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A Rodgers

Publications and source records attributed to A Rodgers.

At least 91 records · Page 5Linked to original sources
PubMed1987

Mechanisms of toxicity of 2- and 5-hydroxy-1,4-naphthoquinone; absence of a role for redox cycling in the toxicity of 2-hydroxy-1,4-naphthoquinone to isolated hepatocytes.

The mechanisms of toxicity to isolated rat hepatocytes of two structurally related naphthoquinones have been studied. Both 5-OH-1,4-naphthoquinone (5-OH-1,4-NQ; juglone) and 2-OH-1,4-naphthoquinone (2-OH-1,4-NQ; lawsone) caused a concentration-dependent cytotoxicity to hepatocytes which was preceded by a depletion of intracellular glutathione. 5-OH-1,4-NQ caused a depletion of intracellular glutathione when incubated either at 4 degrees C or 37 degrees C whereas 2-OH-1,4-NQ caused a depletion of intracellular glutathione when the hepatocytes were incubated at 37 degrees C but not at 4 degrees C. 5-OH-1,4-NQ but not 2-OH-1,4-NQ reacted with glutathione in buffered solution. These results suggested that the depletion of intracellular glutathione by 2-OH-1,4-NQ is enzyme mediated whereas in the case of 5-OH-1,4-NQ the direct chemical reaction with gluathione may be largely responsible for the depletion. A critical role for depletion of protein thiols in menadione-induced cytotoxicity has been proposed. In agreement with earlier work, menadione caused a decrease in protein sulphydryls prior to cell death, however, at cytotoxic concentrations of both 2-OH-1,4-NQ and 5-OH-1,4-NQ this decrease only accompanied rather than preceeded cell death. The mechanism of toxicity of 5-OH-1,4-NQ is similar to that of other naphthoquinones and involves formation of its corresponding naphthosemiquinone, active oxygen species and redox cycling as it stimulated a disproportionate increase in both microsomal NADPH oxidation and oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of time of dosing and age on intravenous aminophylline pharmacokinetics.

The elimination kinetics of theophylline were investigated following intravenous administration of aminophylline in 12 subjects (six fit young, and six healthy hospitalised elderly volunteers) at 09.00 h and 21.00 h on separate occasions at least 5 days apart to determine whether time of administration had significant effects on clearance in young and elderly subjects. We were unable to demonstrate a significant change in kinetic parameters between morning and evening administration in either young or elderly subjects. Our results also demonstrated no difference in kinetics between young and elderly subjects. We conclude that neither time of dosing nor age are important determinants of theophylline elimination kinetics in healthy subjects.

Adult↗
PubMed1986

Mechanisms of toxicity of naphthoquinones to isolated hepatocytes.

The possible mechanisms of naphthoquinone-induced toxicity to isolated hepatocytes were investigated using three structurally-related naphthoquinones, 1,4-naphthoquinone (1,4-NQ), 2-methyl-1,4-naphthoquinone (2-Me-1,4-NQ) and 2,3-dimethyl-1, 4-naphthoquinone (2,3-diMe-1,4-NQ). 1,4-NQ was more toxic than 2-Me-1,4-NQ whereas 2,3-diMe-1,4-NQ did not cause cell death at the solubility-limited concentrations used. All three naphthoquinones extensively depleted intracellular glutathione (GSH). However, the depletion of GSH induced by 1,4-NQ and 2-Me-1,4-NQ prior to cell death was more rapid and extensive than that induced by the nontoxic 2,3-diMe-1,4-NQ. Further studies demonstrated that 2,3-diMe-1,4-NQ was cytotoxic in the presence of dicoumarol, a compound which also potentiates the cytotoxicity of 1,4-NQ and 2-Me-1,4-NQ. To investigate the differential cytotoxicity of these three naphthoquinones, their relative capacities to redox cycle and to bind covalently to cellular nucleophiles were assessed. Redox cycling was investigated using rat liver microsomes where the order of potency for quinone-stimulated redox cycling was 1,4-NQ approximately 2-Me-1,4-NQ much greater than 2,3-diMe-1,4-NQ as indicated by nonstoichiometric amounts of NADPH oxidation and O2 consumption. NADPH-cytochrome P-450 reductase was implicated as the enzyme primarily responsible for naphthoquinone-stimulated redox cycling. The reactivity of the naphthoquinones with glutathione and, by implication, with other cellular nucleophiles was 1,4-NQ greater than 2-Me-1,4-NQ much greater than greater than 2,3-diMe-1,4-NQ. Overall, these studies indicate that 2,3-diMe-1,4-NQ is not cytotoxic (except in the presence of dicoumarol) and this lack of toxicity may be related either to its lesser capacity to redox cycle and/or its inability to react directly with cellular nucleophiles.

