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Biomedical subjects

C C Bird

Publications and source records attributed to C C Bird.

At least 109 records · Page 6Linked to original sources
PubMed1985

Morphometric studies of age related changes in normal human breast and their significance for evolution of mammary cancer.

Ageing changes in the normal human female breast were studied to determine their significance for the evolution of mammary cancer. Employing the morphometric techniques of point counting and planimetry, objective quantitative measurements were made of the structure of the normal female breast in 58 subjects from the prepubertal to late postreproductive period. The relative amounts of epithelial and connective tissue varied with age, and the epithelial elements (combined lobular and extralobular) were unevenly distributed within the gland, with lower containing more than upper quadrants. The upper outer quadrant, however, usually contained the largest proportion of lobular units, which may relate to the higher incidence of lobular carcinoma found in this quadrant. Involution was shown to be a premenopausal rather than postmenopausal phenomenon. Mammary dysplastic changes were uncommon in all age groups.

Adolescent↗
PubMed1985

Quantitation by flow cytofluorometry of response of tumours of the uterine cervix to radiotherapy.

We are presently involved in a project to investigate the use of flow cytofluorometry in assessing, by means of serial biopsies, the response to radiotherapy of tumours of the uterine cervix. This technique enables changes in the DNA content profiles and content of proliferating cells in the tumour biopsies to be determined at intervals as therapy progresses. A means has been devised to quantitate the content of hyperdiploid cells, hypertetraploid cells, and dead and dying cells, by computer analysis of DNA vs. RNA scattergrams obtained by flow cytofluorometric analysis. Plotting of these parameters for the serial biopsies vs. time since start of tumour irradiation presents a graphical indication of the response of the tumour to irradiation. Over 100 patients (stage Ib and IIa) have been followed during intracavitary (Cathetron) therapy with parallel flow cytofluorometric analysis and histopathological assessment of serial biopsies. Patterns are beginning to emerge from these analyses which promise to indicate within 14-21 days and sometimes earlier the extent of radioresponsiveness of the tumour. These patterns may also be of assistance in planning modified dose fractionation schedules to obtain improved therapeutic ratios.

Acridine Orange↗
PubMed1984

Prednisolone levels in plasma and leukemia cells during therapy of chronic lymphocytic leukemia.

The capacity of chronic lymphocytic leukemia cells to concentrate prednisolone has been evaluated in vivo and in vitro employing a radioimmunoassay for prednisolone. No evidence to suggest that leukemia cells are capable of selectively concentrating glucocorticoid was found. The relative uptake of glucocorticoid by leukemia cells was found to be greater in vitro than in vivo. This may be attributable to differences in steroid bioavailability to cells. Substantially lower levels than previously reported of free prednisolone were found in plasma of patients receiving oral treatment with prednisolone. This may result from the failure in previous studies to remove derivatives of prednisolone and other steroids prior to assay for hormones.

Humans↗
PubMed1984

Yorkshire Regional Lymphoma Histopathology panel: analysis of five years' experience.

Five years' experience of operating a Regional Lymphoma Histopathology Panel is described. During this period, approximately 1400 cases were registered of which nearly 1200 were confirmed as malignant lymphoma. Complete concordance of diagnosis was achieved between submitting pathologists and the Panel in two-thirds of cases of Hodgkin's disease and just over half of non-Hodgkin's lymphoma. Most discrepancies in diagnosis were found to be of clinical importance in terms of prognosis and/or therapeutic management of patients. In approximately two-thirds of such instances disagreement arose because of wrong assignment of tumour grade within the main lymphoma class but in one-third of cases the main class of lymphoma was wrongly designated. Panel members experienced similar diagnostic problems as submitting pathologists although to a lesser extent. The existence of the panel has not reduced the proportion of cases causing diagnostic difficulty for submitting pathologists or panel members during the 5 year study period. The principal cause of death was ascertained from death certificates and autopsy findings in nearly half the cases dying during the study period. In approximately half of these infection (largely pulmonary) played a major role while most of the remainder died of various cardiovascular, pulmonary or renal disorders. There was no specific pattern relating to the main lymphoma class. It is concluded that whilst the panel fulfils a useful function in resolving diagnostic difficulties and standardizing lymphoma diagnosis its role is restricted somewhat by the limitations imposed by conventional morphological assessments.

