The natural history of alloimmunization to the PlA1 platelet antigen is uncertain. We followed 50 PlA1-negative pregnant women during pregnancy and for 6 months post-partum in order to determine this natural history. The cohort of PlA1-negative women was obtained by PlA1 typing 5000 women. Three PlA1-negative women formed anti-PlA1 antibodies during this prospective study, two in pregnancy and one in the immediate post-partum period. All three PlA1 antibody producers were HLA-DR3 positive, a histocompatibility phenotype that is strongly associated with alloimmunization to the PlA1 antigen. One of the three infants delivered to these mothers was thrombocytopenic (platelet count 9 x 10(9)/l). The remaining two infants had normal platelet counts at birth (160 and 174 x 10(9)/l). The HLA-A1, -B8, -DR3 and -DRw52 phenotype frequencies in the group of PlA1-negative women who did not form PlA1 antibodies (n = 47) was similar to that found in their husbands, and that expected in a normal Caucasian population. From our data we estimate that alloimmunization to the PlA1 antigen occurs in approximately one out of every 1000 pregnancies in a Caucasian population. It is important to recognize that not all pregnancies in which a mother has formed PlA1 alloantibodies will result in the delivery of a thrombocytopenic infant. These findings are relevant to programs designed to either prevent alloimmunization to the PlA1 antigen (through passive administration of anti-PlA1 immunoglobulin to at-risk PlA1-negative mothers), or to identify women at risk of delivery of thrombocytopenic infants (by antenatal screening to detect women alloimmunized to the PlA1 antigen).
Fetal alcohol spectrum disorder (FASD), caused by gestational ethanol (EtOH) exposure, is one of the most common causes of non-heritable and life-long mental disability worldwide, with no standard treatment or therapy available. While EtOH exposure can alter the function of both neurons and glia, it is still unclear how EtOH influences brain development to cause deficits in sensory and cognitive processing later in life. Microglia play an important role in shaping synaptic function and plasticity during neural circuit development and have been shown to mount an acute immunological response to EtOH exposure in certain brain regions. Therefore, we hypothesized that microglial roles in the healthy brain could be permanently altered by early EtOH exposure leading to deficits in experience-dependent plasticity. We used a mouse model of human third trimester high binge EtOH exposure, administering EtOH twice daily by subcutaneous injections from postnatal day 4 through postnatal day 9 (P4-:P9). Using a monocular deprivation model to assess ocular dominance plasticity, we found an EtOH-induced deficit in this type of visually driven experience-dependent plasticity. However, using a combination of immunohistochemistry, confocal microscopy, and in vivo two-photon microscopy to assay microglial morphology and dynamics, as well as fluorescence activated cell sorting (FACS) and RNA-seq to examine the microglial transcriptome, we found no evidence of microglial dysfunction in early adolescence. We also found no evidence of microglial activation in visual cortex acutely after early ethanol exposure, possibly because we also did not observe EtOH-induced neuronal cell death in this brain region. We conclude that early EtOH exposure caused a deficit in experience-dependent synaptic plasticity in the visual cortex that was independent of changes in microglial phenotype or function. This demonstrates that neural plasticity can remain impaired by developmental ethanol exposure even in a brain region where microglia do not acutely assume nor maintain an activated phenotype.
Intensive plasma exchange therapy with fresh-frozen plasma as the replacement fluid was used to manage ten patients, five with acute and five with chronic immune thrombocytopenic purpura (ITP). Therapy was started because of severe hemorrhage (1 case), failure to respond to steroid therapy (6 cases), or steroid dependence (3 cases). After a median of four exchanges over 6 days (median total volume removed, 11.7 liters), initial responses, defined as a platelet count greater than 100,000 per microliter at the end of the exchange series, were observed in 80 percent of the patients treated. Two adolescents, ages 16 and 17 years, with chronic ITP failed to respond to plasma exchange therapy and subsequently responded to splenectomy. Prolonged remissions of 9 months and greater than 2 years were observed in two patients with acute ITP; in patients with chronic ITP, no prolonged remissions occurred. Neither pre-exchange levels of platelet-associated immunoglobulin G (PAIgG) nor circulating immune complexes predicted the response to plasma exchange, although serially determined PAIgG levels correlated with the severity of ITP and response, or lack of response, to plasma exchange. We conclude that intensive plasma exchange merits further study in patients with acute ITP unresponsive to steroid therapy to determine if the need for splenectomy is reduced. In selected patients with chronic ITP, exchange therapy may provide short-term adjunctive benefit.
Recent treatment for patients with thalassemia and chronic anemia involves transfusion of young red cells (YRBCs) or "neocytes." We developed a technique enabling YRBCs to be separated based on their buoyant density in autologous plasma during centrifugation. Following this procedure, measurement of pyruvate kinase (PK), an age-dependent red cell enzyme, showed neocyte enrichment in the top one-third of the RBC layer corresponding to a mean of 47.5 percent of the total PK present in the unfractionated unit. To provide a neocyte transfusion preparation with an acceptable hemoglobin content, the top one-third fraction from each of three bags of blood was pooled. Leukocytes were removed from this "neocyte unit" by an initial sedimentation with 6 percent hydroxyethyl starch (HES) followed by filtration through a filter (IG 500, Imugard). This process resulted in removal of 99.3 +/- 0.5 percent (mean +/- SD) of the leukocytes with a mean RBC recovery of 89.5 +/- 5.5 percent and a final hemoglobin content of 53.4 +/- 2.3 g. Tests for plasma-free hemoglobin and HES in the supernatant of the final transfusion product gave acceptable mean values of 28 mg per dl and 3.0 mg per ml. Autologous mean RBC survival of Cr51-labeled YRBC fractions was 41.8 +/- 2.9 days (n = 5). This technique yields neocyte enrichment superior to that achieved using a cell processor (model 2991, IBM) and has the added advantage of being less costly to prepare ($45.00 [1984] U.S. per YRBC unit as compared to an estimated $135.00 [1984] U.S., IBM) and more economical in terms of blood use.
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