polyhomeotic: a gene required for the embryonic development of axon pathways in the central nervous system of Drosophila

Hypomorphic alleles of the locus polyhomeotic (ph) produce multiple, homeotic-like transformations in adult flies that mimic dominant mutations in the Antennapedia and Bithorax complexes. Analysis of null alleles of ph has revealed a complex, embryonically lethal phenotype that includes cell death of the ventral epidermis and abnormalities in the patterns of expression of homeotic and segmentation genes. There is also a dramatic alteration in the pattern of axon pathways in the central nervous system, such that the wild-type array of segmentally repeated commissures and connectives is replaced by bundles of axons confined to the hemiganglia of origin. It is possible that this axonal phenotype is the result of loss of neuronal identity caused by abnormal homeotic and segmentation gene expression.     

Biochemical responses during recovery from maximal and submaximal swimming exercise

Summary We set out to demonstrate whether changes in plasma volume, haematocrit and some important blood constituents occurred after swimming 100 m and 800 m, as well as monitoring the duration of these changes. We measured exercise-induced changes in concentration of plasma constituents in eight subjects, and determined the expected effects of haemoconcentration on these constituents. We also investigated the different biochemical responses occurring after maximal exercise (100 m), as compared to submaximal exercise (800 m). The haematocrit increased significantly after the 100 m swim and to a lesser extent after the 800-m swim, returning to basal levels within 30 min. The plasma volume decreased by 16% on completion of the 100 m and by 8% on completion of the 800 m. The blood lactate concentration increased 15-fold and 10-fold after the 100-m and 800-m swims respectively. The plasma potassium concentration increased significantly immediately on completion of the 100-m swim, then decreased significantly at 2 1/2 and 5 min post-exercise, returning to near-basal values at 30 min. The potassium concentration measured after the 800-m event did not differ significantly from basal levels, however the measured concentrations were significantly lower than the concentrations expected on the basis of haemoconcentration. The plasma sodium concentrations measured after both 100-m and 800-m swims were significantly increased. However, calculations correcting for haemoconcentration showed significant losses in toal circulating sodium. Our study demonstrates marked changes in plasma volume and certain blood constituents after maximal intensity swimming, and less marked changes after submaximal exercise. We also demonstrated the importance of taking the effects of haemoconcentration into account when evaluating changes in concentration of plasma constituents.     

Iris (Lisch) nodules in neurofibromatosis

A group of 30 patients ranging from 4 to 56 years of age with the peripheral form of neurofibromatosis were evaluated for the presence of iris (Lisch) nodules. These nodules were observed in 73% of our cases and their presence was directly related to the severity of the skin manifestations of the disease. It is concluded that Lisch nodules are pathognomonic for neurofibromatosis and thus, their presence should be looked for in all suspected cases.     

The mutational spectrum of brachydactyly type C

Growth/differentiation factor-5 (GDF5), also known as cartilage-derived morphogenetic protein-1 (CDMP-1), is a secreted signaling molecule that participates in skeletal morphogenesis. Heterozygous mutations in GDF5, which maps to human chromosome 20, occur in individuals with autosomal dominant brachydactyly type C (BDC). Here we show that BDC is locus homogeneous by reporting a GDF5 frameshift mutation segregating with the phenotype in a family whose trait was initially thought to map to human chromosome 12. We also describe heterozygous mutations in nine additional probands/families with BDC and show nonpenetrance in a mutation carrier. Finally, we show that mutant GDF5 polypeptides containing missense mutations in their active domains do not efficiently form disulfide-linked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5.     

Lateral Differences in the Latency Between Finger Tapping and the Heart Beat

Based upon suggestions that the two cerebral hemispheres may be differentially involved in the perception and regulation of autonomic activity, three studies were designed to explore differences in the relationship between left versus right hand finger tapping and the heartbeat. In each study, right-handed subjects were asked to tap with either their left versus right forefingers regularly at the rate of approximately once per second. When the time from the R-spike immediately preceding their tap to the tap was examined, a significant difference between the two hands was obtained in two of the studies, with the left hand tapping closer to the last R-spike compared with the right. A variety of additional conditions in the experiments suggest that this effect may depend upon tapping rhythmically. The implications of these findings for the differential role of the left and right hemispheres in the perception and regulation of cardiac activity are considered.     

Composite activities on B cells of products released by T cells activated by concanavalin A.

Supernatants from murine spleen cells cultured for 48 h in the presence of 1.0 μg of concanavalin A (Con A) induced polyclonal antibody synthesis in cultures of spleen cells from both normal and athymic mice in the absence of exogeneous antigen. Moreover, the Con A-induced supernatant rescued B cells which had been rendered unresponsive by a tolerogen [haptenated poly(D Glu,D Lys)]. The capacity of the supernatant to induce cell proliferation was studied under both high and low-density culture conditions. In contrast to antibody secretion, proliferation was only detectable in low-density cultures. The Con A-induced supernatant also contained suppressive components, since the primary anti-sheep red blood cell (SRBC) response was markedly suppressed when the antigen added to cultures consisted of SRBC which had previously been used for absorbing the supernatants. Absorbed supernatants displayed enhanced helper activity indicating that only the suppressor component was removable by antigen. The suppressive component was eluted from erythrocytes with ammonium thiocyanate and was itself strongly suppressive when added to cultures with fresh erythrocytes. Furthermore, the suppressive component proved to be highly antigen-specific, as the SRBC-absorbed factor did not affect the response to horse RBC. The results indicate that supernatants from Con A-activated spleen cells contain both helper and suppressor factors, the latter having easily demonstrable antigen specificity. They further suggest that a nonantigen-derived signal is sufficient to trigger both proliferation and antibody synthesis by B cells.     

A new HLA-A allele, HLA-A*6824, identified in three unrelated individuals

A novel allele, human leukocyte antigen (HLA)-A*6824, has been identified in three unrelated individuals of northwestern European origin in a period of less than 4 months, implying that this allele may be quite common in this population. HLA-A*6824 differs from A*680102 by a single nucleotide change at position 275 in exon 2, which results in a conservative amino acid substitution from lysine to arginine in the peptide-binding groove at codon 68.