Faculty Bibliography

Protein C is lower in newborn infants than in adults. There are conflicting reports regarding functional activity and the presence of des-gamma carboxylated species in the newborn. We have compared protein C activity and antigenic level in newborn infants and found the activity: antigen ratio to be lower than in adults (0.69 versus 1.0). We discuss this finding in relation to the previously published reports

Plasma prothrombin levels in newborn humans are lower than in adults. The same is true of many newborn and fetal mammals, including the rabbit. To determine if the lower levels are due to less expression of the protein, we have compared mRNA for prothrombin in fetal and adult rabbit liver. Northern blots were hybridized with a cDNA for rabbit prothrombin revealing a single mRNA of approximately 2 kb in both adult and fetal animals. mRNA specific for prothrombin was quantitated by slot blotting of RNA prepared from adults and fetuses aged 21 d to term (31 d). Prothrombin-specific mRNA in fetuses was greater than 50% of that in adults even when the fetal plasma prothrombin was only 15% of the adult level. This suggests that low plasma levels in the fetuses are not the result of less transcription. Examination of liver sections revealed that the predominant tissue in the fetus is hematopoietic, not hepatic. In the youngest fetuses, less than 20% of the liver consisted of hepatocytes, yet these fetuses expressed more than 50% of the adult level of prothrombin-specific mRNA. Thus, transcription of prothrombin mRNA may be proceeding at a greater rate in the fetal hepatocyte than in the adult, or hematopoietic cells may be expressing the protein. We conclude that in fetal rabbit liver, prothrombin is expressed at a high level relative to the hepatocyte content and that the cause of the low plasma levels is posttranscriptional

A 1466 base pair cDNA for rabbit prothrombin has been isolated and partially sequenced. The deduced amino acid sequence shows considerable homology with the sequences of human and bovine prothrombin. The cDNA extends from the equivalent of nucleotide 516 in the bovine sequence through the coding region and 99 nucleotides in the 3' non-coding region

A method has been developed for the demonstration of increased platelet surface IgG that uses 1 ml of blood regardless of the platelet count. Platelets are gel filtered to remove plasma and contaminating lymphocytes. They are then reacted with fluorescein-conjugated antihuman IgG and analysed by flow cytometry. Percent positive staining cells vary from 10% to 80% of total cells examined. A platelet antibody index is derived from the product of percent positive staining cells X mean fluorescence intensity of positive staining cells. All patients studied with chronic idiopathic thrombocytopenia purpura (ITP) or human immunodeficiency virus-1 (HIV-1)-related thrombocytopenia had increased platelet surface IgG. Twelve acute children and 11 chronic children had indices averaging 3.5- and 8.9-fold greater than 12 normal children, respectively. Five of 12 children with acute ITP had normal platelet IgG. There was no linear correlation between the platelet antibody index and platelet count. Platelets of patients with acute, chronic, or HIV-1-related ITP displayed autofluorescence. In chronic ITP, the percentage of platelets displaying autofluorescence had a significant negative correlation with the platelet count. This technique will be a valuable diagnostic tool in the pediatric population