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Biomedical subjects

G Symonds

Publications and source records attributed to G Symonds.

62 records · Page 4Linked to original sources
PubMed1982

Autoinduction of differentiation in myeloid leukemic cells: restoration of normal coupling between growth and differentiation in leukemic cells that constitutively produce their own growth-inducing protein.

Growth and differentiation of normal myeloid haematopoietic cells are regulated by a family of macrophage- and granulocyte-inducing (MGI) proteins. Some of these proteins (MGI-1) induce cell growth and others (MGI-2) induce cell differentiation. Addition of MGI-1 to normal myeloid cells induces growth and also induces the endogenous production of MGI-2. This induction of differentiation-inducing protein by growth-inducing protein then ensures the coupling between growth and differentiation found in normal cells. There are myeloid leukemic cells that constitutively produce their own MGI-1, but the cells do not differentiate in culture medium containing horse or calf serum. By removing serum from the medium, or in medium with mouse or rat serum, these leukemic cells are induced to differentiate to mature cells, which like normal mature cells, then no longer multiply. Leukemic cells with constitutive production of MGI-1 continuously cultured in serum-free medium with transferrin were also induced to differentiate by removing transferrin. This induction of differentiation was in all these cases associated with the endogenous production of MGI-2 by the cells. The results indicate that changes in specific constituents of the culture medium can result in autoinduction of differentiation in these leukemic cells due to restoration of the induction of MGI-2 by MGI-1, which then restores the normal coupling of growth and differentiation.

Animals↗
PubMed1982

Cell competence for industion of differentiation by insulin and other compounds in myeloid leukemic clones continuously cultured in serum-free medium.

Clones of myeloid leukemic cells varying in their competence for induction of differentiation have been continuously grown in serum-free medium. In the medium used, which contained transferrin, the growth rates of these cells were nearly similar to those found in serum-containing medium. The clones also maintained in this medium their competence for induction of differentiation by the normal macrophage and granulocyte differentiation-induction protein MGI-2, the steroid dexamethasone, and lipopolysaccharide. In contrast to the results with these inducters, some clones continuously cultured in a serum-free medium showed a gain of inducibility by insulin and another clone a gain of inducibility by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in low serum and serum-free medium. Induction of differentiation by these two compounds was therefore inhibited in these clones by the presence of serum. It is suggested that serum-free medium may also show the existence of other inducers of differentiation not detected in serum-containing medium and that these results are relevant to the possible therapeutic use of compounds such as insulin for the induction of normal differentiation in leukemic cells in vivo.

Animals↗
PubMed1979

Activation of normal genes in malignant cells: activation of chemotaxis in relation to other stages of normal differentiation in myeloid leukemia.

Genetically differerent clones of myeloid leukemic cells have been used to study the activation of normal genes in these malignant cells by the normal physiological inducer of myeloid cell differentiation, the protein MGI. In appropriate clones, MGI induced the normal differentiation-associated property of chemotaxis to a variety of compounds including the steroid hormone dexamethasone. The induced cells could also distinguish among different steroids by chemotaxis, suggesting that there are specific membrane interaction sites for steroids. The sequence of differentiation in these cells was the formation of C3 and Fc rosettes leads to phagocytosis of these rosettes and chemotaxis leads to synthesis and secretion of lysozyme leads to mature macrophages or granulocytes. The use of appropriate mutants and the comparison of induction by MGI and dexamethasone has shown that chemotaxis to casein can be dissociated from: chemotaxis to dexamethasone, ATP, and bacterial factor; formation of C3 or Fc rosettes; phagocytosis of these rosettes; synthesis of lysozyme; and the formation of mature cells. It is suggested from this dissection of normal differentiation that there are different membrane changes for specific chemotaxis, formation of these rosettes, and their phagocytosis, and that induction of each of these properties requires activation of different genes.

Animals↗
PubMed1978

Continuous monitoring of temperature in laboratory animals during inhalation exposure.

An automatic system was developed to monitor continuously the colonic temperature of laboratory animals during inhalation exposure to toxic chemicals. It includes: an automatic switchbox, a control circuit, a recorder and a digital voltmeter. The system was calibrated for different temperature ranges and used for a year to assess the effects of household solvents on temperature of Sprague-Dawley rats. Reliable monitoring of temperature in 16 rats was carried out in a sequential manner in the manual mode or in the automatic mode for several consecutive days. Very slight changes (.01 - .02 degrees C) in temperature can be measured with this system.

Animals↗
PubMedDate not supplied

Ribozyme-mediated suppression of v-myc expression abrogates apoptosis in transformed monocytes.

The product of the c-myc oncogene is an important regulator of both cell proliferation and programmed cell death (apoptosis). We have previously shown that a myelomonocytic cell line termed tEMmyc4, with enforced v-myc expression, underwent apoptosis under growth inhibitory conditions. To further investigate the linkage of v-myc expression to apoptosis in these cells, two hammerhead ribozymes were designed and shown to specifically cleave the v-myc though not c-myc transcript in vitro. These ribozymes were then engineered into the pMAMneo vector under the control of MMTV promoter, transfected into tEMmyc4 cells and clonally selected in G418. Molecular analysis revealed reduction of v-myc expression in ribozyme-expressing cells. This reduction was shown to be associated with abrogation of hormone-induced apoptosis (monitored by gel electrophoresis, flow cytometry and TUNEL assay). These results confirm a direct involvement of v-myc in the induction of apoptosis and indicate a potential means to molecularly control apoptosis using a ribozyme-targeting approach.

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