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E A Thompson

Publications and source records attributed to E A Thompson.

At least 163 records · Page 9Linked to original sources
PubMed1983

Glucocorticoid binding properties of mouse thymic lymphosarcoma cell populations selected for resistance to the cytolytic effects of glucocorticoids in vivo.

Thirteen independently derived murine thymic lymphosarcoma lines were assayed for various aspects of sensitivity to glucocorticoid-induced cytolysis. All tumor lines were sensitive to cytolysis, as evidenced by profound tumor regression after pharmacologic doses of cortisol. All tumor lines contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 55 and 88% of these presumptive receptor sites underwent nuclear translocation during a 30-minute incubation at 37 degrees C. Dissociation constants (Kd) for the dexamethasone-receptor complex were between 1.5 and 3.6 nM in all cases. Kd for the triamcinolone acetonide-receptor complex were determined for a few tumor lines and were between 0.5 and 0.9 nM. Cytolysis-resistant subpopulations were selected by prolonged glucocorticoid treatment of BALB/c pi mice bearing tumors from seven of the lymphosarcoma lines. All seven resistant subpopulations contained about 20,000 high-affinity, dexamethasone binding sites/cell. Between 57 and 80% of these presumptive receptor sites underwent nuclear translocation under standard assay conditions. No resistant variants exhibited significantly reduced dexamethasone binding or nuclear translocation properties.

Animals↗
PubMed1981

The relationship between the activity of DNA-dependent RNA polymerase I and the rate of synthesis of rRNA in hepatoma cells in culture.

Cell culture lines were established from the transplantable mouse hepatomas H6 and H129. Both cell lines had a doubling time about 30 h when maintained in medium containing 5% foetal bovine serum. H6 cells contained about 3-4 times more DNA-dependent RNA polymerase I (Pol I; ribonucleoside triphosphate--RNA nucleotidyltransferase, EC 2.7.7.6) than did H129 cells. Moreover, the H6-cell enzyme was more heat-labile than that from H129 cells. Steady-state contents of 28S rRNA were measured in both cell lines. Exponentially growing cultures of H6 cells contained about 6.5pg of 28S rRNA/cell, and similar cultures of H129 cells contained about 5.8pg/cell. Stationary cultures of both cell lines contained about 2pg of 28S rRNA/cell. By two different techniques, the half-time for turnover of 28S rRNA was estimated to be 16-17h for both H6 and H129 cells. Knowing the turnover rate and the steady-state concentration, one may calculate that both H6 and H129 cells synthesize 28S rRNA at a rate of about 0.25 pg/h per cell. The amount of template-bound Pol I activity was similar in nuclei isolated from H6 and H129 cell cultures. These data indicate that, although H6 cells contained 3-4 times more Pol I than did H129 cells, both cell lines synthesized rRNA at about the same rate.

Animals↗
PubMed1981

Pedigree analysis of Hodgkin's disease in a Newfoundland genealogy.

An extensive Newfoundland genealogy shows a large number of cases of lymphoreticular malignancies. A recessive pattern of inheritance had been previously suggested, but no quantitative investigation of the hypothesis was made. Here we have investigated a variety of aspects of the descent structure of the pedigree and shown that for only a subset of the traits can the inference be upheld. For Hodgkin's disease (HD) and generalized immunodeficiency (ID) there is clear evidence for a recessive HD/ID susceptibility allele. The remainder do not follow this pattern, show no evidence of a single-locus effect and little of any genetic effect. The ancestry of the HD/ID cases was therefore investigated in detail, and likelihoods computed on the pedigree. These confirmed the recessive nature of the trait, as also did the risk analysis which quite clearly identified the paths of descent taken by the allele. The determination of these paths is a prerequisite for any linkage analysis which might further confirm the single-locus nature of the trait.

Female↗
PubMed1981

DNA-dependent RNA polymerase I from hepatomas: comparison of activity levels and properties.

Activity levels of DNA-dependent RNA polymerase I (Pol I; ribonucleoside triphosphate: RNA ribonucleotidyl transferase, E.C. 2.7.7.6, eucaryotic type I) have been compared in five transplantable murine hepatomas and livers of three inbred mouse host strains. Three tumors (H6, H4 and H134) contained about 350-450 units of Pol I activity/g of tissue. Two hepatomas (H129 and BW7756) contained about 120-150 units of activity/g of tissue. Livers contained about 100-150 units/g of tissue. Chromatographic comparisons revealed that hepatoma Pol I is slightly less anionic than the liver enzyme. Thermal denaturation studies were carried out using Pol I partially purified from a high-activity line hepatoma (H6), a low-activity line hepatoma (H129) and livers of the appropriate host strains. Pol I from H6 tumors was denatured at 40 degrees C with a half-time of 2 min. The enzyme from H129 tumors and host livers was denaturated with a half-time of 7 min. These data indicate that hepatoma H6 expressed a structural variant of Pol I. This is the first Pol I variant ever reported.

