PubMed Health⌕ Search

Biomedical subjects

B Goodwin

Publications and source records attributed to B Goodwin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Interferon gamma down-regulates cytochrome P450 3A genes in primary cultures of well-differentiated rat hepatocytes.

Administration of interferons of both the gamma and alfa/beta classes down-regulates hepatic cytochrome P450 (CYP) genes when administered to humans or rats. In male rats, interferons decrease expression of CYP3A2 at a pretranslational level, but because interferons also release other cytokines in vivo, it is unclear whether this is a direct effect on hepatocytes. We therefore examined the effects of rat recombinant interferon gamma (IFN-gamma) on CYP3A2, other 3A genes, and 2C11 in stable primary cultures of male rat hepatocytes. Hepatocytes were cultured on matrigel in Williams' E, and messenger RNAs (mRNAs) for 3A2, 3A1-like CYPs, and 2C11 mRNA were determined by RNase protection assays. CYP3A and 2C11 proteins were immunoquantified, and their catalytic activities were estimated by testosterone hydroxylation pathways. In control cells, 3A2 mRNA decreased initially but then recovered, and stable levels (15% of freshly isolated cells) were attained between days 3 and 7. Phenobarbital increased 3A2 mRNA to 60-120% values of freshly isolated cells, and mRNA for 3A1-like CYPs were increased 20-fold. In both control and phenobarbital-treated hepatocytes, rat recombinant IFN-gamma (33 U/mL) reduced mRNA for 3A2 and 3A1-like CYPs, as well as 3A protein and testosterone 6 beta-hydroxylase activity. Interferon had no effect on CYP2C11 at mRNA or protein levels in untreated cells, although a reduction in 2C11 protein was evident in phenobarbital-treated cultures. It is concluded that interferon directly alters expression of constitutive and inducible CYP3A genes in well-differentiated male rat hepatocytes in culture, but has no effect on constitutive expression of CYP2C11.

Animals↗
PubMed1992

Inhibitory potency of some isatin analogues on human monoamine oxidase A and B.

Isatin is an endogenous compound which acts as a selective inhibitor of monoamine oxidase (MAO) B. In this study a range of isatin analogues were tested for their in vitro inhibition of human MAO A and B. Most of the analogues were less potent than isatin. Hydroxylation of the aromatic ring changed the inhibitory potency in favour of MAO A, with 5-hydroxyisatin being a potent and selective MAO A inhibitor (IC50 8 microM). Isatinic acid, which is formed reversibly from isatin at alkaline pH, showed no inhibition.

Blood Platelets↗
PubMed1991

Computing. Guardians or gizmos.

Carefully planned security management strategies are as important as the latest gadgets for ensuring patient details stay confidential, says Barry Barber, while Bill Goodwin examines the case for a risk analysis and management package.

Computer Security↗
PubMed1991

Investigation of the chemical basis of nitroalkane toxicity: tautomerism and decomposition of propane 1- and 2-nitronate under physiological conditions.

Unlike primary nitroalkanes, such as 1-nitropropane, the secondary nitroalkane 2-nitropropane is geno- and hepatotoxic. Nitroalkanes exist in equilibrium with alkane nitronates. In order to investigate the relationship between nitroalkane toxicity and generation and stability of nitronates, propane 1- or 2-nitronate (4-6 mM) were incubated in buffer (pH 3.8 -7.4) in the absence or presence of cysteine. Equilibrium formation and degradation were studied by 1H-NMR spectroscopy and ion pair HPLC chromatography. Propane 1-nitronate generated 1-nitropropane rapidly and almost quantitatively. In the case of propane 2-nitronate equilibrium at pH 7.4 was reached within 8 h, when 48% of initial nitronate had tautomerised to 2-nitropropane. The pKa of the reaction 2-nitropropane less than--greater than propane 2-nitronate measured by HPLC was 7.63. Equilibrium formation, hydrolysis and reduction of nitronates were pH-dependent and, in the case of propane 2-nitronate, yielded mainly acetone, nitrite and acetone oxime, apart from 2-nitropropane. Hydrolysis of propane 2-nitronate (4 mM) to nitrite was modulated by cysteine (4 mM) and p-methoxyphenol (0.4 mM). At pH 7.4 they increased nitrite generation by 300 and 28%, respectively, at pH 4.8 they decreased nitrite formation by 91 and 82%, respectively, probably by scavenging radical intermediates. Differences between nitroalkanes in terms of content of nitronate tautomer at equilibrium are probably an important chemical determinant of their toxic potential.

