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Biomedical subjects

C C Bird

Publications and source records attributed to C C Bird.

At least 91 records · Page 5Linked to original sources

Immunocytochemical application of monoclonal antibodies to rat liver glucocorticoid receptor.

Seven per cent (10/145) of hybridomas raised against partially purified activated glucocorticoid receptor from rat liver produced monoclonal antibody to receptor. Six IgM secreting clones selected for further investigation bound equally well to activated and non-activated receptor from fresh rat liver, but significantly less well (11-25 per cent) to receptor from frozen rat liver. No interaction was found with oestrogen receptor from rat uterus but extensive cross reaction occurred with progesterone receptor. Although none of the antibodies bound to glucocorticoid receptor from human or porcine liver or lymphoid cells, several cross-reacted with mouse liver glucocorticoid receptor. Immunoelectroblotting of proteins from fresh and frozen rat liver cytosol showed the antibodies bound to 90,000 and 40,000 MW forms of receptor respectively. Immunostaining of both frozen and paraffin embedded sections of rat tissue showed that receptor is preserved during fixation and processing of tissues. Using both indirect immunoperoxidase and immunogold silver staining methods, the pattern of receptor staining observed correlates with the known glucocorticoid responsiveness of the tissues studied.

Animals↗

DNA content and prognosis of non-Hodgkin's lymphoma.

Ninety cases of non-Hodgkin's lymphoma diagnosed prior to the use of modern therapeutic regimens (1963-67) and 88 cases treated with such chemotherapy (1980-85) were studied using conventional morphology and flow cytometry. DNA aneuploidy as determined by flow cytometry was more common among high grade (38%) than low grade (19%) tumours (P less than 0.01). Measurements of proliferative index (S + G2 phase cells) revealed significantly increased values for high grade as compared with low grade lymphomas (P less than 0.001). In the first group of cases (1963-67) the relationship between histological grade and survival just failed to reach statistical significance over the long term (20 yr) (P = 0.1) but proved significant over 3 yr (P = 0.012). Differences in ploidy and proliferative index status were not associated with survival. In the second patient group (1980-85) attainment of complete remission following chemotherapy was associated with the presence of DNA aneuploidy in high grade tumours (P less than 0.05). The limited follow up of this group precluded assessment of survival in relation to ploidy.

Adolescent↗

Rising incidence of lymphoid malignancies--true or false?

The report contrasts the ascertainment of cases by the regional cancer registry with a specially designed search for records and pathology material which was then submitted to critical review irrespective of the original diagnosis. Boundary changes over the intervening years were accounted for and the results contrasted between time periods and with the cancer registry records. A large proportion of cancer registry cases were never subjected to histopathological diagnosis and comparisons between the new data and records are not easy to undertake. The study describes a probable true rise in the incidence of follicular non-Hodgkin's lymphoma in certain parts of Yorkshire over the last 20 years; there is less evidence of a similar change in Hodgkin's disease incidence over the same period of time.

Adolescent↗

DNA aneuploidy in colorectal adenomas.

The frequency of DNA aneuploidy was investigated by flow cytometry in 156 colorectal adenomas including 56 associated with 36 synchronous adenocarcinomas. Nine of 156 adenomas (6%) were DNA aneuploid. DNA aneuploidy correlated with increasing size (P less than 0.005) and histopathological type P less than 0.05) but not with dysplasia. Adenomas in associated with a synchronous adenocarcinoma did not have an increased incidence of DNA aneuploidy. Adenocarcinomas found in association with adenomas tend to have a lower incidence of DNA aneuploidy then the generality of colorectal cancers.

Adenocarcinoma↗

Kinetic and physical studies of cell death induced by chemotherapeutic agents or hyperthermia.

