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Biomedical subjects

J M Davidson

Publications and source records attributed to J M Davidson.

At least 199 records · Page 11Linked to original sources

Negative feedback control of LH by testosterone: a quantitative study in male rats.

Adult male rats were castrated and implanted sc with testosterone (T)-filled Silastic capsules of different sizes which produce stable plasma T levels proportional to capsule length. T and LH levels were determined in blood samples obtained at 3-day intervals for 21 days. Plasma T values greater than 1.8 ng/ml suppressed plasma LH to levels below the intact range, while a plasma T of less than 0.5 ng/ml yeilded no significant inhibition of the post-castration LH rise. Animals with a plasma T of about 0.7 ng/ml, however, showed intact, castrate, or immediate LH levels. The feedback-effective range for all animals was between 0.5 ngT/mg (castrate-like LH response) and 1.8 ng/ml (LH at or below intact levels), but individual rats seemed to have a more restricted feedback range than that indicated by these group data. To test this hypothesis further, rats were implanted at the time of castration with five 5-mm T-filled capsules. One capsule was removed each week, producing step function drops in plasma T, and allowing examination of the LH responses of individual animals. Plasma t levels greater than 1.6 ng/ml maintained LH values at or below intact levels. However, when plasma T dropped to 1.1 ng/ml, some rats showed castration-like LH increase and others did not respond until after a further drop to 0.6 ng/ml. It was concluded that the feedback-effective range of plasma T is very restricted and differs in individual rats.

Animals↗

Intermediates in the limited proteolytic conversion of procollagen to collagen.

The conversion of chick bone procollagen to collagen proceeds in a stepwise fashion to produce a limited number of intermediates. Initial proteolytic cleavages remove NH2-terminal nonhelical extensions and yield an intermediate which remains disulfide-bonded via COOH-terminal extensions. Subsequent stepwise scission of one or two chains of the triple-stranded molecule in its COOH-terminal domain produces intermediates which can only be distinguished after dissociation of the noncovalently bonded alpha chains. A final cleavage in this region produces the collagen molecule and a disulfide-bonded triple-stranded fragment which represents the COOH-terminal domain. In all likelihood the endopeptidases which effect cleavage in the NH2- and COOH-terminal regions differ. More than two enzymes may be required for conversion of procollagen to collagen if the nonhelical domains are not released in an en bloc fashion.

Animals↗

Cellular immunity in cancer: comparison of delayed hypersensitivity skin tests in three common cancers.

Cellular immunity was studied in three homogenous groups of patients with cancer to determine whether the pattern of depression of immune competence varied between solid tumours with different patterns of clinical behaviour. Delayed hypersensitivity skin responses were measured in patients with carcinoma of the breast, stomach, and colon and matched controls. Response to 2,4-dinitrochlorobenzene (DNCB) was used as an indication of primary responses and the Mantoux reaction as an index of recall responses. Responses were diminished in all three cancer groups, but there were significant differences between each type of cancer and even between different control groups. Cellular immunity was lost earliest and to the greatest extent in patients with colonic cancers and tended to be retained until a late stage in breast cancer, with gastric cancer occupying an intermediate position. Thus, while there was some degree of correlation between depressed immunity and prognosis our results gave no evidence that general host immune competence could explain the worse prognosis of gastric than colonic cancer. Paradoxical findings in patients with breast cancer suggested a great complexity in the host tumour interaction. Assessments of immune competence in cancer patients must be related to specific types of neoplasms with appropriate control groups if the results are to be meaningful.

Antibodies, Neoplasm↗

A computer program for the analysis of parallel-line bioassays of clotting factors.

An interactive computer program for the analysis of clotting factor assays is described. The program provides potency estimates against a standard, and will compare the observed and expected responses of a treated patient. Tests for validity of curve fitting are provided, with a number of optional transforms. If asked, the program will provide the user with a list of valid commands at any given step, and will identify certain errors in input.

Blood Coagulation Factors↗

Effects of a non-steroidal antiandrogen on sexual behavior and pituitary-gonadal function in the male rat.

An investigation was conducted on the effects of the non-steroidal antiandrogen flutamide (F; alpha-alpha-alpha-tri-fluoro-2-methyl-4-nitro-m-propionotoluidide) on two neuroendocrine mechanisms in the male rat, androgen-dependent sexual behavior, and LH regulation. F was administered in the dose of 50 mg/kg/day SC. In intact, sexually experienced adult males, no quantitative or qualitative behavioral effects were noted. In long-term castrates, F completely suppressed the effects of 100 mug testosterone propionate (TP) per day on accessory sexual glands and penes, but only partially inhibited the marked stimulatory effects of this moderate TP dose on mating. Although the incidence of testosterone (T)-activated ejaculatory behavior was markedly diminished, there was no statistically significant effect on occurrence of mount and intromission behavior. The rapid and profound elevations of circulating LH and T in intact males indicate an effective antagonism of the negative feedback effect of endogenous androgen, and suggest the usefulness of F as a provocative test of pituitary-testicular function. Pituitary LH response to exogenous LHRH was markedly enhanced, as previously found in castrated rats. The administration of F did not affect circulating T levels in T-treated or untreated castrates, indicating lack of interference of circulating F in the T assay. It was concluded that, like the steroidal antiandrogen cyproterone, non-steroidal F shows a divergence between its effects on peripheral androgen-dependent and central feedback mechanisms on the one hand, and sexual behavior on the other. It was not determined whether the inhibition of ejaculatory behavior following F treatment is centrally mediated or results from failure of the peripheral, androgen-dependent structural or functional elements.

Androgen Antagonists↗