Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S.

Four patients with overhydrated cation leak stomatocytosis (OHSt) exhibited the heterozygous RhAG missense mutation F65S. OHSt erythrocytes were osmotically fragile, with elevated Na and decreased K contents and increased cation channel-like activity. Xenopus oocytes expressing wild-type RhAG and RhAG F65S exhibited increased ouabain and bumetanide-resistant uptake of Li(+) and (86)Rb(+), with secondarily increased (86)Rb(+) influx sensitive to ouabain and to bumetanide.

Effect of concentrated ambient particulate matter on blood coagulation parameters in rats.

Epidemiologic studies have shown that exposure to particulate air pollution is associated with short-term increases in cardiovascular morbidity and mortality. These adverse effects of inhaled particulate matter (PM*) may be the indirect result of a PM-induced increase in blood coagulability. This explanation is biologically plausible because prospective studies have shown that increases in blood coagulation parameters are significantly associated with risk of adverse cardiovascular events.

The upward spiral of drug costs: a time series analysis of drugs used in the treatment of hemophilia.

Background: Hemophilia is an expensive disease because its treatment is heavily dependent on costly clotting factor drugs. Over the last nine years,a consortium of three Comprehensive Hemophilia Treatment Centers and other hospitals, which purchased clotting factors for their patients, has seen treatment costs escalate on average 17% annually. Currently, new, even more expensive drugs are entering the market.

Mendelian diseases among Roman Jews: implications for the origins of disease alleles.

The Roman Jewish community has been historically continuous in Rome since pre-Christian times and may have been progenitor to the Ashkenazi Jewish community. Despite a history of endogamy over the past 2000 yr, the historical record suggests that there was admixture with Ashkenazi and Sephardic Jews during the Middle Ages. To determine whether Roman and Ashkenazi Jews shared common signature mutations, we tested a group of 107 Roman Jews, representing 176 haploid sets of chromosomes.

Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis-cirrhosis, and HIV-1 infection by platelet and serum immunological measurements.

A method and approach are described to differentiate classic autoimmune thrombocytopenia (ATP) from immune complex-associated thrombocytopenia in systemic lupus (SLE), hepatitis/chronic liver disease (LIV-ITP) and HIV-1 related thrombocytopenia (HIV-1-ITP). The platelet immunologic profile of IgG, C3C4 and IgM was measured with a solid-phase ELISA, employing 125I-staphylococcal protein A to detect indicator antibody binding. Polyethylene glycol was employed to precipitate immune complexes (PEG-IC).

Prothrombin synthesis in the adult and fetal liver.

Plasma levels of blood coagulation zymogens are lower in the newborn than in the adult, with the lowest levels being in preterm infants. It is not known if the lower coagulation factor levels reflect differences in synthesis, secretion or catabolism. Using a rabbit model we have compared prothrombin synthesis in the fetus and adult.

Severe factor XI deficiency in an Arab family associated with a novel mutation in exon 11.

We investigated an 8-year-old Arab girl with severe factor XI deficiency; one sibling and her father also have severe factor XI deficiency. Her parents and her father's parents are first cousins. Restriction analysis and DNA sequencing excluded the type I, II, III and IV mutations.

Thrombocytosis after major lower extremity trauma: mechanism and possible role in free flap failure.

Microvascular thrombosis and free flap failure are complications of free tissue transfer for coverage of lower extremity soft-tissue and bony defects despite appropriate vessel selection and adherence to meticulous technique. Increased rates of flap failure have been associated with reconstruction performed between 3 days and 6 weeks after injury, as well as in patients with thrombocytosis. We have found that serum platelet levels rise significantly after lower extremity injury.

Transient hemorrhagic diathesis associated with an inhibitor of prothrombin with lupus anticoagulant in a 1 1/2-year-old girl: report of a case and review of the literature.

Acquired inhibitors of coagulation causing bleeding manifestations are rare in children, particularly without an associated underlying disorder such as autoimmune disease. We describe an otherwise healthy 1 1/2-year-old girl who had extensive spontaneous bruising and prolonged bleeding from venipuncture sites. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged, with evidence of an immediate-acting inhibitor.

Functional activity of protein C in newborn infants. A report of a study and a review of the literature.

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.

Thrombocytopenia in children infected with human immunodeficiency virus: long-term follow-up and therapeutic considerations.

Among 180 children infected with human immunodeficiency virus (HIV-1), 14 (8%) developed thrombocytopenia during the course of the disease and have been followed for an average period of 18.8 months. Eight of 14 patients had clinical signs of bleeding.

Prothrombin expression in the adult and fetal rabbit liver.

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.

Cloning and partial sequence of a cDNA for rabbit prothrombin.

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.

Micromethod for demonstrating increased platelet surface immunoglobulin G: findings in acute, chronic, and human immunodeficiency virus-1-related immunologic thrombocytopenias.

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.

Protein S in the first year of life.

Total protein S, free protein S and C4b binding protein were measured in healthy term infants in order to establish the normal levels of these proteins during the first year of life. Total protein S rose from 36.5% of the adult mean level on day 1 of life to 90% between 6 and 12 months of age.

Effect of warfarin on prothrombin synthesis and secretion in human Hep G2 cells.

Prothrombin synthesis and secretion were studied in a human hepatoma cell line (Hep G2) incubated with 35S-methionine for 2 to 24 hours at 37 degrees C. Extracellular and intracellular prothrombin were detected by immunoprecipitation with affinity-purified antiprothrombin antibody. Incorporation of 35S-methionine into prothrombin was monitored by counting specific bands excised from 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).

An epidemic of maternal thrombocytopenia associated with elevated antiplatelet antibody. Platelet count and antiplatelet antibody in 116 consecutive pregnancies: relationship to neonatal platelet count.

Twenty-eight (24%) of 116 pregnant women studied prospectively during an 8-month period in 1983 had platelet counts of less than 150,000/mm3 at least once during pregnancy. Thirteen of these were thrombocytopenic in both the prenatal and the peripartum period. Eighteen were restudied 3 to 12 months after delivery.

Low protein C in the neonatal period.

Protein C was measured by electroimmunoassay in 47 infants within 24 h of delivery. Gestational age ranged from 28 to 43 weeks. The mean level was 27% (range less than 10-67%) of the normal adult mean.