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Biomedical subjects

C Woolley

Publications and source records attributed to C Woolley.

At least 19 recordsLinked to original sources

Relatives' perceptions of role change, social support and stress after traumatic brain injury.

There is general agreement between researchers and clinicians alike that relatives of people with head injuries experience heightened stress as a result of the injury and its consequences. In the present study a single structured interview, including both verbally administered and written response questionnaires, was completed by 18 parents and 11 partners. Measures included the Daily Hassles and Uplifts Scale, the Arizona Social Support Interview Schedule and questions regarding role change and health problems. The combined parents and partners group indicated that they experienced moderate levels of stress and role change. A relatively small proportion of participants reported experiencing health problems. Partners indicated a slightly higher degree of stress and a greater degree of role change than parents, and a larger proportion of partners indicated the presence of health problems. Qualitative differences between the two groups were found in terms of sources of stress. There was little quantitative or qualitative difference between the two groups in sources, utilization of and satisfaction with social support. Positive correlations were found between stress and role change and stress and health problems.

Activities of Daily Living

Steroid hormones as mediators of neural plasticity.

Steroid and thyroid hormone receptors are expressed in the developing brain and persist throughout adult life. They mediate a variety of effects on the brain, ranging from developmental effects of thyroid hormone and the process of sexual differentiation to the cyclic changes during reproductive cycles in adult female animals. This review summarizes data from the author's laboratory on three topics: (1) actions of extradiol and progesterone on the ventromedial nucleus of the hypothalamus in adult female and male rats, showing both the cyclicity and the consequences of brain sexual differentiation; (2) actions of estradiol on the cholinergic neurons of the basal forebrain of the female and male rat, reflecting the plasticity of the adult cholinergic system as well as sex differences which are developmentally programmed; and (3) diverse actions of estrogens, thyroid hormone and glucocorticoids on the morphology of hippocampal neurons. The review concludes by discussing the interactions between "organizational" (i.e. developmental) effects and the "activational" effects of steroids on the mature nervous system in relation to the environmental control of brain gene expression.

Animals

The strong binding of luzopeptin to DNA.

The effect of luzopeptin on the mobility of DNA in polyacrylamide gels has been determined. Experiments on a mixture of DNA fragments of various lengths have shown that the drug does not form intermolecular cross-links. Gel analysis of complexes of the drug with short DNA fragments (15-35 base pairs) reveals a ladder of discrete bands in which each band appears to correspond to the addition of a further drug molecule. The results suggest that luzopeptin binds very strongly to DNA, occupying about four base pairs and displays little or no sequence selectivity. Luzopeptin renders certain adenine residues hyperreactive to diethylpyrocarbonate, these occur in different positions to those affected by echinomycin.

Antibiotics, Antineoplastic

Deoxycytidylate hydroxymethylase: purification, properties, and the role of a thiol group in catalysis.

Deoxycytidylate (dCMP) hydroxymethylase from Escherichia coli infected with a T-4 bacteriophage amber mutant has been purified to homogeneity. It is a dimer with a subunit molecular weight of 28,000. Chemical modification of the homogeneous enzyme with N-ethylmaleimide (NEM) and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) leads to complete loss of enzyme activity. dCMP can protect the enzyme against NEM inactivation, but the dihydrofolate analogues methotrexate and aminopterin alone do not afford similar protection. Compared to dCMP alone, dCMP plus either methotrexate or aminopterin greatly enhances protection against NEM inactivation. DTNB inactivation is reversed by dithiothreitol. For both reagents, inactivation kinetics obey second-order kinetics. NEM inactivation is pH dependent with a pKa for a required thiol group of 9.15 +/- 0.11. Complete enzyme inactivation by both reagents involves the modification of one thiol group per mole of dimeric enzyme. There are two thiol groups in the totally denatured enzyme modified by either NEM or DTNB. Kinetic analysis of NEM inactivation cannot distinguish between these two groups; however, with DTNB kinetic analysis of 2-nitro-5-thiobenzoate release shows that enzyme inactivation is due to the modification of one fast-reacting thiol followed by the modification of a second group that reacts about 5-6-fold more slowly. In the presence of methotrexate, the stoichiometry of dCMP binding to the dimeric enzyme is 1:1 and depends upon a reduced thiol group. It appears that the two equally sized subunits are arranged asymmetrically, resulting in one thiol-containing active site per mole of dimeric enzyme.

