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P N Goodfellow

Publications and source records attributed to P N Goodfellow.

At least 181 records · Page 10Linked to original sources
PubMed1984

Human muscle cell surface antigen 16.3A5 is encoded by a gene on chromosome 11.

A monoclonal antibody (McAb), 16.3A5, has been characterized that reacts with a cell surface antigen of human muscle cells and a variety of nonmuscle cells. The gene controlling synthesis of 16.3A5 antigen has been assigned to human chromosome 11 by assessing McAb reactivity on a panel of mouse-human cell hybrids. The 16.3A5 has a novel specificity distinct from other chromosome 11-encoded antigens such as W6/34, F10.44.2, TRA1.10, and 4D12 antigens.

Adult↗
PubMed1984

The use of cloned gene probes to study differentiation in teratocarcinomas.

The molecular control of early embryonic gene expression can be studied in teratocarcinoma derived cell lines. Several genes known to be regulated during in vitro differentiation have been cloned and used to measure mRNA levels. In all cases studied there is good agreement between protein levels and mRNA levels, strongly implying transcriptional regulation. Two non-exclusive hypotheses have been proposed to explain transcriptional control: methylation of DNA and the interactive effects of cis-acting enhancer sequences and trans-acting proteins. Experiments with oncoviruses suggest both mechanisms may play a role.

Animals↗
PubMed1984

Regional localization of 3 Y-derived sequences on the human X and Y chromosomes.

The structure of the Y chromosome and the relationship between the human sex chromosomes have been studied using Y-derived sequences cloned in cosmids. Two probes recognize different unique sequences which map to the heterochromatic part of the long arm of the Y chromosome. A third sequence is shared by the long arm of the X chromosome and the euchromatic part of the Y chromosome. Thus homology between the sex chromosomes occurs outside the pairing region.

Animals↗
PubMed1984

Assignment of tissue-type plasminogen activator to chromosome 8 in man and identification of a common restriction length polymorphism within the gene.

The plasminogen activators (PAs) are serine proteinases which convert the inactive proenzyme plasminogen into plasmin, a proteinase associated with processes such as fibrinolysis and tissue remodelling. There are two immunologically distinct types of PA: tissue-type (t-PA), the main form involved in thrombolysis, and urokinase-type (u-PA), primarily involved in tissue degradation. Two or possibly more genes encode PA activity, and one locus has been provisionally assigned to chromosome 6 in man. We have isolated cDNA clones which encompass the entire coding sequence of the t-PA gene, and have used these to probe DNA on Southern blots isolated from 18 independent human-rodent somatic cell hybrid lines. The presence of the human gene for t-PA showed complete concordance with human chromosome 8 in the hybrids. In addition, the cDNA clones recognize a restriction fragment length polymorphism, where the two common alleles each have a frequency of approximately 0.5. t-PA and u-PA activities have been found in a wide variety of malignant cells, where they are thought to play a role in metastatic invasion of normal tissue. The results reported here will enable us to investigate whether genetic changes associated with the chromosome encoding t-PA are associated with altered t-PA expression in neoplasia.

Chromosome Mapping↗
PubMed1983

High-molecular-weight glycoproteins are the major carriers of the carbohydrate differentiation antigens I, i and SSEA-1 of mouse teratocarcinoma cells.

The carriers of the carbohydrate differentiation antigens I, i and SSEA-1 were investigated in embryonal carcinoma cell lines of mouse and differentiated cell lines derived from them. Glycoproteins were studied by immunostaining ('Western blotting') of total cell lysates and immunoprecipitation from lysates of galactose oxidase/NaB3H4-labelled cells; glycolipids were investigated by immunostaining of thin layer chromatograms. The antigenic activities detected by immunofluorescence of cell smears were reflected in the antigenicities of high-molecular-weight glycoproteins. These were polydisperse and markedly susceptible to digestion with endo-beta-galactosidase. Only the I antigen was detected on minor glycolipids. These observations indicate that glycoproteins rather than glycolipids are the major carriers of carbohydrate differentiation antigens I, i and SSEA-1 in the teratocarcinoma cell lines.

Animals↗
PubMed1983

Human-mouse hybrids with an embryonal carcinoma phenotype continue to transcribe HLA-A,B,C.

We previously constructed a hybrid cell line, MCP6, which contains an X/6 translocation chromosome as its sole human genetic component in a mouse embryonal carcinoma (EC) cell background. This chromosome, which carries the major histocompatibility complex (MHC) originated from a human B cell which expresses class I and class II MHC antigens. EC cells do not express class I or class II antigens on their cell surface. Northern blot analysis has now shown that in the MCP6 hybrid, human class I genes, i.e., HLA-A,B,C, continued to be transcribed, and cellular levels of the transcripts were similar to, or only slightly lower than, levels in hybrids with a non-EC phenotype. However, very low levels of mRNA species recognised by a mouse class I gene (H-2) probe were also detected in EC cells and EC hybrids. Comparison of the relative levels of H-2 and HLA class I gene transcripts in the EC hybrids and non-EC hybrids indicated that the introduced HLA-A,B,C genes were not appropriately regulated in the EC cell but were subject at least in part to cis control. In contrast to the class I genes, no class II gene (i.e. HLA-DR alpha) transcripts were detected in MCP6. Hybrid EC lines thus provide a system to investigate the different levels of control of MHC gene expression during development and may help to elucidate mechanisms whereby the embryonic genome programs expression of differentiated cell functions.

