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Biomedical subjects

L Turnbull

Publications and source records attributed to L Turnbull.

31 records · Page 2Linked to original sources

Localization of basic fibroblast growth factor and transforming growth factor beta 1 in the human mammary gland.

The presence and distribution of basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 in benign and malignant human breast tissue were determined by immunohistochemistry and immunoblotting. Peroxidase staining of biopsy specimens using a polyclonal antibody to amino acids 1-24 of bFGF and a monoclonal antibody to whole recombinant bFGF showed this growth factor to be localized in the myoepithelial cells of the benign breast. Epithelial cells and stroma were negative. In hyperplasia and intraductal carcinoma in situ staining was still seen around the perimeter of enlarged ducts. In malignant biopsies, however, staining was seen only when benign elements were present or residual myoepithelial cells and basement membrane remained. Antigen absorption and immunoblotting confirmed the antibody staining to be specific for bFGF. Transforming growth factor beta 1 was shown, using the same techniques, to be located in the periductal and intraductal stroma, closely associated with epithelial or myoepithelial cells in the benign and malignant breast. The relative localization of these two growth factors in the mammary gland may be significant in the control of breast development and/or tumor formation and progression.

Antibody Specificity↗

Estrogen and progesterone receptors in the normal female breast.

We have studied estrogen receptor (ER) and progesterone receptor (PR) in normal breast by immunocytochemistry using tissue biopsies and fine needle aspirates (FNA) and, in the case of ER, by enzyme immunoassay. For ER we found a high degree of reproducibility for biopsies taken from the upper outer quadrant: FNA, r = 0.56 (P less than 0.002); tissue section immunocytochemistry, r = 0.89 (P less than 0.0001); and enzyme immunoassay, r = 0.76 (P less than 0.0001). For PR, FNA (r = 0.56, P less than 0.002) and tissue section (r = 0.97, P less than 0.0001) were also found to be reproducible techniques. Using enzyme immunoassay, we were able to measure ER accurately in normal breast tissue. In 59 samples we found a range of 0-37 fmol/mg cytosol protein (mean, 4 fmol/mg). In an age-matched group of 126 women with breast cancer, we found a significantly higher ER [range, 0-139 fmol/mg; mean, 37 fmol/mg (P less than 0.001)]. We then analyzed the ER and PR content of FNAs obtained from the upper outer quadrant of the normal breast in 143 normal women. We found that in only 23 of 143 samples (16%) were greater than or equal to 50% epithelial cells stained. There was a relationship between ER and PR (P = 0.03) and a higher ER content in European women than in non-European women (P less than 0.03). The PR content was related to high body mass index (P less than 0.02) and family history of breast cancer (P = 0.04). Samples tended to be more frequently ER positive by FNA if taken in the follicular phase of the menstrual cycle. We conclude that, although the levels of ER and PR are low in normal breast, they can be accurately measured. There is significant variation of ER and PR with several clinical parameters.

Adolescent↗

The effects of minocycline and tetracycline on the mitotic response of human peripheral blood-lymphocytes.

The effects of minocycline and tetracycline on the mitotic response of human peripheral blood lymphocytes was investigated in vitro. The effects of the antibiotics on the mitotic response of purified lymphocytes stimulated with Interleukin-1 beta varied according to the individual from whom the lymphocytes were obtained. At concentrations above those reported to be present in serum during conventional therapy (2-8 mg/l), there was a tendency for both minocycline and tetracycline to suppress the mitotic response. Minocycline was superior to tetracycline in this respect. However, at physiological concentrations the antibiotics either had no significant effect, suppressed the mitotic response (minocycline at 2 mg/l with one of six donors), or enhanced the mitotic response (tetracycline at 2 and 8 mg/l with four of six donors). The stimulatory effect of tetracycline was not demonstrated when lymphocytes were cultured in whole blood for up to seven days with the antibiotic alone. Similar effects of the antibiotics were observed when mononuclear cell fractions isolated from six donors were stimulated with an optimal concentration of phytohaemagglutinin (PHA). Stimulation of lymphocytes in whole blood cultures with PHA in the presence of minocycline and tetracycline revealed that, under these culture conditions, the antibiotics could suppress the mitotic response of lymphocytes at physiological doses with cells from a majority of donors.

Adult↗

Extended role for needle biopsy in the management of carcinoma of the breast.

Treatment choice in primary breast cancer is wide and still controversial; it seems likely that the optimum treatment for individual patients could be dictated by biological indicators of tumour behaviour. If biopsy could provide prognostic information as well as detailed tissue diagnosis then definitive treatment, with or without adjuvant systemic therapy, could be planned from the outset. We studied 140 patients with a clinical diagnosis of primary breast cancer to determine how much information could be obtained from Tru-Cut needle biopsies performed at the first clinic visit. Ten patients were found to have benign disease. Of 130 carcinomas, 123 (95 per cent sensitivity) were diagnosed correctly from the needle biopsies, with seven false negative and no false positive results (100 per cent specificity). Precise histopathology was predicted in 121 (93 per cent). Grade was correctly assessed in 77 of 112 (69 per cent), but needle biopsy was not accurate for assessment of lymphatic invasion nor elastosis. Steroid hormone receptors were assayed in 59 needle biopsies, and the incidence of oestrogen receptor positivity (34, 58 per cent) was similar to the resected tumours (35, 59 per cent), but the incidence of progesterone receptor positivity (26, 44 per cent) was lower (33, 56 per cent, P less than 0.04). Immunostaining with monoclonal antibody human milk fat globule membrane was accurate in the needle biopsies. DNA analysis by flow cytometry was performed in 37 tumours and the concordance between needle biopsies and resected samples was high. Tru-Cut needle biopsy obviates open biopsy and gives reliable detailed information.

