Biomedical subjects
Publications and source records attributed to A Busuttil.
A patient is described with an unusual presentation of ulcerating skin lesions in Philadelphia chromosome-positive chronic granulocytic leukaemia. Treatment with topical mustine ointment (nitrogen mustard, mechlorethamine) achieved a good palliative result.
Continuous fluid-inflation proctometrograms were performed in men with the symptoms of chronic radiation proctitis and in age and sex-matched control subjects (n = 10). Rectal volumes and compliance were measured. There was a significant reduction in the rectal volumes at sensory threshold, constant sensation and maximal tolerance and in rectal compliance (P less than 0.01). Comparable pressure measurements did not demonstrate significant differences. The maximum tolerable volume, symptomatic and sigmoidoscopic scoring correlated to rectal compliance (r = 0.77, -0.8, -0.73; P less than 0.01, less than 0.01, less than 0.02, respectively). Reduction in volume and compliance is often not obvious radiologically. Histological evidence suggests that smooth muscle hypertrophy and myenteric plexus damage are contributory.
We have measured the activities of two androgen metabolizing enzymes in tissue obtained from thirty-nine patients with carcinoma of the prostate (CaP). The enzyme activities were correlated to the histological differentiation of the tumours based on the Gleason Score and also compared to the activities measured in fourteen age matched patients with nodular prostatic hyperplasia (BPH). Although the mean values for the 5 alpha-reductase in CaP (9.29 +/- 1.47 pmol/mg protein/30 min) were found to be significantly lower than the corresponding values in BPH (16.26 +/- 3.04 pmol/mg protein/30 min) (P less than 0.05), there were nonetheless significant differences within the cancer group and these were totally dependent on the degree of differentiation of the tumour. A progressively suppressed enzyme activity was measured as the carcinomatous tissue became more anaplastic. No correlation was, however, observed between tumour bulk which was also estimated histologically and 5 alpha-reductase, indicating that the activity of this enzyme is purely a function of the histological grade of the cancer and as such 5 alpha-reductase could be used as a biochemical marker for tumour differentiation. We also measured the 3 alpha (beta)-hydroxysteroid dehydrogenase activities in cancer of the prostate but our findings indicated no significant differences between the various stages of the cancer. Furthermore we were unable to correlate the activities of this enzyme with that of the 5 alpha-reductase. Nonetheless two interesting patterns relating to the 3 alpha (beta)-hydroxysteroid dehydrogenase emerged.(ABSTRACT TRUNCATED AT 250 WORDS)
A series of monoclonal antibodies that react with human lymphocyte subsets was used in an indirect immunoperoxidase technique to study representative blocks from normal human testis, epididymis, vas deferens, prostate and seminal vesicles. Biopsies of testis, epididymis and vas obtained during surgical procedures directed at the investigation and treatment of infertile males were also studied. In all normal tissues, apart from the peripheral testis where no lymphocytes were identified, T lymphocytes were the predominant cell type (Leu 4+). These lymphocytes were largely of the suppressor/cytotoxic phenotype (Leu 2a+) and were more abundant in between the epithelial cells in the rete testis, epididymis, vas deferens, seminal vesicles and prostatic acini. Cells of the helper/inducer phenotype (Leu 3a+) were identified mainly within the interstitium of the epididymis and the prostate. B-lymphocytes (Leu 12+) were few in number and were mainly in the stroma of the prostate. In each organ the ratio of the T-cell subsets was determined and changes in this ratio were observed in epididymal and vasal biopsies from some infertile males. Finally, in testis biopsies from infertile men, suppressor/cytotoxic T-cells were demonstrated between the germinal epithelium and the fibrous tunica of the seminiferous tubules and as focal aggregates in the interstitium.
Tumorigenicity of human lymphoma and lymphoblastoid B-cell lines was assessed by their ability to form growing and transplantable masses on subcutaneous inoculation into neonatally thymectomized, Ara-C-protected, total-body-irradiated mice. By these criteria, 12 lines of known malignant origin were tumorigenic, 11 lymphoblastoid lines, tested after less than one year of in vitro growth, were non-tumorigenic and 8/18 long-established lymphoblastoid lines produced transplantable tumours. All of the long-established lines had acquired karyotypic changes on prolonged culture, the predominant characteristic being a gain of whole chromosomes or of major chromosome segments. None showed the classical 8:14 translocation associated with Burkitt's lymphoma. Comparisons with nontumorigenic precursors (recovered from liquid nitrogen storage) and with other non-tumorigenic but chromosomally abnormal, lymphoblastoid lines suggest that imbalance of the dosage of genes carried on chromosomes 7,8 and 9 may be important in determining the tumorigenic phenotype.
Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.
Gum arabic (GA) is a water-soluble polysaccharide (molecular weight approximately 850 000) containing rhamnose, arabinose, glucuronic acid and galactose. The metabolism of GA has been studied in the rat. Adult male Wistar rats were given GA incorporated into either an Oxoid breeders (OB) diet or an elemental (Elem) diet. Intestinal contents were examined for precipitable GA using acidified ethanol. GA was found from stomach to small intestine but not in the caecum, colon or rectum. Caecal excision and restoration of intestinal continuity resulted in GA recovery from stomach to rectum. Excreted methane, hydrogen and volatile fatty acids (VFA) were measured as indicators of bacterial activity in the caecum and colon. Methane excretion increased on the OB + GA diet and H2 concentrations remained unaltered. The Elem diet abolished gas production. When the animals were given the Elem + GA diet, H2 and methane were only produced after 28 d. Faecal VFA increased with increasing GA intake, acetate concentration increased and butyrate concentration decreased with increasing GA dosage. Significant decreases in concentrations of VFA were found from caecum to left colon and from left colon to faeces. It can be concluded that GA degradation occurs in the caecum and is associated with increased methane excretion, increased VFA concentrations and changes in the proportions of various VFA in the faeces.
We report an analysis of 68 of 1112 couples who attended an infertility clinic where the man had past or present evidence of testis maldescent. The age at orchiopexy for these 68 men was later than would be expected, taking into account surgical practice in Scotland for the relevant time period and this supports the view that late orchiopexy is a risk factor for subsequent infertility. There was no evidence that antisperm antibodies are responsible for the damage to spermatogenesis in unilateral cases; however, measurement of the serum hormones showed elevations of LH and FSH which cannot be entirely explained as secondary to the damaged spermatogenesis. There was weak but nevertheless significant evidence that testis maldescent may be a poor prognostic factor as far as subsequent fertility is concerned and that this is independent of the length of time the couple have been trying and the man's motile sperm density. In two men there was intra-abdominal undescent and both were found to have testis tumours; we would re-emphasise that abdominal exploration is mandatory in such cases.
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.
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.
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.
Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell count in 27 control subjects was 146/mm2, SD 29. Significantly higher values were obtained in untreated coeliac disease (mean 243, SD 41, p less than 0.001) returning to the normal range in coeliacs treated with a gluten-free diet with normal jejunal biopsy morphology. In seven patients mucosal mast cell counts were performed in multiple jejunal biopsies, and these showed that mucosal mast cell distribution was not patchy. There was no evidence of degranulation of intestinal mucosal mast cells under the conditions of routine biopsy (overnight fast). An increase in mucosal mast cells in untreated coeliac disease may be one explanation for the high number of IgE positive stained cells in the intestinal mucosa that has been reported by some authors.
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Young Wistar rats were fed gum arabic (GA) at dietary concentrations of 0% (two control groups), 1, 2, 4, 8 and 20% for 13 weeks. The criteria studied were body weights, food and water consumption, urinalysis, liver and kidney weights, clinical chemistry, haematology, and histology. No untoward effects were observed at dose levels below those which caused dietary imbalance. At the top dose, female rats showed a small reduction in kidney weight, caecal enlargement, and changes in serum urea and total CO2. Male rats showed no differences from the control groups at dietary concentrations up to approx. 8%, but food and water consumption, body weight, liver and kidney weights all decreased significantly and caecal enlargement was evident at the top dose tested. There were no histological changes and no significant changes in haematological parameters in male or female rats at the top dose tested. The no-untoward effect concentrations were 8.6% (5.2 g/kg/day) and 18.1% (13.8 g/kg/day) for male and female rats respectively.
The relationship between testicular histopathology, follicle stimulating hormone levels, sperm density and the presence of antisperm antibodies was investigated. There was no association between damage to the seminiferous tubules and the presence of agglutinating or immobilising antisperm antibodies. In 2 patients with congenital obstructive azoospermia and pre-biopsy circulating antisperm antibody there was extensive lymphocytic, macrophage and plasma cell infiltration, fibrosis and perivasculitis on epididymal biopsy. Breaches in the blood epididymis barrier are worthy of further investigation when considering the genesis of antisperm antibodies.
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