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Biomedical subjects

G Moore

Publications and source records attributed to G Moore.

At least 145 records · Page 8Linked to original sources
PubMed1987

Enhancer-mediated activation of a growth-regulated promoter.

We have demonstrated that the collagen alpha 2 type 1 promoter inserted in an expression vector, behaves as a growth-regulated promoter, which is consistent with previous observations that collagen synthesis is growth-regulated in vivo. In contrast, the activity of the H2-K or the simian virus 40 early promoters does not seem to be affected by the rate of cell proliferation. The insertion of a polyoma enhancer 5' or 3' to the collagen transcription unit activates the collagen alpha 2 type 1 promoter, by a threefold greater factor in slowly growing cells compared to cells growing exponentially. These results show that enhancers can also function in slowly proliferating cells and activate the normally low activity of a promoter in these cells.

Animals↗
PubMed1987

Localization of the oncogene c-erbA2 to human chromosome 3.

The human c-erbA1 gene has been previously mapped to chromosome 17. We have now mapped c-erbA2 to the short arm of chromosome 3, using a human genomic probe in Southern analysis of DNA from a panel of human/mouse somatic cell hybrids. In situ hybridization using the same probe on metaphase chromosomes has enabled fine chromosome mapping of c-erbA2 to the chromosome region 3p21-pter.

Animals↗
PubMed1987

Thermogenin amount and activity in hamster brown fat mitochondria: effect of cold acclimation.

To investigate the acclimation process in a hibernator, four different parameters of thermogenin amount and activity were investigated in brown adipose tissue mitochondria from cold-exposed and cold-acclimated Syrian hamsters. Hamsters, which are hibernators, have been considered to be "primed" for thermogenesis and thus not to show cold-acclimation effects, but here a significant increase in [3H]GDP-binding capacity was observed (from 0.5 nmol in control to 0.9 nmol GDP/mg in cold-acclimated hamsters), and this increase was paralleled by an increase in thermogenin antigen amount, as measured in an enzyme-linked immunosorbent assay. The transient nature of the effect of cold exposure on [3H]GDP binding, characteristically observed with rat mitochondria, was not observed with hamster mitochondria, and the increase in [3H]GDP binding occurred without a change in the dissociation constant (0.7 microM). The increase in thermogenin amount was paralleled by an increase both in GDP-sensitive Cl- permeability of the mitochondria and in GDP-sensitive respiration. It was established that it is the maximal activity of thermogenin that is rate limiting for thermogenesis in isolated mitochondria, provided that an optimal substrate is used (such as palmitoyl carnitine). Cold acclimation also increased the total amount of mitochondria in the tissue, leading totally to a sixfold increase in thermogenin content of the hamster. It is concluded that (contrary to the general view) hamsters show the expected physiological, pharmacological, and biochemical signs of cold acclimation (i.e., an increased capacity for nonshivering thermogenesis).

Acclimatization↗
PubMed1986

Studies on the expression of an H-2K/human growth hormone fusion gene in giant transgenic mice.

Transgenic mice carrying the H-2K/human growth hormone (hGH) fusion gene were produced by microinjecting into the pronucleus of fertilized eggs DNA molecules containing 2 kb of the 5' flanking sequences (including promoter) of the class I H-2Kb gene joined to the coding sequences of the hGH gene. Thirteen transgenic mice were obtained which all contained detectable levels of hGH hormone in their blood. Nine grew larger than their control litter-mates. Endogenous H-2Kb and exogenous hGH mRNA levels were analysed by S1 nuclease digestion experiments. hGH transcripts were found in all the tissues examined and the pattern of expression paralleled that of endogenous H-2K gene expression, being high in liver and lymphoid organs and low in muscle and brain. Thus 2 kb of the 5' promoter/regulatory region of the H-2K gene are sufficient to ensure regulated expression of hGH in transgenic mice. This promoter may therefore be of use to target the expression of different exogenous genes in most tissues of transgenic mice and to study the biological role of the corresponding proteins in different cellular environments.

