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Biomedical subjects

C J Stewart

Publications and source records attributed to C J Stewart.

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

Expression of epidermal growth factor receptor in normal ovary and in ovarian tumors.

Increased expression of epidermal growth factor (EGF) receptor has been recorded in many types of human tumors and has been associated with reduced survival in ovarian carcinoma. The purpose of this study was to examine the immunocytochemical distribution of the EGF receptor in normal ovaries (n = 30) and in ovarian tumors (n = 126). Staining was observed in two normal ovaries, in the granulosa cells of a developing follicle, and in surface epithelium. Forty-seven of 103 malignant common epithelial tumors were immunopositive. Staining was usually focal, always confined to the neoplastic epithelium, and showed a cytoplasmic distribution. There was a slight trend for increased EGF receptor expression in more advanced common epithelial malignancies, but this was not statistically significant. No correlation between immunoreactivity and histological subtype or grade of tumor was seen. A few other tumors were also examined: one each of Brenner tumor, mature teratoma, mature teratoma with squamous carcinoma, borderline serous tumor and fibroma; all were immunopositive.

Carcinoma

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

Distribution of type IV collagen immunoreactivity to assess questionable early stromal invasion.

AIMS: To determine if the immunocytochemical delineation of subepithelial basement membrane can be used in the assessment of questionable early invasive cervical carcinoma. METHODS: The distribution of immunoreactive type IV collagen was examined in 15 cervical biopsy specimens in which the reporting pathologist had specifically described difficulty in assessing or excluding early invasion of subepithelial stroma associated with cervical intraepithelial neoplasia (CIN). The results were compared with those from biopsy specimens showing CIN III (N = 8), carcinoma with definite early stromal infiltration (FIGO stage 1a1) (n = 6), and more advanced invasive squamous tumours (FIGO stages 1a2 to 3) (n = 8). In all cases the immunocytochemical findings were assessed in relation to serial sections stained with haematoxylin and eosin. RESULTS: Six of the 15 diagnostically problematic biopsy specimens were considered, on review, to show early infiltration of subepithelial tissue and putative invasive foci were consistently absent in basement membrane. A similar pattern was observed in the "definite" early invasive cases. Eight problematic biopsy specimens were considered to show only in situ neoplasia; five of these had intact though occasionally attenuated basement membrane, three showed focal type IV collagen defects. In the remaining case biopsy trauma precluded further assessment. Basement membrane defects were identified in five of eight cases of CIN III, while three of eight squamous carcinomas showed partial retention of type IV collagen immunoreactivity around invasive tumour cell nests. CONCLUSIONS: Defects in subepithelial basement membrane occur in in situ and invasive neoplasia in the uterine cervix. Immunocytochemical staining for type IV collagen is of limited diagnostic value in the assessment of biopsy specimens with questionable early stromal invasion.

Basement Membrane

Breast carcinoma with osteoclast-like giant cells.

The cytological and histological findings of a case of breast carcinoma with osteoclast-like giant cells are presented. A fine needle aspiration specimen demonstrated the characteristic combination of malignant epithelium and reactive multinucleated cells and enabled identification of this rare variant of breast cancer. Immunocytochemical studies using the monoclonal antibody KP1[CD68] support a histiocytic origin for the osteoclast-like cells.

Aged

Malacoplakia of the uterine cervix and endometrium.

A rare case of malacoplakia involving the female genital tract is presented. The characteristic granular histiocytes with intracytoplasmic Michaelis-Gutmann bodies were identified in a cervical smear. The cytological preparation also showed prominent capillary vessels and differed from biopsy material in that cytoplasmic bacteria were easily identified.

Cervix Uteri

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

Peritoneal mesothelioma.

We report two patients who presented with small bowel obstruction secondary to peritoneal mesothelioma. The difficulties in establishing this diagnosis at an early stage are illustrated. Recent advances in the management of peritoneal mesothelioma are reviewed.

Adult

Timolol side effects and inadvertent overdosing.

The case reports demonstrate that significant and potentially dangerous side effects from timolol maleate occur as a result of inadvertent overdosing. Because many glaucoma patients are elderly and vision is frequently impaired, overdosing may be the mechanism of side effects in many patients especially the elderly. A simple dropper that would withdraw only one drop and deliver the same would resolve this problem.

Aged

The morphological effects of dexamethasone on the pituitary-adrenal axis of the rat--a quantitative study.

Adult Sprague-Dawley rats received a daily intraperitoneal injection of dexamethasone (100 or 200 micrograms/kg) for 2 or 6 weeks. Quantitative assessment of the anterior pituitary corticotroph population performed using the stereological measurement of volume density (Vv). An indirect assessment of corticotroph function was also made, based on adrenal weight and histology. Adrenal changes were consistent with dose-related inhibition of corticotroph function in all dexamethasone-treated animals. Immunopositive corticotrophs were easily identified and in no treatment group was corticotroph Vv significantly less than in the appropriate vehicle-injected control group. In male animals, there was a significant increase (P less than 0.05) in Vv with 100 micrograms/kg at both 2 and 6 weeks. These results suggest that it is possible to produce inhibition of corticotroph function by the administration of such doses of dexamethasone without causing a significant reduction in the anterior pituitary corticotroph population. This may be related to the mode of negative feedback of such a regime.

