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Biomedical subjects

V R Marshall

Publications and source records attributed to V R Marshall.

At least 73 records · Page 4Linked to original sources
PubMed1989

Steroid hormone and epidermal growth factor receptors in meningiomas.

A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

Adult↗
PubMed1987

Macromolecules inhibit calcium oxalate crystal growth and aggregation in whole human urine.

Removal of macromolecules with Mr greater than 10,000 had no discernible effect on the detectable nucleation of calcium oxalate crystals from undiluted human urine, but promoted the deposition of crystalline material and markedly increased the degree of aggregation of the precipitated crystals. Calcium oxalate crystals and crystal aggregates precipitated from ultrafiltered urine were, on average, 68% larger than those deposited from whole urine. These findings suggest that urinary macromolecules play a key role in preventing calcium oxalate kidney stone disease by inhibiting the formation of large crystal aggregates and thereby reducing the probability of particle retention in the kidney tubules.

Calcium Oxalate↗
PubMed1987

The effect of serum on the crystallization of calcium oxalate in whole human urine: inhibition disguised as apparent promotion.

The effect of serum on calcium oxalate crystallization was studied in whole human urine. At concentrations between 0.005% to 0.10% (v/v), serum had no effect on the metastable limit of urine as detected by the Coulter Counter. However, serum caused a marked increase in the number and volume of calcium oxalate crystals deposited in response to an oxalate load. That this increase in volume reflected true deposition of calcium oxalate was confirmed by determining calcium concentration and by including control urines containing added serum but no exogenous oxalate. Analysis of particle size distributions showed that the crystals deposited in the presence of serum were smaller than those occurring in the control. Since serum did not affect the limit of metastability, the enhancement of crystal volume is unlikely to be a result of heterogeneous nucleation. We hypothesize that the apparent promotion effect of serum is due to its inhibition of crystal aggregation which increases the crystal surface area available for calcium oxalate deposition.

Blood↗
PubMed1987

Sexual dysfunction after prostatectomy.

One of the major and disconcerting complications of prostatectomy is impotence. Several studies have reported only a small reduction in potency rates following prostatectomy but have not examined the effect of surgery per se on a group of men in whom one could expect a significant incidence of reduced potency. In order to rectify this defect, a prospective study was undertaken to assess the effect of transurethral resection of the prostate (TURP) and other general surgical procedures on two age-matched populations. In all cases potency and ejaculatory function and frequency of intercourse were assessed pre- and post-operatively. Potency was retained in 86% of men undergoing TURP and in all of the men undergoing general surgical procedures (p less than 0.01). Of those men who indicated that they were capable of having sexual intercourse prior to operation, 88% were unaffected by TURP. In the general surgical group 97% were unaffected. Thus it would appear that TURP has a significant effect on sexual function which cannot be accounted for by the stress of surgery or the age of the population undergoing operation.

Aged↗
PubMed1987

Urinary risk factors in calcium oxalate stone disease: comparison of men and women.

The daily excretion of calcium, oxalate, uric acid and glycosaminoglycans, the 24-h urinary pH and volume, and the inhibitory effects of the urines on calcium oxalate crystal growth and aggregation, were measured in 44 normal women, 41 normal men, 32 female stone formers and 63 male stone formers. No significant differences could be found between the normal men and women, the male and female stone formers, or between the patients and their normal controls with regard to the excretion of oxalate and glycosaminoglycans, and the urinary pH. The normal women exhibited significantly lower urinary volumes and excreted less calcium per day than did the other subject groups. The excretion of calcium by the female stone formers was indistinguishable from that of both groups of men. The male and female stone formers did not differ from their corresponding control groups with regard to the excretion of urate, but both groups of male subjects had significantly higher daily urate excretions than did either female category. This was attributed to the greater body weights of the men. There were no discernible differences between any of the subject groups with regard to the inhibitory effects of their urines on calcium oxalate crystal growth, but urines from both groups of female subjects demonstrated a significantly greater inhibitory influence on crystal aggregation than did those of the men. It would appear that the relatively low incidence of uninfected calcium oxalate urolithiasis in women compared with men may be attributable to (a) a lower daily calcium excretion and (b) a higher inhibitory activity of their urines towards crystal aggregation.

Adult↗
PubMed1987

Effects of ageing and hormonal manipulations on the level of oestrogen receptors in the guinea-pig prostate.

