Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity

We report that the tumor neurosis factor homolog APRIL (a proliferation-inducing ligand) stimulates in vitro proliferation of primary B and T cells and increases spleen weight due to accumulation of B cells in vivo. APRIL functions via binding to BCMA (B cell maturation antigen) and TACI (transmembrane activator and CAML-interactor) and competes with TALL-I (also called BLyS or BAFF) for receptor binding. Soluble BCMA and TACI specifically prevent binding of APRIL and block APRIL-stimulated proliferation of primary B cells. BCMA-Fc also inhibits production of antibodies against keyhole limpet hemocyanin and Pneumovax in mice, indicating that APRIL and/or TALL-I signaling via BCMA and/or TACI are required for generation of humoral immunity. Thus, APRIL-TALL-I and BCMA-TACI form a two ligands-two receptors pathway involved in stimulation of B and T cell function.     

Recommendations on performance characteristics of diagnostic exposure meters: report of AAPM Diagnostic X-Ray Imaging Task Group No. 6.

Task Group 6 of the Diagnostic X-Ray Imaging Committee of the American Association of Physicists in Medicine (AAPM) was appointed to develop performance standards for diagnostic x-ray exposure meters. The recommendations as approved by the Diagnostic X-Ray Imaging Committee and the Science Council of the AAPM are delineated in this report and provide specifications on meter precision, calibration accuracy, calibration reference points, linearity, energy dependence, exposure rate dependence, leakage, amplification gain settings, directional dependence, the stem effect, constancy checks, and calibration intervals. The report summarizes recommendations for meters used in mammography, general purpose radiography including special procedures, computed tomography, and radiation safety surveys for x-ray radiography.     

Conventional and enhanced plaque neutralization assay for polio antibody

HEp-2 cells were more suitable as a cell substrate than Vero cells for plaque assay of wild or attenuated strains of poliovirus. Polio antibody titration by plaque neutralization was on the average 3.4 to 4.8 times more sensitive than antibody titration by virus CPE assay. The most pronounced effect on virus neutralization was achieved by extending the time of serum-virus interaction. Incubating the virus-antiserum mixture for 20 h instead of 1 h at 36 degrees C increased antibody titer to all three poliovirus types about 11- to 28-fold. Potentiation of poliovirus neutralization by heterologous antiglobulin was considerably less effective than with other virus-antibody systems. The virus plaque neutralization technique described should be capable of measuring minute amounts of antibody as required in special circumstances.     

Theology and bioethics: a marriage not made in heaven

Boone reviews the 20th volume in the Philosophy and medicine series, Theology and Bioethics: Exploring the Foundations and Frontiers, edited by Earl E. Shelp (D. Reidel; 1985). The volume's theme, if and how "theology can make a unique contribution to bioethics in our time," is addressed by L. Walters, B. Mitchell, R. McCormick, M. Farley, P. Lehmann, C. Hartshorne, H.T. Engelhardt, S. Hauerwas, J. Childress, and W. Frankena, with a prologue by J. Nelson and an epilogue by J. Cobb. Boone briefly summarizes and critiques each essay. While he responds favorably to the volume, he also believes the work would have been stronger if more attention had been focused directly on the metaethical issues arising from the "gap between theological belief and moral action."     

Antimicrobial activity and durability of a novel antimicrobial-impregnated bladder catheter

The main objective of this study was to examine the antimicrobial activity and durability of a novel indwelling bladder catheter impregnated with minocycline and rifampin. Thirty antimicrobial-impregnated bladder catheters were inserted transurethrally in spinal cord-injured patients and removed, in six groups of five catheters each, at 3, 7, 10, 14, 17 or 21 days. Removed catheters had detectable zones of inhibition against two different clinical isolates of each of the 10 tested uropathogens (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter diversus, Enterococcus faecalis, Enterococcus faecium, Staphylococcus saprophyticus and Candida albicans) for greater than 14 days after catheter insertion. The residual zones of inhibition and levels of antimicrobial agents in removed catheters were both inversely related to the duration of catheter placement. Minocycline and rifampin were undetectable in serum and urine. These results support the ongoing efforts for examining the clinical efficacy of these experimental bladder catheters.     

Big or small, room for all

In today's world of high demand, nurses have more of an opportunity than ever to get just what they want. Nurses find rewards in what they do no matter where they work. SH profiles nurses from two Texas hospitals.     

Vasoformative sarcomas arising from BALB/3T3 cells attached to solid substrates.

The BALB/3T3 mouse embryo cell line, noted for its marked postconfluence inhibition of proliferation, anchorage dependence, and high serum requirement, and frequently studied as a prototype nontumorigenic "fibroblast" line that is compared with tumorigenic sublines transformed with various agents, produced tumors within 2 to 3 months when an average of 3 X 10(4) cells were implanted s.c. attached to 1- X 5- X 10-mm polycarbonate platelets. Plastic platelets alone produced no tumors after 1 year of observation. The tumors, as well as others arising from implants of BALB/3T3 cells attached to 3-mm glass beads, were given the histological diagnosis of "vasoformative saroma" because the tumor cells frequently formed vascular channels. The vasoformative pattern and the results of specific staining for reticulin and collagen support the likelihood that BALB/3T3 cells originated from endothelial cells rather than from fibroblasts. That the tumors were derived from BALB/3T3 cells and not host cells was proved when tumors arising in BALB/c X C57BL/6 F1 hybrids were shown to be transplantable to BALB/c but not to C57BL/6 mice. The cultured tumor cells showed loss of both postconfluence inhibition of proliferation and anchorage dependence. Evidence of the induction of endogenous oncornaviruses was obtained in only one of four tumors tested. These tumors also exhibited tumor-unique transplantation rejection antigens. We conclude that BALB/3T3 cells are preneoplastic and give rise to different spontaneously transformed clones bearing unique tumor rejection antigens when implanted in vivo attached to a solid substrate.