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Biomedical subjects

J W Pollard

Publications and source records attributed to J W Pollard.

126 records · Page 7Linked to original sources
PubMed1979

Characterization of cell lines showing growth control isolated from both the wild type and a leucyl-tRNA synthetase mutant of Chinese hamster ovary cells.

The genetic approach to the problem of cellular growth control is limited by the availability of recessive mutations in cell lines which are capable of growth control in vitro. The CHO cell line has yielded many recessive mutations including, for example, tsH1, a temperature sensitive leucyl-tRNA synthetase mutant, which under non-permissive conditions rapidly shuts down protein synthesis and generates uncharged tRNA. Both CHO and tsH1 are transformed, however, and do not respond to environmental stimuli with the coordinated regulation of macromolecular processes observed in normal diploid fibroblasts. We describe here the isolation and characterization of growth control revertants obtained from both CHOwt and tsH1. The best of these GRC+L-73, isolated from tsH1, had 20 chromosomes, one less than tsH1, had normal fibroblastic morphology, would not grow in suspension, required high serum concentrations for growth, grew to relatively low cell densities at saturation in monolayer culture and showed a stationary phase characterized by arrest in a G1-like state with maintenance of high viability for several weeks. It is expected that this line as well as a ts revertant GRC+LR-73 will greatly facilitate the genetic investigation of growth control and, in particular, will help to elucidate the role of uncharged tRNA in the regulation of macromolecular synthesis in mammalian cells.

Amino Acyl-tRNA Synthetases↗
PubMed1979

Transformed cells have lost control of ribosome number through their growth cycle.

Previous studies on the synthesis and function of the protein synthetic machinery through the growth cycle of normal cultured hamster embryo fibroblasts (HA) were extended here to a series of four different clonal lines of polyoma virus-transformed HA cells. Under our culture conditions, these transformed cells could enter a stationary phase characterized by no mitotic cells, very low rates of DNA synthesis, and arrest in a post-mitotic pre-DNA synthetic state. Cellular viability was initially high in stationary phase but, unlike normal cells, transformed cells slowly lost viability. The rate of protein synthesis in the stationary phase of the transformed cells fell to 25-30% of the exponential rate. Though this reduction was similar to that seen in normal cells, it was accomplished by different means. The specific reduction in the ribosome complement per cell to values below that of any cycling cell seen in normal cells, was not seen in any of the transformed lines. This observation, which implies a loss of normal control of ribisome synthesis through the growth cycle after transformation, was confirmed in normal Chinese hamster embryo fibroblasts and transformed CHO cell lines. Normal control of ribosome synthesis was restored in L-73 and LR-73, growth control revertants of one of the transformed CHO lines. The transformed lines reduced their protein synthetic rates in stationary phase either by a greater reduction in the proportion of functioning ribosomes than that seen in normal cells or by a decrease in the elongation rate of functioning ribosomes; the latter effect was not seen in the normal cells. A model for growth control of normal cells and its derangement in transformed cells is presented.

Animals↗
PubMed1978

Stuttering: high-level mistranslation in animal and bacterial cells.

In both bacterial and mammalian cells, extreme starvation for certain amino acids resulted in translational errors that could be easily detected by two-dimensional polyacrylamide gel electrophoresis. On two-dimensional gels, the faulty proteins were shown as a trail of spots with molecular weights similar to those of the authentic proteins but separated in the isoelectric focusing dimension, a phenomenon we call "stuttering." The direction of charge shift depended on the amino acid substituted and could be predicted from misreading of pyrimidines for purines at the third position of the codon. It is expected that this phenomenon will provide a rapid means of measuring the fidelity of the translational machinery from cell type to cell type.

Amino Acids↗
PubMed1977

The effects of sex-steroids on the synthesis of uterine non-histone proteins.