Cytosolic oestrogen receptor levels in guinea-pig prostate tissue were found to decrease with increasing age, irrespective of whether the binding was expressed relative to cytosolic protein or cellular DNA. This decrease in oestrogen receptor levels was also observed using enriched fibromuscular stromal tissue prepared by mechanical fractionation of the prostate. The most pronounced change in cytosolic oestrogen receptor levels (from 133 to 35 fmol/mg protein) occurred at the onset of puberty. The pubertal decrease in receptor levels could not be attributed to an increase in the level of proteolytic activity in prostatic cytosol fractions derived from mature animals, a change in the affinity of the receptor for oestradiol or an increase in oestrogen receptor levels in salt-extracted nuclear fractions. Administration of tamoxifen (1 mg/day) to intact guinea-pigs throughout the transpubertal growth phase did not influence the age-related decrease in cytosolic and nuclear oestrogen receptor levels. In contrast, the decrease in oestrogen receptor levels was prevented by castration. Administration of dihydrotestosterone (DHT; 1 mg/day) to intact prepubertal animals for 4 days before study resulted in diminished cytosolic oestrogen receptor levels; this effect of DHT was blocked by the non-steroidal antiandrogen flutamide (2 mg/day). Furthermore, elimination of testicular hormones by castration during the late-pubertal growth phase resulted in a greater than twofold increase in prostatic oestrogen receptor levels. Collectively, these observations suggest an age-related decrease in oestrogen receptor levels in the guinea-pig prostate which, in part, may be due to increased testicular function at puberty.

Aging↗
PubMed1986

The influence of serum and serum proteins on calcium oxalate crystal growth and aggregation.

The effects of serum, albumin, alpha-globulin, and a mixture of alpha- and beta-globulin on the growth and aggregation of calcium oxalate crystals were measured in a standard seeded crystallisation system. At concentrations below 0.01% blood, which corresponded to microscopic haematuria, all were potent inhibitors of crystal aggregation whilst only having a minor effect on crystal growth. It was found that albumin, alpha-globulin and beta-globulin can account for the total inhibitory effect of serum on crystal growth and crystal aggregation.

Alpha-Globulins↗
PubMed1986

Inhibitory activity of whole urine: a comparison of urines from stone formers and healthy subjects.

The inhibitory activity of whole urines from 32 healthy subjects and 50 calcium oxalate renal stone formers was assessed in terms of their ability to withstand increasing quantities of oxalate before undergoing spontaneous nucleation of calcium oxalate, and their response to a standard 30-mumol challenge of oxalate above their measured metastable limits. The concentrations of calcium (p less than 0.05), oxalate (p less than 0.05), urate (p less than 0.01) and glycosaminoglycans (p less than 0.005) were significantly lower in the stone formers than in the controls and were associated with a significantly higher 24-h urinary volume (p less than 0.001). The majority of urine samples precipitated envelope crystals of calcium oxalate dihydrate, while the remainder precipitated the monohydrate. A significantly (p less than 0.02) greater proportion of the urines from stone formers than from controls deposited calcium oxalate monohydrate, and this was attributed to a lower concentration of calcium in these urines. The minimum amounts of oxalate necessary to induce crystal nucleation did not differ between the two groups, but when the measured metastable limits were expressed as the product of the total (i.e. endogenous + that added to induce nucleation) concentrations of oxalate and calcium at which precipitation occurred, then these limits were significantly lower (p less than 0.05) in the stone formers than in the healthy subjects. However, when the metastable limits of a subgroup of stone formers and controls matched for 24-h urinary volume and calcium and urate concentrations were compared, no differences between the groups could be discerned.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1986

The effect of crystalline monosodium urate on the crystallisation of calcium oxalate in whole human urine.

Samples of undiluted urine from normal men were preincubated with crystalline monosodium urate and their metastable limits and responses to a standard oxalate challenge were compared with results obtained from control samples preincubated without urate. Preincubation with urate had no significant effect on the metastable limits of the urines, the morphology, size, or growth rates of calcium oxalate crystals precipitated from the urines, or on the total amount of calcium oxalate deposited in a given time. It was concluded that particulate monosodium urate is unlikely to influence calcium oxalate stone formation by binding to and attenuating the potency of urinary inhibitors.

Calcium Oxalate↗
PubMed1986

The assessment of urinary catheter toxicity using cell cultures: validation by comparison with an animal model.

