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)

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 protein B of group B streptococci can bind in a nonimmune reaction to Ig of the IgG and IgM classes of various mammalian species (i.e., human, mouse, rabbit, and bovine). Protein B binding involves the Fc parts of both IgG and IgM molecules. Monoclonal or polyclonal IgG or IgM and the IgM-FC5 mu fragment of human myeloma protein combined with the protein B thereby inhibiting protein B-induced hemolysis in the CAMP reaction. The protein B/Ig complex can be dissociated with 1% Triton or guanidine-HCl (6 M). Mice infected intraperitoneally with sublethal doses of group B streptococci (GBS) and that received seven repeated intravenous injections of highly purified protein B during the first 9 h of infection developed fatal septicemia within 24 h with colony counts of up to 10(8) CFU/ml in the blood. Animals treated in the same way with either PBS or trypsinized protein B recovered. The protein B itself was not pathogenic when injected into healthy mice. Tissue sections of liver or spleen from mice infected with a lethal dose of GBS revealed the presence of protein B together with large numbers of cocci when stained by the peroxidase method using specific antibodies raised against purified protein B in the rabbit.
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PMID:Unspecific binding of group B streptococcal cocytolysin (CAMP factor) to immunoglobulins and its possible role in pathogenicity. 354 80

The effects of intragastric prostaglandin E2 (PGE2) on the occurrence of acute GI hemorrhage in intensive care patients were investigated in a prospective, double-blind, placebo-controlled study. Ninety patients with two or more risk factors (major surgery, multiple trauma, respiratory insufficiency, renal insufficiency, jaundice, hypotension, peritonitis, sepsis) were randomized for treatment with either PGE2 (0.5 mg) or placebo, administered every 4 h via a nasogastric tube. Blood loss in gastric aspirates was measured by 51Cr-erythrocyte labeling and a peroxidase test (orthotolidine). Of 57 patients who could be evaluated, 29 received PGE2 and 28 received placebo. Hemorrhage occurred in nine PGE2 patients and 13 placebo-treated patients, not a significant difference. The occurrence of hemorrhage was related to the number of risk factors, and GI hemorrhage was rarely the major factor determining mortality. Results of the orthotolidine test were not positively correlated with those of erythrocyte labeling, indicating that peroxidase tests should not be relied upon to detect blood in gastric aspirates.
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PMID:Intragastric prostaglandin E2 and the prevention of gastrointestinal hemorrhage in ICU patients. 390 62

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

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

This review has concentrated on clinical syndromes for which a congenital basis of polymorphonuclear neutrophil dysfunction has been identified. The first clinical syndrome found to be associated with dysfunctional polymorphs was chronic granulomatous disease of childhood. Identification of a cellular defect in oxidative metabolism and microbicidal activity of polymorphonuclear neutrophils from patients with CGD stimulated intense investigation of the function of phagocytes in several clinical entities characterized by increased susceptibility to infection. Other diseases with a probable congenital basis for polymorph dysfunction include Chediak-Higashi syndrome, myeloperoxidase deficiency, severe glucose-6-phosphate dehydrogenase deficiency, and Down's syndrome. Functional defects have also been identified in neutrophils with morphologic abnormalities, such as the Pelger-Huet anomaly and the May-Hegglin anomaly, and in neutrophils without alkaline phosphatase or with a disorder of the glutathione system. The evidence for a relation between these cellular disorders and susceptibility to infection is tentative. Patients with congenital disorders of polymorphonuclear neutrophil microbicidal function frequently suffer prolonged infections in spite of appropriate antimicrobial therapy, and severe lesions recur with discouraging frequency. These lesions are usually soft tissue or bone abscesses, and the etiologic agents are typically staphylococci, gram-negative enteric species, or fungi. The infectious disease problems of patients with phagocytic cell disorders are usually quite distinct from the problems of patients without immunoglobulins or with complement deficiency. Patients with agammaglobulinemia, for example, suffer recurrent septicemia or meningitis due to Streptococcus pneumonia or H. influenzae. Septicemia, especially with the pyogenic bacterial species, is unusual in patients with polymorphoinuclear dysfunction. A major contribution of the currently intense investigation of cells from patients with congenital disorders of phagocyte function has been the greatly increased understanding of the molecular events necessary for the normal function of these cells. The role of the oxidative metabolic burst during phagocytosis has been clearly identified as essential to the microbicidal function of polymorphs and monocytes, and the glutathione system has been identified as essential to the regulation of these oxidative reactions. It is anticipated that these studies may lead to practical methods for "stimulating the phagocytes" in patients with increased susceptibility to infection.
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PMID:Congenital disorders of the function of polymorphonuclear neutrophils. 625 30

