A study of early Los Alamos internal exposures to plutonium.

Internal dose caused by exposure to (239)Pu/(240)Pu is calculated for a group of 210 former Los Alamos workers who participated in the urine bioassay programme during the years 1944-45. An iterative Bayesian procedure is employed, where the distribution of intake amounts resulting from an initial calculation is used to define a prior probability distribution of inhalation intakes for an iterated second calculation. The urine bioassay data from this time period were not of high quality, and the more accurate intake prior tempers the effect of spurious high samples, which were probably caused by sample contamination.

Synthesis and biochemical evaluation of guanidino-alkyl-ribitol derivatives as nucleoside hydrolase inhibitors.

Nucleoside hydrolase (NH) is a key enzyme in the purine salvage pathway. The purine specificity of the IAG-NH from Trypanosoma vivax is at least in part due to cation-pi-stacking interactions. Guanidinium ions can be involved in cation-pi-stacking interactions, therefore a series of guanidino-alkyl-ribitol derivatives were synthesized in order to examine the binding affinity of these compounds towards the target enzyme. The compounds show moderate to good inhibiting activity towards the IAG-NH from T. vivax.

1,2,3-Triazolylalkylribitol derivatives as nucleoside hydrolase inhibitors.

A range of novel 1,2,3-triazolylalkylribitol derivatives were synthesized and evaluated as nucleoside hydrolase inhibitors. The most active compound (11a) has low micromolar potency and is structurally diverse from previously reported nucleoside hydrolase inhibitors, which, along with the simplicity of the chemistry involved in its synthesis, makes it a good lead for the further development of novel nucleoside hydrolase inhibitors.

Changing urine testing protocols through audit.

A multidisciplinary audit to monitor the introduction of a ward-based urine screening test using Multistix 10 SG was associated with a 40% reduction in the number of culture-negative samples being sent for laboratory testing. Ongoing education and support was provided for nursing staff throughout the process of change.

Genetic variation segregating in natural populations of Tribolium castaneum affecting traits observed in hybrids with T. freemani.

We investigated patterns of within-species genetic variation for traits observed in hybrids (hybrid numbers, hybrid sex ratios, and hybrid male deformities) between two species of flour beetles, Tribolium castaneum and T. freemani. We found genetic variation segregating among four natural populations of T. castaneum as well as within these populations. For some hybrid traits, we observed as much variation among populations 750 km apart as between populations on different continents, suggesting genetic differentiation at a local scale. Within natural populations, the variation segregating among sires is greater than that found in an earlier study for an outbred laboratory population and comparable to that observed between inbred lines derived from the outbred stock by eight generations of brother-sister mating. When sires from T. castaneum are mated to conspecific and heterospecific females, we do not observe a significant correlation at the level of the family mean between the intraspecific and interspecific phenotypes, suggesting the independence of the hybrid traits from comparable traits within species. We discuss our findings in relation to the evolutionary genetics of speciation and the expression of epistatic genetic variance in interspecific crosses.

Incipient speciation in the flour beetle, Tribolium confusum: premating isolation between natural populations.

We report the existence of partial reproductive isolation between two natural populations of the flour beetle, Tribolium confusum, collected in Kaduna, Nigeria and Zagreb, Croatia. When a female from either population is paired with a single sympatric or allopatric male, she produces near normal numbers of semifertile offspring. However, when females are multiply mated with allopatric and sympatric males, the sympatric males sire the large majority of offspring. When measured in offspring numbers, the mean relative fitness of allopatric males is 0.425 with Nigerian females and 0.085 with Croatian females. Thus, the reproductive isolation is reciprocal but asymmetric. Behavioural observations indicate that only a fraction of mating attempts by allopatric males are successful because females do not become quiescent as often when mounted by allopatric males. The premating isolation is also reciprocal but asymmetric: Nigerian females are more accepting of allopatric males as mates than are Croatian females. The prezygotic behavioural isolation between these two populations is different from the postmating, prezygotic isolation observed between two other species in the genus, T. castaneum and T. freemani. Furthermore, the T. confusum interpopulation hybrids are fertile although they exhibit a weak female bias.

The relationship among stress, depression, locus of control, irrational beliefs, social support, and health in Alzheimer's disease caregivers.

This study evaluated the hypothesis that Alzheimer's disease caregivers and control subjects who experienced stressful life events, held the belief that external factors control one's destiny, endorsed irrational beliefs, and had decreased social support would experience more depression and poor health than less stressed individuals who were more internal, had less rigid cognitive beliefs, and had better support. A battery of psychosocial and health measures were administered at baseline and 6 months later. The results suggest that, overall, the experience of marked adversity, increased externality, and the endorsement of irrational beliefs were related to depression and poor health. While diminished social support was not associated with poor health in this study, satisfaction with social support and diminished adherence to irrational beliefs were related to improved ratings of subjective health over time. These findings indicate that psychosocial interventions designed to modify cognitive reactions to stress might improve the quality of life and the physical well being of a population at risk for poor health as a result of their age and life circumstances.

Newborn conjunctivitis associated with triclosan 0.5% antiseptic intrinsically contaminated with Serratia marcescens.

