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G D Chisholm

Publications and source records attributed to G D Chisholm.

At least 145 records · Page 8Linked to original sources
PubMed1984

Characterization of the retinol and retinoic acid binding proteins in the human prostate.

A retinol-binding protein has been detected in the cytosol of human prostates with benign hyperplasia. The binding was of high affinity and specific for retinol (Kd = 35 nM), with other retinoids such as trans-retinoic acid, retinal, and the synthetic analogues, all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nona tetraenoic acid and p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propenyl] benzoic acid, showing little or no competition. The retinol binding, which sedimented as a 2S component on sucrose density gradients, was also unaffected by the addition of excess unlabeled steroid hormones. Furthermore, pretreatment of the cytosol proteins with heat and/or trypsin totally abolished the retinol binding. Parallel experiments with trans-retinoic acid suggest that the hyperplastic prostate possesses a second retinoid-binding site which is specific for retinoic acid and distinct from the retinol-binding component. Experiments with serum from patients with benign prostate hyperplasia revealed no binding at the 2S sedimentation position; this suggests that the retinoid-binding proteins were exclusively associated with prostatic tissue and were not therefore derived from serum.

Carrier Proteins↗
PubMed1983

Factors affecting the reproducibility of androgen receptor determinations in human prostate.

Several factors affecting the reproducibility of androgen receptor assays in the human prostate gland have been identified. Experiments in the presence of proteolytic inhibitors such as PMSF, leupeptin and aprotinin resulted in no change in the estimates of androgen receptors. The androgen binding was also unaffected by the concentrations of endogenous steroids in the tissue. Although the receptor assay was reliable down to protein concentrations of about 5 g/l, at lower concentrations the reliability of the method was significantly reduced. Similarly, tissue storage at -25 degrees C drastically lowered the binding capacity of the prostatic tissue extracts to 50% of initial receptor content over a period of 3 months. The high degree of correlation between receptor levels in the stroma and epithelium suggests that the binding in the total gland will not be drastically affected by the proportion of stroma and epithelium it contains. Following the widely practised 2-h extraction of the nucleus with 0.6 mol/l KCl buffer, a highly significant non-extractable binding component remained. Analysis of data by the single-point assay produced results comparable to those obtained by standard Scatchard analysis and seemed reliable so long as careful quality control was employed.

Aprotinin↗
PubMed1983

Towards a reproducible method of estimating androgen receptors in human prostate.

The effect of sodium molybdate and the stability of [3H]-R1881 on the reproducibility of androgen receptor assays in the human prostate gland have been investigated. The drying down of radio-labelled methyltrienolone, prior to incubation with cytosolic and nuclear extracts, resulted in a marked disintegration of the compound and a loss of specific binding of up to 40%. By contrast, the inclusion of sodium molybdate in the homogenisation buffer significantly increased the specific nuclear and cytosolic binding. In the cytosol, this increase was directly proportional to the amount of molybdate added up to 50 mM whereas in the nucleus binding was maximal at a molybdate concentration of 10 mM and declined at higher concentrations.

Chemical Phenomena↗
PubMed1983

The distribution of 5 alpha-reductase and 3 alpha(beta)-hydroxysteroid dehydrogenase activities in the hyperplastic human prostate gland.

This study examines the distribution of 5 alpha-reductase and 3 alpha(beta)-hydroxysteroid dehydrogenase activities throughout the intact hyperplastic prostate gland and relate these measurements to the fibromuscular/epithelial composition and to the gross glandular morphology. The relative capacities of the stroma and epithelium to metabolize testosterone and dihydrotestosterone were also examined. The results indicate that under optimum reaction conditions an uneven distribution of 5 alpha-reductase and 3 alpha(beta)-hydroxysteroid dehydrogenase could be measured across the prostate. These regional variations reflect true differences in metabolic activity and were independent of any morphological changes: caution is therefore advised when interpreting hormonal metabolic data obtained from single sampling of the gland. Our investigations also suggest that the capacity to metabolize testosterone was evenly distributed between stroma and epithelium and that both tissue components are primary sites for 5 alpha-reductase activity. The reductive 3 alpha(beta)-hydroxysteroid dehydrogenase was also found in both tissue types but the mean stromal activity was marginally higher than the levels measured in the epithelium.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Management of renal carcinoma--a questionnaire survey.

