Growth and development of the tibia, fibula, and ankle joint

Deformities of the leg and ankle may result from growth abnormalities of the tibia and fibula. Measurements of the distance between the proximal tibial and fibular physes, the distal tibial and fibular physes, and the angle between the long axis of the tibia and the distal tibial physis and talar dome were made to determine the changes that occur during normal skeletal development. These measurements demonstrate that early detection of growth discrepancy is possible.     

Association of the p85 regulatory subunit of phosphatidylinositol 3- kinase with an essential erythropoietin receptor subdomain

Using an active, HAI epitope-tagged form of the murine erythropoietin (EPO) receptor and via direct coimmunoprecipitation, the p85 regulatory subunit of phosphatidyl inositol-3 kinase (p85/PI3-K) is shown to associate with the EPO receptor in transfected FDC-P1 cell lines. Coimmunoprecipitation of p85 with epitope-tagged EPO receptors was observed initially in FDC-HER cells labeled metabolically with [32P]orthophosphate, and association of these factors was confirmed by Western analyses of receptor immunoprecipitates using p85 antiserum. Interestingly, this association occurred in the absence of ligand, and exposure of FDC-HER cells to EPO did not detectably affect levels of receptor-associated p85 or overall levels of p85 phosphorylation. However, EPO was observed to stimulated the rapid formation of phosphatidylinositol 32P-phosphate in FDC-HER and FDC-ER cells. Through baculovirus-mediated expression of epitope-tagged EPO receptor forms in SF9 cells, domains for p85 association were mapped. Analyses of receptor forms with cytosolic truncations and deletions delineated a candidate subdomain for p85 binding to an essential extended box-2 region (P329-E374; including a putative motif for SH2 binding, Y343LVL). These findings extend a mechanistic alignment between the EPO receptor and protein tyrosine kinase-encoding receptors that likewise activate PI3-K, and expand the importance of further defining pathways to PI3-K activation.     

Synaptogenesis in the ventromedial hypothalamus of the prenatal mouse.

Mouse embryos from day 13 to day 19 of gestation (E13 through E19) were removed by Caesarean section and their brains were prepared for electron microscopy. Coronal sections were examined in three planes through the ventromedial hypothalamus: anterior, the level at which the optic tracts pass posterolaterally to become partially enclosed in the major brain mass; middle, the level at which the floor of the third ventricle begins to widen and flatten; posterior, the level at which the most anterior infundibulum appears. Three types of junctional complexes were examined. Close junctions are identified as straight, parallel areas of two apposed membranes which appear more electron-dense than immediately adjacent regions. The membranes are separated by a clearly visible cleft. Unlike synapses, no clear synaptic vesicles are found in either of the adjacent profiles unless randomly distributed and accompanied by ribosomes or glycogen. Close junctions are seen most frequently on day E15, then decrease in number through E19. Their participation in synaptogenesis is discussed from temporal, morphological, distributional and quantitative perspectives and is provisionally rejected. Immature synapses show only the minimal membrane specialization found in close junctions, but vesicles are present, ribosomes absent in at least one of the adjacent cytoplasms. Their appearance peaks on E17-E18, paralleling and slightly preceding that of the mature synapses. Their evolution from close junctions has only weak temporal support. Mature synapses display the cytoplasmic densities which immature synapses lack. They attain their greatest prenatal numbers on E18, then decrease in number on E19. The conclusion is advanced that synaptogenesis does--or at least can--occur without the prior appearance of avesicular regions of increased membrane density.     

Traumatic events and alcohol use disorders among American Indian adolescents and young adults

This study examined the relationship between severe traumatic events and alcohol use disorders in American Indian adolescents and young adults. Interviews of 432 adolescents and young adults who were enrolled tribal members living on or near two closely related American Indian reservations were used. Results indicated that severe trauma increased the odds of alcohol use disorders (p <.001), with the number of traumas having a dose-dependent effect. The authors conclude that trauma is associated with alcohol use disorders in this population. This study's findings yield important insights into the risks in American Indian adolescents and young adults that may result from early trauma, as well as implications for the timing and possible settings for intervention.     

Malignant clear cell acrospiroma.

The histologic features of a malignant clear cell acrospiroma were those of infiltrative local growth, frequent mitoses and angiolymphatic invasion. The histochemical and ultrastructural findings were similar to those reported for benign clear cell acrospriomas. Amputation of the leg and regional node dissection were required for clinical control. Evaluation of this case and review of the literature suggests that the malignant clear cell acrospiroma often behaves in an aggressive manner and frequently metastasizes. As a consequence, thereapeutic strategies should be appropriately planned.