A. Busuttil

Immunocompetent cells in human testis in health and disease

The authors have investigated lymphocyte subpopulations and macrophages in normal human testes and the testes of patients under investigation and treatment for subfertility. Specific monoclonal antibodies were used in an indirect immunoperoxidase technique. In normal tissues, T lymphocytes (Leu 4-positive cells) were present in the rete testis with a preponderance of cells of the suppressor/cytotoxic phenotype. In contrast, no lymphocytes were detected within the peripheral portions of the testis. Cells reacting with the anti-Leu M3 monoclonal antibody, which defines monocytes/macrophages, were detected in appreciable numbers in peripheral testis with a specific location around the seminiferous tubules. HLA-DR-positive cells (human leukocyte antigens--class II [DR] determinants of the major histocompatibility complex) also were identified and showed a similar pattern of distribution to that of the Leu-M3 positive cells. While no lymphocytes were seen in the normal peripheral testis, T lymphocytes were detected in testicular biopsies from subfertile patients. Suppressor/cytotoxic T cells (Leu 2a-positive) predominated in patients with oligozoospermia and obstructive azoospermia while T cells of the helper/inducer phenotype predominated in patients with unilateral testicular obstruction and in postvasectomy patients. Sperm antibody measurements correlated with these findings.

Prevalence and “incidence” of celiac disease in Edinburgh and the Lothian region of Scotland

After review of hospital records and jejunal biopsy sections, 703 cases of celiac disease, including 74 cases with dermatitis herpetiformis, were identified in Edinburgh and the Lothian region up to December 31, 1979. Of these, 469 were resident in Lothian, resulting in an overall prevalence of 50/100,000 in men and 74/100,000 in women. The prevalence in men showed no significant variation with age, whereas in women age-specific prevalence varied markedly, with a peak of 126/100,000 at ages 35-44 yr and a low of 28/100,000 at ages 45-54 yr. This variation could not readily be explained, although reduced case ascertainment among women born between 1925 and 1934 could be the basis of a modest cohort effect. There was no evidence that migration or increased mortality at particular ages might be alternative explanations. In children the incidence of celiac disease, as measured by cumulative prevalence with age, increased more than twofold between 1960 and 1975, but since 1976 it has fallen sharply. The fall in incidence in children and the unexplained variations in prevalence in women provide epidemiologic evidence for the role of environmental factors other than gluten ingestion in the etiology of celiac disease.

Identifying leucocytes and leucocyte subpopulations in semen using monoclonal antibody probes

An indirect immunoperoxidase technique employing specific monoclonal antibodies has been used to identify leucocyte subpopulations in cytocentrifuge smears of washed human ejaculate. Cells reacting with the pan antihuman leucocyte monoclonal antibody (HLe-1) were demonstrated in 63/67 specimens from subfertile patients with a mean count of 14.5 +/- 17.1 leucocytes per HPF (X 320). Cells with similar reactivity were observed in all specimens examined from 10 fertile men with a mean count of 41.6 +/- 26.3 leucocytes per HPF (X 320). Leu-T4+ cells (T-lymphocytes) were demonstrated in only 13/63 of the subfertile group with a mean count of 4.46 +/- 3.3 T-lymphocytes per HPF (X 320). Studies with the anti-leu 2a antibody revealed that these leu-4+ cells were mainly of the suppressor/cytotoxic phenotype. In contrast, no leu-4+ cells were detected in the control group. No leu-12+ cells (B-lymphocytes) were detected in any of the 80 specimens examined.

Submucosal collagen changes in the normal colon and in diverticular disease

Full thickness specimens of normal colon (n=15), and colon from patients with diverticular disease (n = 5) were obtained at operation or autopsy. In the isolated submucosa the ultrastructure of the constituent collagen fibres was examined by transmission electron microscopy. Collagen fibrils in the left colon become smaller (p < 0.001) and more tightly packed (p< 0.001) than those in the right colon with increasing age. This difference is accentuated in diverticular disease (p<0.01). Factors which contribute to the development of colonic diverticulosis, such as raised intraluminal pressure, may be responsible for premature change in submucosal structure.

A study of the effects of dietary gum arabic in the rat

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.

5α‐REDUCTASE ACTIVITY IN HUMAN PROSTATE CANCER IS RELATED TO THE HISTOLOGICAL DIFFERENTIATION OF THE TUMOUR

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 5α‐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 < 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 5α‐reductase, indicating that the activity of this enzyme is purely a function of the histological grade of the cancer and as such 5α‐reductase could be used as a biochemical marker for tumour differentiation.

Malignant mesothelioma of the tunica vaginalis testis: a case report.

We report a case of malignant mesothelioma of the testicular tunica vaginalis. A preceding hydrocele showed mesothelial hyperplasia of its lining. The tumor was treated surgically as well as with a combination of radiotherapy and chemotherapy but it progressed, resulting in death within 21 months from the diagnosis. The relationship of the tumor to mesothelial hyperplasia and to previous exposure to asbestos is discussed.

The submucosa of the human colon

Full-thickness specimens of colon were obtained at operation or autopsy from 20 patients. The submucosa was isolated from the mucosa and muscularis externa, with confirmation by light microscopy. Submucosal specimens were then fixed and prepared for scanning and transmission electron microscopy, with preservation of their orientation. The submucosa was found to consist of a series of layers of collagen fibres, each layer 0.5-2.0 microns thick. The fibres within each layer were co-directionally orientated. The autopsy specimens were comparable in appearance with the operative ones. The mean diameter of the collagen fibrils was 69 +/- 13 nm, and the mean fibril count per unit area was 159 +/- 58/microns2.

Androgen receptors in cancer of the prostate. Correlation with the stage and grade of the tumor

The authors have measured the androgen receptor concentrations in the cytosol and nucleus of 13 carcinoma of the prostate (CaP) patients and compared these values to those in an age‐matched group of 23 patients with benign prostatic hyperplasia (BPH). Histologic classification of the tumors was carried out and the receptor content was correlated to the grade and stage of the disease. The mean ± SEM receptor values for BPH (cytosol: 115 ± 18 fmol/g tissue; nucleus: 140 ± 34 fmol/g tissue) were not significantly different from those measured in CaP (cytosol: 105 ± 23 fmol/g tissue; nucleus: 83 ± 23 fmol/g tissue). There was a positive correlation between nuclear and cytosolic receptors in both BPH and CaP. Our data revealed, however, the absence of any correlation between histologic grade in CaP and receptor content. If, however, the tumors were classified according to the stage of the cancer using the TNM system, “early disease” tumors maintained significantly lower Gleason score (4.4 ± 0.61) and receptor levels (cytosol: 63.8 ± 31.2 fmol/g tissue; nucleus: 46.2 ± 26.5 fmol/g tissue) than those measured in the “late disease” (Gleason score: 7.0 ± 0.56; cytosol receptor: 146.2 ± 20.5; nuclear receptor: 117.2 ± 31.6) (P < 0.05); therefore the staging of the disease bears a great impact on the capacity of the tumor to specifically bind androgens. Cancer 57:2351–2356, 1986.

Skin lesions in chronic granulocytic leukemia. Treatment of a patient with topical nitrogen mustard

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.