Questionnaires on the management of renal carcinoma were returned by 134 British urologists. Analysis revealed that ultrasound is used, as a routine investigation, by 93% of the respondents, whereas abdominal CT scanning is used routinely by only 16%. Renal arterial embolisation is used by 60% of respondents; a further 12% indicated that, having tried the technique, they had given it up. Of 81 surgeons using embolisation, 44% were hopeful that it offered systemic benefit to the patient and 54% delay nephrectomy after embolisation. Regression of metastases following treatment was reported by 58 surgeons. Details of metastatic regression in 60 patients revealed that pulmonary metastases were involved in 83%. Embolisation featured in the management of only 11 such patients.

Embolization, Therapeutic↗
PubMed1983

Prognostic significance of biopsy results of normal-looking mucosa in cases of superficial bladder cancer.

Quadrant biopsies of normal-looking mucosa were used as part of the assessment of cases with superficial Ta,T1 transitional cell cancer of the bladder. Patients with one or more abnormal biopsies were shown to have a significantly greater chance of developing recurrent tumour compared to patients with normal mucosal biopsy findings. Other factors noted at the time of initial assessment, such as size, number of tumours, Ta,T1 category or grade of tumour did not predict recurrence, although recurrences that invaded muscle were associated with G3 histology in the primary tumour. The results of mucosal biopsy identified patients at risk for recurrence and it is possible that this group would derive particular benefit from adjuvant chemotherapy.

Carcinoma, Transitional Cell↗
PubMed1983

Progress in transrectal ultrasonography for prostatic disease.

The accuracy of ultrasonographic measurement of volumetric changes within the prostate was assessed using a hand-held transrectal probe. This was effected by comparing the ultrasonically calculated weight change following TURP with the measured weight of resected prostatic tissue in a group of 30 patients with benign prostatic hypertrophy. A high correlation was found (r = 0.978) in BPH, but potential difficulties were found in applying the method to the malignant prostate. In the 30 benign cases studied, ultrasound indicated the presence of calculi in 60% of patients and an echo pattern consistent with malignant tissue in 23%. These findings suggest a poor diagnostic accuracy for the technique.

Humans↗
PubMed1983

Incidental carcinoma of the prostate: selection for deferred treatment.

Fifty-one of 212 consecutive patients with prostatic cancer presented with incidentally diagnosed (TO) cancer. The average age at presentation was 73 years and follow-up ranged from 1 to 62 months. Deferred treatment was selected in 39 cases, 10 of which progressed. Of 15 deaths only 3 were related to prostate cancer and these were patients who had presented with metastases. Histological grading by the Gleason system demonstrated a significant correlation with metastatic stage at presentation and tumour bulk, but not with age or progression in deferred treatment cases. It is concluded that there is a need to subdivide patients presenting with incidental carcinoma, that tumour bulk correlates with histological grade and that future treatment protocols for TO disease should stratify for histological grade.

Aged↗
PubMed1983

Comparison of Bolton-Hunter and chloramine-T techniques for the radioiodination of prostatic acid phosphatase.

A double antibody, semi-automated radioimmunoassay for serum prostatic acid phosphatase (PAP) is described, which uses the 125I-labelled N-succinimidyl-3-(4-hydroxyphenyl) propionate ester of PAP. This type of label has substantially higher immunoreactivity than that prepared using the chloramine-T method of radioiodination. Chromatographic purification of either label on Ultrogel ACA44 further improved immunoreactivity. The lowest detection limit (0 . 35 micrograms/l) was achieved with the chromatographically purified ester label.

Acid Phosphatase↗
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↗
PubMed1983

The natural history of renal carcinoma.

In summary, some evidence indicating an increase in incidence of renal parenchymal malignancy has been presented. The nature of renal adenoma and its relationship to renal carcinoma remain uncertain, but it is possible that improved computerized tomography will allow in vivo identification of these lesions and initiate a long-term study to provide some clear data on their natural history. The heterogeneity of clinical presentation of this disease has been reviewed and the paraneoplastic syndromes and their importance summarized. Careful clinical and postmortem studies of disease spread, especially lymphatic spread, have been shown to provide useful information to the debate on the role of lymphadenectomy. Many of the unusual aspects of the natural history have been interpreted in terms of the hosts immune response and some data on the complexity and specificity of the host tumor interaction presented. In conclusion, an understanding of the natural history of renal carcinoma forms an important background on which to base clinical management and identifies areas worthy of further investigation in this curious tumor.

Adenoma↗