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E B Austin

Publications and source records attributed to E B Austin.

26 records · Page 2Linked to original sources
PubMed1986

Patterns of reactivity of the monoclonal antibody 791T/36 with different tumour metastases in the liver.

Reactivity of the monoclonal antibody 791T/36 with secondary malignant deposits has been investigated in frozen sections of 74 human liver biopsy specimens. There was no reactivity with hepatocytes but in some instances binding to fibrous tissues and in one case to portal tract lymphocytes was observed. Sections from 9 biopsy specimens contained malignant deposits. In seven of these 791T/36 bound either to malignant cells or to pseudoacinar contents (3 colorectal adenocarcinomas; 1 probable pancreatic adenocarcinoma; 1 medullary cell carcinoma of thyroid; 1 oat cell carcinoma of bronchus and 1 deposit of nodular sclerosing Hodgkins Disease). Two undifferentiated tumours (1 gastric adenocarcinoma and 1 oat cell bronchial carcinoma) showed no antibody binding. The histological pattern of reactivity previously reported with primary tumours appears to be similar in secondary deposits. A wider range of tumours than recognised hitherto binds 791T/36. Whether the binding to fibrous tissue seen in some instances is sufficient to cause diagnostic uncertainty when 791T/36 is used for scanning requires further investigation.

Adenocarcinoma↗
PubMed1984

Flow cytometric analysis of proflavine uptake into normal rat hepatocytes and cells arising during AAF-induced hepatocarcinogenesis.

The uptake of the fluorescent drug proflavine was measured in suspensions of hepatocytes from normal and carcinogen (2-acetylaminofluorine, AAF)-fed rats by flow cytometry. Drug uptake into hepatocytes from carcinogen-fed animals was consistently lower than that into hepatocytes from normal animals. Isolated nuclei, prepared from the livers of normal and AAF-fed rats showed similar proflavine uptake. Drug uptake into hepatocytes from AAF-fed animals, however, was increased by prior exposure to a metabolic inhibitor. Thus, differences in drug uptake may reflect changes in the cell membrane, together with an alteration in the metabolic integrity of the cells. The uptake of drug in hepatocytes from AAF-fed rats was uniformly low within each cell preparation. However, drug uptake varied not only between tumours arising in the livers of these animals but also within each tumour cell preparation. This study indicates that flow cytometry can provide an effective means for analysing drug uptake into cell populations arising during hepatocarcinogenesis.

2-Acetylaminofluorene↗
PubMed1984

Monoclonal antibodies reacting with normal rat liver cells as probes in hepatocarcinogenesis.

A series of four monoclonal antibodies was raised against suspensions of normal adult WAB/Not rat hepatocytes. An immunoperoxidase-staining technique was used to examine the distribution of determinants detected by these antibodies on frozen sections of fetal, neonatal, adult, and regenerating liver and on a range of 4-dimethylaminoazobenzene-induced liver lesions, including a panel of 32 primary liver carcinomas. Three of the antibodies were directed against hepatocytes, while a fourth antibody stained stromal elements within the liver. The determinants detected by the anti-hepatocyte monoclonal antibodies arose in a specific sequence during normal liver development and, when assessed in conjunction, characterized several phenotypes associated with stages in normal hepatocyte differentiation. These same antibody-defined phenotypes were expressed by the primary liver carcinomas, and the distribution of phenotypes among the tumors revealed a heterogeneity which was not evident from a conventional morphological classification. Primary liver tumors expressed a total of four antibody-defined phenotypes, whereas gamma-glutamyl transpeptidase-positive foci of hepatocytes and neoplastic nodules expressed, respectively, only one or 2 antibody-defined phenotypes. We suggest that monoclonal antibodies directed against normal liver cell components may provide a means to establish lineage relationships between cell populations involved in hepatocarcinogenesis.

Animals↗
PubMed1983

A monoclonal antibody reactive with human hepatocytes.

