Search PubMed⌕ Search

Biomedical subjects

R L Hancock

Publications and source records attributed to R L Hancock.

At least 19 recordsLinked to original sources
PubMed1992

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XXVII. Intermediate generalizations (Part B).

In this second section of generalizations, methylation, differentiation and carcinogenesis are reviewed. Special consideration is given to the alpha-fetoprotein gene which is used extensively as a model embryonic gene. Specific correlations are made between the glucocorticoid response element and the alpha-fetoprotein gene. A further correlation was made between retinoic acid and alpha-fetoprotein synthesis.

Animals↗
PubMed1992

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XXVIII. Intermediate generalizations (Part C).

This is the final section of an intermediate phase of generalizations dealing with aspects of enhancers. It is concluded that a binding type protein(s) complex near a LTR segment. This creates destabilization of heterochromatin that allows transcription mechanisms. If this process is promoted by anomalous enhancer activity such as those produced by chemical inducers which modify chromatin states or cause hypomethylated enhancer regions, then normally repressed embryonic gene products, such as protooncogene growth factors, can be transcribed inappropriately to a specific developmental stage, eg post-embryonically.

Animals↗
PubMed1992

Derivation of a basic mechanism of control for embryonic genes as a specific subset.

The alpha-fetoprotein gene is conceived as being methylated in the zygote and according to the model is in a heterochromatic state and is therefore in a non-functional condition. Specific DNA methylase genes would produce methylases capable of alkylating enhancer regions of alpha-fetoprotein and certain proteins that would alter the heterochromatin condition. Also involved is a gene for the synthesis of a conformational-inducer protein that is proposed to be capable of blocking genic regions from reheterochromatizing. One of the pivotal events is the accumulation of S-adenosyl-L-methionine that reaches intracellular pool concentrations allowing other redundant active S-adenosyltransferase genes to become active. During embryogenesis specific conformational-inducer proteins would block genes such as the gene for albumin from reheterochromatizing while alpha-fetoprotein gene becomes heterochromatized during subsequent cell cycles. This heterochromatin is formed with embryonic type proteins sensitive to ribosylation-induced conformational changes. The increase in synthesis of alpha-fetoprotein followed by a decrease as albumin synthesis increases during embryogenesis is predicted by the scheme.

Animals↗
PubMed1992

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XXVI. Evolutionary significance of carcinogen-induced embryonic gene activity.

Besides the major theme of this series of writings--that chemically derepressed embryonic genes are fundamental to the mechanisms of carcinogenesis, there appear to be other significant aspects to this process. Yeast cells have the ability to differentially respond to carcinogens and non-carcinogens by the activation of embryonic type genes that are also found in mammals. This strange relationship is interpreted here as being due to certain phylogetically conserved genes from yeasts existing also in mammals that are used in both organisms for the same process. For example, a protooncogene found in yeast cells or embryonic cells serves for rapid mitosis. Also yeast mating type genes have high homologies to homeotic domains and therefore may be prototype genes of homeotic genes, which are embryonic type genes in animals.

Biological Evolution↗
PubMed1992

Generalizing the control process for embryonic genes.

Embryonic genes are considered as a separate subset of genes with unique chromatin properties. There is a problem of defining the duration of perturbations of embryonic gene activity that has been chemically induced and the normal relatively longer lasting changes that occur during differentiation. This problem may be related to unique properties of the chromatin of embryonic genes. Methylation of DNA is thought to be only one level of control and the superstructure of chromatin involving heterochromatin is of equal importance to embryonic gene expression. Proto-oncogenes are considered to be embryonic type genes whose activities are regulated under the same mechanisms by which other embryonic genes are regulated. Control aspects are discussed in the light of i) repressor-derepressor and blocking-deblocking mechanisms, ii) activator genes, pseudogenes, LINES, SINES, v-type position effects, iii) effects of ethionine, and iv) steroid hormone effects especially with respect to a subset of repeated rRNA genes which are considered to be structured in embryonic type chromatin.

Animals↗
PubMed1992

Maintenance of embryonic gene activity into the adult state.

