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Biomedical subjects

A Leake

Publications and source records attributed to A Leake.

At least 37 records · Page 2Linked to original sources
PubMed1990

Reduced gastrointestinal absorption of calcium in dementia.

Several reports have suggested that the neurodegenerative change in Alzheimer-type dementia (ATD) may be related to alterations in calcium homoeostasis. The absorption of radiocalcium (45Ca) in 26 ATD subjects and 11 patients with multi-infarct dementia (MID) was compared to 24 normal age- and sex-matched controls. The absorption of radiocalcium was significantly lower in both ATD and MID when compared to controls. The reduced 45Ca absorption in ATD occurred in the presence of normal plasma concentrations of PTH and vitamin D metabolites and the serum concentrations of calcium and aluminium were in the normal range. The data suggest that the reduced uptake of radioactive calcium observed in ATD is a non-specific derangement.

Aged↗
PubMed1990

Plasma N-POMC, ACTH and cortisol concentrations in a psychogeriatric population.

Elderly patients with depression and Alzheimer-type dementia (ATD) were compared with age-matched control subjects using a protocol which measured cortisol, adrenocorticotrophic hormone (ACTH) and N-terminal pro-opiomelanocortin (N-POMC) to determine diurnal variation and the effect of dexamethasone administration. Depressed patients had significantly elevated cortisol concentrations both before and after dexamethasone administration. Basal ACTH and N-POMC concentrations were normal in depressed patients but were both elevated, compared with controls, after dexamethasone. By contrast, in ATD patients, cortisol was elevated only after dexamethasone, as was ACTH, but not N-POMC. This may imply that the pattern of secretion of POMC-derived peptides underlying increased cortisol secretion is different in ATD from that in depression.

Adrenocorticotropic Hormone↗
PubMed1989

Corticosteroid-binding globulin in depression.

We undertook this study to evaluate the role of plasma free and total cortisol, and corticosteroid-binding globulin (CBG) in depression. Plasma was collected from 15 drug-free depressed patients and 15 age and sex-matched control subjects at 0900 and 2300 and at 1600 following an oral dose of dexamethasone. Depressed patients had elevated concentrations of both free and total cortisol at all time points studied. The binding capacity and affinity of plasma CBG for cortisol was similar in both groups at all times studied. No differences in CBG measures were noted if the depressed subjects were divided into elderly or younger subjects and dexamethasone suppression test (DST) suppressors or non-suppressors.

Aged↗
PubMed1988

Cortisol, ACTH, and dexamethasone concentrations in a psychogeriatric population.

Cortisol and adrenocorticotrophic hormone (ACTH) were measured at 2 time points before the administration of 1 mg of dexamethasone (day 1) and 1 time point on the following day (day 2). Thirteen severely depressed elderly patients, 15 patients with Alzheimer-type dementia (ATD), and 16 normal controls were studied. Cortisol was markedly elevated in depressed patients compared with the other subjects in day 1 samples. Following dexamethasone, both the depressed and ATD patients showed a similar elevation of cortisol compared with controls. ACTH concentrations were not significantly different between the groups before dexamethasone, but were significantly higher in both depressed and ATD patients after dexamethasone. More depressed patients than ATD patients exhibited hypersecretion of ACTH after dexamethasone. This implies that ACTH is less responsive to glucocorticoid feedback in elderly depressed patients, which may be a factor in causing hypercortisolemia.

Adrenocorticotropic Hormone↗
PubMed1988

A multiple timepoint study of N-terminal pro-opiomelanocortin in depression using a two-site recognition immunoradiometric assay.

N-pro-opiomelanocortin (N-POMC) is secreted from the same precursor as ACTH and beta-endorphin. Elevated plasma ACTH and beta-endorphin/beta-lipotrophin concentrations have been reported in depression, however there have been no previous studies of N-POMC. Twenty-five patients with major depression and 18 control subjects were studied at five timepoints to examine diurnal rhythm and the effect of a dexamethasone suppression test. N-POMC was measured using a newly developed two-site recognition immunoradiometric assay (IRMA). This demonstrated advantages of sensitivity, specificity and simplicity compared with existing radioimmunoassays. N-POMC exhibited a pattern of diurnal rhythm and suppression in response to dexamethasone as described for other POMC derived peptides. Depressed subjects had higher levels of N-POMC at 0900 h post-dexamethasone than did control subjects. In conclusion, the results of this study are consistent with a hypothesis of cosecretion of POMC-derived peptides. N-POMC has a similar pattern of abnormal concentrations to ACTH and beta-endorphin/beta-lipotrophin in depression. This constitutes probable evidence of POMC-derived peptide resistance to glucocorticoid feedback in this condition.

Adult↗
PubMed1988

Somatostatin content and receptors in the cerebral cortex of depressed and control subjects.

