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Biomedical subjects

J R Brown

Publications and source records attributed to J R Brown.

At least 163 records · Page 9Linked to original sources
PubMed1982

Orthograde transport of Nuclear yellow: a problem and its solution.

Nuclear yellow injections into the striatum of rats led to staining of both neuronal and glial nuclei even after less than 24 h 'transport time'. The distribution of some of the glial nuclei suggested that the dye was being transported along the striato-nigral pathway. Staining in these areas was greatly reduced if kainic acid was co-injected with the Nuclear yellow.

Animals↗
PubMed1982

Preparation and evaluation of 2-substituted anthraquinones based on the anthracyclines.

Anthraquinones substituted at the 2 position with a basic side chain were prepared, and their binding to DNA was evaluated. All compounds showed an intercalative mode of binding to DNA; 1,4-dihydroxy derivatives bound more strongly than 1-hydroxy or nonhydroxylated compounds. Greatest DNA-binding activity was found where there were five atoms between the anthraquinone ring and the basic nitrogen.

Animals↗
PubMed1982

Distribution of daunorubicin, a potent in vitro trypanocide which lacks in vivo activity, in the blood of trypanosome-infected mice.

Daunorubicin is a highly potent trypanocide in vitro but lacks significant in vivo activity. Distribution in the drug in the blood components and in trypanosomes from mice infected with Trypanosoma rhodesiense was therefore examined. Drug is accumulated in the trypanosomes in a similar manner to, but to a greater extent than, its accumulation in platelets; it is, however, taken up by erythrocytes to a much smaller extent, Drug concentrations in trypanosomes, platelets and erythrocytes declined with its decline in plasma whereas in white blood cells the drug was retained at a constant level. Daunorubicin concentrations in plasma were several orders of magnitude higher than in vitro trypanocidal concentration. Fluorescence microscopy showed that although daunorubicin reaches the trypanosome nucleus, its concentration decreases rapidly so that adequate levels of drug may not be sustained in the bloodstream form of the organism for a sufficient length of time to give a trypanocidal effect in vivo.

Animals↗
PubMed1981

Interaction of prolactin and testosterone in the human prostate.

Three experiments were performed to determine whether human prolactin (hPr) affects prostatic uptake and metabolism of testosterone (T). 1) Patients with prostatic cancer were infused twice with radio-labelled androgens, the first time with basal hPR, the second time with oral thyrotrophin-releasing hormone (TRH)-elevated hPr. In 5/7, significant increases in metabolic clearance of dihydrotestosterone (DHT) and in conversion of T to DHT accompanied increased hPR. 2) The incorporation of labelled T into minced benign prostatic hypertrophy (BPH) tissue from subjects with high (40 ng/ml) hPR was measured and was found to be more than twice the uptake into tissue from those with low hPR (6.5 +/- 1.9 ng/ml). 3) Uptake and metabolism in vivo of a bolus of 3H-T by BPH and carcinomatous prostates was measured and was far greater in subjects whose hPR was elevated by chlorpromazine than in untreated controls. It is concluded that prolactin increases prostatic uptake and metabolism of T. It is suggested that the best management of prostatic cancer should include depletion of prolactin as well as androgen.

Dihydrotestosterone↗
PubMed1980

Immobilization of DNA for affinity chromatography and drug-binding studies.

A method is described in which double-stranded DNA is alkylated with 4-bis-(2-chloroethyl)amino-L-phenylalanine and the product immobilized on an insoluble support via the primary amino group of the phenylalanine moiety. The DNA is hence irreversibly bound to the matrix by both strands at a limited number of points.

Alkylation↗
PubMed1980

Problems in evaluating new treatments for multiple sclerosis.

There are multiple difficulties in evaluating new treatments for multiple sclerosis (MS). The clinical diagnosis is imprecise, and the correlation between lesion and clinical dysfunction is incomplete. The neurologic evaluation is complex and lacks full precision. The course of MS is complex and has limited predictability. There is no laboratory test that can be accepted now as compensating for the defects in diagnosis, lesion-symptom correlation, course, and neurologic evaluation. Because of these problems, which appear inherent in MS, there are limitations to the statistical methods that can be properly applied to trials of therapy. Most trials of definitive nature will require a random design. When improvement is seen in a trial of therapy, there may be difficulty in determining the mechanism.

Adrenocorticotropic Hormone↗
PubMed1979

The interaction of adriamycin and adriamycin analogues with nucleic acids in the B and A conformations.

The reinforced intercalative binding to DNA typical of adriamycin and daunomycin can still occur if there is epimerisation at C4' or if the O-methyl group is lost or if the 9-substituents are deleted or if the 4'-hydroxyl group is lost. In the latter two cases however, there is a reduction in affinity for the DNA, supporting the suggested role of the 9-hydroxyl and 4'-hydroxyl groups in secondary stabilization of the complex. Epimerisation at C-1' or at C-3' alters but does not abolish the intercalative mode of binding to DNA whereas epimerisation at C-7 precludes intercalation of the chromophore into the helix of DNA. In contrast to the interaction with the B-form found in DNA, the parent drugs do not intercalate into nucleic acids possessing the A-conformation and none of the above-mentioned structural changes will allow intercalation into A-form nucleic acids.

DNA↗