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)

Cold-insoluble globulin is normally present in plasma and serum at concentrations of 27.52 +/- 4.60 and 23.46 +/- 5.18 mg/dl, respectively (means +/- SD). The concentration of CIg in blood samples was significantly decreased in DIC syndromes (14.69 +/- 6.55 mg/dl; p less than 0.001). A strong, positive correlation was found with AT-III (r = 0.68) and a less striking one with Plg. Although alpha 2-PI was shown to be significantly decreased in DIC syndromes (p less than 0.001), a weak, inverse correlation was found between CIg and alpha 2-PI (r = -0.29). Immunologically cross-reactive substances were found to be widely distributed in association with the cells and tissues of mesenchymal origin, including fibroblasts, adipose cells, smooth muscle cells, and basement membranes. The glomerular basement membrane was an exception and is currently believed to be of different origin. In the kidney, fluorescence was found in the mesangium. Cold-insoluble globulin is also present as a component of cryofibrinogen that forms a solid gel at low temperatures. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that CIg in this fraction was rather homogeneous. Although closely migrating doublets were occasionally seen in the 440,000-dalton region on gels of unreduced samples, monomeric derivatives with a molecular weight of 220,000 or less, which have been claimed to occur in circulating plasma, were not observed. Thus, intact dimeric CIg appears to be the form of the molecule that complexes with fibrinogen. Cold-insoluble globulin is the fraction that was shown to exist as an independent entity from fibrinogen at an ambient temperature by immunoelectrophoresis and ultracentrifugation. However, very rapid formation of highly polymerized complexes in the sol phase at low temperatures was manifested by the finding of a sharp increase in light-scattering intensity using the technique of quasielastic light scattering. A control study on a mixture of normal CIg and fibrinogen disclosed no appreciable change in the temperature range between 37 and 8.5 degrees C. A comparative study on a mixture of cryofibrinogen-derived CIg and normal fibrinogen revealed an intermediate light-scattering pattern. After 2 hr at 8 degrees C, this mixture reached a state of equilibrium, where no further polymerization occurred. The secondary structures of normal and cryofibrinogen-derived CIg, determined by circular dichroism, showed no appreciable difference. A noteworthy finding was the almost complete absence of alpha-helices and a relatively high proportion of beta-structure in both forms of CIg. Amino termini of the fibrinogen moiety of cryofibrinogen were found to consist of alanine, tyrosine, and a small quantity of aspartic acid, consistent with the NH2 terminal moiety composition of normal fibrinogen but not of soluble fibrin monomer complex.
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PMID:Distribution of cold-insoluble globulin in plasma and tissues. 29 82

A radioimmunoassay for fibrinopeptide A (FPA) has been developed. This assay uses rabbit antibodies induced by injection of native FPA-human serum albumin conjugates and 125I introduced into tyrosine-FPA synthesized in out laboratory. Plasma FPA is separated from fibrinogen by TCA extraction. The assay is capable of detecting as little as 50 pg/ml of FPA. In 20 normal donors this assay revealed a mean concentration of 0.9 ng/ml (0.3 SD). In five patients with disseminated intravascular coagulation, FPA concentrations ranged from 13.0 to 346 ng/ml. Two groups of patients with systemic lupus erythematosus (SLE) whose disease had achieved complete remission were studied; one consisted of four patients with no history of lupus nephritis and another with a history of nephritis. Mean FPA concentrations of 1.5 ng/ml (range, 0.7-1.8 ng/ml) and 2.7 ng/ml (range, 1.1-5.6 ng/ml) were found in these two groups, respectively. Another group of nine patients with active SLE, but without evidence of lupus nephritis, had a mean FPA concentration of 4.5 ng/ml (range, 2.4-7.8 ng/ml). Finally, a group of seven patients with active SLE, including active nephritis, had a mean FPA concentration of 10.2 ng/ml (range, 5.3-17.0 ng/ml). A positive correlation was found between the concentration of plasma FPA and serum DNA-binding activity and an inverse correlation was found between plasma FPA and the concentration of serum C3. No correlation existed between plasma FPA and concentration of serum creatinine. Several possibilities for the origin of plasma FPA in patients with SLE were considered; at present it seems most likely that FPA arises through the action of thrombin on fibrinogen.
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PMID:Fibrinopeptide A in plasma of normal subjects and patients with disseminated intravascular coagulation and systemic lupus erythematosus. 93 2

The total synthesis of the insect neuropeptide derivative Z-Gly-Gly-Ser-Leu-Tyr-Ser-Phe-Gly-Leu-NH2 has been carried out by a convergent solid phase strategy. For the coupling of the N-terminal pentapeptide to the C-terminal tetrapeptide, three different methods were assayed. Racemization of the acyl activated amino acid during the fragment condensation reaction was monitored by HPLC. Best results were obtained by enzymatic coupling in a low water containing media using adsorbed alpha-chymotrypsin. An optically pure product was obtained in 82% yield after 1 h of reaction. Chemical methods such as DIC/HOBt and BOP/HOBt/NMM always rendered highly optically impure products containing 10-20% of the D-epimer.
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PMID:Racemization free coupling of peptide segments. Synthesis of an insect neuropeptide. 139 72

