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Biomedical subjects

A K Foulis

Publications and source records attributed to A K Foulis.

At least 19 recordsLinked to original sources

The distribution and possible function of gamma interferon-immunoreactive cells in normal endometrium and myometrium.

T-lymphocytes are present in normal endometrium, where they may have a role in the control of glandular maturation. T-cell activity could be related to the local secretion of cytokines such as gamma interferon, which has an anti-proliferative effect on endometrial epithelial cells in vitro. We have examined gamma interferon immunoreactivity and T-cell distribution in 24 normal pre-menopausal uteri. Endometrial appearances were representative of all stages of the menstrual cycle. Most cells in the lymphoid aggregates in the stratum basalis were stained by T-cell and gamma interferon antisera. T-lymphocytes were also scattered in glandular epithelium and throughout the stroma of basal and functional layers; immunoreactivity for gamma interferon was less consistent in these cells. There was no alteration in the intensity or distribution of gamma interferon staining in different phases of the menstrual cycle. Endometrial granulocytes (K-cells) present mainly in the late secretory endometria were not reactive with the gamma interferon antiserum. In addition to endometrial staining, T-cells were distributed in all areas of the myometrium in most uteri, and many myometrial lymphocytes were gamma interferon positive. These results support a role for gamma interferon in endometrial physiology, possibly as an inhibitor of epithelial proliferation.

Adult

Characterization of the inflammatory infiltrate in ovarian dysgerminoma: an immunocytochemical study.

The inflammatory infiltrate has been characterized in 10 cases of ovarian dysgerminoma using a panel of antisera to T-cells, B-cells and macrophages. The expression of Class II major histocompatibility complex (MHC) antigens and the distribution of interferons alpha and gamma were also examined. T-lymphocytes were present in all tumours, often closely admixed with neoplastic elements. T-cells in most areas were immunoreactive with gamma interferon. B-cells were generally scanty although germinal centres were present in three tumours. Immunocytochemistry revealed greater numbers of macrophages than had been appreciated on routinely stained sections. Macrophages were closely related to both lymphoid and tumour cells, and many macrophages were immunoreactive for alpha interferon. Class II MHC expression was mainly restricted to macrophages and B-cell areas although occasional T-cells were also stained. Dysgerminoma cells did not express Class II MHC antigens.

Biomarkers

The distribution of immunoreactive interferon-gamma-containing cells in normal human tissues.

An immunohistochemical technique has been used to study the distribution of lymphocytes expressing interferon-gamma in normal adult tissues. The greatest concentrations of these cells were seen in mucosal sites exposed to a resident microflora. It is proposed that such organisms, by eliciting immune responses, provide the stimulus for the production of 'physiological' interferon-gamma. This in turn may act to preserve the 'tone' or readiness of the immune system.

Adult

Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells.

This study sought to determine, firstly, the relative frequency of lymphocytes and macrophages and, secondly, the percentage of lymphocytes containing interferon-gamma in inflamed islets (insulitis) of patients with type 1 (insulin-dependent) diabetes. Autopsy pancreases of 12 patients who had died of recent-onset type 1 diabetes and one pre-diabetic patient who had died of cardiomyopathy were examined immunohistochemically. In the 87 islets that were studied, the lymphocyte macrophage ratio was 9.7:1 and approximately 40 per cent of the lymphocytes contained interferon-gamma. Interferon-gamma release in the insulitis process may be involved in the pathogenesis of type 1 diabetes.

Adolescent

Spatial correlation between thyroid epithelial cells expressing class II MHC molecules and interferon-gamma-containing lymphocytes in human thyroid autoimmune disease.

