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Biomedical subjects

M J Reed

Publications and source records attributed to M J Reed.

At least 217 records · Page 12Linked to original sources
PubMed1984

The interrelationship between plasma 5-ene adrenal androgens in normal women.

Plasma concentrations of 5-androstene-3 beta,17 beta-diol (ADIOL) dehydroepiandrosterone (DHA) dehydroepiandrosterone sulphate (DHAS) and cortisol were measured by radioimmunoassay in a group of women aged between 27 and 88 years of age. There was a significant negative correlation with increased age for all three adrenal androgens but not for cortisol. The decrease in adrenal androgens was not related to an excessive divergence from ideal body weight. There was a highly significantly positive correlation between plasma concentrations of all three adrenal androgens which supports a metabolic interrelationship.

Adult↗
PubMed1984

Adrenal androgen concentrations in breast tumours and in normal breast tissue. The relationship to oestradiol metabolism.

Concentrations of ADIOL, DHA and DHAS were measured in human breast tumours and normal tissue from the same breast and related to 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) activity in these tissues. ADIOL and DHA were significantly higher in tumour tissue compared to normal tissue from the same breast (paired t-test: P less than 0.05 and P less than 0.01 respectively) whereas the difference between concentrations of DHAS in normal tissue and tumour tissue was not significant. There was a positive correlation between ADIOL and DHA in both tissues (P less than 0.001) but for DHAS the relationship was only significant in normal tissue (ADIOL:DHAS, P less than 0.001; DHA:DHAS, P less than 0.002). An increase in 17 beta-HSD activity was associated with an increase in DHAS concentrations in both normal and tumour tissue (P less than 0.01 and P less than 0.001 respectively) and with an increase in DHA concentrations in normal tissue (P less than 0.05). These results might be explained by an impairment in the balance between sulphatase and sulphotransferase activity in breast tumours.

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

Evidence for heterosynaptic pairing of the inverted segment in pericentric inversion heterozygotes of the deer mouse (Peromyscus maniculatus).

Silver-stained pachytene cells of male deer mice, Peromyscus maniculatus, which were heterozygous for a naturally occurring pericentric inversion of chromosome 6, were analyzed by light microscopy. The presence of the terminally positioned inversion, involving approximately 30% of the length of chromosome 6, was detected by G-banding. Within the inversion, C-band-positive heterochromatin was restricted to the centromeric region. Silver-staining of spermatocytes revealed the synaptonemal complexes (SCs) of the autosomal bivalents and the X-Y chromosome association. Pachytene cells were scored for the presence of inversion loops corresponding to the pericentric inversion of chromosome 6. Possible loop 6 configurations were detected in less than 1% of the cells examined, the vast majority of cells having regularly formed autosomal SCs similar to those reported for homomorphic chromosome pairs in other rodent species. It appears, therefore, that in these mice the inverted region of chromosome 6 was heterosynaptic throughout pachytene. Heterosynapsis is hypothesized as a mechanism which might obviate the production of duplication and deletion chromatids expected from crossing-over in pericentric inversion loops. The observation of heterosynaptic pairing in the inverted segment and the hypothesis of inversion heterosynapsis as a mechanism averting gametic loss are consistent with the widespread occurrence of pericentric inversion polymorphisms in P maniculatus and the apparent failure of pericentric inversions to genetically isolate populations of this species.

Animals↗
PubMed1984

Adrenal androgen concentrations in endometrium and plasma during the menstrual cycle.