It has been shown that epitopes reactive with one group of rabbit antibodies to human fibrinopeptide A (hFPA, A alpha 1-16) are included in its COOH-terminal region (A alpha 7-16). It was further established that Asp-7, Phe-8, and Arg-16 contribute to immunoreactivity and that intact fibrinogen and hFPA-containing fragments react poorly with such antibodies. The purpose of this investigation was to prepare a synthetic peptide corresponding to A alpha 7-16 and use it for generation of FPA-specific monoclonal antibodies (MoAbs). Such probes would allow for development of assays that could measure hFPA directly in plasma. In our approach, an ovalbumin-conjugate of the hFPA homologue served as immunogen. Mouse spleen cells were fused with the immunoglobulin nonsecretor myeloma (P3X63Ag8.653). A hybridoma (8C2-5) has been isolated that secretes an antibody (MoAb/8C2-5) with the following characteristics: (a) IgG1, kappa isotype; (b) equilibrium dissociation constant of 1.5 +/- 0.2 x 10(7) L/mol with the [125I]-labeled N-tyrosyl derivative of hFPA [( 125I] Tyr-hFPA) as ligand; (c) reacts with hFPA and dog FPA (dFPA) but not with the des Arg (A alpha 1-15) or shorter peptides; (d) does not react with intact fibrinogen or A alpha-chain of human or dog origin; (e) does not react with the elastase-generated hFPA-containing peptide A alpha 1-21. Enzyme-based immunoassays (EIAs) have been developed for measuring plasma hFPA levels in the range 3 x 10(-8) to 5 x 10(-7) mol/L. Since it has already been shown by a number of investigators that hFPA levels in patients with overt defibrination fall into this range, we propose that the MoAb/8C2-5-based assays may serve as useful clinical tools in screening patients at risk of thrombosis. The 8C2-5 antibody may also be helpful in studies dealing with congenital dysfibrinogenemias, particularly in identifying heterozygous propositi with amino acid substitutions at any position within the A alpha 7-16 region. Finally, due to its cross-reactivity with dFPA, assays using this antibody should also be valuable in the canine experimental thrombosis model studies.
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PMID:Use of a synthetic homologue of human fibrinopeptide A for production of a monoclonal antibody specific for the free peptide. 275 51

A series of patients with meningococcal infections have been studied and divided in two groups: Group I patients with meningococcal sepsis and group II, those with meningococcal meningitis. Patients in group I presented with more severe encephalopathy, shock, DIC and acute systemic complications. Both groups showed a marked hypoaminoacidemia compared with normal controls (other than for the sulfur containing amino acids and phenylalanine). The concentration of aromatic and basic amino acids, the phenylalanine/tyrosine ratio, the transaminase levels and the negative nitrogen balance were higher in group I patients. The ratio of branched chain to aromatic amino acids was lower in group I. All these differences were statistically significant. The close association between the metabolic derangements and clinical manifestations may help in the understanding of several physiopathological aspects of meningococcal infections.
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PMID:Significance of the changes in plasma amino-acid levels in meningococcal infection. 365 98

Muscle protein degradation and intracellular protease activities were investigated in disseminated intravascular coagulation (DIC), which is frequently associated with severe catabolic states such as sepsis and multiple organ failure. DIC was introduced in rats by repeated intravenous thrombin injections. Saline was injected in control rats. In the 28 rats (14 with DIC and 14 controls), the bilateral soleus (SOL) muscles were incubated in an oxygenated medium without cycloheximide (CH) to determine the release of tyrosine (Tyr) into the incubated medium. From 24 rats (12 with DIC and 12 controls), the SOL and extensor digitorum longus (EDL) muscles were harvested to measure the activities of proteasome and of cathepsins L and B. The contralateral muscles were incubated in a medium with 0.5 mM CH to determine the release of Tyr and 3-methylhistidine (3-MH). The release of Tyr without CH (net proteolysis) from SOL muscles with DIC was greater than in controls (218 +/- 83.3 vs. 145 +/- 47.7 pmol/mg/h. However, the release of Tyr and 3-MH with CH (total proteolysis) and the activities of proteasome and cathepsins in DIC were nearly the same as those in controls. In both DIC and control rats, the total release of Tyr and proteasome activity were greater in SOL than in EDL muscles. These results suggest that reutilization of Tyr, reflecting protein synthesis, is suppressed in DIC and that the red slow muscle is more active in nonfibrillar proteolysis than the white fast muscle.
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PMID:Modulation of muscle protein metabolism in disseminated intravascular coagulation. 764 9