Adult↗

The expression of milk fat globule antigens within human mammary tumours: relationship to steroid hormone receptors and response to endocrine treatment.

The value of steroid hormone receptors for the management of advanced carcinoma of the breast is often limited by the lack of availability of fresh tissue. Differentiation antigens may be estimated on paraffin-embedded fixed material by immunostaining, and the aim of this study was to determine whether staining with the monoclonal antibody raised to human milk fat globule (HMFG-1) could replace receptor measurements. The indirect immunoperoxidase technique was used to stain formalin-fixed paraffin-embedded tumour samples from 168 patients. All received tamoxifen or ovarian ablation as first-line systemic therapy, and all were evaluable for response (UICC criteria). One hundred and sixty-seven had oestrogen (ER) and progesterone receptors (PR) estimated. HMFG-1 staining was assessed as the percentage of tumour cells stained, and by the site of stain. The proportion of cells stained was highly correlated with both ER (P less than 0.0001) and PR (P less than 0.0001) and with response. When greater than or equal to 30% cells stained, 53 of 69 (77%) responded; when 20-29% stained 10 of 19 (53%) responded, when 10-19% stained seven of 19 (37%) responded, and when less than or equal to 9% cells stained 16 of 61 (26%) responded (P less than 0.0001). The median survival of patients with tumours that stained greater than or equal to 30% cells was 36 months, and with no cells stained, 11 months (P less than 0.0001). ROC (receiver operator characteristic) curves found that the optimum threshold for sensitivity and specificity of response prediction was greater than or equal to 20% cells stained. Cox's multiple regression analysis of 42 variables indicated that PR was the most important predictor of survival (P less than 0.000001), but that after PR the percentage of cells stained with HMFG-1 was the most important (P less than 0.0001). We conclude that immunostaining for HMFG-1 gives similar information to receptor status, and has the advantage that fixed archival tissue may be used.

Adult↗

Epstein-Barr virus and jaw tumors in North Nigeria.

Nigerian patients with tumors of the jaw were compared with controls in respect of antibodies to the viral capsid antigens of Epstein-Barr Virus (EBV) and of total immunoglobulin levels. Immunoglobulin levels did not differ between patients and controls but increased two weeks postsurgery. Immunoglobulin A (IgA) antibodies to EBV were detected in a small number of patients, and mean titers of IgG antibodies to EBV were lower in the patient group, indicating a lack of association between EBV and tumor formation. An association was noted between the presence of Hepatitis B surface antigen, and depressed antibody titers to EBV in patients with tumors. Of 78 patients studied, 12% were Hepatitis B surface antigen positive.

Ameloblastoma↗

DNA analysis by flow cytometry, response to endocrine treatment and prognosis in advanced carcinoma of the breast.

The relationship between DNA content of mammary cancer and subsequent response to endocrine therapy was studied in 136 patients with advanced disease. All were treated with tamoxifen or ovarian ablation as first-line systemic therapy after relapse and were evaluable for response according to UICC criteria. DNA characterisation by flow cytometry was used on formalin fixed paraffin-embedded samples of tumour. Tumours were grouped according to DNA index into diploid (n = 52, 38%), 'tetraploid' (n = 46, 34%) and 'other DNA-aneuploid' (n = 38, 28%). The highest proportion of oestrogen receptor positive tumours (ER + ve) was found in the 'tetraploid' tumours (38/46, 85%, Chi-square = 8.53, P less than 0.02), and response rates, (SD + PR + CR), were 26/52 (50%), 34/46 (74%), and 15/38 (39%) respectively (Chi-square = 10.88, P less than 0.005). Patients with diploid or 'tetraploid' tumours survived longer and stayed in remission longer than those with 'other DNA-aneuploid' tumours. We suggest that 'tetraploid' or 'near tetraploid' human mammary tumours may comprise a distinct group of endocrine responsive tumours within the overall group of aneuploid tumours. The conventional interpretation of DNA histograms, grouping into diploid and aneuploid, may be masking important features of some tumour groups.

Adult↗

The relationship between disease activity, immunoglobulins and lymphocyte sub-populations in ankylosing spondylitis.

Fifteen patients with active ankylosing spondylitis (ESR greater than 30 mm/h and persistent well-defined symptomatology) and 15 patients with inactive ankylosing spondylitis were studied to investigate the effect of disease activity on T and B cell numbers, plasma viscosity (PV), C reactive protein (CRP) and immunoglobulins. The ability of patients' sera to inhibit normal T cell rosette formation was also assessed. We were able to confirm the close correlation of CRP and PV with clinical disease activity, but were unable to confirm the previously reported T lymphopoenia in ankylosing spondylitis in either of our disease groups. There was no evidence of a serum factor capable of inhibiting T cell rosette formation. B cell numbers, IgG and IgA levels were significantly higher in the active disease group, reflecting increased activity in the humoral immune system during active phases of ankylosing spondylitis.

Adolescent↗