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Biomedical subjects

D Alexander

Publications and source records attributed to D Alexander.

At least 55 records · Page 3Linked to original sources
PubMed1997

Drug resistant organisms and their implications for the outpatient dialysis setting.

Ever since antibiotics have been used to combat infection, resistance to them has also developed. The elderly and immunosuppressed populations found in today's dialysis facility comprise a group at risk for acquiring infection caused by drug resistant organisms. By utilizing antibiotics prudently and developing infection control strategies based on the disease/organism epidemiology, mode of transmission and individualized needs of the patient as well as the care setting, the proliferation of drug resistant organisms may be curtailed.

Ambulatory Care Facilities↗
PubMed1996

Characterization of mutations induced by 300 and 320 nm UV radiation in a rat fibroblast cell line.

The cytotoxic and mutagenic activities of monochromatic ultraviolet light (UV) at four wavelengths (254, 290, 300 and 320 nm) were determined using a rat fibroblast cell line CREF stably infected with a retroviral vector carrying the neo and HSV-tk markers. In this system, mutations can be positively detected as acyclovir-resistant colonies. Although the action spectra for these activities closely fit some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing and mouse skin carcinogenesis, they diverge at 320 nm from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of the HSV-tk mutants detected after irradiation with 300 and 320 nm UV revealed (1) CC dimers and C oligomers as predominant targets at both wavelengths; (2) increased incidence of relatively large deletions at 300 nm; and (3) greatly increased frequency of tandem double mutations at both wavelengths and of clustered multiple mutations at 320 nm. These results suggest the involvement of distinct mechanisms specifically operating, or becoming evident, in UV-mediated mutagenesis at these different wavelengths in mammalian cells.

Acyclovir↗
PubMed1996

The health effects of earthquakes in the mid-1990s.

This paper gives an overview of the global pattern of casualties in earthquakes which occurred during the 30-month period from 1 September 1993 to 29 February 1996. It also describes some of the behavioural and logistical regularities associated with mortality and morbidity in these events. Of 83 earthquakes studied, there were casualties in 49. Lethal earthquakes occurred in rapid succession in Indonesia, China, Colombia and Iran. In the events studied, a disproportionate number of deaths and injuries occurred during the first six hours of the day and in earthquakes with magnitudes between 6.5 and 7.4. Ratios of death to injury varied markedly (though with some averages close to 1:3), as did the nature and causes of mortality and morbidity and the proportion of serious to slight injuries. As expected on the basis of previous knowledge, few problems were caused by post-earthquake illness and disease. Also, as expected, building collapse was the principal source of casualties: tsunamis, landslides, debris flows and bridge collapses were the main secondary causes. In addition, new findings are presented on the temporal sequence of casualty estimates after seismic disaster. In synthesis, though mortality in earthquakes may have been low in relation to long-term averages, the interval of time studied was probably typical of other periods in which seismic catastrophes were relatively limited in scope.

Building Codes↗
PubMed1995

In situ isolation of mRNA from individual plant cells: creation of cell-specific cDNA libraries.

A method for isolating and cloning mRNA populations from individual cells in living, intact plant tissues is described. The contents of individual cells were aspirated into micropipette tips filled with RNA extraction buffer. The mRNA from these cells was purified by binding to oligo(dT)-linked magnetic beads and amplified on the beads using reverse transcription and PCR. The cell-specific nature of the isolated mRNA was verified by creating cDNA libraries from individual tomato leaf epidermal and guard cell mRNA preparations. In testing the reproducibility of the method, we discovered an inherent limitation of PCR amplification from small amounts of any complex template. This phenomenon, which we have termed the "Monte Carlo" effect, is created by small and random differences in amplification efficiency between individual templates in an amplifying cDNA population. The Monte Carlo effect is dependent upon template concentration: the lower the abundance of any template, the less likely its true abundance will be reflected in the amplified library. Quantitative assessment of the Monte Carlo effect revealed that only rare mRNAs (< or = 0.04% of polyadenylylated mRNA) exhibited significant variation in amplification at the single-cell level. The cDNA cloning approach we describe should be useful for a broad range of cell-specific biological applications.

