Biomedical subjects
Publications and source records attributed to C J Smart.
Thirteen patients with metastatic non-seminomatous germ cell tumours and enlarging metastases consisting of teratoma differentiated only were identified. Patients were managed with surgical resection soon after the growing lesions were documented. Surgical morbidity was minimal and 12 patients are alive (10 are disease-free) at a median follow-up of 28 months.
T cells expressing the gamma delta heterodimer of the T cell receptor (TCR) were studied with respect to their occurrence and expression of gamma delta TCR variable region (V) genes in the normal gastrointestinal mucosa and in a variety of inflammatory conditions. In controls, gamma delta TCR+ cells were a minority population confined to the epithelial compartment of stomach, small bowel and colonic mucosae. Unlike in the periphery, gastro-intestinal gamma delta TCR+ intraepithelial lymphocytes (IEL) were mainly V delta 1+ (89.98 +/- 17.70%); few were V delta 2+ (6.04 +/- 13.8%) or V gamma 9+ (11.38 +/- 10.73%). All gamma delta TCR+ IEL were CD5low; nearly half were CD8+ and the remainder were CD4-CD8- 'double negatives'. There was no significant change from normal in percentages of gamma delta TCR+ IEL in H. pylori-associated gastritis, Crohn's disease and ulcerative colitis. However, in coeliac disease, gamma delta TCR+ IEL were elevated from 2.54% (+/- 1.71) in controls to 29.6% (+/- 16.1) in untreated patients (P less than 0.001) and 18.5% (+/- 7.2) in treated patients (P less than 0.001) and more were CD4-CD8-. Otherwise, gamma delta TCR+ IEL phenotypes were little changed: the majority remained V delta 1+V delta 2-V gamma 9- and all were CD5low. These data suggest that increased gamma delta TCR+ IEL are not a generalized response to intestinal inflammation or to stress proteins, although the typical V delta 1+V delta 2-V gamma 9- CD5low phenotype is retained.
T-cell subsets and their activation state were examined by double-label immunofluorescence of cryostat tissue sections of the colon from 21 patients with ulcerative colitis (UC) and 30 histologically normal controls. Expression of MHC class I (HLA-A, B, C) and class II (HLA-D) antigens was studied in parallel. In the normal colonic mucosa, the CD4:CD8 ratio in the epithelial compartment approximated 1:1, and in the lamina propria, 2.55:1. Of the CD8+ (cytotoxic/suppressor) subset, approximately half did not express the CD5 "pan-T" marker in either compartment. Virtually no Leu8+ cells were observed, implying that the CD4+ subset consisted of helper, rather than suppressor-inducer cells. Classical markers of T-cell activation (CD25, HLA-D) and proliferation were absent, and strong expression of the CD7 "immunostimulation" marker was approximately equal in both CD4 and CD8 subsets. The epithelium was uniformly negative for class II antigens, but positive for class I. In UC, there were no significant alterations in CD4:CD8 ratios in either compartment, and there were no changes with respect to phenotype of the subsets. In 11 of 19 patients (mainly with total colitis), enterocytes were HLA-D+. In this HLA-D+ group, there was an increase in the percentage of CD4+ cells coexpressing CD7; this difference was significant (P less than 0.02) in the lamina propria. Increased expression of CD7 was also found by the CD6+ T cell subset (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Recent evidence suggests that the four electrophoretically defined gliadin subfractions (alpha, beta, gamma and omega) of wheat can induce the typical pathological finding of coeliac disease. We have prepared long-term murine T cell lines to gliadin and its four major subfractions. The cell lines were tested in proliferative assays with each homologous gliadin subfraction, and to the other gliadin subfractions. There was some cross-reactivity, with unfractionated gliadin and its alpha-subfraction being the most antigenic, while omega-gliadin was the least. These data demonstrate that gliadin components are effective stimuli for specific T cell responses, and further suggest that the alpha-gliadin subfraction generates the highest specific responses. This accords with observations in man that all four gliadin subfractions exacerbate coeliac mucosa, but that the alpha-subfraction is the most active.
The description of an amino acid sequence homology between the E1B-58-kDa protein of adenovirus 12 and gliadin has led to the suggestion that previous infection by this virus and subsequent exposure to gliadin could trigger the development of coeliac disease in susceptible individuals as a result of immunologic cross-reactivity. We have sought to measure specific antibodies to the E1B-58-kDa protein in 23 coeliac patients and 10 normal subjects. The sera were analysed by radioimmunoprecipitation with metabolically labelled adenovirus-12-transformed rat cells (which express the E1B-58-kDa protein), followed by separation on polyacrylamide gels. None of the coeliac sera had evidence of antibodies to the E1B-58-kDa protein. These data suggest that coeliac patients show little evidence of humoral immunity to the specific adenovirus 12 E1B-58-kDa protein implicated in the aetiology of coeliac disease.
