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Biomedical subjects

D A Rew

Publications and source records attributed to D A Rew.

At least 55 records · Page 3Linked to original sources
PubMed1999

Objective quantitative analysis of eosinophils and bronchial epithelial cells in induced sputum by laser scanning cytometry.

BACKGROUND: Sputum induction is an important non-invasive technique for measuring airway inflammation in asthma. Cell numbers are often too low for flow cytometric analysis. Laser scanning cytometry (LSC) is a novel technique that allows objective multicolour fluorescence analysis of cells on a microscope slide. METHODS: LSC was used to determine sputum eosinophil and bronchial epithelial cell counts. We first confirmed that we could measure eosinophil counts accurately in peripheral blood using alpha-major basic protein (MBP) immunofluorescent staining. Sputum induction was performed according to standard protocols. Sputum samples from eight normal controls and 12 asthmatic patients were analysed by LSC and manual counting by two independent observers. Octospot cytospins were fixed and stained with mouse-alpha-human-MBP monoclonal antibody or mouse-alpha-human-cytokeratin antibody and goat-alpha-mouse Oregon Green conjugated second antibody. RESULTS: Sputum induction provided a mean (SE) of 0.99 (0.2) x 10(6) cells per donor. More than 3000 cells on three cytospins per slide were analysed per cell type. The intraclass correlation coefficient (R) and standard deviation (SD) of differences in eosinophils determined by manual counting and LSC were 0.9 and 2.1, respectively, and for bronchial epithelial cell counts they were 0.7 and 2.0. Selective detection of labelled cells was confirmed visually after relocation. CONCLUSION: Eosinophils and bronchial epithelial cells can be accurately and reproducibly counted in an objective manner. LSC is therefore a potentially powerful new method for immunophenotyping leucocytes and epithelial cells objectively in induced sputum in patients with asthma.

Asthma↗
PubMed1998

Comparison of flow and laser scanning cytometry for the assay of cell proliferation in human solid tumors.

The introduction of the laser scanning cytometer offers new capabilities in cell proliferation research, through its capacity for validation of each and every cell event through direct visualization on the microscope slide. In this study, we report a direct comparison of proliferation data derived from flow and laser scanning cytometry of human tumor nuclei labeled in vivo with bromodeoxyuridine (BrdUrd). Nuclear suspensions from 19 invasive ductal breast carcinomas and 12 gastric adenocarcinomas were prepared and analysed for BrdUrd uptake and DNA content. Specimens were analysed using a FACScan and then prepared on cytocentrifuge preparations for laser scanning cytometry. DNA index, labeling index (LI), duration of S-phase (Ts) and potential doubling time (Tpot) were calculated using standard procedures. There was an excellent correlation between the two techniques in the calculation of DNA index (R = 0.983, P > 0.0001) and LI (R = 0.924, P > 0.0001). The Ts proved more problematical (R = 0.448, P = 0.0115) but the Tpot showed closer agreement (R = 0.851, P > 0.0001) as the LI was the dominant determinant of Tpot. No single parameter could be identified as the major source of variation between the two techniques. We conclude that the laser scanning cytometer produces data equivalent to that obtained by flow cytometry.

Adenocarcinoma↗
PubMed1998

Image analysis enhancement of the laser scanning cytometer.

The laser scanning cytometer offers a range of novel applications and the capacity for direct visual validation of experiments through sample analysis on a microscope slide. Linkage of the instrument to an image analysis system through standard connections and software enhances the capabilities of the instrument in image capture and manipulation. In this technical note, we describe a simple linkage between the LSC and the Kontron KS100 Image Analysis System, an example of a standard commercial image processing instrument.

Image Cytometry↗
PubMed1998

Campaign strategy and tactics for clinical trials in surgical oncology.

The strategic planning of the campaign against cancer and the employment of clinical trials on a national and supranational basis could be improved. Lessons and principles derived from other spheres of ordered activity might be usefully applied to the realm of clinical trials. Principles taught by military strategists may find practical applications in the development and prosecution of successful clinical trials of cancer therapy. In this paper we reflect upon the parallels and divergences between the principles of campaign strategy needed for the successful prosecution of military objectives and the efficient and effective prosecution of major clinical trials.

Clinical Trials as Topic↗
PubMed1998

Cancer--a degenerative disorder?