Animals↗
PubMed1983

Genetic analysis of the 15;17 chromosome translocation associated with acute promyelocytic leukemia.

Somatic cell hybrids have been constructed between a thymidine kinase-deficient mouse cell line and blood leukocytes from a patient with acute promyelocytic leukemia showing the 15q+;17q- chromosome translocation frequently associated with this disease. One hybrid contains the 15q+ translocation chromosome and very little other human material. We have shown that the c-fes oncogene, which has been mapped to chromosome 15, is not present in this hybrid and, therefore, probably is translocated to the 17q- chromosome. Analysis of the genetic markers present in this hybrid has enabled a more precise localization of the translocation breakpoints on chromosomes 15 and 17. Our experiments also have enabled an ordering and more precise mapping of several genetic markers on chromosomes 15 and 17.

Adult↗
PubMed1983

Differentiation in vitro of human-mouse teratocarcinoma hybrids.

The mouse embryonal carcinoma (EC) line, PCC4, was used to construct a series of somatic cell hybrids which contain a single or a few human chromosomes. The hybrids all retained the EC phenotype as determined by morphology, expression of SSEA-1, lack of cell surface H-2 antigen and cytokeratin filaments, high alkaline phosphatase levels, the ability to form EC tumors ectopically in nude mice, and the ability to differentiate in response to retinoic acid. Constitutively differentiated cloned lines were derived from retinoic acid-treated hybrid cultures. Several derived lines had a phenotype indistinguishable from that of parietal endoderm cells, which includes synthesis of large amounts of laminin, type IV procollagen, and plasminogen activator. One differentiated line showed a fibroblast-like morphology. The differentiated lines derived from two of the hybrids, MCP6 and GEOC4, stably maintained the sole human chromosomal component present in the EC progenitors. These EC hybrids therefore provide a system to study developmental regulation of the introduced and stably maintained human genetic material derived from a variety of cell types.

Alkaline Phosphatase↗
PubMed1982

Cell-surface antigens of a clonal human embryonal carcinoma cell line: morphological and antigenic differentiation in culture.

A cloned human embryonal carcinoma (EC) cell line has been derived from a testicular teratocarcinoma, and reproducibly forms EC tumors when injected into athymic (nu/nu) mice. These human EC cells are characterized by a newly described stage-specific embryonic antigen, SSEA-3. Unlike murine EC cells, they express major histocompatibility antigens (HLA-A, B, C and beta 2-microglobulin) but do not express the embryonic antigen SSEA-I. We also report that these cells appear to be capable of differentiation and that this can be induced by initiating cultures at low cell density. Differentiation is marked by the appearance of morphologically distinct cells and by the induction of SSEA-I, whereas the expression of other antigens, including SSEA-3, is initially diminished. This well-characterized system of human EC cells provides a model for the future investigation of other human teratocarcinoma cell lines and for the analysis of cellular differentiation during early human development.

Animals↗
PubMed1982

The gene, MIC4, which controls expression of the antigen defined by monoclonal antibody F10.44.2, is on human chromosome 11.

The monoclonal antibody, F10.44.2, is directed against a human antigenic determinant of restricted tissue distribution. In this report it is shown that this determinant is coded for by a gene, MIC4, which is on human chromosome 11, as shown by its reactivity with a panel of somatic cell hybrids. Synteny with an antigen recognized by another monoclonal antibody, W6/34, is demonstrated by hybrid and fluorescence-activated cell sorter analysis, although it is clear from absorption analysis that the determinants involved are on different molecules.

Animals↗
PubMed1982

A monoclonal antibody to the human epidermal growth factor receptor.

A monoclonal antibody of the IgG class, EGFR1, has been isolated using cells of the epidermoid carcinoma line A431 as immunogen. The A431 antigen recognized by EGFR1 has an apparent molecular weight of approximately 175,000, is a cell-surface molecule which can be specifically cross-linked to EGF, exhibits an EGF-stimulated protein kinase activity, binds to EGFR1 in a number of human cell lines to a degree which parallels EGF binding, and shows EGF-dependent internalization in A431 cells and human fibroblasts. We therefore conclude that EGFR1 is directed against an antigenic site on the human EGF receptor. EGFR1 is not mitogenic for human fibroblasts and does not inhibit EGF binding under a variety of assay conditions. The characterization of EGFR1 has allowed the unambiguous assignment of the structural gene for the human EGF receptor to chromosome 7. Preliminary results suggest that a convenient method for isolating a range of anti-EGF receptor monoclonal antibodies can be developed, based on a hybridoma supernatant screening assay in which positive supernatants bind selectively to a human-mouse cell hybrid containing human chromosome 7.

Antibodies, Monoclonal↗
PubMed1982

Expression of human transferrin receptor is controlled by a gene on chromosome 3: assignment using species specificity of a monoclonal antibody.

The monoclonal antibody OKT-9 has been shown to recognize the human transferrin receptor. We have exploited the species specificity of OKT-9 to map a gene controlling human transferrin receptor expression to chromosome 3, using human-mouse somatic cell hybrids. The gene for the human transferrin receptor and the gene controlling transferrin expression may be linked in humans.

Animals↗