Animals↗
PubMed1986

Vagal body tumors: diagnosis and treatment.

This presentation includes a report of four vagal body tumors bringing the total number in the English literature to approximately 80. The diagnosis and treatment of this lesion, its familial incidence and the propensity for multiple secreting or nonsecreting chemodectomas, and appropriate clinical and pathologic studies required will be reviewed in some detail. Appropriate differential diagnostic features will be illustrated by comparison of these tumors with other primary vagal tumors from our experience such as neurofibromas, neurilemmomas, and cystic degeneration of neurilemmomas.

Adult↗
PubMed1985

The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+.

The effects of acetaminophen and its major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), have been investigated in hepatocytes isolated from 3-methylcholanthrene-pretreated and -untreated rats, respectively. The two compounds produced qualitatively similar changes although the quinone imine was toxic with shorter incubations periods and at lower doses. Both agents caused an elevation of cytosolic Ca2+, assessed by phosphorylase a activity, which was accompanied by the concomitant appearance of plasma membrane blebs. A loss of mitochondrial Ca2+ was also observed. This disruption of Ca2+ homeostasis always preceded cell death. Studies with NAPQI showed that low doses were able to cause complete Ca2+ release from isolated liver mitochondria which was accompanied by pyridine nucleotide oxidation and preceded membrane damage. NAPQI also produced a rapid, dose-dependent depletion of both cytosolic and mitochondrial reduced glutathione as well as a loss of protein-bound SH groups. This loss of protein thiols may have been responsible for the observed inhibition of the high-affinity Ca2+-ATPase activity of the plasma membrane fraction isolated from NAPQI-treated cells. In addition, NAPQI inhibited microsomal Ca2+ uptake which would further contribute to the elevation in cytosolic Ca2+. Our results suggest that acetaminophen and N-acetyl-p-benzoquinone imine exert their cytotoxic effects via a disruption of Ca2+ homeostasis secondary to the depletion of soluble and protein-bound thiols. This mechanism may prove to be of general applicability to a variety of hepatotoxins.

Acetaminophen↗
PubMed1985

[3H]Nicotine binding sites in developing fetal brains in rats.

[3H]Nicotine binding sites were examined in developing fetal brains in rats. The fetal brain membranes bound [3H]nicotine with a similar affinity to that of adult brain membranes. This binding was displaced by unlabelled nicotine or carbamylcholine, the inhibition concentrations being approximately the same for fetal and adult brain preparations. alpha-Bungarotoxin had no effect on [3H]nicotine binding to fetal brain membranes as well as to adult brain preparations. The specific [3H]nicotine binding was first detectable on day 16 of gestation and it increased several folds until birth.

Aging↗
PubMed1985

A thermodynamic treatment of passive monitors.

Previous mathematical descriptions of sampling using passive monitors have used Fick's First Law of diffusion and the assumption that the concentration of adsorbate in the vapor phase above the sorbent is zero. This paper shows that by introducing a simplified expression for the equilibrium vapor pressure, behavior more nearly resembling that observed for passive monitors is predicted. The theory can also be applied to the case of loss of sample from a diffusive monitor. Experimental evidence is also provided which demonstrates that the theory adequately describes the observed results.

Air Pollutants↗
PubMed1984

Regulation of protein synthesis in lymphoblastoid cells during inhibition of cell proliferation by human interferons.

Treatment of human lymphoblastoid (Daudi) cells with interferons inhibits cell proliferation in culture within 24 h. The failure of cell growth has been shown to be associated with impaired processing and decreased stability of newly replicated DNA. Because there is a close relationship between DNA replication and protein synthesis we have measured protein synthesis in intact Daudi cells. Protein synthesis declined steadily between 24 and 96 h after interferon treatment to a value which is only 20-30% of the rate in control cells. The enzyme 2',5'-oligo(A) synthetase is induced but our data do not support a role for the 2',5'-oligo(A)-activated ribonuclease in the control of translation in this system.