Cancer is primarily a disease of ageing epithelia, and of ageing individuals. We now possess detailed insights into the changes in cell regulatory genes and DNA repair systems which accumulate with time and which manifest in malignancy. These demonstrate how cancer is frequently characterized by degenerative change in the genotype, from the most subtle base pair mutations to gross aneuploidy, and by deterioration in cell and tissue regulatory control, be it of proliferation, programmed cell death or signalling. Cancer may thus be as much a phenomenon of loss or deterioration of normal genomic control as of the acquisition of new, neoplastic functions. This distinction may be more than semantic, not least because it governs our approach to the search for therapeutic strategies. This essay considers the concept of cancer as a degenerative disease and its implications, and proposes the neologism aldoplasia to describe this phenomenon of cancer biology.

Aged↗
PubMed1998

The importance of heterogeneity in tumor pathology.

Heterogeneity of cell, tissue, and tumor genotype, form, and function confounds clinicopathologic research and therapeutic strategies. Its significance and importance usually are underestimated and underreported, and there is no consistent statistical or biomathematical framework for its interpretation. New technologies for the quantitative study of pathology specimens and a growing awareness of the clinical importance of biodiversity within individual tumors and populations of tumors herald new approaches to the problems posed by dynamic structural and functional complexity in human tumors.

Genetic Heterogeneity↗
PubMed1998

Cell and molecular mechanisms of pathogenesis and treatment of cancer.

Surgery remains the mainstay of treatment for most classes of human solid tumours, with the principal exception of lymphomas, but it is insufficient in many cases to guarantee cure. With few exceptions, recurrent and metastatic solid tumours continue to defy attempts to develop effective adjuvant therapies. Recent insights into tumour biology reveal an increasingly complex picture of cell and molecular processes which confer heterogeneity and resistance to treatment upon tumours. These insights may also yield new targets for more effective adjuvant therapies.

Apoptosis↗
PubMed1997

New technology in the analytical cell sciences: the laser scanning cytometer.

New technologies are making a major contribution to progress in applied clinical research in surgical oncology. The laser scanning cytometer is a new machine which combines the analytical capabilities of flow cytometry with the ability to inspect and visualize labelled cells and particles. This substantially reduces the uncertainty associated with assays in a wide range of surgical oncology research applications. This article introduces this new technology.

Equipment Design↗
PubMed1996

http://www.hbuk.co.uk--the European Journal of Surgical Oncology and the Internet.

The popularization of the Internet through the World Wide Web heralds a new era in public and professional communication. The European Journal of Surgical Oncology is now represented on the Web at a site provided, developed and maintained by the publisher. We may expect to see rapid developments in electronic publishing, although the direction and general utility of these changes are not yet clear. This article introduces the EJSO Web site to the readership and considers the ways in which the Internet Revolution may bring benefits to the readership, the publisher, the editorial process and the Journal staff.

Computer Communication Networks↗
PubMed1996

Heterogeneity, biodiversity and bioperversity in solid neoplasms.

Heterogeneity of biological structure and function is an impediment to the analysis and treatment of human solid tumours. Its importance is frequently underestimated in clinico-pathological research. This article reviews the many facets of heterogeneity in tumour systems, and its importance to the interpretation of tumour biology.

Cell Division↗
PubMed1996

The flow cytometric analysis of total p53 protein content and proliferation indices in colorectal cancer, in relation to clinical outcome.

This study was undertaken to assess the value of flow cytometric measurements of total p53 protein content and proliferation indices derived from in vivo halogenated pyrimidine labelling. Two series of colorectal cancer specimens were studied for which clinical outcome data were recorded. A series of 84 archival, ethanol-fixed, bromodeoxyuridine (BrdUrd) labelled colorectal tumours were analysed by flow cytometry for their total and cell cycle phase p53 protein content using the pAb1801 monoclonal antibody. A second series of 33 freshly obtained tumours was used for assay evaluation and for comparison with the archival material. In the archival series (n=84), the median p53-pAb1801 LI was 81.9% (range: 11.1-99.8%). In only three tumours could significant amounts of p53 protein not be detected. The median phase specific p53-pAb1801 LI in G0/G1 was 71.6%, in S was 95.5%, and in G2/M was 98.5%. In the series of fresh tumours (n=33), the median p53-pAb1801 labelling index (LI) was 94.6% (range: 17.9-99.9%). Only two tumours failed to express significant amounts of p53 protein. There was no significant difference in the generally high levels of p53 protein content between the fresh and archival series. Life-table analysis of the patients in the archival series failed to demonstrate a statistical difference in life expectancy in relation to Dukes' stage when tumours were stratified by the median total p53 labelling index. In this study, p53 content and proliferative indices measured by flow cytometry do not have independent predictive value over Dukes' grading in determining the outcome of colorectal cancer. Flow cytometry is confirmed as a practical tool for multi-parametric and cell cycle analysis of oncoprotein expression in human tumour biopsies.

Adenocarcinoma↗