Animals↗
PubMed1991

Oxidative denitrification of 2-nitropropane and propane-2-nitronate by mouse liver microsomes: lack of correlation with hepatocytotoxic potential.

2-Nitropropane (2-NP) is an industrial chemical with hepatotoxic and genotoxic properties. It exists in chemical equilibrium with propane-2-nitronate, which is much more genotoxic than 2-NP. In this work the link between toxicity and metabolism of 2-NP and its nitronate was investigated. To that end 2-NP or propane-2-nitronate were incubated with murine hepatic microsomes at concentrations of up to 10 mM, and generation of nitrite was measured as product of metabolic oxidation of the two species. Under the acidic reaction conditions of the colorimetric nitrite assay propane-2-nitronate decomposed chemically to nitrite. Therefore an ion-pair HPLC assay at neutral pH was developed which enabled determination of nitrite formed from the nitronate. The rate of metabolic nitrite generation from propane-2-nitronate was 5-10-fold that obtained with 2-NP. Metabolism of either species to nitrite was dependent on the presence in the incubate of viable microsomes and of NADPH, and it was inhibited in the presence of carbon monoxide or the cytochrome P-450 inhibitor SKF525A. Acetone could also be measured as a metabolite of 2-NP. Optical difference spectra were recorded in mixtures of propane-2-nitronate with liver microsomes from phenobarbital-pretreated rats. The spectral dissociation constant was found to be 30 mM, which compares with 10 mM reported for 2-NP. 2-NP and propane 2-nitronate were incubated with mouse hepatocytes in suspension and cytotoxicity was determined by measurement of leakage of cellular lactate dehydrogenase into the medium. Both species were hardly toxic, as concentrations of 20 mM were required to elicit significant damage to the cells. The results demonstrate that propane-2-nitronate, like 2-NP, undergoes microsomal oxidative denitrification, probably catalysed by cytochrome P-450. Metabolism of both species occurs at markedly different rates, but the difference in metabolism is not reflected by a difference in hepatocytotoxic potential.

Animals↗
PubMed1986

A randomized trial of low doses of alpha interferon in patients with breast cancer.

A randomized Phase II study was planned to test two doses of human lymphoblastoid interferon (Wellferon) in patients with metastatic breast cancer. Thirty-seven patients were entered and received either 0.5 or 3.0 million units three times a week for three months. The dose selection was based on earlier Phase I studies in order to maximize NK (natural killer) stimulation and the amount tolerated without undue toxicity. Twenty-nine patients were evaluable. There was only one excellent partial remission, sustained for one year. There were small and statistically insignificant NK increases in both groups. From this and a review of the literature, we conclude that alpha interferon has negligible activity in breast cancer.

Breast Neoplasms↗
PubMed1980

Mass spectrometer measurement of oxygen uptake and carbon dioxide exchange during cardiopulmonary bypass.

Oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured continuously in four children during cardiopulmonary bypass, using the variation in concentration of a tracer gas, argon, as a measure of flow, and a mass spectrometer to monitor gas concentrations. Normal values for the ratio of VCO2:VO2 (= 0.8) indicated that gas exchange equilibrium had been established following sudden changes in body temperature. During rapid cooling, 10% carbon dioxide is necessary to ensure carbon dioxide homeostasis within the body.

Body Temperature↗