Adrenal Glands

Evidence for transcriptional and post-transcriptional control of the cellular thymidine kinase gene.

We have studied the cell cycle-regulated expression of the thymidine kinase (TK) gene in mammalian tissue culture cells. TK mRNA and enzyme levels are low in resting, G0-phase cells, but increase dramatically (10- to 20-fold) during the S phase in both serum-stimulated and simian virus 40-infected cells. To determine whether an increase in the rate of TK gene transcription is responsible for this induction, nuclear run-on transcription assays were performed at various times after serum stimulation or simian virus 40 infection of growth-arrested simian CV1 cells. When assays were performed at 12-h intervals, a small (two- to threefold) but reproducible increase in TK transcription was detected during the S phase. When time points were chosen to span the G1-S interface a larger (six- to sevenfold) increase in transcriptional activity was observed in serum-stimulated cells but not in simian virus 40-infected cells. The large increase in TK mRNA levels and the relatively small increase in transcription rates in growth-stimulated cells suggest that TK gene expression is controlled at both a transcriptional and post-transcriptional level during the mammalian cell cycle. To identify the DNA sequences required for cell cycle-regulated expression, several TK cDNA clones were transfected into Rat-3 TK- cells, and their expression was examined in resting and serum-stimulated cultures. These experiments indicated that the body of the TK cDNA is sufficient to insure cell cycle-regulated expression regardless of the promoter or polyadenylation signal used.

Animals

Transformation by polyoma ts-a mutants. I. Characterization of the transformed phenotype.

Seven clonal lines of Fischer rat cells transformed with ts-a mutants of polyoma virus were studied. Four clones are characterized by a temperature-sensitive (ts) and three clones by a temperature-insensitive-transformed phenotype. Six clones have retained a functional though temperature-sensitive large T antigen, as judged by a 10- to 20-fold amplification of viral sequences in clones grown at low temperature compared to those grown at high temperature. No amplification is observed in one non-ts clone. As analyzed by Southern blotting, no obvious difference appears in the integration pattern of viral sequences in ts and non-ts clones concerning the number of sites of genome integration, the presence or absence of tandem repeats of the viral genome, or the absence of specific viral sequences. In autoradiograms of gel-electrophoresed immunoprecipitates, no correlation can be drawn between the amounts of either large T antigen or middle T antigen and the type of transformed state of the clones under the conditions tested. In assays of the middle T-antigen-associated kinase, no reproducible difference can be observed between the non-ts and ts clones. Finally, no correlation was observed between a temperature-insensitive phenotype and the production of an N-terminal fragment of large T antigen. Thus the molecular basis for the difference between ts-a transformants with ts or non-ts phenotypes remains elusive.

Antigens, Viral, Tumor

Are asthma mortality rates changing?

Published asthma death rates have risen during recent years. This may be due to a number of possible factors and it is important to assess whether or not the increase is genuine. Evidence from the BTA confidential enquiry into asthma deaths together with the results of bridge coding by the Office of Population Censuses and Surveys suggest that published death rates in the 15-44 year age group are reasonably accurate and comparisons before and after recent changes in the International Classification of Diseases are valid. The death rate in females in this age group has almost halved since the pre-epidemic levels of the 1960s, whereas the rate for males is little changed. This should alert all those involved in the management of severe acute asthma to the seriousness of the problem that remains.

Adolescent

Circumstances of death from asthma.

Mortality from asthma in England and Wales has remained unchanged for at least 20 years, even in the age group 15-44. Yet in those 20 years "modern" drugs have been introduced for the treatment of asthma, such as beta 2 agonist bronchodilators and corticosteroids. Why do patients still die? Detailed review of the circumstances of 90 deaths from asthma showed that a few were inevitable but that in the remainder four main sets of circumstances in the fatal attack contributed to the death. These were, firstly, the patient's failure to recognise the severity of the asthma; secondly, very rapid progress in the severity of the attack; thirdly, misjudgment in the management of the attack; and, fourthly, delay from many causes. Patients admitted to hospital with severe acute asthma usually survive. Those at risk of a life threatening attack should be identified and taught to monitor the severity and progress of their asthma objectively. Their direct admission to hospital should be facilitated.

Acute Disease

The corticotrophic cells of the canine pituitary gland in pituitary-dependent hyperadrenocorticism.

The distribution of specifically stained corticotrophic cells has been studied in the pituitary glands of 11 dogs with pituitary-dependent hyperadrenocorticism. The results suggest that the disease is not a single entity, and that some cases are caused by primary abnormality of the pituitary gland whereas others appear to be the result of dysfunction of the hypothalamus or central nervous system. The patterns correspond closely to those demonstrated in the human pituitary gland in Cushing's disease, and confirm that the canine disease is a useful model for the study of the pathogenesis of the variants of the condition.

Adrenocorticotropic Hormone