The kinetics of three physical parameters: cell density, relative cytoplasmic viscosity and DNA stability to denaturation have been measured during the period preceding cell death induced by hyperthermia, methylprednisolone and a series of cancer chemotherapeutic agents. This series of measurements employed cultured human lymphoblastoid cells as an experimental system to establish the changes that can be observed in the early stages of cell death, prior to applying such measurements to tissue biopsies from solid human tumours. Cell death, induced by hyperthermia up to 43 degrees C, methylprednisolone, vincristine, 5-fluorouracil, BCNU and melphalan, showed essentially identical and reproducible changes corresponding to those which characterize programmed cell death (apoptosis). Such changes could also be observed following hyperthermia above 43 degrees C, but reproducibility was poor and increasing damage to the cell membranes was evident. In cells treated with adriamycin or methotrexate, cell sub-populations showing an increase in cell density were not detected. Measurements of DNA stability were readily performed by flow cytofluorometry thus allowing rapid quantitation of the fraction of cells in the early stages of cell death. Modified flow cytometric instrumentation would further allow measurement of cytoplastic viscosity as an additional parameter to indicate entry into programmed cell death. This suggests that these measurements could readily be applied to cell suspensions derived from tumour tissue biopsies for a more accurate assessment of tumour growth rate, and to allow monitoring of response to therapy in sequential tumour biopsies.

Antineoplastic Agents↗

Immunohistological demonstration of factors XIIIa and XIIIs in reactive and neoplastic fibroblastic and fibro-histiocytic lesions.

Factor XIII sub-units a and s (XIIIa and XIIIb) have been localized previously in fibroblasts of the liver and in other tissues. An immunoperoxidase technique was used to localize these factors in benign and malignant fibroblastic and fibro-histiocytic lesions. Positive staining was present in cells in almost all of the benign and fibro-histiocytic lesions but was reduced in the malignant group. However, the pattern of staining was not sufficiently consistent to justify the use of the factors XIII as diagnostic markers in soft tissue neoplasia.

Factor XIII↗

DNA aneuploidy in ulcerative colitis.

The prevalence of deoxyribonucleic acid (DNA) aneuploidy in 297 samples from 38 patients with ulcerative colitis of varying duration was investigated by flow cytometry. In 12 patients colitis was complicated by the development of colorectal carcinoma: one had three synchronous carcinomas. Only four of 14 carcinomas were DNA aneuploid. Deoxyribonucleic acid aneuploidy occurred focally in the colorectal mucosa in the presence and absence of carcinoma: rates of aneuploidy (67% in cancer patients and 42% in non-cancer patients), were not significantly different (chi 2 = 1.0962, p = 0.295). A higher rate of DNA aneuploidy was found in dysplastic tissues (21%) compared with non-dysplastic tissues (15%), but again these differences did not reach statistical significance (chi 2 = 1.0747, p = 0.299). Deoxyribonucleic acid aneuploidy and dysplastic change occurred more often with increasing duration of ulcerative colitis (p less than 0.001, p less than 0.005 respectively). We conclude that flow cytometric analysis of cellular DNA content should not replace present morphological methods of assessment of premalignancy in ulcerative colitis, but may be a useful adjunct in the identification of abnormal mucosa.

Adult↗

Pre-operative staging of rectal neoplasm and its impact on clinical management.

A sophisticated staging technique (extended staging, ES) employing modern technology has been compared prospectively with conventional clinical assessment (initial staging, IS) in 45 patients with low rectal carcinoma (less than 12 cm from the anal verge) to determine its potential merit and its impact on clinical management. ES consisted of computerized tomography of liver and pelvis, ultrasound scan of liver, measurement of serum concentrations of carcinoembryonic antigen (CEA) and acute phase reactant proteins and multiple superficial and deep biopsies to determine not only the histological grade of the tumour but also its DNA cellular content as measured by flow cytometry. ES proved statistically superior to IS in the assessment of local spread and dissemination. Although histological grade proved to be more accurate on ES than IS this was only true when one specialist pathologist interpreted the slides. When several pathologists were involved interobserver variation made interpretation unreliable. Assessment of DNA content using flow cytometry, being quantitative, was more accurate and perhaps should be used in the future as a prognostic indicator. The improved accuracy of ES would have altered both pre- and intra-operative clinical decisions. It would have prevented some patients receiving inappropriate adjuvant therapy as well as selecting patients more accurately for the correct treatment.

Adult↗

Surface membrane phenotypic expression and treatment response of malignant lymphomas.

Cryopreserved lymphoid tissue has been used from 113 patients for an analysis of cell surface membrane phenotypes using a panel of monoclonal antibodies. Dual heavy chain expression was common in many B-cell malignant lymphomas and in the B-cell lymphomas as a whole there was a predominance of lambda light chains. The expression of lambda light chain was associated with a poorer response to treatment and there was a tendency for such tumours to fall into the high grade lymphoma category. Surface membrane heavy chain expression, as assessed by staining intensity, was greatest in the lymphomas composed mostly of centrocytes and IgD expression was reduced in high grade lymphomas. The ratio of helper to suppressor T-cells was reduced in centroblastic and immunoblastic lymphomas. In Hodgkin's disease a predominance of T-cells was found in most instances although the series included a large proportion of nodular sclerosis cases.