Somatostatin-like immunoreactivity is reduced in the cerebrospinal fluid in depression and this is presumed to reflect alterations in cerebral somatostatinergic systems. We have examined this hypothesis by measuring this immunoreactivity and somatostatin receptors in post-mortem cortical tissue from depressed patients and control subjects. There was no significant difference in the temporal and occipital cortex in somatostatin-like immunoreactivity or in somatostatin receptor affinity and binding capacity between depressed and control groups. It is concluded that there may not be an alteration of cortical somatostatin function in depression.

Aged↗
PubMed1988

The dexamethasone suppression test in bulimia nervosa.

In a study of the dexamethasone suppression test (DST) in patients with bulimia nervosa, a non-suppression rate of about 50% was found. The only clinical correlates of DST non-suppression were a previous history of weight loss and/or of anorexia nervosa. These results suggest that DST non-suppression in these subjects may be a trait rather than a state marker of anorexia nervosa.

Adult↗
PubMed1987

A combined study of cortisol, ACTH and dexamethasone concentrations in major depression. Multiple time-point sampling.

The pathophysiology of hypercortisolaemia in major depression was examined. ACTH was measured using a novel immunoradiometric assay of high specificity and sensitivity. Twenty-eight patients with major depression and 18 control subjects were studied. Blood samples for basal hormone concentration were taken at 09:00, 16:00 and 23:00 on day 1, followed by administration of 1 mg dexamethasone at 23:00. Further samples were taken at 09:00 and 16:00 on day 2. Dexamethasone concentration was measured in day 2 samples and no significant difference was found between the depressed group and control subjects. In the depressed group cortisol concentration was elevated at 23:00 on day 1, and ACTH concentrations were elevated in post-dexamethasone samples. ACTH and cortisol concentrations were not directly correlated in individual patients. The elevated plasma cortisol associated with major depression is not solely mediated by changes in ACTH.

Adrenocorticotropic Hormone↗
PubMed1984

The effect of zinc on the 5 alpha-reduction of testosterone by the hyperplastic human prostate gland.

The present studies were performed to evaluate the role of zinc in the regulation of testosterone 5 alpha-reduction by the 800 g supernatants prepared from human benign prostate hyperplasia specimens. The results show that when zinc is added at low concentrations the 5 alpha-reduction of testosterone is increased but at higher cation concentrations the metabolism is significantly inhibited. This decrease was mediated by both a non-competitive inhibition of the binding of testosterone to the 5 alpha-reductase enzyme and by a reduction in the formation of the NADPH cofactor. We have also demonstrated that the decreased synthesis of NADPH was produced by a competitive inhibition of both G6P and NADP binding to the G6PD enzyme. The data also suggests that the increase in testosterone metabolism observed at low zinc concentrations does not produce any changes in the binding of testosterone to the 5 alpha-reductase enzyme. In spite of the above observations we were unable to establish any correlation between the endogenous zinc content of the tissue and the in vitro capacity of the BPH samples to 5 alpha-reduce testosterone. The present study suggests a possible physiological role for the regulation of testosterone metabolism by zinc in the human prostate gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

Subcellular distribution of zinc in the benign and malignant human prostate: evidence for a direct zinc androgen interaction.

The subcellular distribution of zinc and its interaction with androgens has been examined in the benign and malignant human prostate. Endogenously, most of the zinc was associated with the nuclear fraction but significant concentrations were also found in the cytosol. Furthermore, the epithelium contained more zinc than that found in either the stroma or the intact gland. Zinc concentrations were lower in the subcellular fractions of the cancerous tissue when compared to hyperplastic specimens. In vitro uptake of zinc into prostatic homogenates was rapid and at equilibrium the binding was stable for both the 4 degrees C and the 37 degrees C incubations. At low zinc concentrations (less than or equal to 5 mM) the uptake was higher in the nucleus, whereas at higher concentrations, the cancerous tissue exhibited a greater capacity for the metal which was predominantly retained by the cytosol. Our data suggest the presence of a saturable zinc retention mechanism in the nucleus. The zinc uptake was found to be independent of any added androgen. In contrast, the total androgen uptake by prostate was significantly enhanced by the addition of zinc. This effect was not due to increases in the nuclear and cytosolic receptor binding since zinc inhibited the binding of the androgen to these receptors.

Cell Nucleus↗
PubMed1984

Interaction between prolactin and zinc in the human prostate gland.

The interaction between prolactin and zinc was examined in vitro in the human prostate gland. The results indicated that prolactin did not modulate the acute uptake of zinc into benign prostatic hypertrophy tissue whereas zinc, in contrast, increased the uptake of prolactin into the prostate gland. Our study further showed that the augmented uptake of prolactin by zinc was partly due to an increase in the non-specific binding properties of the peptide hormone. We were also able to demonstrate that the specific binding of 125I-labelled human prolactin to the receptor was reduced in the presence of zinc by a competitive mechanism.