Animals↗
PubMed1986

Assessment of depression and diagnosis of depressive disorder among psychiatrically disturbed children.

This study examined the relations between performance on alternative measures of childhood depression and diagnosis of depressive disorder. Hospitalized inpatient children (N = 170, ages 7-13) with a diagnosis of depressive disorder (Research Diagnostic Criteria) were compared with a matched sample of patients whose diagnoses excluded depression. Children and parents completed four standardized depression scales plus measures designed to assess associated features including hopelessness, self-esteem, and internalizing symptoms. The results indicated that alternative depression measures, whether completed by children or parents, yielded scores that were significantly higher for children with a diagnosis of depression; parent ratings of severity of depression were consistently higher among the measures than the child ratings; optimal cutoff scores derived for each measure correctly classified approximately 60% of depressed and nondepressed cases; different cutoff scores were required for the same measure, depending on whether children or parents were the raters; and using a battery of measures and combining these in a stepwise discriminant function yielded over 80% classification accuracy. The implications of the results for selection of cases for clinical research are discussed.

Adolescent↗
PubMed1984

The effects of verbal and numerical quantifiers on questionnaire responses.

Three experiments are described which assess the effects of responding to different sets of verbal quantifiers (e g, always, often, sometimes). In Experiment 1, participants were asked to give percentage equivalents to three sets of supposedly equivalent quantifiers. The responses differed significantly. In Experiment 2, participants completed different versions of a questionnaire in order to see if the three sets of quantifiers produced equivalent responses in a more concrete situation. The results again showed that the three sets were not equivalent. In Experiment 3, participants completed one version of the questionnaire with a set of verbal quantifiers and two versions of the questionnaire with numerical quantifiers (e g, I do this about 75% of the time). The verbal quantifiers produced virtually the same results as before: the numerical quantifiers produced different but quite consistent results. It is concluded that numerical quantifiers are probably more useful than verbal ones, and should be used if possible.

Journal Article↗
PubMed1981

Human stones.

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Adolescent↗
PubMed1979

Detection of small amounts of human DNA in human-rodent hybrids.

A method of measuring semi-quantitatively small amounts of human DNA in irradiated human x mouse and irradiated human x Chinese-hamster somatic cell hybrids is described. One method uses molecular hybridization of cell DNA bound to nitrocellulose filters with a cRNA probe to Cot 0--1 human DNA. Alternatively hybrid cell DNA is reassociated in solution with a Cot 0--1 fraction of nick-translated human DNA. Formamide buffers give specificity to the reaction. The detection limit of the filter method is 0.2--0.5% equivalents and reassociation kinetics 0.005--0.1% equivalents of a human genome. Experiments with cell hybrids suggest that a fragment of repetitive DNA may be retained along with the selected genes after a cell fusion. In one case however, of a hybrid cell in which malignancy is suppressed, highly repetitious sequences were not found.

Animals↗
PubMed1966

Magnesium ions and the structure of Escherichia coli ribosomal ribonucleic acid.

1. The effect of removing Mg(2+) from a purified high-molecular-weight (1.07x10(6)) fraction of Escherichia coli ribosomal RNA was examined by ultracentrifugation, thermal denaturation and optical rotation. 2. At moderate I (0.1m-sodium chloride), EDTA at 2-50mm has little effect on RNA; at low I, 0.01-0.04 (with tris as counter-ion), two boundaries appear. 3. The leading boundary, S(20,w) about 20s, is identified with the original material with counter-ion Mg(2+) (;ionic atmosphere') removed, leading to an expanded form. 4. The slow boundary, 15-16s, is associated with a further loss of Mg(2+) and a further expansion, sensitive to EDTA concentration: it is proposed that this Mg(2+) is localized on the polynucleotide chain, i.e. ;site-bound'. 5. I is important and the EDTA effect at low I is reversible if Na(+) is added immediately after the EDTA: this Na(+) reversibility is lost on standing at 0 degrees . It is suggested that changes in the tertiary structure may be associated with this loss of reversibility. 6. Thermal-denaturation studies show that there is no loss of secondary structure associated with these changes: change in the optical-rotatory-dispersion spectrum in the region of the Cotton effect may be associated with this change in tertiary structure.

Chemical Phenomena↗