It is now apparent that certain embryonic gene activities may be maintained before the transition from embryonic to the adult state takes place. The consequence of such a condition could have far reaching results and create a totally new approach to biotechnology by dealing with epigenetic methods and not gene-splicing methods. For example, if a group of c-oncogenes, believed to be of the embryonic type (1) that are responsible for growth factors which regulate embryonic rates of growth, then large increases in growth rates during the adult stage should occur. Two major alterations seem to be required. One is the interference of DNA methylation patterns using such agents as ethionine (interfering with S-adenoysl-1-methionine synthesis) or azacytidine (interfering with DNA methylase activity). Secondly, a change in chromatin configuration (deheterochromatization?) with agents such as n-butyrate or hexamethylenebisacetamide (HMBA). Maintenance methylases would make the altered (hypomethylated) pattern of the perturbed chromatin invariant after the initial perturbation. Enhancer-promoter mechanics are probably pertinent to this process.

Animals↗
PubMed1991

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: intermediate generalizations.

A previous rendition of a mechanism for the induction of embryonic gene activity, derived from the viewpoint of agents capable of such inductions, concluded that a perturbed methylation pattern of DNA and/or chromatin proteins would be an essential feature. A more specific treatment of the mechanism centers on enhancer regions of proto-oncogenes as being the point of modification for any induction of new gene activity. DNA binding type proteins may be involved with deheterochromatization processes after complexing near long terminal repeat segments containing enhancer elements. Chemical carcinogens and steroids would modify the chromatin and directly or indirectly interfere with maintenance DNA methylation. The resulting hypomethylated enhancer and promoter regions would allow for enhancer mechanisms to activate repressed embryonic genes inappropriate to the developmental stage forcing embryonic features to be expressed by differentiating (or differentiated) cells.

Animals↗
PubMed1991

Hereditary and environmental influences on blood pressure values of premenopausal women and their college-age daughters.

Blood pressure (BP) and environmental (dietary/lifestyle) variables were measured in 62 healthy normotensive pairs of premenopausal mothers (44.3 years) and their college-age consanguineous daughters (18.7 years) to estimate the relative contributions of genetic vs environmental factors on BP. As expected, the mothers had significantly higher systolic (SBP) and diastolic (DBP) blood pressures than the daughters (p less than 0.004 and 0.012, respectively). Among the dietary/lifestyle variables measured, mothers were found to have significantly higher mean weight and body mass index (BMI) (p less than 0.009 and 0.001, respectively), and significantly lower lean body mass (LBM) and calcium intake than their daughters (p less than 0.003 and 0.037, respectively). Significant correlations were found between mean BP of the mothers and their mean weight and BMI. No significant correlations existed for the daughters. The familial resemblances between BP of the mothers and daughters were relatively low, i.e., 0.14 for SBP and 0.19 for DBP. From these findings we conclude that the higher BP values with increased age among this healthy female population primarily result from an increase in BMI and a shift from lean to fat mass, as measured by midarm circumference. Our results suggest that environmental factors, i.e., excessive energy intake over time, accompanied by decreased physical activity, are primarily responsible for the greater indices of body fat and the higher BPs observed in this sample of healthy premenopausal women.

Adipose Tissue↗
PubMed1979

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: IV. The viruses.

Speculations are developed for a mechanism by which oncogenic viruses can induce alterations in cells allowing them to express embryonic genes. It is suggested that if viral deoxyribonucleic acid, directly or via ribonucleic acid directed deoxyribonucleic acid polymerase activity becomes inserted at particular euchromatin - heterochromatin junctions of quasidifferentiated stem-like cells, then deheterochromatization may result, causing in turn derepression of genes for acidic protein phosphokinases. This sets into motion a series of events including altered acid protein repressors of embryonic genes which are repressed by uniquely weak type repressors. This explains how viruses can act as specific embryonic gene-inducing agents similar to chemical inducing agents such as the hepatocarcinogen ethinine.

Adult↗
PubMed1979

Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins. V. The steroids.

Since the induction of neoplastic cells by steroids has been well documented, an attempt is made to formulate a mechanism for explaining the resultant embryonic features of such tumour cells. Special emphasis is given to estrogen receptor complexes and their effect on chromatin proteins. Specifically a mechanism is presented for estradiol-17-beta and its ability to alter the gene expression (derepression) of mammary gland epithelial cells. In this model we explore the possible effects of small differences in receptor or repressor proteins associated with estrogens to translate quantitative steroid administration into qualitative cellular responses.

Animals↗
PubMed1978

Heterologous radioimmunossay of monkey alpha-fetoprotein.