Drug Interactions↗
PubMed1983

The biological activity of a single dose of tamoxifen in the adult ovariectomized rat.

1 The peripheral and central activities of tamoxifen were studied in the ovariectomized adult rat, up to 16 d after a single dose of 7.0 or 0.7 mg/kg. 2 Food consumption and body weight were decreased; only food consumption returned to control values after 16 d. 3 The weights of the uterus and of the uterine luminal fluid were increased for up to 8 d. 4 Serum follicle-stimulating hormone (FSH) concentrations decreased, but only significantly 1 and 8 d after 7.0 mg tamoxifen/kg. Serum luteinizing hormone (LH) and prolactin concentrations were elevated for up to 4 d. 5 Lordosis behaviour was absent throughout the period studied. 6 Within 3 d of administration, tamoxifen partially antagonized the oestrogen-induced changes in uterine luminal fluid, prolactin and LH secretion and lordosis behaviour. 7 Tamoxifen did not alter oestrogen-induced changes in uterine weight, food consumption and body weight. 8 The experiments demonstrate that tamoxifen is active for up to 16 d after a single intraperitoneal dose; oestrogen agonist, partial agonist and antagonist activities were demonstrated. The duration and type of activity depends upon the dose of tamoxifen and the target tissue response examined.

Animals↗
PubMed1983

Characterization of the prolactin receptor in human prostate.

The uptake of 125I-labelled human prolactin by subcellular fractions obtained from the human hyperplastic prostate was investigated and the specific binding sites were characterized. The binding was both time- and temperature-dependent with maximum specific uptake achieved after incubation for 20 h at 4 degrees C (dissociation constant = 2.4 x 10(-10) mol/l). The present studies also indicate that the bulk of the specific prolactin binding was confined to the 105 000 and 15 000 g membrane fractions whilst the cytosol and nuclear pellet exhibited a lower capacity for the peptide hormone. Attempts to optimize the binding revealed that pretreatment of the subcellular fractions with 4 mol MgCl2/l quadrupled the binding sites; a similar effect was produced after pretreatment with dextran-coated charcoal, but the changes were less pronounced. Furthermore, our studies suggest that the binding was specific for the human prolactin, with other hormones such as ovine prolactin, human LH, human FSH and human GH showing little or no competition. The addition of magnesium and copper ions to the incubation medium also markedly increased the specific binding, whereas calcium, manganese and EDTA inhibited the prolactin uptake. Freezing and storage of tissue at -70 degrees C did not greatly affect the binding sites. The results suggest that we are clearly dealing with a specific prolactin-binding protein.

Cold Temperature↗
PubMed1982

Hypothalamic, pituitary and uterine cytoplasmic and nuclear oestrogen receptors and their relationship to the serum concentration of tamoxifen and its metabolite, 4-hydroxytamoxifen, in the ovariectomized rat.

High-affinity oestrogen receptors were measured in the cytosol and nuclei prepared from the hypothalamus, pituitary gland and uterus of the ovariectomized rat up to 16 days after a single dose of tamoxifen or 4-hydroxytamoxifen. Tamoxifen produced a dose-related fall in the concentration of cytosol receptors in the hypothalamus, pituitary gland and uterus. Minimum values were observed after 24 h; cytosol receptor concentrations were restored slowly and only reached expected control values between 4 and 8 days and 2 and 4 days for 7.0 mg/kg and 0.7 mg/kg doses of tamoxifen respectively. The nuclear receptor changes were inversely related to the cytosol receptor changes, except that hypothalamic nuclear receptor concentrations after 0.7 mg tamoxifen/kg were not changed. 4-Hydroxytamoxifen (0.14 mg/kg) depleted cytosol and raised nuclear oestrogen receptors in the pituitary gland and uterus. Receptor concentrations had returned to the expected control values by day 4. Oestrogen receptor concentrations in the hypothalamus were unchanged. The apparent resistance of the receptor system in the hypothalamus to translocation by tamoxifen and 4-hydroxytamoxifen was probably due to the blood-brain barrier since the apparent affinity of tamoxifen for the cytosol receptor was similar for all three tissues (dissociation constant 4 nmol/l). Serum concentrations of tamoxifen and 4-hydroxytamoxifen measured after a single dose of 7.0 mg tamoxifen/kg were maximal after 24 h and undetectable by 4 days, at which time nuclear and cytosol receptor levels were still changed. Concentrations of 4-hydroxytamoxifen were approximately one-third those of tamoxifen. The results suggest that the receptor changes after tamoxifen are not simply related to the serum concentration of tamoxifen and its metabolites and that the retention of ligand within the target tissue may be an important determinant.

Animals↗