Base Sequence↗
PubMed1995

Antigenic heterogeneity of avian paramyxoviruses of serotype 2 ("Yucaipa-like") isolated from domestic and wild birds in Israel.

Thirty-three viruses of PMV-2 serotype isolated in Israel from domestic and wild birds during epizooty of a respiratory disease in 1979-1981 were studied comprehensively in comparison with a set of reference PMV-2 viruses using cross reaction hemagglutination inhibition tests, elution-hemagglutination pattern and pattern of migration of viral proteins in polyacrylamide gel electrophoresis. The results demonstrated considerable heterogeneity amongst the local isolates by the above three criteria which were not correlated with each other. There was no significant correlation between the differences found and chronology of isolation of the viruses. The results indicated that there may have been simultaneous co-circulation of different PMV-2 strains in the local avian reservoir at the beginning of the epizootic rather than temporal accumulation of variants as a result of antigenic drift of an "ancestor" virus which caused the initial infection.

Animals↗
PubMed1995

Strike-through contamination in saturated sterile dressings: a clinical analysis.

This multisite study examined the risk of strike-through contamination of 4" x 4" gauze sponges using a shortcut method of saturating sterile sponges directly on their wrappers. Sterile gauze sponges were saturated directly on their wrappers on hospital over-bed tables of postoperative general surgical patients. Cultures were taken at 0.5, 1, 3, and 5 minutes after saturation to ascertain whether strike-through contamination occurred. Saturated sponges showed significant microorganism growth when compared to expected zero microorganisms at all sampling times following saturation. Although microorganisms identified in strike-through contamination were not microbiologically or pathogenically threatening, the basic principle of asepsis was violated. There was no significant difference in strike-through contamination between sponges saturated on coated wrappers and sponges saturated on uncoated wrappers. Clinicians should be aware that coated wrappers do not provide a moisture-proof barrier against strike-through contamination. The findings suggest the shortcut method should not be used for saturating sponges.

Asepsis↗
PubMed1995

Ventilatory muscle strength and endurance in myasthenia gravis.

Patients with generalized myasthenia gravis (MG) often have associated ventilatory muscle involvement. It is not known whether patients with isolated ocular muscle involvement have identifiable involvement of their ventilatory muscles. Most studies have assessed muscle involvement by measuring muscle strength; however, we hypothesized that measures of ventilatory muscle endurance may be more sensitive tests of ventilatory muscle involvement in myasthenia gravis. We studied 17 patients with myasthenia gravis (four with ocular involvement alone and 13 with varying degrees of generalized myasthenia gravis). Spirometry, ventilatory muscle strength (maximum inspiratory and expiratory pressures (MIP and MEP)) and endurance (2 min incremental threshold loading test) were measured before and 20 min after i.m. neostigmine. We compared the results with those of 10 normal controls. We found no difference between patients with isolated ocular involvement and controls. Ocular myasthenia gravis patients did not improve after neostigmine. The patients with generalized myasthenia gravis had reduced baseline ventilatory muscle strength (MIP 67 cmH2O (70% of predicted), MEP 86 cmH2O (50% of pred) and endurance (mean maximal load achieved = 246 g, mean pressure at highest load (P) = 19.4 cmH2O) compared with controls. After neostigmine, there was a significant increase in MIP in patients with generalized myasthenia gravis and a trend towards an increased MEP. As a group, the patients with generalized myasthenia gravis did not demonstrate a change in their ventilatory muscle endurance after neostigmine; however, there was considerable interpatient variability in response. We conclude that patients with isolated ocular MG have normal ventilatory muscle strength when tested conventionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

FK506 and cyclosporin A each inhibit antigen-specific signaling in the T cell line 171 in the absence of a calcium signal.

