Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component

A study was carried out to explore requirements for the inhibition of tissue factor-factor VIIa enzymatic activity in plasma. Reaction mixtures contained plasma, 3H-factor IX or 3H-factor X, tissue factor (vol/vol 2.4% to 24%), and calcium. Tissue factor-factor VIIa activity was evaluated from progress curves of activation of factor IX or factor X, plotted from tritiated activation peptide release data. With normal plasma, progress curves exhibited initial limited activation followed by a plateau indicative of loss of tissue factor-factor VIIa activity. With hereditary factor X-deficient plasma treated with factor X antibodies, progress curves revealed full factor IX activation. Adding only 0.4 micrograms/mL factor X (final concentration) could restore inhibition. Inhibition was not observed in purified systems containing 6% to 24% tissue factor, factor VII, 0.5 micrograms/mL, factor IX, 13 micrograms/mL, and factor X up to 0.8 micrograms/mL, but could be induced by adding barium-absorbed plasma to the reaction mixture. Thus, both factor X and an additional material in plasma were required for inhibition. The amount of factor X needed appeared related to the concentration of tissue factor; adding more tissue factor at the plateau of a progress curve induced further activation. These results also indicate that inhibited reaction mixtures contained active free factor VII(a). Preliminary data suggest that inhibition may stem from loss of activity of the tissue factor component of the tissue factor- factor VII(a) complex.     

Fetal intracranial teratoma: US diagnosis of three cases and a review of the literature

We describe three cases of fetal intracranial teratoma diagnosed by ultrasound and review the literature. Sonographic features include cranial enlargement, gross distortion of normal cerebral architecture by a hyperechoic, multicystic mass, and polyhydramnios. Despite early diagnosis, the cesarean section rate is high and the overall prognosis is dismal.     

Cytomegalovirus infections in seropositive patients after transfusion. The effect of red cell storage and volume

Antibody responses to cytomegalovirus (CMV) after red cell (RBC) transfusion were studied in 84 seropositive surgery patients and 82 seropositive oncology patients. The surgery patients were randomized to receive RBCs stored either 3 to 8 or 20 to 42 days after donation. Of 38 patients receiving RBCs stored 8 days or less, 3 developed a rise in titer (4-fold increase) of IgG antibody to CMV 8 to 12 weeks after transfusion. This rate of response (8%) did not differ significantly (p = 0.23) from that (16%) in the 46 patients receiving RBCs stored 20 to 42 days. Seropositive oncology patients were randomized to receive RBCs from seronegative or random donors. Five (19%) of 27 oncology patients receiving seronegative RBCs and 13 (23%) of 55 patients receiving random RBCs (mean, 2 seropositive RBC units/patient) developed a rise in titer of antibody to CMV. No CMV morbidity occurred in either patient group. For both patient groups, a rise in titer of antibody to CMV was associated with the number of transfused RBC units. These results confirm that CMV-seronegative RBCs are unnecessary for infrequently transfused seropositive patients. They also suggest that multiple transfusions of stored RBCs are as immunosuppressive as multiple transfusions of RBCs used within a few days after donation.     

Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria

The purpose of these studies was to determine the molecular basis of the phenotypic mosaicism that is a defining feature of paroxysmal nocturnal hemoglobinuria (PNH). Analysis of T cell clones from a female patient revealed four distinct phenotypes based on surface expression of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). When PIG-A (the gene that is mutant in PNH) from these clones was analyzed, four discrete somatic mutations were identified. Analysis of X chromosomal inactivation among the abnormal T cell clones was consistent with polyclonality. Together, these studies demonstrate that the phenotypic mosaicism that is characteristic of PNH is a consequence of genotypic mosaicism and that, at least in this case, PNH is a polyclonal rather than a monoclonal disease. That four distinct somatic mutations were present in a single patient suggests that in conditions that predispose to PNH PIG-A may be hypermutable.     

Relative carriage rates of nuclear dehydrogenating clostridia in two populations of different colorectal cancer risk

Carriage of nuclear dehydrogenating clostridia has been associated with colon cancer and implicated in its aetiology. This study has compared the carriage of these organisms in a British population at high risk for the development of colon cancer with a low risk Nigerian population. Clostridia were found in all of the stools from both populations. Nuclear dehydrogenating clostridia were only found in the stools of the British subjects (32%). These results support the suggestion that the carriage rate of nuclear dehydrogenating clostridia in a population is related to the risk of colon cancer.