Concentrations of 5-androstene-3 beta, 17 beta-diol (androstenediol), dehydroepiandrosterone (DHA) and DHA sulphate (DHAS) were measured in endometrium and plasma from normal premenopausal and perimenopausal women (average ages 37 and 48 years respectively) at different stages of the menstrual cycle. Plasma levels did not vary with the stage of the cycle for any of the three steroids. Mean plasma levels of androstenediol ranged between 2.03 and 2.92 nmol/l for premenopausal women and 1.38 and 1.58 nmol/l for perimenopausal women while mean concentrations of DHA were 20.80-36.41 nmol/l (premenopausal women) and 13.87-19.07 nmol/l (perimenopausal women). The values for DHAS were more variable and ranged between 3.20 and 4.56 and 2.94 and 4.25 mumol/l for pre- and perimenopausal women respectively. In premenopausal women endometrial tissue concentrations of androstenediol and DHA increased three to fourfold in the secretory phase while no increase was observed in DHAS. There was a similar increase in androstenediol but not DHA or DHAS during the secretory phase for perimenopausal women. A significant positive correlation was found for tissue androstenediol and DHA in both groups of women but the relationship between DHAS and the other androgens was significant only for perimenopausal women. We suggest that the increase in androstenediol and DHA concentrations could be due to an increase in a receptor or binding protein, possibly progesterone dependent, present in secretory phase endometrium.

Adult↗
PubMed1983

Inhibition of 17 beta-hydroxysteroid dehydrogenase activity in human endometrium by adrenal androgens.

The effect of dehydroepiandrosterone sulphate (DHA-S) and its metabolites dehydroepiandrosterone (DHA) and 5-androstene-3 beta, 17 beta-diol (ADIOL) on the activity of 17 beta-hydroxysteroid dehydrogenase in human endometrial tissue was investigated by an isotope ratio technique. The apparent KM for oestradiol was 1.59 X 10(-6) M. All three androgens inhibited the metabolism of oestradiol and the apparent Ki values were: ADIOL, 2.05 X 10(-6) M; DHA-S and DHA, 1.59 X 10(-6) M. However, ADIOL acted by direct competition with oestradiol for the active enzyme site whereas inhibition by DHA and its sulphate was non-competitive. DHA-S and DHA were more potent inhibitors of oestradiol metabolism than was ADIOL. These results support the hypothesis that adrenal androgens could be involved in the development of endometrial hyperplasia and adenocarcinoma. Inhibition of oestradiol metabolism could increase the concentration of oestradiol in endometrial tissue and if unopposed by progesterone, e.g. after the menopause or in subjects with ovulatory defects, could stimulate abnormal endometrial growth.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Endometrial tissue and plasma concentrations of 5-androstene-3 beta, 17 beta-diol during the menstrual cycle in normal premenopausal and perimenopausal women.

A radioimmunoassay for 5-androstene-3 beta, 17 beta-diol (ADIOL) in human endometrium and plasma is described. The recognised criteria of reliability have been fulfilled. Plasma and endometrial tissue concentrations of ADIOL were determined in samples obtained from normal premenopausal and perimenopausal women (average ages 37 and 48 years respectively) at different phases of the menstrual cycle. In perimenopausal women plasma concentrations of ADIOL did not vary throughout the cycle (proliferative phase: 411 +/- 95 (SEM) pg/ml; secretory phase: 462 +/- 28.5 (SEM) pg/ml). For the premenopausal group the pattern was similar (proliferative phase: 568.4 +/- 56.9 (SEM) pg/ml; secretory phase: 663.1 +/- 64.7 (SEM) pg/ml) although a significant difference (P less than 0.05) was noted between late proliferative and late secretory phase levels in these women. A different pattern was observed for endometrial tissue concentrations of ADIOL. In both groups of women a significant (3-4-fold) increase occurred during the secretory phase. There was no apparent relationship between plasma and tissue concentrations of ADIOL either during the proliferative or the secretory phase. There was, however, an age associated decrease for both tissue and plasma ADIOL. Theories are proposed to account for the increase in ADIOL concentration during the luteal phase.

Adult↗
PubMed1983

The relationship between 17 beta-hydroxysteroid dehydrogenase activity and oestrogen concentrations in human breast tumours and in normal breast tissue.

