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Biomedical subjects

J M Skinner

Publications and source records attributed to J M Skinner.

18 recordsLinked to original sources

Mononuclear cells in normal colon and colonic carcinoma express the same T cell activation markers.

The proportion of mononuclear cells (MC) expressing some of the T cell activation markers in normal colon and colonic carcinomas was determined by immunoperoxidase staining and computer-assisted video image analysis (VIA). Tissue sections were stained with monoclonal antibodies against the T cell activation markers which included the MHC class II antigens DR, DP and DQ, interleukin 2 receptor (CD25) and the p180 (CD45RO) form of the leucocyte common antigen. The mean values for the proportion of leucocytes expressing these activation markers were 92% for DR, 61% for DP, 68% for DQ and 60% for CD45RO in tumours and 90, 62, 70 and 55% in normal tissue respectively. Few cells were stained for the IL2 receptor (mean values 7% for tumours and 5% for normal tissue) or the p220 form (CD45RA) of the leucocyte common antigen (mean values 6% for tumours and 4% for normal tissue). The proportion of MC bearing any of these markers in the normal colon was not significantly different from the matched colonic carcinomas.

Antibodies, Monoclonal

The use of computer-assisted video image analysis in the enumeration of immuno-stained cells in tissue sections.

A novel method of computer-assisted video image analysis (VIA) was used to determine the number of immunostained cells in tissue sections. This method permitted an accurate and objective quantification of cells of a particular phenotype. This enumeration was achieved by measuring the area stained by a test monoclonal antibody (such as the T cell marker, CD3) and comparing it with the area stained by a leukocyte common (LCA) monoclonal antibody (CD45). The proportion of T cells within the total leukocyte population in a particular tissue was then calculated. The differentiation of positive (stained) and negative (unstained) cells was uniformly maintained by setting the computer to detect a threshold for staining intensity. This enabled consistency to be maintained within a tissue section as well as between sections stained with the same antibody. In the present study, we determined the phenotype of leukocytes in colonic carcinomas by VIA and compared this with results obtained by normal visual analysis. The VIA method showed distinct advantages over normal visual analysis especially in sections which contained moderate numbers of stained cells.

Antibodies, Monoclonal

Measuring intraepithelial lymphocytes, surface area, and volume of lamina propria in the jejunal mucosa of coeliac patients.

An accurate morphometric method is described for quantifying the intraepithelial lymphocytes (IEL), the area of the epithelium, and the volume of the lamina propria in jejunal mucosa of coeliac patients. All measurements are related to a unit-length of muscularis mucosa which is unaltered by the disease process. The results show a significant decrease in the epithelial surface area and an increase in the volume of the lamina propria in coeliac jejunal mucosa compared with normal levels, even after treatment. The number of IEL is the same as normal before or after treatment. Other workers have shown an apparent increase in IEL in untreated disease which returns to normal levels after therapy. This discordance is explained and the importance of accurate quantitative methodology is stressed.

Celiac Disease

Ultrastructural analysis of plasma cells in coeliac patients.

By accurate morphometry the length of the rough endoplasmic reticulum (RER) was estimated in electron micrographs of a population of jejunal plasma cells in biopsies obtained from normal volunteers, untreated coeliac disease patients, and coeliac disease patients treated for one year on a gluten free diet. Increase in length or hypertrophy of the endoplasmic reticulum is an indication of increased protein synthesis of the cell (Ghadially, 1977). An increase compared with normal length was demonstrated in the mean length of the plasma cell rough endoplasmic reticulum in plasma cells obtained from both groups of coeliac patients. This estimate of increased protein production--in this case immunoglobulin--indicates an increase in the immunological activity of plasma cells even after treatment and suggests not only a reaction to dietary gluten but probably to other antigens also.

Anthropometry

Morphometric electron and light microscope analysis of lymphoid cells in coeliac disease.

Lymphocytes in jejunal biopsies from normal subjects and from untreated, treated, and gluten-challenged coeliac patients were examined by accurate morphometric methods. There was no significant difference between lymphocytes from different sources and those in the jejunum. Transforming lymphocytes were ultrastructurally quite different from non-transforming lymphocytes. The appearance of transforming lymphocytes in the lamina propria in different groups of coeliac patients is in accordance with the increase in the number of plasma cells. In treated patients the results indicate a rapid humoral response to gluten challenge.

Celiac Disease

Abnormalities in the apparently normal bowel mucosa in Crohn's disease.

The uninvolved intestinal mucosa away from the affected areas in Crohn's disease has always been considered to be macroscopically and microscopically normal. Rectal biopsy specimens from 13 patients who had had Crohn's, disease elsewhere in the bowel, but never in the rectum, showed significant increases in the plasma-cell density in the lamina propria, in the volume of the lamina propria, and in the glucosamine-synthetase activity of the specimens, compared with a control series of patients with the irritable-colon syndrome. It is suggested that the colonic mucosa is always abnormal in Crohn's disease even if macroscopical and histological examination shows an apparently normal mucosa.

Biopsy

Waldenström's disease of the jejunum.

