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Biomedical subjects

A E Bird

Publications and source records attributed to A E Bird.

13 recordsLinked to original sources

Expression of the oncogene c-erbB-2 in canine mammary cancers and tumor-derived cell lines.

OBJECTIVE: To determine, for canine mammary tumors, whether malignancy, with or without local invasion or regional metastasis, was associated with overexpression of the oncogene c-erbB-2. DESIGN: c-erbB-2 expression was measured in canine mammary tumor-derived cell lines and in mammary tumor tissues from clinical cases. Clinical samples were examined histologically to determine whether they were benign or malignant and, if malignant, whether they had evidence of local invasion or regional metastasis. Canine fibroblast cultures and normal canine mammary epithelial tissues were used as reference standards for cell lines and mammary tumors, respectively. SAMPLE POPULATIONS: 28 canine mammary tumor tissue samples obtained surgically from clinical cases and samples from 7 canine mammary tumor cell lines derived from primary canine mammary tumors. PROCEDURE: c-erbB-2 mRNA levels were determined by means of hybridization of total polysomal RNA with a 32P-labeled human c-erbB-2 probe on dot blots, and results were quantified by means of scanning densitometry. Overexpression of c-erbB-2 was defined as an autoradiographic density > or = 2 times the density of reference samples on the same blot. RESULTS: Overexpression of c-erbB-2 was detected in 17 of 23 malignant tumors, 0 of 5 benign tumors, and 2 of 7 mammary tumor cell lines. c-erbB-2 overexpression was correlated with a histopathologic diagnosis of malignancy (P = 0.005) but not with the presence of local invasion or regional metastatic disease (P = 0.621). CONCLUSIONS: Results suggest that overexpression of c-erbB-2 occurs prior to the development of metastatic disease in canine mammary tumors and plays a role in the development of malignancy.

Animals

Antigen expression in normal and neoplastic canine tissues defined by a monoclonal antibody generated against canine mesothelioma cells.

Monoclonal antibody (MAb) 3B5 generated against canine mesothelioma cells was applied to canine tumors and normal tissues via immunohistochemical and immunoblotting techniques to evaluate antigen binding. By use of an avidin-biotin immunoperoxidase complex (ABC) method, immunoreactivity was noted in reactive mesothelial cells and in normal tissues was observed primarily in mesothelial cell linings, endothelial cells, and smooth muscle of blood vessels and soft tissues; the reactivity was nearly equivalent in frozen or formalin-fixed, paraffin-embedded tissue sections. Use of the ABC method on formalin-fixed, paraffin-embedded tumors yielded moderate to strong cytoplasmic immunostaining of neoplastic cells in 10/11 (91%) mesotheliomas, 18/23 (78%) hemangiosarcomas, 4/10 (40%) intestinal and lung carcinomas, and < or = 20% of hemangiomas, leiomyosarcomas, leiomyomas, mammary carcinomas, and squamous cell carcinomas. No immunostaining of tumor cells was observed in fibrosarcomas, hemangiopericytomas, perianal gland carcinomas, and melanomas. Immunoblotting was performed on samples that demonstrated strong immunoreactivity with MAb 3B5 by the ABC method: mesothelioma, hemangiosarcoma, urinary bladder (smooth muscle), and lung (alveolar capillaries). These analyses showed that MAb 3B5 bound a major antigen of 78 kilodaltons (kd) and minor antigens at 56 and 54 kd in normal and neoplastic tissues. The preliminary immunohistochemical results suggest that MAb 3B5 may possess utility in diagnosis of mesotheliomas and hemangiosarcomas, discrimination of cell types in proliferative serosal lesions, and demonstration of vascularity or angiogenesis in neoplastic and inflammatory lesions.

Animals

Assignment of the C-5 configuration of penicilloic acids.

Penicilloates prepared by the method of Munro et al (1978) were examined by nuclear magnetic resonance spectroscopy and optical rotation to assign the configuration at C-5. The configuration was 5S for carbenicillin and ticarcillin penicilloates and 5R for the other seven penicilloates examined. The chemical shift and coupling constants of 5-H and 6-H showed consistent differences between the isomers and the optical rotation of the 5R-isomers is consistently more positive than that of the corresponding 5S-isomer.

Amoxicillin

N-formylpenicillamine and penicillamine as degradation products of penicillins in solution.

The degradation of several penicillins in unbuffered aqueous solution produces N-formylpenicillamine, in some cases in high yield. Very little or no penicillamine is formed under these conditions. N-Formylpenicillamine was produced from benzylpenicillin at pH values between 2.5 and 7, with a maximum yield of 30% at pH 5, whereas penicillamine was produced only at pH 5 or below in a yield of less than 1%. Benzylpenicillenic acid at pH 5 gave a 20% yield of N-formylpenicillamine and no penicillamine whereas benzylpenicilloic, penilloic and penillic acids gave no N-formylpenicillamine and a small amount of penicillamine.

Amoxicillin

Structure re-assignment of a metabolite of ampicillin and amoxycillin and epimerization of their penicilloic acids.

Products formed in-vitro from ampicillin and amoxycillin penicilloates have been examined by high-performance liquid chromatography, ultraviolet and nuclear magnetic resonance spectroscopy and thiol group determination and were found to be the 5S epimers of the penicilloic acids. This is in contrast to a published claim that the corresponding penamaldic acids were formed by the treatment used.

Amoxicillin

Hansch analysis of interaction of haptens with benzylpenicilloyl antibodies.

Hansch analysis is applied to inhibition data obtained from the interaction of penicilloic and penilloic acid haptens with benzylpenicilloyl specific antibodies. Significant regressions with partition coefficient and molar volume parameters indicate the importance of hydrophobic and steric effects in these interactions.

Antibodies

Overexpression of c-erbB-2 and c-myc but not c-ras, in canine melanoma cell lines, is associated with metastatic potential in nude mice.

Overexpression of the proto-oncogenes c-erbB-2, c-myc, and c-ras have been associated with neoplastic transformation in a variety of tumours. We investigated expression of these oncogenes in 5 canine melanoma cell lines and 6 clonal derivatives of 1 of the cell lines, CML-6M, to determine what impact overexpression had on tumour cell growth and metastatic potential. All 11 cell lines were tumourigenic at subcutaneous inoculation sites in nude mice, but spontaneous metastasis to lung was a characteristic of only the CML-6M cell line and 3 of 6 clonal derivatives of CML-6M. Investigation of oncogene overexpression revealed no obvious pattern of expression among the 5 tumour-derived cell lines whereas overexpression of c-erbB-2 and c-myc was consistently found in the 3 clonal cell lines characterized by high metastatic potential, and in primary and metastatic mouse xenografts induced by these lines. This data suggests involvement of overexpression of these genes in development of canine melanoma and associates their overexpression with metastatic potential in nude mice.

Animals