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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 307 records · Page 17Linked to original sources
PubMed1986

Identification of a distinct class of vinblastine binding sites on microtubules.

Vinblastine, at concentrations above approximately 1 to 2 microM, causes depolymerization of steady-state bovine brain microtubules in vitro by a fraying of microtubule ends into protofilament-like spirals. Microtubule depolymerization is associated with the binding of vinblastine in approximately molar stoichiometry to tubulin in microtubules with apparent low affinity, as determined by binding experiments with radiolabeled vinblastine and by the ability of vinblastine to inhibit DEAE-dextran decoration of microtubule surfaces. Our data suggest that depolymerization occurs by a propagated mechanism, initially involving binding of vinblastine to a limited number of available sites on microtubule surfaces. This appears to cause loosening of protofilament associations which results in the exposure of new vinblastine-binding sites. Additional vinblastine binding in turn results in further loosening of protofilament associations. Such loosening, when it occurs at microtubule ends, results in protofilament-like splaying and end-wise depolymerization. Microtubule depolymerization appears mechanistically distinct from inhibition of microtubule polymerization by the drug, which is associated with the binding of vinblastine to small numbers of high-affinity binding sites on tubulin at one or both microtubule ends.

Animals↗
PubMed1986

Tactual-kinesthetic matching of horizontal extents by the long-term blind: absence or reversal of normal left-side underestimation.

Ten adults, who were blind from infancy or childhood, laterally slid a horizontal rod within a short length of pipe located at the body midline, until the rod extremities were tactually-kinesthetically judged to be equidistant from the ends of the pipe. Whereas sighted subjects normally set the left extremity of the rod closer to the midline than the right irrespective of arm posture, crossed or uncrossed, blind subjects, especially those blind from birth showed trends in the opposite direction. The role of vision is discussed with respect to the development and expression of asymmetries relating to the coding of extracorporeal space.

Adult↗
PubMed1986

Radiation studies on multicellular tumour spheroids derived from human neuroblastoma: absence of sparing effect of dose fractionation.

In vitro experiments were carried out to compare the effects of single-dose and split-dose irradiation on a cell line (NB1-G) derived from human neuroblastoma and grown as multicellular tumour spheroids (MTS). The radiation response was evaluated in terms of regrowth delay; estimates of in situ cell survival were made by back-extrapolation of regrowth curves. These studies showed no significant difference in the effectiveness of single as compared to split dose irradiation i.e. no sparing effect of fractionation. If MTS constitute a realistic model for micrometastases in vivo, these results provide a radiobiological rationale for hyperfractionated treatment regimes in the adjuvant radiotherapy of neuroblastoma.

Cell Line↗
PubMed1986

Radiobiological considerations in the treatment of neuroblastoma by total body irradiation.

Neuroblastoma is a radiosensitive neoplasm for which total body irradiation (TBI) is presently under clinical consideration. Collated data on the radiobiology of human neuroblastoma cells in vitro (11 cell lines derived from seven patients) indicates moderate cellular radiosensitivity and low capacity for accumulation of sublethal damage (median survival curve parameters: Do = 104 cGy, Dq = 32 cGy, n = 1.36). Mathematical studies incorporating these parameters suggest that low dose fractionated TBI is unlikely to achieve significant levels of tumour cell kill. When high dose TBI is used in conjunction with bone marrow rescue a tumour "log cell kill" of 4-5 should be achievable. This effect would be additional to that achieved by chemotherapy. The optimum schedule for exploitation of radiobiological differences between neuroblastoma cells and the dose-limiting normal tissues has a hyperfractionated structure. Twice-daily treatments with fraction sizes in the region 120-150 cGy seems appropriate. Single dose treatments at high dose rate are contraindicated. Fractionated TBI with bone marrow rescue may be curative for some patients in clinical remission who are presently destined to relapse.

Cell Survival↗
PubMed1986

Mechanism of action of the marine natural product stypoldione: evidence for reaction with sulfhydryl groups.

Stypoldione, a marine natural product that possesses an o-quinone functional group, has been shown to inhibit a variety of biological processes including cell division. We found that stypoldione binds covalently to sulfhydryl groups of thiol-containing compounds via addition of sulfur to the C-4' position of the quinone ring. We examined the ability of stypoldione to add to sulfhydryl groups of a number of thiol-containing substances, including glutathione, thiophenol, beta-mercaptoethanol, and the protein tubulin. We suggest that the biological actions of stypoldione may be caused by the addition of this compound to thiol groups of biological molecules.

Cell Division↗
PubMed1986

Medical screening in the workplace: proposed principles.