2',5'-Oligoadenylate Synthetase↗
PubMed1984

Inhibition of cell proliferation by interferons. 1. Effects on cell division and DNA synthesis in human lymphoblastoid (Daudi) cells.

Treatment of Daudi cells with human lymphoblastoid interferons for up to 5 days progressively inhibits cell proliferation. For the first 3 days cells continue to grow but with prolonged doubling times; subsequently, net proliferation ceases and is accompanied by a loss of cell viability. We have investigated the changes in labelling of DNA with radioactive precursors which occur during the first phase of the response to interferon treatment. We have shown previously [Gewert et al. (1981) Eur. J. Biochem. 116, 487-492] that inhibition of incorporation of [3H]thymidine into DNA can be accounted for by impairment of thymidine transport and thymidine kinase activity. In spite of this inhibition, the total intracellular dTTP pool is larger in interferon-treated than in control cells. Because of these changes it has been necessary to use other methods to determine whether interferon treatment inhibits the overall rate of DNA synthesis. The results of experiments employing (a) moderately high thymidine concentrations or (b) incorporation of radioactivity from deoxynucleoside triphosphates into DNA in detergent-lysed or permeabilised cell systems indicate that there is in fact relatively little inhibition of the overall rate of DNA synthesis in cells exposed to up to 100 units/ml of interferons for at least 48 h. Furthermore, a similar proportion of cells incorporate [3H]thymidine in control and interferon-treated cultures and there is only a small decrease in the number of cells in S phase after interferon treatment, as revealed by fluorescence-activated cell sorting. These results indicate that cell proliferation may be regulated in this system by a mechanism in which there is a loss of coordination between the initiation of DNA synthesis and the subsequent events required for cell division.

Biological Transport↗
PubMed1984

Inhibition of cell proliferation by interferons. 2. Changes in processing and stability of newly synthesized DNA in human lymphoblastoid (Daudi) cells.

The inhibition of proliferation of Daudi cells in culture by human interferons is characterized by a change in the kinetics of labelling of different size classes of newly synthesized DNA. Initially, labelled precursors are incorporated exclusively into small DNA (Okazaki fragments) in both control and interferon-treated cells, as revealed by alkaline sucrose gradient centrifugation. In the interferon-treated cells, there is enhanced labelling of this small DNA after short periods of incorporation and slower conversion to larger DNA size classes, in comparison with the DNA of control cells. This effect is apparent after 12 h of interferon treatment, coincident with the onset of the inhibition of cell proliferation. It becomes progressively more marked up to 4 days, by which time cell growth has ceased completely. Experiments using bromodeoxyuridine as a density label and analysis of radioactive DNA on caesium chloride/caesium sulphate gradients also reveal that some newly replicated DNA may be unstable and may turn over within a few hours of its synthesis. The label derived from DNA breakdown is efficiently reincorporated into newly synthesized molecules. It is suggested that interferon treatment inhibits DNA replication by activating DNA turnover rather than by directly inhibiting synthesis. This effect, together with the progressive retardation of conversion of Okazaki fragments to larger DNA, may lead to the eventual failure of cell proliferation.

Bromodeoxyuridine↗
PubMed1984

The effect of treatment on zinc, copper and calcium status in children with phenylketonuria.

The trace element status of 25 children receiving a low phenylalanine diet for a treatment of phenylketonuria was studied using hair and serum samples. Hair trace element and calcium concentrations were assayed using X-ray microanalysis and compared with samples from sibling controls. Plasma, zinc and copper levels were compared with unselected hospital attenders. PKU patients were found to have significantly lower hair zinc (P less than 0.001) and calcium (P less than 0.01) concentrations and significantly hair copper (P less than 0.001) concentrations compared with controls. Plasma zinc levels were below the lower limit of normal (9.6 mumol l-1) in 8 of 19 patients (42%) in whom it was measured. The relative zinc deficiency in PKU patients may result from a competitive inhibition of absorption by copper or other metals supplemented in the diet.

Adolescent↗