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.     

Temporal effects of a COX-2-selective NSAID on bone ingrowth

The effects of a short course of a COX-2 inhibitor on bone healing when the drug is discontinued are unknown. We examined the effects of rofecoxib on bone ingrowth over a 6-week period using a well-defined animal model. The Bone Harvest Chamber was implanted bilaterally in mature rabbits. After osseointegration of the chamber, the following treatments were given for 6 weeks each, followed by a harvest in each case: control-no drug; oral rofecoxib (12.5 mg/day) for the first 2 of 6 weeks; washout period-no drug; oral rofecoxib for the last 2 of 6 weeks; washout period-no drug; rofecoxib given continuously for all 6 weeks. Harvested specimens were snap-frozen, cut into serial 6-microm sections, and stained with hematoxylin and eosin and alkaline phosphatase (osteoblast marker), and processed using immunohistochemistry to identify the vitronectin receptor (osteoclast-like cells). Rofecoxib given continuously for 6 weeks yielded statistically less bone ingrowth compared to the control treatment. Rofecoxib given during the initial or final 2 weeks of a 6-week treatment did not appear to interfere with bone ingrowth. This suggests that the effects of COX-2 inhibitors on bone are less profound when the drug is administered for a short period of time.     

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.     

Variation in distribution of the three flavivirus-specified glycoproteins detected by immunofluorescence in infected Vero cells

Summary Indirect immunofluorescence with rabbit antisera was used to probe the intracellular locations of the antigens of envelope, prM (precursor to structural protein M) and the nonstructural glycoproteins NS 1 (formerly described as NV 3 or SCF) specified by the flaviviruses dengue-2 and Kunjin. Perinuclear staining in various types of foci was prominent for all antigens, and the distribution was influenced by whether cells were fixed with acetone or formaldehyde. Staining of Golgi-like masses or inclusions by anti-envelope sera occurred regularly and prominently in cells infected and stained with homologous anti-envelope antibodies; in the cross reactions, such staining was largely absent, especially in dengue-2 infected cells in which it was replaced by many small circular foci scattered throughout the cytoplasm. Anti-NS 1 also stained large perinuclear inclusions and small cytoplasmic foci, but the distribution of these was dissimilar to that observed with anti-envelope sera. Anti-prM appeared to contain a mixture of antibodies of different specificities, evident at different dilutions, possibly because of different cytoplasmic locations of prM and its cleavage products. All antisera produced small discontinuous foci on the plasma membrane of unfixed infected cells; antigens of NS 1 were sometimes prominent on the surface of acetone-fixed cells.With 5 Figures     

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.