Plasmin-induced redistribution of platelet glycoprotein Ib

Platelet membrane glycoprotein Ib (GPIb), a receptor for von Willebrand factor and thrombin, is present on the platelet surface membrane, in intraplatelet stores, and in plasma (as the proteolytic fragment glycocalicin). We examined the hypothesis that after plasmin-mediated cleavage of platelet surface GPIb, platelets can replenish their surface GPIb pool. Incubation of washed platelets with plasmin (1 hour, 22 degrees C) resulted in loss of platelet surface GPIb, but further incubation (3 hours, 37 degrees C) in autologous plasma resulted in restoration of platelet surface GPIb, as determined by ristocetin- induced platelet agglutination and a flow cytometric assay of platelet binding of three GPIb-specific monoclonal antibodies. Despite the restoration of platelet surface GPIb after the 3-hour incubation of plasmin-treated platelets in autologous plasma, the whole platelet GPIb content (measured by enzyme-linked immunosorbent assay [ELISA], sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and flow cytometry) remained reduced, quantitatively corresponding to an increase in plasma glycocalicin concentration (measured by ELISA). The loss and restoration of platelet surface GPIb occurred on all platelets and, as evidenced by lack of inhibition by prostaglandin E1, EDTA, and cytochalasins, was not mediated by cyclic AMP, extracellular Ca2+, or the platelet microfilament system. In summary, this study shows that after plasmin-mediated cleavage of platelet surface GPIb, platelets can replenish their surface GPIb pool by recruitment of GPIb molecules from the intraplatelet pool (or from a sequestered surface site).     

垂体柄断层解剖与MRI对照研究

给垂体和垂体柄病变的影像学诊断提供解剖学和影像学依据。     

In utero gene transfer and expression: a sheep transplantation model

Retroviral-mediated gene transfer was used to insert a Neo R gene into fetal sheep hematopoietic cells obtained by exchange transfusion from lambs in utero. After gene transfer the cells were returned to the donor fetus. The lambs were examined after birth for the presence of a functioning Neo R gene. Of ten analyzable animals, six were positive for G418 resistant progenitor cells (CFU-Mix, CFU-C, BFU-E, CFU-E). Two animals were studied for extended periods of time: 8 and 24 months. Each has demonstrated a pattern wherein positive periods are interspersed with times when there were no detectable G418-resistant cells. We conclude that retroviral-mediated gene transfer can be used to insert genes into early progenitor cells of fetal sheep in utero and that the animals can continue to demonstrate blood cells expressing the gene for more than 2 years after birth. This is a US government work. There are no restrictions on its use.     

Bone marrow cell count per cubic millimeter bone marrow: a new parameter for quantitating therapy-induced cytoreduction in acute leukemia

A new technique is introduced for determining the number of bone marrow cells per cubic millimeter marrow, providing an accurate and objective means for quantitating therapy-induced cytoreduction. The method requires a correction for admixed peripheral blood in bone marrow aspirates to measure the fraction of remaining pure marrow. While cell kinetic differences between blood, aspirates, and biopsies identify the proportion of contaminating blood cells, the ratio of red cell hematocrits in blood and aspirate gives the volume of trapped blood. By combining both procedures, bone marrow cell counts per unit volume pure marrow result (BMC/cu mm BM), which were found highly reproducible. Blast cell counts (BMBC/cu mm BM) were obtained by additional morphological differentiation. BMC and BMBC/cu mm BM were monitored in 16 patients with acute nonlymphoblastic leukemia treated with daunorubicin, cytosine arabinoside, and 6-thioguanine in combination and in 4 patients with end-stage acute leukemias and non-Hodgkin's lymphomas during high-dose thymidine therapy. Total and daily therapy- induced cytoreduction rates were significantly greater (P less than 0.01) in responders than nonresponders to either regimen. Changes in BMC/cu mm BM were also found representative for changes in BMBC/cu mm BM, since the majority of bone marrow cells were blasts. In acute leukemia. BMC/cu mm BM thus provides accurate and objective measurements of treatment efficacy in vivo and after short periods of drug exposure. Differences in cytoreduction rates within the group of responders also suggest possible prognostic implications.     

Effects of albumin and urea on hydrostatic edema in the perfused lung

Hydrostatic interstitial pulmonary edema was induced in isolated perfused canine lungs to evaluate the effects of treatment with osmotic agents. In 14 preparations after induced venous hypertension adding fluid weights of 20, 30, 40, or 60 g representing 33–100% of normal lobe weight, venous pressure was returned to levels of zero or below without additional treatment. Albumin (25 g) was added to 23 preparations and urea (10 g) added to 10 lungs prepared in a similar fashion. Reductions in pulmonary venous oxygen tension and effective compliance occurred at all levels of edema and persisted after release of venous constriction. Albumin improved venous PO₂ only after the minimal load but there was no significant effect on pulmonary compliance. No improvement in either parameter occurred after urea treatment. Significantly lower weights after albumin or urea treatment were noted after varied fluid loads but were not accompanied by proportional improvement in lung function. In the isolated lung preparation with no outlet for fluid excretion, the therapeutic effectiveness of osmotic agents alone is obviously limited, but the deleterious effects of hydrostatic interstitial edema are not readily reversed by addition of osmotic agents to the perfusate. The previously noted adverse effects of mannitol do not seem to be explained adequately on the basis of lower molecular weight alone since urea did not prove to be deleterious in this preparation.     

Factor X deficiency in the neonatal period

An infant with a severe deficiency of factor X presened in the neonatal period with uncontrollable bleeding from heel prick sites, spontaneous bruising, and haematoma. The deficiency was controlled by infusions of dried human factors II, IX, and X concentrate; the half-life of the infused factor X material is only 18 hours. Despite prophylactic weekly infusions of factor X concentrate, the child developed a fatal intracerebral haemorrhage when only 4 months old. Coagulation studies on both parents and the elder sister showed no obvious coagulation abnormality.