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)

Recently, we have found that defibrination of rats with Malayan pit viper venom induces a 10-38-fold increase in the levels of translatable fibrinogen mRNA in the liver. We have used this response to obtain cDNA clones for the three polypeptide chains of rat fibrinogen. A large cDNA library was created in pBR322 from induced rat liver polyadenylated RNA by the poly(dG, dC)-tailing method. Part of this library was screened using colony hybridization with [32P]cDNA prepared from induced and noninduced rat liver RNA. Colonies consistently giving a more intense signal with the induced [32P]cDNA were considered possible fibrinogen recombinants and were used for hybrid selection and translation of mRNA. In this way, cDNA clones for each of the three fibrinogen mRNA's were identified. Analysis of polyadenylated RNA by Northern blotting indicates that the three chains are synthesized from mRNA's of 2300, 2050, and 1950 nucleotides for the alpha, beta, and gamma chains, respectively. The fact tha each of the three chains has a separate mRNA indicates that the highly coordinated regulation of the three messages for rat fibrinogen does not occur by translation of a common cytoplasmic RNA.
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PMID:Molecular cloning of cDNA for the alpha, beta, and gamma chains of rat fibrinogen. A family of coordinately regulated genes. 616 15

As the spherical diameter of pulmonary capillaries is smaller than that of neutrophils, increased neutrophil stiffness or conversely, decreased neutrophil deformability is a key step in the initial sequestration of neutrophils within the lungs during inflammatory processes. Antithrombin III (AT) is known to exert a therapeutic effect against disseminated intravascular coagulation, and accumulating evidence suggests that AT also has anti-inflammatory properties. The mechanisms of its anti-inflammatory effects remain unclear, but in a rat endotoxin model, AT apparently inhibited neutrophil sequestration in the lung. In the present in vitro study, therefore, we examined the effect of AT on the deformability of human neutrophils and correlated those findings with their F-actin content. Isolated human neutrophils were stimulated with formyl-Met-Leu-Phe (1 muM, 2 min) in the presence or absence of the alpha, beta, or low heparin-affinity isoforms of AT (1 IU/ml, 20 min), and deformability was evaluated using a filter assay system. Neutrophils were also stained with fluorescein isothiocyanate-phalloidin and subjected to a fluorescein-activated cell sorter scan to assess F-actin content. The results showed that pretreatment with any of the three AT isoforms similarly inhibited the decreased neutrophil deformability and increased F-actin content of stimulated cells. Notably, heparinase had no effect on deformability or F-actin content in the presence or absence of AT, which was somewhat unexpected, as heparin sulfate proteoglycans likely function as AT receptors. These findings suggested that AT inhibits the increase in neutrophil stiffness seen during inflammatory processes by inhibiting actin polymerization via a heparin-independent pathway.
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PMID:Effect of antithrombin III on neutrophil deformability. 1600 Mar 88