Newly synthesized non-histone proteins (NHP) labelled with [35S] methionine were isolated from uterine epithelium and stroma after different hormone treatments and examined by isoelectric focusing in polyacrylamide gels. Progesterone increased the proportion of basic NHP in the epithelium. This effect was detectable within 4 h and was maintained unchanged after oestrogen stimulation, which increased the synthesis of all classes of NHP. The proportion of basic NHP was higher in the untreated stroma than in the epithelium. Progesterone pretreatment did not increase the proportion of basic NHP in the stroma but prevented the increase in the more acidic NHP which followed treatment with oestrogen alone. The tendency to synthesize a higher proportion of basic NHP did not in any way correlate with the tissue's proliferative status.

Animals↗
PubMed1976

Word imagery modalities and learning in the deaf and hearing.

The study explored the modality specific hypothesis of imagery concreteness. Twenty-four male and female deaf and hearing adolescents learned lists of paired associates that were either high visual and low auditory imagery words or the obverse. It was predicted that the deaf group would perform as well as the hearing group with pairs of high visual imagery, but worse with materials of high auditory imagery. The results failed to demonstrate the expected interaction. However, indirect support for the hypothesis was provided by a third order interaction trend analysis which suggested that the deaf group experienced difficulty in learning the high auditory imagery word pairs.

Adolescent↗
PubMed1976

Oestriol, oestradiol-17beta and the proliferation and death of uterine cells.

It has been suggested that oestriol protects against breast cancer, because in some experiments on uterine growth it is only weakly active, and partially inhibits the effects of oestradiol-17beta. When its effects are measured 24 h after a single injection, oestriol behaves as a typical impeded oestrogen with low potency and a flat dose-response line. This does not result from failure to stimulate certain critical stages of growth but from failure to sustain the products of growth. We found that oestriol induced all phases of uterine growth including DNA synthesis and cell division. It was as effective as oestradiol in stimulating early increases in protein synthesis and uterine weight, and half as effective in stimulating epithelial cells to replicate DNA and divide. However, epithelial cell numbers did not increase after a single injection of oestriol because cell death rate increased at the same time as mitotic rate, apparently as a result of the more rapid loss of oestriol from the uterus. Repeated injections of oestriol prevented premature cell death and produced as much uterine hypertrophy and hyperplasia as oestradiol-17beta. These results support the thesis that the oestrogenic potency of a substance is largely determined by the duration of its occupation of receptors. Thus in situations of continuous production, (e.g. pregnancy) oestriol would be as active as oestradiol and unlikely to exert any significant 'buffering' or protective action. The findings are also discussed in relation to a new model for the regulation of cell proliferation.

Animals↗
PubMedDate not supplied

Apparent role of the macrophage growth factor, CSF-1, in placental development.

Colony stimulating factor-1 (CSF-1) is a glycoprotein growth factor required for the proliferation and differentiation of mononuclear phagocytic cells (reviewed in ref. 1). A 10,000-fold elevation of mouse uterine CSF-1 during pregnancy, suggested by studies of the bone marrow colony stimulating activity of uterine extracts, was recently demonstrated by radioimmunoassay (RIA). This increase and the observations that placenta and choriocarcinoma cell lines express c-fms messenger RNA and the c-fms proto oncogene product (CSF-1 receptor) respectively, suggest an additional role for CSF-1 in pregnancy. We now show that uterine CSF-1 concentration is regulated by the synergistic action of female sex steroids, oestradiol-17 beta (E2) and progesterone (P) and that the elevation in CSF-1 concentration can be attributed to the preferential expression of an alternatively spliced CSF-1 mRNA by uterine glandular epithelial cells. These findings indicate that CSF-1, under hormonal influence, plays a role in placental development and function and that steroid hormones may regulate developmental processes via their effects on the expression of tissue-specific growth factors.

Animals↗
PubMedDate not supplied

Skills needed by physician CEOs. Interview by Barbara J. Linney.

How do you transition from physician executive to physician CEO? Three physician CEOs were interviewed to explore the skills they needed to land in the top position. They share their views on what it takes to be a successful CEO. They describe the skills that they needed when they moved into the CEO role and how they acquired them. Some of the qualities it takes to be a CEO include the ability to: Articulate your values; use your people skills; describe a vision; solve problems; listen; walk around; and use analytical skills.

Career Mobility↗