Animals↗
PubMed1981

Optimal sampling for pedigree analysis: sequential schemes for sibships.

Methods for inferring the mode of inheritance of a trait from familial data are becoming widely used. It is therefore important to assess alternative procedures for the collection of the relevant data. Cannings and Thompson (1977, Clinical Genetics 12, 208-212) and Thompson and Cannings (1979. In Genetic Analysis of Common Diseases, 363-382, New York: Liss) have advocated sequential schemes on the grounds that these admit simple methods for the correction of the likelihood function for ascertainment bias. Here it is shown that sequential procedures may also greatly increase efficiency, as measured by (statistical) information gained per individual sampled. Although attention is restricted to sampling sibships, and to a simple genetic model, the measures introduced are more widely applicable. A practical procedure for the construction of schemes, via a relationship between expected log likelihood and entropy, is also presented. This too is more widely applicable. A numerical example demonstrates the gains which can be achieved in practice, relative to alternative hypotheses which have been considered in several medical-genetic studies.

Data Collection↗
PubMed1981

Optimal sampling for pedigree analysis: relatives of affected probands.

Criteria and rules are derived for the most statistically efficient sampling of relatives of affected probands under a simple class of standard genetic models. Results show that the optimal relative type depends on the alternative hypotheses of particular interest. Thus, there is no uniformly optimal strategy, but the criteria can be used to derive the best strategy in any particular case; examples are given.

Female↗
PubMed1980

Properties of a cell-culture line derived from lymphosarcoma P1798.

A cell culture line has been derived from lymphosarcoma P1798. Cells will not divide in the prescence of 10(-8) M dexamethasone. Half-maximal inhibition of proliferation occurs at about 10(-9) M. Half-maximal inhibition of [3H] thymidine incorporation occurs at somewhat higher concentrations of dexamethasone. When cells are cultured in the presence of 2 x 10(-7) M dexamethasone they remain 88% viable after 5 days. No decrease in cell number occurs. These cells can be rescued by in vivo passage, and they responded in culture to dexamethasone in exactly the same fashion as do untreated cells. Both dexamethasone rescued and untreated cultured cells contain about 104 dexamethasone receptor sites which bind with a dissociation constant of 4 x 10(-9) M. Cultured cells retain the ability to proliferate both subcutaneously and in ascites. The properties of such tumors resemble those of the parental tumor cell lines.

Animals↗
PubMed1980

Genetic etiology and clusters in a pedigree.

As a preliminary tool in the investigation of a rare medical trait in a single extended pedigree or small community, some tests of non-random distribution of cases are constructed. The metrics quantifying this distribution are functions of relationship or descent. Rejection of the null hypothesis of random distribution is thus an indication of possible genetic effects, although this is not the only viable explanation. The methods are applied to a study of lymphoreticular malignancies in a Newfoundland community. This community has attracted interest by the preponderance of cases, and offers a unique opportunity for a study of the etiology of the conditions. On such a large extended pedigree it may eventually be possible to assess the relative importance of environment, infection and genetics.

Genetic Diseases, Inborn↗
PubMed1980

Hormonal effects upon the rate of proliferation of the murine plasmacytoma MOPC 315.

The growth rate of the transplantable murine plasmacytoma MOPC 315 is decreased by daily injections of 2 mg cortisol. Estradiol injections (0.01 mg/day) have a slight stimulatory effect while testosterone has no detectable effect. Growth rate is unaffected by propylthiouracil, triiodothyronine, and growth hormone. MOPC 315 contains glucocorticoid binding proteins which bind 3H-dexamethasone with high affinity. In intact cells there are 3-4 x 10(4) dexamethasone binding sites per cell as judged by competition experiments in which cells were incubated with a saturating concentration of 3H-dexamethasone in the presence and absence of a 1,000-fold molar excess of unlabelled dexamethasone. Scatchard analysis of binding data reveals the presence of a class of sites which binds about 2 x 10(4) molecules of dexamethasone/cell with an equilibrium dissociation constant (Kd) of about 3 x 10(-8)M. In intact cells, only half of the saturable dexamethasone binding sites have stereochemical specificity for dexamethasone. This was deduced from the observation that dexamethasone binding to about half of these sites was displaced by the addition of a 1,000-fold molar excess of estradiol. Nuclear binding sites for dexamethasone were detected at a level of about 1 x 10(4)/cell. Nuclear dexamethasone binding sites were not displaced by the addition of a 1,000-fold molar excess of estradiol.