In this immunohistochemical study we addressed the question whether aberrant class II MHC expression by thyroid epithelial cells (thyrocytes) in established thyroid autoimmune disease is the result of release of interferon-gamma (IFN-gamma) by adjacent lymphocytes. Thyroids from eight cases of Hashimoto's thyroiditis, 13 cases of Graves' disease and 10 cases of focal thyroiditis were studied. Both thyrocytes expressing class II MHC and lymphocytes containing immunoreactive IFN-gamma were found in all 31 autoimmune thyroids. In a serial section study of these thyroids, IFN-gamma-expressing lymphocytes were found within 50 microns of class II MHC-positive thyrocytes in 89% of 282 randomly selected fields. Conversely, class II MHC-positive thyrocytes were found within 50 micron of aggregates of IFN-gamma-positive lymphocytes in 82% of 272 randomly selected fields. These findings support the view that in established thyroid autoimmune disease expression of class II MHC by thyrocytes is the result of local release of IFN-gamma.

Autoimmune Diseases

A search for the presence of the enteroviral capsid protein VP1 in pancreases of patients with type 1 (insulin-dependent) diabetes and pancreases and hearts of infants who died of coxsackieviral myocarditis.

Using an antiserum raised to a recombinant coxsackie virus B 3 capsid protein, VP1, an immunocytochemical technique was developed which was capable of detecting the presence of all coxsackie B viruses in formalin fixed paraffin embedded infected tissue culture cells. This technique was tested on autopsy heart and pancreas from 21 patients who were thought to have died of acute coxsackievirus B myocarditis. Cardiac myocytes were positive for the VP1 protein in 12 of 20 cases where the heart was available for study. Insulitis was present in the pancreas in seven of these cases and in all seven islet endocrine cells containing VP1 were found. VP1 was only rarely found in exocrine pancreas. In heart and pancreas, cells shown to contain VP1 usually showed signs of necrosis. Autopsy pancreases from 88 patients who had died at clinical presentation of Type 1 (insulin-dependent) diabetes mellitus showed no evidence of the presence of VP1. The continuing destruction of insulin-secreting B cells seen at the time of death in the diabetic pancreas is unlikely to be due to a direct cytopathic effect of a coxsackie B virus. However, this study does not exclude the possibility that a persistent infection of B cells by a defective enterovirus may result in their destruction by an autoimmune mechanism.

Acute Disease

Immunoreactive alpha interferon in cervical flat koilocytic lesions and intraepithelial neoplasia.

Immunocytochemical staining for alpha-interferon was carried out on cervical biopsy specimens showing non-condylomatous koilocytic atypia (n = 12) and cervical intraepithelial neoplasia (n = 18), both of which are associated with human papilloma virus (HPV) infection. Normal cervical tissue obtained from hysterectomy specimens was also assessed. Koilocytes were not immunoreactive for alpha interferon and keratinocyte staining was observed in only four cases of intraepithelial neoplasia. HPV infection alone does not therefore seem to induce the production of alpha interferon in cervical squamous epithelium. There was variable but, in some cases, prominent staining of cells in the stromal inflammatory infiltrate as well as intraepithelial cells which had morphological and immunocytochemical characteristics of Langerhans' cells. Alpha interferon immunoreactivity in Langerhans' cells is in keeping with derivation from the mononuclear phagocyte system and may be important in the host response to HPV infection.

Cervix Uteri

The distribution of immunoreactive interferon-alpha in formalin-fixed paraffin-embedded normal human foetal and infant tissues.

Human foetal and infant tissues were studied to test the hypothesis that microbes have a role in switching on interferon-alpha (IFN-alpha) synthesis. Foetal tissues were essentially 'germ free', while the infants had been exposed to a normal microbial environment in life. IFN-alpha was first seen at 9 weeks gestation in macrophages in the liver and thereafter was seen in macrophages in most other organs. When infant lungs were compared with foetal lungs, a statistically significant increase in the number of macrophages and the percentage of these cells expressing IFN-alpha was noted in the infant lungs. No such change was observed in spleen, liver and thymus following birth. These findings suggest that there is a basal production of IFN-alpha by macrophages that is not dependent on microbial products, but that such products can enhance synthesis of this cytokine.

Child, Preschool

The pancreas in acute graft versus host disease in man.