Medical screening and biological monitoring are two techniques in a continuum of practices used to prevent occupational disease. Medical screening is the examination of workers for pathological conditions. Biological monitoring is the examination of the worker for the presence of an intoxicant or its metabolite. These techniques are common in industry, and are frequently components of health standards recommended by the National Institute for Occupational Safety and Health (NIOSH) to the Occupational Safety and Health Administration. However, an underlying set of principles for medical screening and biological monitoring in the workplace has not been delineated. In this paper, a modification of the principles for screening in the community is proposed that will be more appropriate to the workplace. This modified set of principles is not a statement of the policy of NIOSH on this important subject, but rather a presentation of the authors' views as a starting point for dialogue on these issues.

Humans↗
PubMed1986

Detection and serotyping of Actinobacillus actinomycetemcomitans isolates on nitrocellulose paper blots with monoclonal antibodies.

A combination of blotting of bacterial colonies on nitrocellulose paper discs and immunoenzymatic detection of bound antigens with specific monoclonal antibodies was used to detect and serotype Actinobacillus actinomycetemcomitans directly off the initial agar culture dish. The A. actinomycetemcomitans antigens, representative of specific colonies, were identified immunoenzymatically using monoclonal antibody specific for a species-specific antigen. The serotype of the bacteria in colonies was identified by dividing the blotting paper into sections and immunoenzymatically identifying the serotype antigens with serotype-specific monoclonal antibodies. This procedure provides for simple, rapid, sensitive and accurate identification and characterization of A. actinomycetemcomitans isolates from the initial isolation agar plates.

Actinobacillus↗
PubMed1986

Dynein-like cytoplasmic microtubule translocators.

The eukaryotic flagellum presents an excellent predictive model of microtubule-mediated motility: movement is caused by microtubule translocators, called dyneins, which actively slide outer doublet microtubules against each other. Cytoplasmic movements, such as certain aspects of mitotic motion, may also be powered by dynein-like molecules. It is important, then, to carefully assess potential cytoplasmic dynein-like translocators by applying criteria defined by the properties of axonemal dynein. A cytoplasmic microtubule translocator may be only partially homologous to axonemal dynein; a modular construction may provide the translocator with domains that are shared with dynein, and with other domains that give it functional specificity. Finally, it is important to consider the possibility that a dynein-like enzyme that is found in the cytoplasm may not function in the cytoplasm but rather is awaiting incorporation into an axoneme.

Adenosine Triphosphatases↗
PubMed1986

Valproate causes metabolic disturbance in normal man.

Valproate is an important anticonvulsant which is rarely associated with fatal hepatotoxicity. Previous experiments have shown that valproate inhibits several metabolic processes in isolated rat hepatocytes and when administered to starved rats causes a fall in the blood concentrations of glucose and ketone bodies. Since these changes may be related to the hepatotoxicity, the effect of valproate administration on intermediary metabolism in man was studied. One gram of valproate given orally to fasted normal humans caused a 78% fall in the concentration of 3-hydroxybutyrate and a 60% fall in total ketones. Also the concentrations of lactate, pyruvate, alanine and glycerol increased after valproate administration. Similar changes were observed after intravenous administration of 400 mg of valproate. Valproate clearly has a significant effect on intermediary metabolism in the liver and this is probably related to the mechanism of the hepatotoxicity.

Acetoacetates↗
PubMed1985

Taxol stabilization of microtubules in vitro: dynamics of tubulin addition and loss at opposite microtubule ends.

We have investigated the effects of taxol on steady-state tubulin flux and on the apparent molecular rate constants for tubulin addition and loss at the two ends of bovine brain microtubules in vitro. These microtubules, which consist of a mixture of 70% tubulin and 30% microtubule-associated proteins (MAPs), undergo a net addition of tubulin at one end of each microtubule (A end) and a precisely balanced net loss of tubulin at the opposite end (D end) at steady state in vitro. They do not exhibit to a detectable extent the "dynamic instability" behavior described recently for MAP-free microtubules, which would be evident as an increase in the mean microtubule length and a decrease in the number of microtubules in the suspensions [Mitchison, T., & Kirschner, M. (1984) Nature (London) 312, 237-242]. We used a double-label procedure in which microtubules were labeled with tritium and carbon-14 at A ends and carbon-14 at D ends to distinguish the two ends, combined with a microtubule collection procedure that permitted rapid and accurate analysis of retention of the two labels in the microtubules. We found that taxol slowed the flux of tubulin in a concentration-dependent manner, with 50% inhibition occurring between 5 and 7 microM drug. The effects of taxol on the apparent molecular rate constants for tubulin addition and loss at the two microtubule ends were determined by dilution analysis at an intermediate taxol concentration. The results indicated that taxol decreased the magnitudes of the dissociation rate constants at the two ends to similar extents, while exerting little effect on the association rate constants.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