Adult↗
PubMed1984

New approach to study of in vitro toxicity of multiple sclerosis and other sera.

The in vitro effects of MS and control sera were quantified by the measurement of radiolabel released from myelinated cultures of rat cerebellum and compared with a visual assessment of myelin damage. Radiolabel release gave a sensitive index of serum effects in vitro which was free of the score assignment decisions that are associated with the visual assessment of myelin damage. Examination of the patterns of radiolabel release elicited by MS and control sera on cultures labelled with either L-[5-3H]tryptophan or galacto-D-[6-3H]cerebroside indicates that MS serum effects are not simply a stronger expression of the weak control serum effects.

Animals↗
PubMed1984

Role of complement in demyelination in vitro by multiple sclerosis serum and other neurological disease sera.

Multiple sclerosis (MS) sera can demyelinate and cause selective cellular changes to organ cultures of rodent CNS which suggests possible immunoglobulin involvement. The complement dependence of this serum action was investigated using complement-inactivating agents and radiolabelled rat cerebellar cultures. After heat inactivation at 56 degrees C, the in vitro effects of MS, chronic relapsing experimental allergic encephalomyelitis (cr-EAE) and Guillain-Barré syndrome (GBS) sera were severely reduced or eliminated as measured by radiolabel release. On introducing a source of fresh complement, the cr-EAE and GBS serum effects were largely restored whereas MS serum effects remained suppressed. Inactivation of serum complement with mercaptoethanol and Zymosan was associated with marked reduction in serum myelinotoxicity; some restoration of in vitro effects was possible on adding fresh complement although this occurred to a greater extent with cr-EAE and GBS than with MS sera. Inactivation of the alternative complement pathway brought a limited reduction in MS serum activity in vitro which was not restored with fresh complement. It is concluded that complement is involved only to a limited extent in MS serum myelinotoxic effects and that MS serum effects in vitro are due to several components of which thermolabile substances make a significant contribution and are as yet uncharacterised.

Animals↗
PubMed1984

Aetiologic factors in lymphoid malignancies: a case-control epidemiological study.

A prospective case-control study of the aetiologic factors involved in the production of lymphoid malignancies has been conducted within a defined geographical area covering six health districts in the Yorkshire Region. Among the aspects investigated were past medical events, occupations and certain social factors. A number of possible causal relationships have been identified including Jewish religion, past solvent exposure and ingestion of amphetamines, although the latter did not achieve statistical significance in this study. In addition several new associations have been identified, most notably with the occurrence of adult eczema/dermatitis and with treatment by radiation or steroids. The feasibility of conducting such a broadly based epidemiological investigation has been established.

Adrenal Cortex Hormones↗
PubMed1984

Flow cytofluorometric analysis of serial biopsies of tumours of the uterine cervix.

The technique of flow cytofluorometry has been employed to assess, by means of cell suspensions prepared from serial biopsies, the radioresponsiveness of tumours of the uterine cervix. This enables DNA profiles and content of proliferating cells to be determined prior to treatment and during external beam and intracavitary therapy. Results show that elimination of hyperdiploid and hypertetraploid cells and reduction in the proliferating fraction of cells can readily be monitored by this method during therapy. This information, quickly available during treatment, may assist in estimating radioresponsiveness of the tumour and possible prognosis for the patient. Dose fractionation schedules may also be adjusted according to tumour response to therapy. Our results, however, show no relationship between histopathological classification of a tumour (WHO) and its ploidy state. The advanced stages of the disease (II and III) do, however, show an increased content of hypertetraploid cells in the tumour biopsies.

Brachytherapy↗
PubMed1984

Relationship between cell ploidy and glucocorticoid induced death in human lymphoid cell lines.