Cryostat sections of histologically normal human colon were studied by double-label immunofluorescence techniques using a panel of monoclonal antibodies to T-lineage antigens and activation markers, with particular reference to the CD6 antigen. In the lamina propria, the majority population of T cells was of the CD3+, CD6+, CD4+ subset, of which virtually all were of the UCHL1+, CD45R-, Leu 8- phenotype of antigen-committed helper T cells. This majority lamina propria population did not express markers associated with blastogenesis (CD7), activation (MHC class II, CD25, CD38) or proliferation (OKT9, Ki67). In both intra-epithelial and lamina propria compartments, a subpopulation of CD3+ T cells was identified which did not express either the CD6 or CD5 peripheral 'pan T' markers. Most of the CD3+, CD6- cells were of the CD8+ (cytotoxic-suppressor) subset which co-expressed the CD7 antigen with a much higher frequency than did the CD6+ subpopulation. Expression of CD25, CD38 and HLA-D antigens, although infrequent, was confined to this CD8+, CD5-, CD6- population. Our data thus imply that the colonic mucosa is largely populated by mature, antigen-committed resting T cells of the helper-inducer phenotype.
Cryostat sections of normal human adult gastrointestinal mucosae were studied by double-label immunofluorescence with antibodies to CD3, CD4, CD8, CD5 and CD6, in parallel with antibodies beta F1 and TCR delta 1 against beta-chains and delta-chains of the T-cell receptor (TcR) types TcR2 (alpha/beta) and TcR1 (gamma/delta), respectively. Virtually no TcR1+ were found within the lamina propria. In the epithelial compartment, TcR1+ cells were infrequent: in the small bowel, congruent to 2% of T cells were TcR1+. In the colonic epithelium, the percentage of T cells expressing gamma/delta-chains was higher, with a mean value approximating 15-20%, although this apparently large percentage increase compared with small bowel reflects in part a much lower density of colonic IEL, as absolute numbers of TCR delta 1+ cells were comparable. Of the TcR1+ population, about half were CD4- CD8-, 'double negatives' and the remainder were CD8+. TcR1+ cells were also CD5- CD6-, irrespective of expression of CD8. No CD4+ cells expressing TcR1 were observed: essentially all CD4+ cells were beta F1+, with some variability of labelling intensity. Approximately 30-50% of the CD8+ subset expressed the beta F1 antigen strongly. However, in the remaining TcR1- CD8+ cells, which were all of the CD5- CD6- phenotype, expression of the beta F1 antigen was only detectable when streptavidin and biotin conjugates were used for amplification of labelling. Thus, the CD8+ CD5- subset, a prominent population of the epithelial compartment of the small bowel, was either TcR2dull in the majority or TcR1+ in a minority. Our data imply that gamma/delta TcR1 cells may be actively excluded from intestinal lamina propria, and that any preferential localization that does occur is limited and is rather a feature of the colonic mucosa, rather than the small bowel.
Normal human colonic lymphocyte populations were isolated for both phenotypic analysis by double-label immunofluorescence and assessment for regulatory effects on Ig production by co-culture with responder cells from colonic mucosa and peripheral blood. Mean CD4:CD8 ratios for colonic intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) were comparable to values obtained from tissue sections. IEL alone did not produce Ig in vitro and were without effect on Ig production when co-cultured with LPL. However, T-enriched LPL had a marked helper effect for T-depleted LPL. Maximal help was for IgA production, increasing with numbers of T-enriched cells. In colonic LPL T-depleted and T-enriched co-cultures, pokeweed mitogen (PWM) had no significant effect. By contrast, in co-cultures of T-enriched and T-depleted peripheral blood mononuclear cells, Ig production was PWM-dependent. In all experiments with colonic mucosal responder cells, IgG production was low. The effects of unfractionated colonic biopsy lymphocytes on T-depleted peripheral blood mononuclear cells were additive for IgM production and synergistic for IgA synthesis, although almost no IgG was produced. Moreover, PWM had helper effects for IgM, but was suppressive for IgA production. These data suggest that colonic mucosal regulatory cells reside in the lamina propria, and predominantly provide help for IgA and IgM synthesis. The data further suggest the existence of a pre-stimulated IgA-specific T helper cell population.
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A double-blind trial comparing the effect of Permixon (160 mg bd) against placebo in the treatment of benign prostatic hypertrophy is described. In both groups a significant improvement in flow rate and subjective assessment of symptoms was seen. There was no significant difference between the results of treatment in either group.
A combined approach between Departments of Urology and Geriatric Medicine to the diagnosis and management of urinary incontinence in disabled elderly men with neurological lesions where outflow obstruction is thought to be a contributory factor is described. After a dual out-patient assessment, patients have a planned admission to a geriatric ward where urodynamic studies and cystoscopy are performed, followed, where necessary, by appropriate surgery. The results in 75 patients are presented. Single urodynamic studies alone are effective in establishing the diagnosis in only 20% of cases. The largest group needing surgical treatment are those with combined cerebrovascular disease and prostatic enlargement. The degree of disability, but not age, influences the outcome of surgery in such cases. The benefits of collaboration to such patients and to the departments are discussed.
Forty-two bone images carried out on 33 patients with renal carcinoma have been evaluated. The bone image seems more sensitive than conventional radiology in detecting bone secondaries, but covert metastases are unlikely in the patient presenting with purely urological symptoms.
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Two simple methods of assessing the presence and likely cause of impotence are described. The mechanism of sexual dysfunction is discussed with particular relevance to the surgical patient.
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