Adult↗

Primary small intestinal lymphoma: a study of 39 cases.

Thirty-nine cases of primary small intestinal lymphoma were studied by morphological and immunohistochemical methods. The adjacent uninvolved mucosa was also examined for features suggestive of coeliac disease. Employing the immunogold silver staining (IGSS) technique and polyclonal primary antisera against alpha-l-antitrypsin, lysozyme and kappa and lambda light chains, 29 cases (74.5 per cent) were found to be B-cell lymphomas, seven (18 per cent) histiocytic tumours, one (2.5 per cent) Hodgkin's disease and two (5 per cent) remained unclassified. No specific lymphoma subtype was found to be associated with cases having the histological features of coeliac disease in the uninvolved adjacent mucosa. In 35 cases sufficient clinical information was available to assess the significance of histological type and stage in relation to survival. Although the histological type did not correlate with survival, stage did and tumours extending beyond the local lymph nodes were associated with a significantly worse prognosis.

Adolescent↗

Comparison of in vitro demyelination and cytotoxicity of humoral factors in multiple sclerosis and other neurological diseases.

The distribution and nature of serum factors causing in vitro demyelination and glial lysis were investigated in multiple sclerosis (MS), other neurological diseases (OND), ill control and control groups. MS sera were unique in affecting only CNS myelin and glia whereas stroke and Guillain-Barré syndrome (GBS) sera brought changes to both CNS and PNS tissue. Through both visual scoring of myelin damage and the quantitative measurement of radiolabel release from cerebellar cultures, it was evident that the MS and OND groups have similar myelino- and cytotoxic effects. This may reflect MS and OND sera sharing similar humoral factors. 74% MS, 68% OND and 22% of control scores were above a score threshold designed to exclude culture handling trauma effects. When classified by their current disease state MS patients with severe and mild disease yielded higher in vitro scores than did those with moderate disease who comprised an older age group. No other clinical features of MS patients gave any association with in vitro serum effects. The rare demonstration of bound Fab IgG in cultures after MS serum tests indicates that immune mechanisms are unlikely to make a large contribution to serum-induced demyelination and cellular change in vitro.

Central Nervous System Diseases↗

Association between Bell's palsy and lymphoid malignancies.

Eight cases of lymphoid malignancy preceded by Bell's palsy are reported. There was a disproportionate number of ALL cases, two of which were of T-cell type. The possible pathogenic association of these conditions is discussed.

Facial Paralysis↗

Heterogeneity of colorectal adenocarcinomas evaluated by flow cytometry and histopathology.

Flow cytometry and histopathology were utilised in evaluating 50 primary and 16 metastatic colorectal carcinomas to determine the influence of heterogeneity and proportion of dying cells on pathological assessments. A new procedure was developed for staining unfixed whole cells with acridine orange and ethidium bromide to quantify DNA and RNA content and number of dead and dying cells. Attempts were made to reduce interobserver variation in histological assessment and to determine whether flow cytometry could refine current grading and staging procedures. Interobserver variation in grading was not improved by estimating proportions of differing grades in multiple samples from individual tumours. Considerable heterogeneity was observed within tumours although this was less apparent when defining ploidy status than histological grade. No consistent differences were observed between superficial and deep parts of tumours or between primary and secondary tumours by either method of analysis. The proportion of dead and dying cells varied widely between tumours but there was no correlation with tumour grade or stage. Non-diploid tumours were not of more advanced stage or poorer histological grade than diploid tumours. Since ploidy status may be an important prognostic factor, analysis of colorectal carcinomas by flow cytometry could be of greater value than conventional grading and staging procedures.

Adenocarcinoma↗

Concurrent T-cell lymphocytic lymphoma and malignant histiocytosis.

A case in which both malignant histiocytosis and T-cell lymphocytic lymphoma occurred together is presented. Examples of malignant histiocytosis-like syndromes associated with lymphoreticular malignancies have been previously reported. Many of these represent reactive haemophagocytic syndromes, probably virally induced. The considerable degree of cytological atypia and frequent mitotic figures seen in the histiocytes in this case were indicative of a true malignant histiocytosis.

Adult↗