Immunoelectrophoresis showed that rabbit anti-human alpha-fetoprotein (AFP) cross-reacts with monkey AFP which was not detectable in the serum from an adult non-pregnant monkey. A heterologous radioimmunoassay of monkey AFP was developed using this antiserum which circumvented the need for purified monkey AFP. The radioimmunoassay is of sufficient sensitivity to measure AFP in maternal and fetal serum and amniotic fluid in the rhesus monkey.

Amniotic Fluid↗
PubMed1978

Hepatocarcinogen-induced tRNA methylase activity in rat liver.

Dimethylaminoazobenzene, carbon tetrachloride, and ethionine, which can induce cancer cells in rat liver, were found to increase rat liver tRNA methylase activity. Other chemicals (aminoazobenzene, acetylaminofluorene, alpha-naphthylisothiocyanate, beta-naphthylisothiocyanate, dimethyl and diethylnitrosamine, and methylcholanthrene), which may be hepatotoxic or carcinogenic, produced either no increase or only slight increases in liver tRNA methylase activity of rat liver tissue. Although no increase was observed with the powerful hepatocarcinogen aflatoxin, others have recently reported an increase in tRNA methylase activity using larger doses than those reported here. Ethionine was able to increase liver tRNA methylase activity in guinea pigs as well as rats, as previously described, but not in chicks.

Animals↗
PubMed1976

Maternal serum alpha-fetoprotein in normal pregnancy.

Serial measurements of alpha-fetoprotein (AFP) were made in 63 normal pregnancies throughout gestation using a radioimmunoassay. Significant levels of AFP, which were detected as early as at 10 weeks gestation, showed a gradual rise until 32 weeks, after which the levels declined until term. The limits of the normal gestational pattern have been defined and the intrapatient variability of the assay was examined. A comparison of the clinical characteristics of the pregnancies with levels of AFP was made. Higher birth weights were correlated with later attainment of peak levels of AFP and peak levels were achieved earlier in gestation in female fetuses. Higher levels of AFP and lower oestriol/AFP ratios were correlated with an earlier onset of labour.

Birth Weight↗
PubMed1976

Rat alpha-fetoprotein: isolation, radioimmunoassay and fetal-maternal distribution during pregnancy.

A method is described for the isolation of mg quantities of two forms of rat alpha-fetoprotein (AFP) from amniotic fluid by preparative disc-gel column electrophoresis using a continuous elution system. AFP isolated by this method is suitable for use as an antigen, can be labelled for use in a radioimmunoassay and serves as a reference standard. The characteristics of a new antiserum to AFP are also described. The protocol for a radioimmunoassay is outlined which permits the measurement of AFP in several fetal-maternal physiological compartments throughout gestation. Levels of AFP in fetal liver and fetal plasma suggest that secretion of AFP from liver occurs soon after synthesis with minimal hepatic storage. The pattern for AFP in maternal serum parallels that observed in amniotic fluid and fluctuations in maternal serum levels of AFP appear to be buffered by AFP accumulation in amniotic fluid. Fetal clearance of AFP under normal conditions may be relatively constant from Days 11-20 of gestation since an amniotic fluid: maternal serum AFP ratio of 30:1 is maintained during this period.

Amniotic Fluid↗
PubMed1976

Rat alpha-fetoprotein in experimental utero-placental ischaemia.

Retardation of growth and death of fetal rats were produced after uteroplacental ischaemia was induced by surgical ligation of the uterine arteries. Changes in maternal plasma levels of alpha-fetoprotein (AFP) were measured by radioimmunoassay. In rats in which the uterine blood supply was totally occluded, the resultant increase in maternal plasma AFP was due to resorption of fetal elements, because AFP levels in maternal rat plasma did not increase following hysterectomy in a control group. Maternal plasma AFP levels in rats with a partly occluded blood supply (and therefore some dead and some live fetuses) paralleled those of sham-operated rats, suggesting that increased placental transfer of AFP to maternal plasma may have offset the anticipated decline of AFP due to a decreased number of live fetuses.

Animals↗
PubMed1976

Effect of the hepatocarcinogen ethionine on hepatic messenger RNA synthesis.

An experiment was conducted to determine if any changes resulted in the proportion of hepatic messenger RNA following treatment with ethionine, a hepatocarcinogen. The relative specific activity of the total RNA isolated from nontumor-like tissues was increased in Sprague-Dawley rats fed ethionine. However, the percentage of total RNA that was message was found to be decreased in the ethionine-treated rats.

Animals↗