Animals↗
PubMed1980

Nonmutational alteration in glucocorticoid sensitivity of lymphosarcoma P1798.

The sensitivity of lymphosarcoma P1798 to glucocorticoids varied as a function of growth conditions. Cells grown in the ascitic fluid were very sensitive to cortisol inhibition of tritiated thymidine ([3H]dThd) incorporation. When ascites cells were inoculated sc into BALB/c mice receiving daily injections of 2 mg cortisol, tumors did not form. However, as tumors grew subcutaneously in control mice, glucocorticoid sensitivity decreased to the arrested by cortisol injection. Cortisol also did not inhibit incorporation of [3H]dThd in cells prepared from large subcutaneous tumors. Measurement of cytoplasmic receptors in cell-free extracts revealed that both ascites and subcutaneous tumor cells contained about 11-12 x 10(4) glucocorticoid binding sites per cell. Receptors in ascites cells had a higher affinity for glucocorticoids than did receptors in subcutaneous cells, which indicated that sensitive and resistant cells contain chemically different classes of receptors. Loss of sensitivity occurred as tumors attained a diameter greater than approximately 1.5 cm. The reproducibility of this transition did not appear to be consistent with a random mechanism for loss of glucocorticoid sensitivity in vivo. Thus the acquisition of resistance by lymphosarcoma P1798 in vivo was concluded to be nonmutational and probably resulted from differentiational alteration in gene expression.

Animals↗
PubMed1980

Glucocorticoid effects of lymphosarcoma P1798 on DNA replication and growth of subcutaneous tumors in mice.

Injection of cortisol into BALB/c mice inhibited tritiated thymidine ([3H]dThd) incorporation into ascites cells of lymphosarcoma P1798 but not into cells isolated frm large subcutaneous tumors. The DNA synthetic index (SI), estimated autoradiographically after pulse labeling with [3H]dThd in vitro, was 0.25-0.29 for ascites cells and cells isolated from tumors having a radius squared (r2) less than 200 mm2. Cortisol decreased the SI of ascites cells by 90-95% within 5 hours. Similarly, cortisol decreased the SI of cells from subcutaneous tumors having an r2 less than 90 mm2. Growth and [3H]dThd incorporation were also inhibited by cortisol treatment of tumors with an r2 less than 90 mm2. However, when tumors became larger than 90 mm2, the SI did not decrease after cortisol treatment. Neither growth nor [3H]dThd incorporation was inhibited in tumors with an r2 greater than 90 mm2. These data indicate that tumors of lymphosarcoma P1798 became resistant to cortisol in a size-dependent manner. Loss of sensitivity ws not due to a gradual increase in the percentage of resistant cells.

Animals↗
PubMed1980

Kinship structure and heterozygosity on Tristan da Cunha.

Although there are many factors influencing the genotype proportions in a small population [1], a heterozygote excess, caused by avoidance of incestuous matings, will often be the expected observation. In the population of the small South-Atlantic islands of Tristan da Cunha, such an excess if observed [2], and we have investigated its origin, partitioning the population by sex and by generation. Although for such a small population the test for random pairing of genes [3, 4] is not sufficiently powerful to produce significant results, the pattern of homozygote deficiency is suggestive of avoidance of close matings. We have also investigated the effect of current nuclear family structure and family-size distribution.

Adolescent↗
PubMed1979

Fission models of population variability.

Most models in population genetics are models of allele frequency, making implicit or explicit assumptions of equilibrium or constant population size. In recent papers, we have attempted to develop more appropriate models for the analysis of rare variant data in South American Indian tribes; these are branching process models for the total number of replicates of a variant allele. The spatial distribution of a variant may convey information about its history and characteristics, and this paper extends previous models to take this factor into consideration. A model of fission into subdivisions is superimposed on the previous branching process, and variation between subdivisions is considered. The case where fission is nonrandom and the locations of like alleles are initially positively associated, as would happen were a tribal cluster or village to split on familial lines, is also analyzed. The statistics developed are applied to Yanomama Indian data on rare genetic variants. Due to insufficient time depth, no definitive new inferences can be drawn, but the analysis shows that this model provides results consistent with previous conclusions, and demonstrates the general type of question that may be answered by the approach taken here. In particular, striking confirmation of a higher-than-average growth rate, and hence smaller-than-previously-estimated age, is obtained for the Yan2 serum albumen variant.

Biological Evolution↗