Sepsis, abscess formation or development of purulent exudates in closed cavities expresses insufficient host defense against pyogenic infections. An attempt is made to analyse the reasons for diminished host resistance and/or increased virulence of the invading microbes. While the role of cellular defense mechanisms is not considered, a number of humoral components, such as lysozymes glycolipids, lactoperoxidase, fibronectin, esterases and haptoglobin, participate in efficient defense. Special emphasis is placed on serum complement, both with regard to its unspecific but nevertheless efficient alternative pathway, and with respect to its phylogenetically much more recent classical pathway. Recognition of bacteria by either mechanism of complement activation leads to C3b deposition on the microbial surface for efficient opsonization, while the juxtaposition of at least two molecules of antibodies contained in the immunoglobulin fraction of plasma safely leads to complement activation via the classical pathway. Therefore, specific recognition of bacteria by immunoglobulin-antibodies remains the core of anamnestic antimicrobial defense, the more so since some antibodies may also confer on the bacterial surface the capacity to activate the alternative pathway. The recent description of monoclonal antibody directed at bacteria relevant in sepsis opens perspectives in the near future when such components will eventually be used for therapeutic purposes, along with antibodies also directed towards the pathogenetic bacterial products endo- and exotoxin.
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PMID:[The role of complement and specific antibodies in the development and defense mechanism of sepsis and septic shock]. 662 30

Thrombocytopenia occurs frequently in newborn infants with sepsis, but the exact mechanism remains obscure in those infants who do not have evidence of disseminated intravascular coagulation. Since recent work has suggested a possible immune mechanism for thrombocytopenia observed in adults with sepsis, we have investigated the role of platelet-associated immunoglobulin in severe neonatal infections. To detect PAIgG we use a method employing protein A and peroxidase-antiperoxidase as a labeled antibody. PAIgG was quantitated by phase contrast microscopy and expressed as a reactive index. Our control group included 16 normal newborn infants whose mean RI was 0.65 +/- 0.01 SE. In addition to the control group, five infants with nonimmune thrombocytopenia were included; their mean RI was 0.66 +/- 0.01 SE. Seventeen newborn infants with severe infections were assayed for PAIgG. Eight of nine infants with bacterial infections had increased RI, with a mean of 1.16 +/- 0.03 SE (P less than 0.01). Six of the eight infants with viral infections had elevated RI, with a mean of 1.23 +/- 0.03 SE (P less than 0.01). These findings suggest that an immune mechanism may be involved in the thrombocytopenia of severe neonatal infection.
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PMID:Immune thrombocytopenia in severe neonatal infections. 705 22

Unbound bilirubin, bilirubin binding capacity, and bilirubin binding affinity were determined by the horseradish peroxidase method at the time of maximum hyperbilirubinemia and/or before exchange transfusions in 13 preterm infants who later died and had autopsies performed. Five of the 13 infants had kernicterus at autopsy. There were no significant differences in weight, gestational age, highest indirect bilirubin level, albumin concentration, severity of acidosis, use of assisted ventilation, sepsis, or other major clinical complications between the five infants with kernicterus and the eight infants without kernicterus. Compared with the eight nonkernicteric infants, the five kernicteric infants had significantly higher unbound bilirubin concentrations (13 +/- vs 27 +/- 9 nmoles/liter, respectively, P less than .05) and significantly lower bilirubin binding capacity and affinity. The data suggest an association between low bilirubin binding capacity and affinity, increased unbound bilirubin, and kernicterus in preterm infants with severe clinical complications.
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PMID:Unbound bilirubin and kernicterus in low-birth-weight infants. 720 Feb 29

Free bilirubin concentration, bilirubin-binding capacity, and bilirubin-binding affinity were determined by peroxidase oxidation in 66 newborn infants. Twelve healthy term infants whose unconjugated bilirubin concentration was 15.8 +/- 3.7 mg/dl (mean +/- SD) had a binding capacity of 31.9 +/- 3.7 mg/dl (bilirubin: albumin molar ratio = 0.89 +/- 0.07) and Ka = 28 +/- 11 x 10(7)/M. Twelve term infants with clinical complications of asphyxia, acidosis, respiratory distress, or sepsis, and 17 preterm infants with no complications had lower serum albumin concentrations and slightly reduced binding capacity and affinity compared to the healthy term infants. Free bilirubin concentrations were similar in these three groups, averaging 8 to 9 nmol/l in each group. Twenty-five preterm infants with complications had significantly higher free bilirubin (19 +/- 11 nmol/l), lower binding capacity, and lower binding affinity than any of the other three groups (P less than 0.01 for all comparisons). Five of the 25 sick preterm infants had kernicterus at autopsy. These five infants were similar to the other 20 in birth weight, gestational age, serum bilirubin, and serum albumin level, but had significantly higher free bilirubin and significantly lower binding capacity and affinity. The data suggest that serious neonatal illness is associated with a marked reduction in bilirubin-binding capacity and affinity and an increased risk of kernicterus in preterm infants. The mechanism by which neonatal morbidity decreases bilirubin binding is not known.
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PMID:Free bilirubin concentrations and bilirubin-binding affinity in term and preterm infants. 735 54


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