Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood and urine concentrations of antithrombin-III, plasminogen, alpha 2-macroglobulin, alpha 1-antitrypsin, degradation products of fibrinogen-fibrin were studied in patients with abdominal suppuration. Noticeable deviations from the normal values especially marked in the severe process indicated the development of DIC syndrome and renal failure. Heavy combined treatment promoted normalization of the hemostasis shifts and eliminated pyo-inflammatory processes in the abdominal cavity.
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PMID:[Several components of plasma hemostasis in patients with suppurative processes in the abdominal cavity]. 138 May 86

We developed an ELISA to quantitate complexes of activated protein C (APC) with a major plasma APC inhibitor, alpha 1-antitrypsin (alpha 1AT) in human plasma based on the sandwich principle using two different antibodies directed towards protein C and alpha 1AT, respectively. This ELISA test was specific for APC:alpha 1AT complexes and sensitive to greater than or equal to 150 pg complex. Fifty-one of 56 healthy donors had APC:alpha 1AT complex levels above the detection limit (3 ng/ml) ranging from 4 to 14 ng/ml (mean value +/- SD: 7.6 +/- 2.5 ng/ml). Patients (n = 10) with disseminated intravascular coagulation (DIC) had detectable levels of APC:alpha 1AT complex ranging from 21 to 125 ng/ml (median: 69 ng/ml). Complexes of APC with plasma protein C inhibitor (PCI) were also measured using an ELISA sandwich assay. None of the 30 healthy donors had detectable levels (greater than or equal to 5 ng/ml) of APC:PCI complex, and plasma samples from 9 of 10 DIC patients had detectable concentrations of APC:PCI complex ranging from 10 to 63 ng/ml (median: 22 ng/ml). APC:alpha 1AT complex was detected in 25 of 26 patients with deep venous thrombosis (DVT), with levels ranging from 5 to 136 ng/ml (median: 23 ng/ml), whereas APC:PCI was detected in only 6 DVT patients, with levels between 11 and 105 ng/ml. PCI antigen levels in 70 normals ranged from 56 to 175% (mean +/- SD: 99.1% +/- 24.2%). PCI antigen levels were decreased in DIC patients, in patients with cerebral arterial thrombosis, and in DVT patients undergoing heparin therapy, but not in patients with myocardial infarction. PCI antigen levels were decreased much further in DVT patients receiving heparin compared to those not receiving heparin, showing that heparin therapy is associated with a decrease in PCI levels. The detection in normal subjects and in thrombotic patients of circulating APC:inhibitor complexes supports the view that the protein C pathway is activated during DIC and DVT. Moreover, it emphasizes that both PCI and alpha 1AT are physiologic inhibitors of APC. Thus, measurement of APC complexes may provide sensitive parameters for specific detection of activation of the clotting and protein C pathways.
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PMID:Determination of plasma protein C inhibitor and of two activated protein C-inhibitor complexes in normals and in patients with intravascular coagulation and thrombotic disease. 217 67

In organ culture experiments, the induction of pemphigus acantholysis is known to be blocked by the addition of serine proteinase inhibitors. Recently, nontoxic synthesized low molecular weight proteinase inhibitors have been clinically available for the treatment of disseminated intravascular coagulation and pancreatitis. To determine if these drugs are useful aids to treat patients with pemphigus, we examined the effect of omega-guanidino ester analogues, i.e., 1) gabexate mesilate, 2) camostat mesilate, and 3) nafamostat mesilate, on experimental pemphigus acantholysis in both organ culture and neonatal BALB/c mice. Furthermore, the effect of plasma natural proteinase inhibitors (alpha-1-proteinase inhibitor) isolated from human plasma was similarly examined. Results revealed that synthesized low molecular weight inhibitors (drugs) were able to inhibit the induction of acantholysis in organ culture system, but had little or no effect on lesion formation in the neonatal mouse system. By contrast, alpha-1-proteinase inhibitor could completely inhibit acantholysis formation in mice. These findings implied a possible new therapeutic approach using proteinase inhibitors for patients with pemphigus.
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PMID:Proteinase inhibitors block formation of pemphigus acantholysis in experimental models of neonatal mice and skin explants: effects of synthetic and plasma proteinase inhibitors on pemphigus acantholysis. 252 84

