Management development. How to be top.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D Cottam.
Explore the source record for details and available documents.
Matrix metalloproteinase (MMP) expression was investigated in patients with prostatic adenocarcinoma and benign prostatic hyperplasia (BPH). Forty-one men were studied: 26 had histologically proven prostate cancer, with 14 (54%) showing metastatic disease; 15 patients had BPH. Prostatic tissue was obtained from transurethral resection and needle core biopsies; gelatinolytic activity was determined by zymography. Seven gelatinolytic bands were detected, with molecular weights ranging from > 100 kilodalton (kDa) to 29 kDa. Nine of 14 patients (64%) with skeletal metastases had 92 kDa activity, present in only two of 12 patients (17%) with a negative bone scan, and absent in BPH. The 92 kDa gelatinolytic activity was expressed in 73% of aneuploid tumours compared with 20% of diploid tumours. A 97 kDa gelatinase was expressed in 80% of BPH samples and 23% of carcinoma patients. Enzyme bands of 72, 66 and 45 kDa were equally expressed in malignant tissue, irrespective of metastatic status, but were expressed in fewer BPH patients. The 97, 92, 66 and 45 kDa enzymes were identified as being pro-MMP-9 sequences by Western blotting, using a specific antibody directed against the pro sequence of the mature protein. MMP activity appeared to be increased in malignant prostatic tissue compared with BPH. Pro-MMP-9, in its 92 kDa form, was shown to be exclusively expressed by malignant prostatic tissue, and in particular by tumours that exhibited the aggressive and metastatic phenotype.
Since the expression of class I major histocompatibility antigens by the retinal pigment epithelium (RPE) may be important with regard to ocular immune responses, we investigated this using flow cytometry and compared the RPE cells with the colon carcinoma cell line SW742. Six cultured RPE cell lines were examined. All showed strong basal expression of class I antigen. However, this expression was not maximal, and all the RPE lines tested showed a marked capacity for up-regulation of expression by culture in the presence of interferon-alpha, interferon-gamma, or tumour necrosis factor alpha, cytokines involved in immunological responses.
We have investigated the expression of c-myc in 24 ocular melanomas by immunohistochemistry, using two monoclonal antibodies raised against a mid-sequence portion of the c-myc product (6E10) and against the C-terminus (9E10). The results were compared with other putative prognostic factors, including tumour size, cell type, proliferation index (determined by flow cytometry), and ploidy, as well as immunohistochemical staining for HMB-45 and S-100 antigens. Staining, often focal, for c-myc was found in both the nucleus and the cytoplasm of a proportion of the cells in most tumours studied. Total cell staining for myc protein correlated with proliferative index in diploid tumours; seven out of nine aneuploid and mixed aneuploid/diploid cells showed strong staining in at least one cellular compartment. A positive correlation with myc expression was also found for HMB-45 staining, but not for cell type or staining for S-100. The results support the hypothesis that myc protein is involved in cellular proliferation in uveal melanomas and indicate that immunohistochemistry for myc antigen may be a useful prognostic marker in these tumours.
Explore the source record for details and available documents.
Flow cytometry was used to evaluate ploidy and tumour cycle kinetics in fresh tissue samples obtained from 19 uveal melanomas. The results were compared with other parameters including, histological cell type, tumour size and anatomical location. Three tumours (15.8%) were aneuploid (two mixed cell, one epithelioid cell). Cell turnover was estimated in the 16 diploid tumours by summating the total percentage of cells in S and G2/M phases. We found the mean percentage of cells in G2/M/S to be 5.96% (range 2.2-9.8%). Spindle cell neoplasms appeared to have lower cell turnover rates (4.5 +/- 1.2%) than epithelioid cell turnover (8.4 +/- 1.2%). There was no correlation between cell turnover and either tumour size or anatomical location.
An indirect solid-phase radioimmunoassay (RIA) procedure was developed to determine its usefulness in assessing antigenic variation in the surface antigens of type A influenza virus strains. The importance of several test variables was examined, and those having a significant effect on the binding ratios were identified. The reproducibility of the RIA procedure was investigated. Maximum variation of the mean binding ratios encountered in repetitive tests was found to be approximately 20%. The antigenic characteristics of the A/Aichi/68 virus strain were compared with several different type A virus strains. Utilizing anti-A/Aichi/68 immune serum together with specific anti-hemagglutinin and antineuraminidase immune sera, the RIA method was shown to quantitatively differentiate the surface antigens of the A/Aichi/68 virus strain from the surface antigens of the type A strains that preceded, as well as from those that succeeded, the introduction of the Aichi virus strain in 1968. Using antigen-specific serum, both the hemagglutinin and neuraminidase antigens can be independently characterized in one test system. This advantage, together with the ease and greater sensitivity of the RIA, should make it a useful serological test for evaluating antigenic variation of type A influenza viruses.