. Following an operative injury on children the lactoferrin concentrations changed very little. More than six hours after an operation, however, a marked increase in CRP-values was observed, possibly indicating differentiation of this response from that of bacterial infection. The concomitant study of serum alpha 1-antitrypsin, alpha 1-antichymotrypsin, orosomucoid and haptoglobin did not uncover results of great significance with regard to early changes.
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PMID:The latency of serum acute phase proteins in meningococcal septicemia, with special emphasis on lactoferrin. 660 36


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