The activity of 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) was measured in human breast tumours and in normal breast tissue from premenopausal, perimenopausal and postmenopausal women. Enzyme activity was higher in tumour tissue than in normal tissue from the same breast and under the conditions of the assay the oxidation of oestradiol was higher than the reduction of oestrone. The physiological status of the women in the study did not relate to the activity of the enzyme in either normal or tumour tissue although fibroadenomas had less activity than adenocarcinomas. In postmenopausal women tumour tissue oestrogens were 2-3 fold higher than in normal tissue from the same breast. Furthermore, tumour tissue concentrations of oestradiol tended to be higher than those of oestrone although in normal tissue the two oestrogens were present in similar concentrations. In plasma from the same women oestrone was the predominant oestrogen. There appears to be no direct relationship between 17 beta HSD activity and oestrogen concentrations but the enzyme may play a part in determining the balance between oestrone and oestradiol according to substrate and cofactor availability.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Plasma levels of estrone, estrone sulfate, and estradiol and the percentage of unbound estradiol in postmenopausal women with and without breast disease.

To investigate the possibility of increased tissue exposure to estrogen in breast cancer patients, plasma levels of estrogens and the percentage of unbound estradiol were measured in postmenopausal women with benign or malignant breast disease and compared with levels in normal postmenopausal women. The percentage of unbound estradiol in breast cancer patients [1.85 +/- 0.35% (S.D.)] was significantly higher (p less than 0.001) than in normal postmenopausal women [1.52 +/- 0.33%] and was still significantly higher when patients were matched with control subjects for weight (p less than 0.001) or ideal body weight (p less than 0.001). The binding capacity of sex hormone binding globulin was similar in both groups of women. No significant differences in the plasma levels of estrone, estradiol, or estrone sulfate were detected between breast cancer and normal subjects. It is concluded that, given similar concentrations of estradiol in plasma of normal and breast cancer subjects, the significant increase found in the unbound estradiol fraction may result in a very small increment in tissue exposure to estrogens in breast cancer subjects. However, even such a small increase in tissue exposure to estradiol may be significant, given the length of time required for breast tumor development.

Aged↗
PubMed1982

Oestrogen production in adipose tissue from normal women and women with endometrial cancer in vitro.

The in vitro conversion of androstenedione to oestrone and oestrone to oestradiol was investigated in human adipose tissue. Higher rates of oestrone (range 1.2-44.0 pg/mg protein/3h) and oestradiol (range 0.6-15.2 ng/mg protein/h) production were observed in tissue samples obtained from women aged 40-50 years compared with the rates measured using adipose tissue from younger women (range 0.7-7.7 pg oestrone/mg protein/3 h and 0.4-1.8 ng oestradiol/mg protein/h). Five subjects studied with endometrial cancer did not show a market increase in conversion of androstenedione to oestrone or oestrone to oestradiol in subcutaneous adipose tissue compared with normal women of similar age and weight. A sample of omental adipose tissue from one subject with endometrial cancer did show a high conversion rate of androstenedione to oestrone (104.0 pg oestrone/mg protein/3 h), although the rate of conversion of oestrone to oestradiol was lower than that observed in subcutaneous adipose tissue, indicating that steroid metabolism is not uniform in adipose tissue throughout the body.

Adipose Tissue↗
PubMed1981

Immune response to keyhole limpet hemocyanin and oral Actinomyces viscosus antigens in Macaca arctoides.

The humoral and cell-mediated immune response to keyhole limpet hemocyanin and antigens from a monkey oral strain of Actinomyces viscosus were investigated in Macaca arctoides. Prior to immunization no responses were detected. Immunization resulted in the production of antibodies to both antigen preparations, the development of a positive skin test and significant stimulation of peripheral blood lymphocytes using the in vitro lymphocyte blastogenesis technique. Furthermore, these responses were continuously detectable for more than 1 year postimmunization with keyhole limpet hemocyanin and for up to 6 months postimmunization with A. viscosus antigens. The capability of developing immune responses in these animals, particularly to A. viscosus antigens, added further to their use as a model for the study of the role of the host immune response to these antigens in the pathogenesis of human periodontal disease.

Actinomyces↗