A monoclonal antibody, RL23/36, reacting preferentially with a determinant expressed on normal human hepatocytes is described. Use of an immunohistochemical technique on frozen sections from a range of 75 human liver biopsy specimens revealed that the determinant detected by RL23/36 was not expressed on hepatocytes from a number of patients with biopsy-proven liver disease. Although a normal staining pattern was observed in 28 of 29 biopsy specimens from patients with no evidence of liver disease, the antibody did not bind to hepatocytes in some cases of chronic active hepatitis (2/13), alcoholic liver disease (2/9), haemochromatosis (1/1), cirrhosis (1/2) and liver metastases (2/8). Furthermore, as in a previous study undertaken in the rat, the antibody failed to bind to tumour cells in the single human hepatoma observed in this study. These results suggest that further studies using RL23/36 may shed light on the pathogenesis of a number of liver diseases, including primary hepatocellular carcinoma.

Animals↗
PubMed1982

Expression of a monoclonal antibody-defined liver-associated antigen in normal rat hepatocytes and hepatocellular carcinoma cells.

In order to examine changes in the expression of normal cellular antigens during hepatocarcinogenesis, we have developed and characterized a monoclonal antibody detecting an antigen which is particularly associated with adult rat hepatocytes. The antibody showed no reactivity with a range of freshly-prepared normal syngeneic adult rat cell types, but showed strong reactivity with hepatocytes derived from several rat strains in antibody binding tests. Immunoperoxidase staining of sections of normal rat liver showed that the antigen was distributed throughout hepatocytes within the liver, but did not stain cells other than hepatocytes. The antigen detected by this monoclonal antibody was not detectable on a number of transplanted and primary dimethylaminoazobenzene-induced hepatomas. Preliminary data indicated that this monoclonal antibody may be suitable for use in flow cytofluorimetric sorting of mixed populations of normal and tumour cells, allowing the investigation of cell phenotypes during hepatocarcinogenesis.

Animals↗
PubMed1981

Tumour cells in metastatic deposits with altered sensitivity to natural killer cells.

If natural killer (NK) cells play a role in immunosurveillance it might by expected that, during the metastatic process, selection would occur for tumour cells with reduced NK sensitivity. This hypothesis was tested in the rat by measuring the NK sensitivity of cells freshly isolated from metastases of syngeneic transplanted spontaneous mammary carcinomas. Lysis was measured in a 6-h chromium release assay using normal syngeneic spleen cells as effectors. Our studies led to the following conclusions. (1) Metastases developing at certain tissue sites (draining lymph node and lung, but not pericardium) were frequently composed of tumour cells with markedly reduced sensitivity to NK cells. (2) This resistance could generally be detected only if freshly isolated tumour cell population were studied; after a few days in culture, resistant metastasis-derived tumour cells usually regained normal NK sensitivity. (3) Resistance to NK cells was not always due to the loss of NK target structures; it could also result from an innate resistance to the NK lytic mechanism. (4) The tissue distribution of NK-resistant metastases suggested that if NK cells exerted an immunoselective pressure they did so at the tissue site rather than in the primary tumour or in the bloodstream.

Adenocarcinoma↗
PubMed1979

Comparative studies of the metastatic potential of three transplantable rat mammary carcinomas of spontaneous origin.

The metastatic potential of 3 spontaneously arising mammary carcinomas (Sp4, Sp15 and Sp22) has been examined when transplanted in the form of a viable cell suspension into the tissue of origin. Primary tumours were excised at different times after implantation and it was found that the metastatic potential of the immunogenic tumour Sp4 was directly correlated with the size of the primary tumour when excised. By contrast, the incidence of metastases from the non-immunogenic tumours Sp15 and Sp22 was similar irrespective of the size of the primary tumour on excision. The pattern of metastasis also differed between the tumours, although here there was no relation to immunogenicity. Thus, resection en bloc of large primary Sp4 or Sp15 tumours plus regional lymph nodes could be completely curative, signifying initial spread of tumours via the lymphatics and only subsequently via the blood stream. On the other hand, resection en bloc of primary Sp22 tumours plus regional lymph nodes at a similar stage of primary tumour development was never curative, signifying early spread via the blood stream. Other studies showed that the metastatic potential of mammary carcinoma Sp4 was an innate characteristic of the tumour and not related to the tissue of implantation since in addition to metastasizing from the mammary pad it metastasized when implanted either s.c. or intradermally in a region devoid of mammary tissue. Furthermore, a rat sarcoma Mc7 showed a negligible tendency to metastasize when implanted either in the mammary pad or in the s.c. tissue, where it had been induced with methylcholanthrene.

Animals↗