We have found a relationship between sensitivity to glucocorticoid induced cell death (at 10 microM glucocorticoid) and ploidy in the human lymphoid cell line CCRF/CEM-C7. Most sensitive clones are diploid, whilst resistant clones and the resistant parent line CCRF/CEM are tetraploid. Diploid sensitive clones have a tendency to become aneuploid within a few months of isolation, with alterations in their kinetic responses to glucocorticoids. This is followed by a doubling in DNA content which results in reversion to the tetraploid glucocorticoid resistant state of the parent line CCRF/CEM. A few sensitive clones have been found to be tetraploid but with different kinetic responses to glucocorticoids as compared to diploid clones. The principal difference being an extended lag period (48-72 h) prior to lethal response. The relationship between ploidy and glucocorticoid sensitivity does not appear to extend to other human lymphoid cell lines.

Cell Line↗
PubMed1984

In vitro toxicity of MS sera correlates with new clinical signs.

In vitro toxicity of sera from 10 MS patients was followed for up to 3 years. Myelinotoxicity and cytotoxicity measured as radiolabel release from rat cerebellar explants were almost continuously higher in than in controls while peaks of radiolabel release were associated with the emergence of new clinical signs in the MS patients.

Adult↗
PubMed1983

Cytolethal sensitivity of human lymphoid cells to glucocorticoids and oxidised polyamines.

A series of clonally-derived glucocorticoid-sensitive and -resistant human lymphoid cell lines was used to investigate the relationship between sensitivity to the effects of oxidised polyamines and initiation of glucocorticoid-induced cytostatic and cytolethal responses. Whilst the exogenous polyamines were found to exert no effect by themselves, incubation of cells for 48 h with 10(-4)M spermine or spermidine in the presence of serum polyamine oxidase produced severe lethal responses in all clones tested. By contrast 10(-5)M exogenous polyamines in the presence of polyamine oxidase produced lethal effects only in glucocorticoid-sensitive clones. Spermine was more potent than spermidine. The significance of these observations is discussed.

Cell Division↗
PubMed1983

Mode of cell death induced in human lymphoid cells by high and low doses of glucocorticoid.

The kinetics, specificity and morphology of cytolethal responses have been studied in human glucocorticoid-sensitive and -insensitive lymphoid cell lines (HLCL) and fibroblasts following treatment with high (10(-3)M) and low (10(-6)M) doses of steroid. The high dose cytolethal response appears non-specific occurring in all cell lines with every steroid tested. By contrast, the low dose (pharmacological) cytolethal response requires an active glucocorticoid and a sensitive HLCL. However, both high and low concentrations of steroid induce virtually identical morphological changes in dying cells and similar changes can be induced in cells killed by deliberate feed exhaustion. Although the morphological features in each case resemble apoptosis, the "programmed" physiological form of cell death, the intracellular events leading to cytolysis seem likely to differ. The earliest morphological changes presaging cell death comprise rounding up of cells and condensation of nuclear chromatin. Nuclear changes progress rapidly thereafter and appear to result from detachment of chromatin from the nuclear matrix. The low dose cytolethal response requires the continuous presence of glucocorticoid for periods in excess of 24h, prior to which cell growth appears unaffected. The constancy of this latent interval suggests glucocorticoids may influence some replication control mechanism unrelated initially to macromolecular biosynthesis.

Cell Line↗
PubMed1983

Epithelioid sarcoma: a tumour of myofibroblasts.

A case of epithelioid sarcoma of scalp has been studied by light and electron microscopy, histochemistry and immunocytochemistry. The results suggest that epithelioid sarcoma is a tumour of myofibroblasts. The epithelioid appearance results from gross and disordered accumulation of cytoplasmic intermediate filaments (10 nm diameter), possibly of desmin type, producing the misleading light microscopical resemblance to epithelioid histiocytes and biphasic pattern of synovial sarcoma. The cause of the filament accumulation is unknown but it may represent a degenerative change leading to necrosis, a characteristic feature of epithelioid sarcoma.