A cell culture technique for assessing the toxicity of urinary catheters is described. The inhibitory effect of catheter extracts on the uptake of 3H-labelled thymidine by L929 mouse fibroblasts and human prostate derived epithelial cells in culture was measured. The concentration of extract which depressed uptake to 50 per cent of control (IC50) was determined for catheters of different composition. When compared to the degree of inflammation caused by the same catheters in an animal model, a significant correlation was observed (rs = -0.87). As a result of this correlation, the cell culture technique has the potential to be used as a valid alternative to the animal model.

Animals↗
PubMed1986

An improved method for the preparation and culture of urothelial cells.

Urothelial cells have been prepared by a new method involving collagenase treatment of the lumen of a ureter. These cells have been identified as epithelial and successfully subcultured. In addition, we have observed that growth rate is significantly increased by the inclusion of an extract of bovine hypothalamus in the growth medium. This system for cell preparation and culture should greatly facilitate studies involving urothelial cells.

Animals↗
PubMed1986

The effect of monosodium urate on the capacity of urine, chondroitin sulphate and heparin to inhibit calcium oxalate crystal growth and aggregation.

In order to investigate the possibility of interaction between urinary glycosaminoglycans and particulate monosodium urate, growth and aggregation rates of calcium oxalate seed crystals were measured in the presence of heparin, chondroitin sulphate and normal urine after preincubation with and without monosodium urate (0.5 mg./ml.). Rates of crystal aggregation in the presence of heparin and chondroitin sulphate were significantly (p less than 0.0005) increased after pretreatment with sodium urate, indicating a reduction in the inhibitory potency of heparin and chondroitin sulphate by this salt. A similar effect was observed with the rate of crystal growth in the presence of heparin (p less than 0.01). In contrast, the rate of growth in the presence of chondroitin sulphate was unaffected. Pretreatment with sodium urate had an inconsistent effect on the rate of crystal growth in the presence of 10 normal human urine samples, but significantly (p less than 0.001) raised the rate of crystal aggregation. It was concluded that the influence of urate on crystal aggregation in the presence of urine may be a result of its binding to endogenous chondroitin sulphate, but may not be of practical consequence in the pathogenesis of calcium oxalate renal stones.

Calcium Oxalate↗
PubMed1986

Relationship between ploidy and steroid hormone receptors in primary invasive breast cancer.

The relationship between ploidy, as measured by flow cytometry, and the presence of oestrogen and progesterone receptors was investigated in 145 primary invasive breast cancers. The tumours were considered as an integral group, and as subgroups of lobular and ductal carcinomas. An association was found between the presence of aneuploid stemlines and an absence of oestrogen receptors (ER), for the total tumour population (P less than 0.02), and for the ductal carcinoma group (P less than 0.05). An association between aneuploidy and an absence of progesterone receptors (PR) was observed for the total tumour group (P less than 0.05). Evaluation of a combined oestrogen and progesterone receptor status indicated that the association between aneuploidy and an absence of both receptors was highly significant. The probability of such an association was P less than 0.001 for the total tumour population, and P less than 0.01 for the ductal tumour group. Assessment of progesterone receptor expression by breast cancers containing oestrogen receptors indicated that aneuploid tumours were as likely to express PR as were diploid tumours. Hence, the biological activity of oestrogen receptors appears unmodified by the presence of aneuploid nuclei.

Aneuploidy↗
PubMed1985

A method for studying inhibitory activity in whole urine.

A method has been developed for inducing and quantifying calcium oxalate crystallisation in whole human urine. The propensity of a given urine to induce crystal formation was described in two ways: its ability to resist spontaneous nucleation of calcium oxalate crystals was assessed by titrating 20 mls of the urine with increasing quantities of sodium oxalate (0-150 mumol) to determine its practical metastable limit. This limit was inversely related to the endogenous calcium concentration; its capacity to inhibit crystal growth was quantified by determining the rate of growth of calcium oxalate crystals precipitated in response to a fixed oxalate load (30 mumol) above its metastable limit. The crystals produced were predominantly calcium oxalate dihydrate and were morphologically identical to those occurring naturally in urine. Citrate had no effect on the metastable limits of 3 urines examined, but markedly inhibited crystal growth. Pyrophosphate had a similar effect on crystal growth, and in addition, raised the metastable limit of one of the urine samples.

Calcium Oxalate↗
PubMed1985

Specific binding of oestradiol to guinea-pig prostate cytosol and nuclear fractions.