Both congenital and acquired antithrombin-III (AT-III) deficiencies are amenable to replacement therapy. We describe two antithrombins produced by recombinant DNA techniques from human alpha 1-antitrypsin (alpha 1AT) cDNA in yeast. Alteration of the alpha 1AT active site, replacing methionine 358 with arginine, results in a thrombin inhibition rate similar to that of heparin-activated AT-III. Alteration of two further residues, to give a five-residue sequence identical to AT-III, does not increase this rate further. Neither antithrombin is activated by heparin; both are unglycosylated and have shorter in vivo half-lives (t1/2) than human alpha 1AT. These antithrombins should be suitable for therapeutic replacement of AT-III in cases of congenital deficiency and in conditions associated with acquired AT-III deficiency, such as disseminated intravascular coagulation.
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PMID:Characterization of antithrombins produced by active site mutagenesis of human alpha 1-antitrypsin expressed in yeast. 264 77

Plasma antithrombin III (ATIII) levels decrease early during gram-negative septicemia, and even a moderate decrease in this major inhibitor of the coagulation system is associated with serious disseminated intravascular coagulation (DIC). Herein the efficacy of high-dose (at least 250 units/kg) ATIII supplementation in animal models of Escherichia coli endotoxemia or bacteremia is reported. An endotoxemic rat model demonstrated that: (1) DIC occurs very early, before the appearance of deleterious cardiovascular abnormalities; (2) ATIII prophylaxis attenuates DIC, metabolic dysfunction, and organ damage; (3) ATIII prophylaxis increases permanent survival; (4) ATIII treatment one hour after endotoxin challenge attenuates DIC, metabolic dysfunction, and organ damage, although not as well as when given prophylactically, and survival is not increased. An endotoxemic sheep pulmonary dysfunction model demonstrated that: (1) ATIII prophylaxis prevents the typical decrease in arterial oxygen partial pressure; (2) ATIII prophylaxis combined with alpha-1-proteinase inhibitor significantly attenuates indices of pulmonary dysfunction. An E. coli bacteremic baboon model demonstrated that ATIII prophylaxis and treatment significantly attenuate indices of DIC and organ damage and prevent death in an otherwise completely lethal dose bacterial challenge. In conclusion, prophylactic treatment with high doses of ATIII may be efficacious in disease states of impending disseminated intravascular coagulation, such as primary or secondary gram-negative septicemia.
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PMID:Efficacy of antithrombin III supplementation in animal models of fulminant Escherichia coli endotoxemia or bacteremia. 267 67

To further define the clinical, pathologic, and biochemical features of hemorrhagic shock and encephalopathy syndrome, we studied 25 affected children (aged 3 months to 14 years) admitted to a single center between 1982 and 1985. A prodromal illness comprising vomiting, diarrhea, listlessness, and fever was present in 84% of the cases. Acute onset of shock, convulsions and coma, bleeding (or laboratory evidence of disseminated intravascular coagulation), elevated plasma activity of hepatic enzymes, acidosis, and impaired renal function was present in every case. Twenty patients died, and all the survivors are neurologically damaged. At postmortem examination, intravascular microthrombi coexisting with hemorrhages and petechiae were found in most organs. Centrilobular liver necrosis and cerebral edema were prominent features. No microbiologic cause for the disorder was identified, but decreased plasma levels of the protease inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin, together with increased levels of circulating proteolytic enzymes, were frequently present. An overrepresentation of the uncommon variant phenotypes of alpha 1-antitrypsin was found in first-degree relatives of affected patients (four had the MZ phenotype, and one each the MS or MC phenotype, of 19 relatives studied). Abnormal accumulation of alpha 1-antitrypsin was detected immunohistochemically in the livers of six of the patients. Defective protease inhibitor production or release may be involved in the pathogenesis of the disorder.
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PMID:Hemorrhagic shock and encephalopathy: clinical, pathologic, and biochemical features. 276 14