In February 1994, three cases of conjunctivitis with Serratia marcescens occurred in infants in the newborn nursery. An epidemiological investigation was conducted including environmental sampling. S marcescens was isolated from the bottle of triclosan 0.5% antiseptic soap that was in use in the nursery and from an unopened bottle on the pharmacy shelf. The manufacturer confirmed that this contaminant was dislodged from the air purification system during a filter change while the packaging was being completed in an adjoining room. The product was withdrawn from use in the nursery and replaced by individual bar soap. No further cases of infection with S marcescens have been identified following the withdrawal of the triclosan 0.5% soap.

Refinement of the rat crush-avulsion femoral artery injury model.

A model for studying arterial crush-avulsion injuries in the rat is described. The model uses a standardized crush of approximately 0.3 joules and a standardized avulsion. The crush is accomplished by gravity acceleration of a 400 g weight over a distance of 7.5 cm. The weight impacts an anvil over the artery distributing the force of the impact over a 10 mm length of the vessel. The avulsion is accomplished by a hemostat attached to a second, 120g weight. Vascular stasis for 90 sec after vessel repair in a 175-225 g rat will consistently result in an 80% anastomotic failure. The model allows evaluation of anticoagulant effects singly or in combination. Agents may be given either systemically by intravenous route or locally by intraarterial route.

The relationship of life adversity, social support, and coping to hospitalization with major depression.

We evaluated the relationship between life events, social support, coping, and depression in 27 male inpatients meeting the requirements for Research Diagnostic Criteria major depressive disorder and in 35 age- and sex-matched nonpatients. Overall, the hospitalized depressed patients reported significantly more events and difficulties than did the controls, but this difference in statistical significance disappeared after excluding from analysis "non-independent" happenings which could have been brought on by depression. More hospitalized depressed patients (23 of 27, or 85%) than controls (8 of 35, or 22.9%) experienced markedly threatening events and difficulties ("marked adversities") in the 6 months before their interview. The depressed group also reported having significantly fewer social supports, being less satisfied with the emotional component of this support, and using more emotion-focused coping than the controls. A discriminant analysis predicted depressive status from a combination of marked adversities, reduced number of social supports, and greater use of emotion-focused coping. The results indicate that the relationship of life events to depression is complex. The excess number of events might be partly a product of dysfunctional behavior that "produces" depression-related events which might, in turn, exacerbate depression; simultaneously, patients are more likely to experience highly adverse events which might precipitate the depression in the first place. Reduced social supports and the use of emotion-focused coping appear to also be associated with hospitalization for major depression.

Binding of monoclonal antibody to the Epstein Barr virus (EBV)/CR2 receptor induces activation and differentiation of human B lymphocytes.

A panel of B cell-specific monoclonal antibodies that identify the CR2/EBV receptor were examined for their ability to mimic the T-independent mitogenic agent, EBV, and thus activate human peripheral blood B lymphocytes. Two of four different anti-CR2/EBV monoclonal antibodies, OKB7 and AB-1, produced a 50-fold to 200-fold dose-dependent stimulation of DNA synthesis of peripheral blood mononuclear cells. One of the other monoclonal antibodies, anti-B2, had slight activity, and the other, HB-5, was completely inactive. One of the mitogenic antibodies, OKB7, which directly inhibits binding and infection of B cells by EBV in the absence of a second anti-immunoglobulin antibody, was examined in further detail. Both the intact antibody in soluble form and its pepsin-derived F(ab')2 fragment stimulated DNA synthesis of unseparated B and T lymphocytes. Peak stimulation of DNA synthesis in peripheral blood mononuclear cells occurred between 4 to 6 days. B cells were responsible for incorporation of [3H]thymidine. However, T cells were required for activation of peripheral blood mononuclear cells by OKB7. OKB7, as well as the other mitogenic monoclonal anti-EBV/CR2 receptor antibody, also induced B cells to differentiate after 6 to 10 days of culture as indicated by polyclonal Ig secretion. IgM was the predominate immunoglobulin secreted. These studies thus indicate that certain epitopes on the EBV/CR2 receptor trigger B cells to divide and differentiate. This pathway of B cell activation, in contrast to that produced by EBV, is T cell dependent.

Identification and characterization of the Epstein-Barr virus receptor on human B lymphocytes and its relationship to the C3d complement receptor (CR2).

In pursuing studies on the early events in the infection of human B cells by Epstein-Barr virus (EBV), we examined the host cell attachment phase with a panel of B-cell-specific monoclonal antibodies. One of the monoclonal antibodies, OKB7, directly blocked the attachment of purified EBV to B lymphocytes in the absence of a second anti-immunoglobulin antibody and thereby prevented EBV infection of tonsil and peripheral blood B cells. Although earlier studies have shown a close association of the EBV and complement receptor (CR2), an anti-CR2 monoclonal antibody, anti-B2, did not directly block the binding of EBV to B cells. A comparison of the structures recognized by these monoclonal antibodies on various cell types and their functional and physiochemical properties was undertaken. Flow cytometric analysis revealed that the molecules detected by OKB7 and anti-B2 were coexpressed to the same extent on B cells but were not expressed on T-cell lines. OKB7 and anti-B2 both immunoprecipitated a 145,000-molecular-weight membrane protein with an isoelectric point of 8.2 from membrane extracts of Raji lymphoblastoid cells. OKB7 and, to a lesser extent, anti-B2 directly blocked the attachment of C3d,g-coated fluorescent microspheres and sheep erythrocytes bearing C3d to B cells, indicating that these antibodies also react with CR2. These studies indicate that the EBV-CR2 receptor is a single membrane glycoprotein which possesses multiple antigenic and functional epitopes.