A case of Waldenströms macroglobulinaemia with characteristic clinical features was investigated in life and at autopsy. Using immunochemical and immunohistochemical methods it was confirmed that the abnormal clone of cells producing IgM formed a solitary tumour in the jejunum causing partial obstruction. Resection of the tumour led to an improvement in the clinical condition and biochemical measurements.

Aged

Evidence for significant hematopoiesis in the human thymus.

Earlier studies on fetal thymus suggested that certain of the large pyroninophilic cells found there might have a hemopoietic role, and it was decided to determine the nature of these cells using histochemical and immunohistochemical methods. Thymic tissue from aborted fetuses, stillbirths, and neonatal deaths was examined histochemically using methods for the detection of chloroacetate esterase, peroxidase, and pseudoperoxidase, and by staining techniques for mast cells and eosinophils. Tissue was also examined using the indirect immunoperoxidase method for the presence of hemoglobin A (HbA) and F (HbF), for lysozyme (muramidase) and immunoglobins alpha, mu, gamma, kappa, lambda. Positive staining to some degree was seen in cells in the connective tissue stroma using all methods, and the cells stained corresponded to one or another of the types of pyroninophilic cells present. The finding of large cells with positive chloroacetate esterase and antilysozyme indicates the presence of granulopoiesis. Similarly, the presence of large nucleated cells with pseudoperoxidase and anti-hemoglobin (A and F) staining indicates the presence of erythropoiesis. Plasma cells were present in small numbers.

Antibody Specificity

Immunosuppression in the treatment of inflammatory bowel disease. II. The effects of azathioprine on lymphoid cell populations in a double blind trial in ulcerative colitis.

Blood lymphocytes and rectal plasma cells have been studied in patients with ulcerative colitis taking part in a double-blind trial of treatment with azathioprine. Treatment for 1 year resulted in a modest fall in blood lymphocyte count, with little change in neutrophils or platelets. There was no major change in the proportions of circulating T and B lymphocytes, suggesting that the number of such cells per millilitre of blood fell in proportion to the change in lymphocyte count. The number of plasma cells in the rectal lamina propria was reduced to a mean less than half that of the control patient group. Blood K-cell cytotoxic activity fell at least 25-fold after 1 year's treatment. PHA-induced cytotoxicity was also reduced, but less consistently. Reduced K-cell activity is interpreted as reflecting depletion of effector cells from the circulation. The fall in lymphocyte count, K-cell activity and gut plasma cells was slow, indicating continuous inhibition of lymphopoiesis or differentiation throughout the trial period. Thus, azathioprine has some immunosuppressive effects which develop only after prolonged treatment. The clinical results of the trial did not show a major beneficial effect of azathioprine in the treatment of ulcerative colitis, nor were there clear correlations between the results of lymphocyte assays and clinical response in individual patients.

Antibody-Producing Cells

Alpha-chain disease with localized plasmacytoma of the intestine. Immunoperoxidase study.

An ileocaecal tumour in a patient with alpha-chain disease in remission was studied immunohistochemically by a quantitive immunoperoxidase method. The tumour which was histologically shown to be a plasmacytoma consisted of 68% alpha cells and 15% lambda cells; no kappa cells were found. Away from the tumour the pattern of immunoglobulin-producing cells was normal. It is concluded that the abnormal cell causing alpha-chain disease remains inactive and that the patient developed a plasmacytoma from a different cell clone.

Adult

Atrophic gastritis in gastrectomy specimens.

Examination of gastrectomy specimens has shown that atrophic gastritis and intestinal metaplasia are widespread and have the same distribution in cancer of the stomach as in gastric ulcer affecting the body. Their distribution is restricted to the distal part of the stomach in pyloric ulcer. After gastrojejunostomy the distribution is also like that seen in cancer. There is a close association of widespread atrophic gastritis and intestinal metaplasia with the development of cancer and a high cancer rate after stomach operation for benign conditions. The similarity of distribution of atrophic gastritis and intestinal metaplasia in the stomach with body ulcer to that in cancer and after gastrojejunostomy points to a higher cancer risk in the stomach containing a body ulcer.

Atrophy

Observations on peripheral and central temperatures with particular reference to the occurrence of vasoconstriction.

The importance is emphasized of the inadequacy of the term 'body temperature', but that both core temperature and the peripheral temperature must be considered. The assessment of vasoconstriction is informative, and advantage should be taken of the exact information that can be provided by an electro-thermometer as opposed, for example, to a touch of the hand. The core temperature is taken from the rectum, the nasopharynx or tympanic membrane, and the peripheral temperature from the great toe. If the peripheral temperature falls the loss of body heat is prevented and the core temperature rises. If this is not understood or not recognized misguided attempts may be made to try to reduce the raised central temperature by cooling the skin. This can result in a further rise of central temperature. The recognition of peripheral vasoconstriction enables a proper assessment to be made of its basic cause and of the necessary treatment. The most important cause is hypovolaemia from blood loss and a detailed account is given of how this should be recognized, especially by a study of the gradient between central and peripheral temperatures. Such studies should be a routine in any severe illness, whether medical or surgical, in which circulatory deterioration is likely, especially after major operations or injuries. Study of the temperature of the heel (hindfoot) as well as of the toe (forefoot) can indicate a selective shutdown of peripheral circulation that reveals an especially critical circulatory state.

Adult