In inflammation, particularly in septicaemia, complex coagulation disorders may lead to a dangerous haemorrhagic diathesis. The conventional concept for this syndrome called DIC implicates the occurrence of active thrombin in the circulation, which may be followed by hyperfibrinolysis due to plasmin formation. In this study data are presented suggesting an important role for a third proteolytic system, granulocytic elastase. The complexes of plasmin and elastase with their specific inhibitors, alpha 2-antiplasmin-plasmin (alpha 2AP-PI) and alpha 1-antitrypsin-elastase (alpha 1AT-ELP) were determined immunologically. The alpha 1AT-ELP appears mainly in gram-negative septicaemia, particularly in meningococcal disease. The estimation of alpha 2AP-PI and alpha 1AT-ELP, together with a method for the detection of the antithrombin III--thrombin complex which remains to be established, is a suitable tool for for the differential diagnosis of the consumption of coagulation proteins. The assumption that at least three proteolytic systems participate in the development of the haemorrhagic diathesis during inflammation leads to the concept of a broad, comprehensive substitution therapy with e.g. concentrates of AT III, PPSB, or fresh frozen plasma. The aim of this treatment is to replace not only the consumed procoagulatory factors, but also the lacking inhibitors in order to control this "abnormal proteolysis syndrome".
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PMID:The clinical significance of alpha 1-antitrypsin-elastase (alpha 1AT-ELP) and alpha 2-antiplasmin-plasmin (alpha 2AP-PL) complexes for the differentiation of coagulation protein turnover: indications for plasma protein substitution in patients with septicaemia. 293 57

Tissue specimens obtained at autopsy from seven childhood cases of malignant histiocytosis were studied by immunohistochemistry. Clinically, the majority of the cases showed sustained fever, hepatosplenomegaly, pancytopenia, and DIC. The pretreatment diagnosis was based on their typical clinical manifestations and bone marrow smear findings. Although three patients temporarily responded to exchange transfusion and chemotherapy, all seven patients eventually died of active disease. Postmortem examination revealed the proliferation of atypical histiocytes appearing in variable degrees of maturation in the lymph nodes, liver, spleen, bone marrow, lungs, and central nervous system. Immunohistochemical staining for lysozyme, nonspecific cross-reacting antigen (NCA), alpha 1-antitrypsin (alpha 1 AT), alpha and beta subunits of S100 protein (S100 alpha, beta), and concanavalin A receptors (ConAR) in cytoplasm demonstrated the presence of two subtypes of malignant histiocytes, ie, S100 beta+/NCA-/ConAR+ (4 cases) and S100 beta-/NCA+/ConA R+ (three cases). The results of lysozyme, alpha 1 AT, and S100 alpha staining were inconsistent. A survey of the literature disclosed that the incidence of S100 protein-positive cases in children was higher than in adults (12/21 v 5/19; chi 2, P less than .05). Further large scale investigation is necessary to confirm the independence and significance of these two subtypes of histiocytes in malignant histiocytosis.
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PMID:Malignant histiocytosis in childhood: clinical, cytochemical, and immunohistochemical studies of seven cases. 337 90

A comparative study of two patients, one affected by haemorrhagic shock and encephalopathy (HSE) and the other by heatstroke is reported. Both presented shock, disseminated intravascular coagulation, neurological damage and hepatopathy. A lowered alpha 1-antitrypsin concentration as well as a slightly increased circulating immune complexes and complement consumption were observed in the HSE patient but not in the heatstroke one. In both, cultures for bacteria were negative, the viral serology was non-specific and hepatitis A and B studies were negative. HSE patient died. A possible relationship between HSE, heatstroke, malignant hyperthermia and halothane hepatitis is postulated. Fever, potentially hepatotoxic drugs or unknown agents (HSE) might trigger this clinical picture.
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PMID:[Hemorrhagic shock and encephalopathy. Its possible relation with heat stroke]. 407 88

In 119 children, predominantly newborns and babies with sepsis, alpha 2-Antiplasmin was determined by the use of the chromogenic substrate S-2251. In healthy newborns, the inhibitor level averaged 65 per cent of the adult level. Already in the initial phase of sepsis, enhanced alpha 2-antiplasmin values were observed. During the further course, they increased markedly. Thus, alpha 2-antiplasmin proved to be an acute phase reactant together with fibrinogen, factors II and X, and alpha 1-antitrypsin measured as trypsin inhibitor capacity. The correlation analysis in all subgroups showed moderately tight binding to fibrin. In patients with shock or in those who decreased, lower levels were measured. The overproduction is assumed to be caused by disseminated intravascular coagulation processes. In other diseases such as respiratory distress, alpha 2-antiplasmin was reduced. In case of disseminated intravascular coagulation that was not caused by sepsis consumption of components dominated. In the probability paper, distribution of the values of the subgroups was found to differ markedly. Thus, the inhibitor proved to be of diagnostic value.
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PMID:[Alpha 2-antiplasmin in childhood]. 617 99


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