Antigen-specific signal transduction leading to IL2 induction and secretion in the T cell line 171 is augmented by association of p56lck with CD4. Although no change in cytoplasmic calcium level ([Ca2+]i) was detectable during antigen-specific signal transduction of 171-CD4+ cells, IL2 induction was inhibited by FK506 and CsA. Since these drugs are thought to act selectively by inhibiting calcineurin, a calcium-calmodulin-dependent protein phosphatase associated with activation of the IL2 promoter, we considered the possibility that calcineurin is constitutively active in 171 cells. However, we found no evidence for this because PMA failed to supplement any putatively active calcineurin to induce IL2 secretion. We suggest that IL2 secretion induced by antigen presentation to TCR/CD4/p56lck requires an FK506 and cyclosporin A-sensitive step which may be independent of calcium signaling. Rapamycin did not inhibit IL2 secretion induced by TCR/CD4/p56lck, emphasizing the specific action of FK506 and cyclosporin A.

Amino Acid Sequence↗
PubMed1994

The CD45 tyrosine phosphatase regulates specific pools of antigen receptor-associated p59fyn and CD4-associated p56lck tyrosine in human T-cells.

A newly isolated T-cell line (CB1) derived from a T-acute lymphoblastic leukaemia (T-ALL) patient contained cells (40% of total) which did not express the CD45 phosphotyrosine phosphatase. The cells were sorted into CD45- and CD45+ populations and shown to be clonal in origin. T-cell receptor (TCR) cross-linking or coligation of the TCR with its CD4/CD8 co-receptors induced tyrosine phosphorylation and calcium signals in CD45+ but not in CD45- cells. Unexpectedly, whole cell p56lck and p59fyn tyrosine kinase activities were not reduced in CD45- compared to CD45+ cells. A novel technique was therefore developed to isolated specific pools of aggregated receptors expressed at the cell surface, together with their associated tyrosine kinases. Using this technique it was shown that cell surface CD4-p56lck kinase activity was 78% lower in CD45- than in CD45+ cells. Phosphorylation of TCR zeta- and gamma-chains occurred in TCR immunocomplexes from CD45+ but not CD45- cells, despite comparable levels of p59fyn and TCR proteins. Furthermore, TCR-associated tyrosine kinase activity towards an exogenous substrate was 84% lower in CD45- than in CD45+ cells. Addition of recombinant p59fyn to TCR immunocomplexes isolated from CD45-cells restored the phosphorylation of the TCR zeta- and gamma-chains. Our results demonstrate that CD45 selectively regulates the pools of p59fyn and p56lck kinases which are associated with the TCR and CD4 at the cell surface. Activation by CD45 of these receptor-associated kinase pools correlates with the ability of the TCR and its coreceptors to couple to intracellular signalling pathways.

CD4 Antigens↗
PubMed1994

FK 506 and cyclosporin each block antigen-induced T cell receptor signalling that is dependent on CD4 co-receptor and operates in the absence of detectable cytoplasmic calcium fluxes.

The T cell hybridoma "171", which lacks CD4 but expresses T cell receptor (TCR) for hen egg white lysozyme, requires introduction of wild-type CD4 for antigen-mediated induction and secretion of interleukin-2 (IL-2). Mutant CD4, which fails to associate with the tyrosine kinase p56lck does not support IL-2 secretion, suggesting that a role of CD4 is to bring cytoplasmic p56lck into alignment for signal transduction to the IL-2 promotor. Using 171, 171-CD4 (wild-type) and 171-CD4 (mutant), we found that IL-2 secretion was inhibited by FK 506 and cyclosporin but not by rapamycin. However, this inhibition was not associated with calcium fluxes since no change in cytoplasmic free calcium levels ([Ca]i; resting level 80 nM) was detectable during antigen stimulation of the 171 or 171-CD4 cells. Thus, although FK 506 and cyclosporin inhibited calcium-dependent signalling to the IL-2 promoter via inhibition of the protein phosphatase calcineurin, it is possible that IL-2 induction via TCR/CD4 requires an FK 506 (and cyclosporin) sensitive step which is independent of cytoplasmic calcium changes.

Animals↗