Dithionitrobenzoic Acid

Genetic controls over activities of tyrosinase and dopachrome conversion factor in murine melanocytes.

We evaluated the three catalytic activities of tyrosinase and one activity of dopachrome conversion factor (DCF) in extracts made from skins of 6-day-old yellow and nonyellow mice. At least one of the catalytic activities of tyrosinase and of DCF correlate with the color of pigment being produced in the hair follicles of the mice. We use these data to evaluate existing hypotheses about the mechanism of the interacting genetic controls over melanogenesis.

Animals

Laser differential light scattering bioassays for selected antitumor agents.

Bioassay methods for actinomycin D, 6-thioguanine, and adriamycin which utilize laser light scattering from suspensions of drug-sensitive bacteria have been developed. In 3 hours, serum and urine levels of the 3 drugs can be reproducibily measured. A sample volume of 0.1 ml may be assayed with a precision of +/- 10%. The linear response range for actinomycin D was 0.03 to 3.0 microgram/ml. For 6-thioguanine and adriamycin the linear responses range was 0.03 to 10.0 and 0.25 to 10.0 microgram/ml, respectively. Thetively. The present studies further confirm the general utility of differential light scattering as a rapid and inexpensive assay procedure of broad application.

Antineoplastic Agents

Laser light scattering bioassay for 1-beta-D-arabinofuranosylcytosine (ARA-C, NSC-63878).

A bioassay method for the estimation of ara-C in biological samples which utilizes laser light scattering from suspensions of drug-sensitive bacteria has been developed. The species employed in the assay was Streptococcus faecium var. durans resistant to methotrexate and 6-mercaptopurine. In less than four hours, serum and urine levels of ara-C can be reproducibly measured using the method. A sample volume of 0.1 ml containing 30 ng/ml may be assayed with a precision of +/-10 percent. The present studies further confirm the utility of the method as a rapid and relatively inexpensive assay methodology of broad application. Time variations of drug serum levels and urinary excretion rates in dogs are compared via the differential light scattering (DLS) assay, standard disc diffusion assay, and radiosotopic assay. The results obtained by the various methods are in excellent agreement.

Animals

Laser differential light-scattering bioassay for methotrexate (NSC-740).

A new bioassay method utilizing laser light scattering from suspensions of drug-sensitive bacteria has been developed for the estimation of antitumor drugs in biologic samples. Changes in the light-scattering patterns of antibiotic-treated bacteria have recently been shown to provide a rapid and accurate indication of antibiotic sensitivity. Similar considerations for several antitumor drugs have shown the method capable of assaying 0.1 ml with drug concentrations as low as a few nanograms of drug per milliliter of sample. The first successful application of the methodology is described for the antitumor agent methotrexate. Studies of both drug-treated human serum specimens and dog serum levels and urinary excretion as a function of time indicate that assay results are available within 3 hours of preparing the serum. Time variations of drug serum levels and urinary excretion rates are compared via laser differential light-scattering assay, standard disc-diffusion assay, and previously published radioisotopic assays.

Animals

Biological assay of streptonigrin (NSC 45383) in body fluids and tissues of mice.

Streptonigrin, a quinone antitumor antibiotic, has been reported to be effective in human trials. A sensitive and precise microbiological assay for the determination of distribution and concentrations of streptonigrin in the body fluids and tissues of treated mice has been developed in an attempt to supplement successful clinical application of this drug.

Animals

Chromomycin A 3 , an antitumor antibiotic: tissue distribution studies in mice as measured by microbial assay.

A microbiological assay has been developed for chromomycin A(3), an antitumor antibiotic showing promise in human trials. The assay bacterium is a derived strain of Streptococcus faecalis resistant to methotrexate. Studies with mice revealed that relatively high concentrations of this antibiotic were maintained in the blood, kidneys, and liver of mice after a single-dose intraperitoneal injection of the drug.

Animals