Actins↗
PubMed1983

Surface membrane staining of immunoglobulins in paraffin sections of non-Hodgkin's lymphomas using immunogold-silver staining technique.

The immunogold-silver staining (IGSS) method is a new immunostaining technique with much enhanced sensitivity for demonstration of antigens in paraffin sections. A series of 10 non-Hodgkin's lymphomas of B cell type were stained for surface membrane immunoglobulins by the IGSS and peroxidase-antiperoxidase (PAP) methods using paraffin sections and polyclonal primary antisera. The resulting staining patterns were compared with those obtained using frozen sections of the same tissues, monoclonal antibodies and the immunoperoxidase technique. The IGSS method gave a clear demonstration of surface membrane immunoglobulins in neoplastic lymphocytes using paraffin sections and the pattern of staining achieved was comparable to that obtained by the immunoperoxidase technique employing frozen sections and monoclonal antibodies. PAP staining of paraffin sections consistently failed to demonstrate the presence of any surface membrane immunoglobulin. The IGSS method provides a new approach to the diagnosis of B cell lymphomas in which routinely fixed and processed tissues may be employed to demonstrate monoclonality.

Adult↗
PubMed1983

Immunogold-silver staining: new method of immunostaining with enhanced sensitivity.

A new method for demonstrating antigens in paraffin sections of formol sublimate-fixed tissue is described that utilizes an "indirect" immunohistological technique employing immunoglobulin adsorbed to colloidal gold as the secondary antiserum. The gold particles introduced to antigenic sites are revealed by a silver precipitation reaction. This technique, the immunogold-silver staining method, is of much enhanced sensitivity (up to 200-fold) as compared with standard immunoperoxidase and immunogold staining methods. The results have been confirmed in a study of immunoglobulins in reactive human tonsil. The use of this new method for double immunolabeling is also described.

Animals↗
PubMed1983

Production of collagenase and inhibitor (TIMP) by intracranial tumors and dura in vitro.

The production of collagenase and collagenase inhibitor (TIMP) by various intracranial tumors (25 meningiomas, eight gliomas, seven metastases, four pituitary adenomas, and five others) was studied in short-term organ culture. While meningiomas produced negligible amounts of collagenase, two metastatic carcinomas of bronchial and breast origin produced significant amounts of the enzyme. Cultures of dura from an invasive meningioma and of bone invaded by a meningioma also produced collagenase. In varying amounts, TIMP was detected in culture media from most of the tumors studied; invasive tumors tended to produce less TIMP than noninvasive tumors. The results are discussed in relation to current views on tissue degradation and mechanisms of tumor invasion.

Brain Neoplasms↗
PubMed1982

Glucocorticoid binding and cytolethal responsiveness of hairy-cell and chronic lymphocytic leukaemia.

The glucocorticoid binding properties and cytolethal responsiveness of leukaemic cells were studied in vitro in seven patients with hairy-cell leukaemia (HCL) and five with chronic lymphocytic leukaemia (CLL). Substantial levels of glucocorticoid binding were detected both in whole cell and cytosol preparations from all patients although the level of binding by HCL cells always exceeded that of CLL cells (P less than 0.05). In both leukaemic cell types the uptake and binding of prednisolone in vitro was significantly greater than that of dexamethasone (P less than 0.05). CLL cells showed a variable dose-related cytolethal response to methylprednisolone sodium succinate (MPSS) treatment in vitro although cytolytic effects were not marked in the usual pharmacological dose range (10(-5)-10(-6)M). Treatment of CLL patients with conventional doses of prednisone for extended periods or high intravenous infusions of MPSS over shorter periods had no consistent effect on the in-vitro level of steroid binding or the cytolethal responsiveness of CLL cells to glucocorticoid treatment. Although HCL cells proved highly resistant to the cytolethal effects of MPSS in vitro, the substantial binding of glucocorticoids by leukaemic cells from all HCL patients indicates the potential value of steroid therapy in this disease should be explored further.

Administration, Oral↗