The effects of activated platelet (Plt) on muscle degradation were investigated, employing the in vivo disseminated intravascular coagulation (DIC) model induced by thrombin injection and the in vitro tissue culture system of skeletal muscles in rats. Both the release of tyrosine and leucine into the culture medium during 2 h incubation from the muscles harvested 30 min after thrombin injection increased by about 50% compared with control muscles. The addition of thrombin-activated platelet supernatant (TAPS) significantly increased the release of leucine into the incubation medium of the soleus muscles dissected from normally fed rats by 31% in comparison with the respective controls. No significant effect was observed in terms of the release of tyrosine or leucine from the incubated muscles by aspirin treatment before obtaining TAPS, or by the addition of thrombin itself up to the concentration of 0.67 micron/ml which was contained in the incubation medium of TAPS. These data suggest that protein catabolism is accelerated in the muscle from the thrombin-treated rats exhibiting DIC. The supernatant of activated Plt might contain a factor which modulates protein metabolism. That factor is different from prostaglandins or thrombin. Thus, active consumption of Plt may contribute to an increase of muscle breakdown in various catabolic states.
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PMID:Effect of platelet on protein degradation in rat skeletal muscle. 827 34

Pichinde virus infection of inbred guinea-pigs is a model for arenaviral infections in humans. Infected animals experience reduced levels of multiple coagulation factors caused by either consumption coagulopathy or impaired factor synthesis. A radioimmunoassay (RIA) of guinea-pig fibrinopeptide A (gFPA) has been developed to measure the degree of thrombin action in vivo. gFPA was synthesized via the solid-phase method and conjugated to bovine serum albumin (BSA). A double antibody RIA was established employing goat anti-rabbit IgG to precipitate the primary complex composed of either 125I-5-Tyr-gFPA or 125I-12-Tyr-gFPA and rabbit anti-gFPA-BSA. The cross-reaching material was removed by mixing the plasma with 3 vol of ethanol. The supernatant was filtered through a hollow fibre apparatus by centrifugation. Plasma gFPA immunoreactivities of outbred guinea-pigs averaged 6.56 ng/ml. The gFPA-RIA was validated by determining the quantity of gFPA released from thrombin-degraded fibrinogen. A transient elevation of gFPA levels was detected in Pichinde-infected animals by the gFPA-RIA using 125I-12-Tyr-gFPA as a tracer. The pathogenic mechanism by which the increased gFPA levels may lead to the lethality of Pichinde virus infection remains to be elucidated. It is possible that the coagulopathy triggers changes in immune and inflammatory pathways that induces high cytokine concentrations, with deleterious effects on organs such as the heart and lungs.
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PMID:Haemostatic derangements associated with arenavirus infection in the guinea-pig: radioimmunoassay of fibrinopeptide A to assess thrombin action in infected animals. 838 97

We report the genetic abnormalities in the protein C genes of a Spanish child with neonatal purpura fulminans and disseminated intravascular coagulation, associated with undetectable protein C levels. Direct sequencing of the nine protein C gene exons and their splice junctions indicated that the proband is a compound heterozygote with two mutant protein C gene alleles, Y124C and Q132X, that do not express protein C in plasma. The Y124C mutation was inherited from the mother and is due to a novel A to G transition at nucleotide 3416, which results in the substitution of cysteine for tyrosine 124, a highly conserved amino acid in EGF-like domains. The paternal inherited mutation (Q132X) is a C to T transition at nucleotide 3439, which replaces glutamine 132 with a Stop codon signal. This mutation, if expressed, should result in the synthesis of a truncated protein of 131 amino acids. Y124C or Q132X are present in the heterozygous state in the asymptomatic parents and siblings of the proband, all of which have half the normal plasma levels of protein C. Q123X has also been identified in families where type I PC deficiency is inherited as a clinically dominant trait. Therefore, the presence of the same mutation in a family showing a clinically recessive pattern of inheritance indicates that other factors, apart from the type of protein C gene mutation, are responsible for the clinical expression of protein C deficiency.
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PMID:Severe type I protein C deficiency in a compound heterozygote for Y124C and Q132X mutations in exon 6 of the PROC gene. 860 97

A female infant with hypoproteinemia and coagulopathy associated with hypertyrosinemia was successfully treated with living-related liver transplantation (LRLT). On the 12th day of life plasma amino acid analysis revealed a marked elevation of tyrosine, so the patient was fed on a low-tyrosine and low-phenylalanine diet. However, hepatosplenomegaly, hypotonia, alopecia, eczema and psychomotor delay did not improve and recurrent episodes of disseminated intravascular coagulation (DIC) caused her condition to deteriorate. Liver biopsy on the 230th day revealed marked fatty change accompanied by mild to moderate cholestasis. Therefore, LRLT from her father was performed on the 286th day resulting in improvement of all the aforementioned signs and symptoms. Despite a thorough examination, no diagnosis of a known disorder could be established. However, her elder brother had also been born with severe hypoproteinemia and coagulopathy, and died of DIC on the second day of life. Thus, the disorder is designated as a new entity, namely 'congenital hypoproteinemia and coagulopathy associated with hypertyrosinemia'.
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PMID:Liver transplantation in a case of hypoproteinemia and coagulopathy. 958 13


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