Can an immunologically, nonreactive potential allograft recipient undergo transplantation without a donor-specific crossmatch?

Performance of the pretransplant crossmatch requires 4 or more hours . Delays in the crossmatch might alter operating room availability and thereby increase donor organ cold ischemia time that might then result in increased risk of delayed graft function. To avoid these problems, recipients could be identified who would be expected to display negative donor crossmatches and who could be transplanted with a concurrent or retrospective rather than a pretransplant crossmatch. We, therefore, evaluated the percent reactive antibodies and donor IgG-antihuman globulin (AHG) crossmatch results of 1165 sera from 220 potential allograft recipients. Twenty-five (11%) of 220 recipients consistently displayed a 0% PRA and, with only one exception, their sera (n= 156) tested IgG-AHG crossmatch-negative against potential cadaveric donors (a 0.6% IgG-AHG positive crossmatch risk). These data suggest that the timing of the pretransplant serum crossmatch could be altered for a highly selected group of immunologically nonreactive recipients.     

How good is the quality of health care in the United States?

Studies over the past decade show that some people are receiving more care than they need, and some are receiving less. Simple averages from a number of studies indicate that 50 percent of people received recommended preventive care; 70 percent, recommended acute care; 30 percent, contraindicated acute care; 60 percent, recommended chronic care; and 20 percent, contraindicated chronic care. These studies strongly suggest that the care delivered in the United States often does not meet professional standards. Efforts to measure quality and report routinely on the results to the public at large would allow more definitive assessments of the status of the nation's health care and would enable us to single out the areas in need of improvement.     

Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways

The Drosophila wing is divided into anterior and posterior compartments, the latter characterized by the expression of the engrailed gene. A comparative analysis is presented here, and suggests that a primary conserved role of engrailed is to drive growth of limbs along the proximo-distal axis. The Apical Ectodermal Ridge in vertebrate limbs resembles the Antero/ Posterior compartment boundary in fly wings, particularly in molecular aspects. Multiple evidence suggests that the fly wing Antero/Posterior boundary is not the result of differential cell affinities between all anterior and posterior cells, but responds to the area of cell communication between anterior and posterior compartments. Arguments are presented here to support the notion that the compartment boundary is a consequence of decapentaplegic function in the control of growth. Patterning, on the other hand, requires the participation of several genes, among which are engrailed, invected and hedgehog. Finally, regulatory interactions between en/En-1 and hh/Shh may be significant in the context of morphogenetic regulation during normal development.     

cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed

Brief elevation in postsynaptic calcium in hippocampal CA1 neurons leads to prolonged changes in synaptic strength. The calcium may enter the postsynaptic neuron via different routes, such as voltage-gated calcium channels or glutamate receptor channels of N-methyl-D-aspartate type, and/or be released from intracellular stores. The manner in which the synapse is altered, leading to the expression of an enhanced/depressed synaptic strength, is still unclear. The present study, performed using whole-cell recording from CA1 pyramidal cells of three- to five-week-old guinea-pigs, shows that postsynaptic depolarization alone, allowing for calcium influx through voltage-gated calcium channels, leads to a synaptic potentiation characterized by an altered time-course of the evoked excitatory synaptic response, an unaltered coefficient of variation of that response and a decreased paired-pulse facilitation likely related to a postsynaptic mechanism. These characteristics contrasted with those of long-term potentiation induced via activation of N-methyl-D-aspartate receptor channels, where the time-course was unaltered, the coefficient of variation was decreased and no change in paired-pulse facilitation was observed. Synapses can thus have mechanistically separate, but co-existent, potentiations of synaptic transmission initiated from separate sources for postsynaptic calcium.     

Inhibition of the Mr 70,000 S6 kinase pathway by rapamycin results in chromosome malsegregation in yeast and mammalian cells

The antifungal and immunosuppressive drug rapamycin arrests the cell cycle in G1-phase in both yeast and mammalian cells. In mammalian cells, rapamycin selectively inhibits phosphorylation and activation of p70 S6 kinase (p70(S6K)), a protein involved in the translation of a subset of mRNAs, without affecting other known kinases. We now report that rapamycin causes chromosome malsegregation in mammalian and yeast cells. Chromosome malsegregation was determined by metaphase chromosome analysis of human lymphocytes and lymphoblasts, detection of CREST-positive micronuclei in human lymphoblasts and Chinese hamster embryonic fibroblast (CHEF) cells, and selection of doubly prototrophic cells in a specially constructed yeast strain. The number of ana-telophases with displaced chromosomes and interphase and mitotic cells with an irregular number of centrosomes was also determined in CHEF cells. In quiescent mammalian cells (human lymphocytes and CHEF cells) induced with growth factor to re-enter the cell cycle, rapamycin was effective when cells were exposed at the time of p70(S6K) activation. In yeast, rapamycin was more effective when treatment was started in G1- than in G2-synchronized cells. Cells from ataxia telangiectasia (A-T) patients are characterized by chromosome instability and have recently been found to be resistant to the growth-inhibiting effect of rapamycin. We found that an A-T lymphoblastoid cell line was also resistant to the induction of chromosome malsegregation by rapamycin, but the level of spontaneous aneuploidy was higher than in normal cells. In yeast, the induction of chromosome malsegregation was dependent on the presence of a wild-type TUB2 gene, encoding the beta-subunit of tubulin. The finding that rapamycin acts in different cell types and organisms suggests that the drug affects a conserved step important for proper segregation of chromosomes. One or more proteins required for chromosome segregation could be under the control of the rapamycin-sensitive pathway.     

Effect of vitamin E on the anticoagulant response to warfarin

To clarify whether vitamin E enhances the pharmacologic effect of warfarin, we completed a double-blind clinical trial in which 21 subjects taking chronic warfarin therapy were randomized to receive either vitamin E or placebo. None of the subjects who received vitamin E had a significant change in the international normalized ratio, and thus it appears that vitamin E can safely be given to patients who require chronic warfarin therapy.     

The use of nonhomologous scatchard analysis in the evaluation of ligand-protein interactions

Scatchard plots are widely used for the graphical presentation of receptor-ligand binding data. When a combination of labelled and unlabelled ligand molecules is used in a binding assay, equations for Scatchard plots are readily available if the labelled and unlabelled ligands have similar binding affinities. In this article, Everardus van Zoelen, Roel Kramer, Herman van Moerkerk and Jacques Veerkamp present mathematical equations to obtain the binding characteristics of an unlabelled ligand in a Scatchard plot, which has a dissociation equilibrium constant different from that of the labelled ligand used.