A high affinity (Kd approximately 0.15 nM), saturable oestradiol binding site, which is specific for natural and synthetic oestrogens has been identified in guinea-pig prostate cytosol fractions. The binding site is protein in nature (heat- and protease-sensitive) and has a sedimentation coefficient of approx. 8S on glycerol gradients. A high affinity (Kd approximately 0.16 nM), saturable oestradiol binding site was also identified in salt-extracted (0.5 M KC1) nuclear fractions. The optimum incubation conditions for measuring the cytosolic and nuclear oestradiol binding sites were determined to be 20 h at 4 degrees C. Saturation analysis studies revealed that following oestrogen treatment of intact animals, approx. 80% of the specific oestradiol binding sites in prostatic cytosol fractions were transferred into the nucleus. The presence of a specific oestradiol binding protein with characteristics of an oestrogen receptor in the guinea-pig prostate, is consistent with oestrogen having biological activity in this tissue. In view of the abundance of stroma in the prostate of this species, and the consistent finding that the stroma of male accessory sex tissues is oestrogen sensitive, the guinea-pig may be an appropriate experimental animal for further investigating the role of oestrogen in the growth and development of the prostate.

Animals↗
PubMed1985

Distribution of oestrogen and androgen receptors between the stroma and epithelium of the guinea-pig prostate.

A procedure is described for separating guinea-pig prostatic tissue into viable epithelial and stromal fractions. Epithelial cells were isolated using 0.1% protease, but this method resulted in significant damage to the stromal cells. However, using a mechanical tissue fractionation technique, a viable stromal matrix consisting predominantly of confluent sheets of smooth muscle cells and intervening collagen fibres was obtained. Although this method selectively spilled-out the epithelial cells, the majority were non-viable and therefore not suitable for receptor studies. Electron microscopy confirmed that cell architecture and organelle morphology were well preserved in both the enzymatic epithelial preparation and the mechanically prepared stroma. Saturation analysis studies indicated that the concentration of high affinity (Kd approximately 0.15 nM) oestrogen receptors was approx. 10-times greater in the separated stroma than in the epithelial fraction. In contrast, the concentration of androgen receptors (Kd approximately 2.2nM) was almost 2-fold greater in the epithelial than in the stromal fraction. These findings suggest that oestrogen, either independently or in association with androgen, may play a role in the growth and development of the stromal component of the guinea-pig prostate.

Animals↗
PubMed1985

Studies on the mechanism of immunosuppression with adenine.

Studies on the mechanism of immunosuppression shown by adenine comprised two areas: (1) Toxicity studies on hepatic, muscle and renal tissues were undertaken to ascertain if immunosuppression was a result of a non specific toxicity. (2) Studies to determine whether immunosuppression is a function of the inhibitory effect on de novo and salvage pathways of purine nucleotide metabolism. Toxicity studies in mice indicated that adenine caused an acute, reversible renal tubular necrosis and that allopurinol, when combined with adenine, could abrogate both the renal toxicity and immunosuppressive activity of the purine base. This result indicated that the toxic and/or immunosuppressive compound may be a xanthine oxidase catalysed product of adenine. Further studies indicated that it was unlikely that a major part of the immunosuppressive activity of adenine was due to the renal toxicity exerted by this compound. Splenic PRPP levels were found to peak on day 4 after antigen administration (day 0) and this corresponded with the peak in antibody plaque response which occurred at day 4 to 5. Adenine given at an immunosuppressive dose of 25 mumoles/mouse on day 0, 1 resulted in a significant inhibition of splenic PRPP levels on day 2 of the response. This effect on splenic PRPP levels on day 2 was also found with hypoxanthine given at an immune enhancing dose and therefore would indicate that depression of splenic PRPP per se is not responsible for the immunosuppression. Adenosine given at immunosuppressive doses was found not to affect PRPP levels in the spleen and hepatic PRPP levels were unaffected by adenine, adenosine and hypoxanthine. The in vivo effects of adenine on hypoxanthine-guanine phosphoribosyltransferase showed that adenine could inhibit significantly this salvage pathway in spleen and liver and that this inhibition could be overcome with concomitant administration of allopurinol. A metabolite of adenine which could contribute to its immunosuppressive activity may be 2-hydroxyadenine since it is derived from the xanthine oxidase catalysed oxidation of adenine inhibited hypoxanthine-guanine phosphoribosyltransferase gave similar renal toxicity to adenine and was immunosuppressive.

Adenine↗