Twenty-six bone marrow transplant recipients, 14 of whom had evidence of acute graft versus host disease at autopsy, were studied. The pancreas in four of these patients exhibited changes thought to be due to acute graft versus host disease. Pathognomonic findings were in exocrine ducts which showed marked epithelial cellular atypia associated with a mild lymphocytic infiltrate. This was accompanied by ulceration and intraluminal haemorrhage in severe cases. In three of these four cases ductal epithelium showed marked hyperexpression of class I and class II major histocompatibility complex molecules. By contrast islets were not inflamed, showed no evidence of endocrine cell damage and no abnormalities of major histocompatibility complex expression were seen.

Adolescent

Use of microwave oven improves morphology and staining of cryostat sections.

The quality of microscopic image of cryostat sections that had been subjected to microwave assisted fixation was compared with that resulting from conventional air drying of the sections. The role of microwaves in producing rapid special stains on cryostat sections was also assessed. Methods used permitted stains such as periodic acid Schiff, alcian blue, Gordon and Sweets's reticulin, Masson Fontana, Elastica, Prussian blue and Van Gieson to be performed within three minutes of cutting a cryostat section. The cytological detail of nuclei was much clearer using the microwave technique, allowing more accurate determination of cell type. The microwave oven seems to have major potential in improving the diagnostic accuracy of surgical frozen sections.

Frozen Sections

Immunolocalization of alpha interferon in liver disease.

The expression of immunoreactive alpha interferon was examined in 78 liver biopsy specimens using an indirect immunoperoxidase technique. Biopsy specimens included cases of acute viral hepatitis, chronic active hepatitis, primary biliary cirrhosis, alcoholic hepatitis, large bile duct obstruction and normal liver. Kupffer cells were positive for alpha interferon in all cases. Hepatocytes were negative for alpha interferon in normal liver but in acute viral hepatitis were positive in perivenular and necrotic areas. Hepatocytes were positive in periportal areas, associated with piecemeal necrosis, in chronic active hepatitis and primary biliary cirrhosis, and were positive in perivenular areas in alcoholic hepatitis and large bile duct obstruction. The unexpected finding of alpha interferon in hepatocytes in non-viral liver disease indicates that the presence of this substance in liver cells cannot be taken as a specific marker of viral infection.

Biomarkers

Hypersplenism due to fungal infection of spleen in a successfully treated patient with Hodgkin's disease.

A 58 year old woman, with dermatitis herpetiformis was found to have Hodgkin's disease following the discovery of an abdominal mass and splenomegaly. Combination chemotherapy was given. Although the abdominal mass and systemic symptoms resolved, the splenomegaly did not and the patient developed severe prolonged anaemia and pancytopaenia. Splenectomy resulted in a complete reversal of the haematological abnormalities. Histopathological examination of the spleen revealed fungal granulomas of Candida albicans. No residual Hodgkin's disease was found. The patient thus had hypersplenism due to fungal granulomas in the spleen. This form of presentation of fungal granuloma is very rare and resulted in delay in diagnosis and considerable morbidity to the patient.

Antineoplastic Combined Chemotherapy Protocols

The distribution of immunoreactive interferon-alpha in normal human tissues.

The cellular distribution of immunoreactive interferon-alpha (IFN-alpha) was studied in formalin-fixed paraffin-embedded normal human tissues from 36 different organs. These samples were drawn from over 300 individuals none of whom had evidence of viral infection. Tissue histiocytes from all organs in the body, with the exception of brain and renal cortex and medulla, stained positively for IFN-alpha. Kupffer cells, pulmonary alveolar macrophages and lymph node macrophages were also positive. Parenchymal cells in some other organs also appeared to contain immunoreactive IFN-alpha. These included cuboidal lining cells of the choroid plexus in the brain, thyroid follicular cells, pituitary endocrine cells, adrenocortical cells and parathyroid principal and oxyphil cells. These findings are compatible with previous suggestions that IFN-alpha may be synthesized and released in the absence of viral infection and may thus have a role in normal physiology. The presence of IFN-alpha in most cells of the mononuclear phagocyte system suggests that these cells may play a major part in defence against viral infection.

Endocrine Glands