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Biomedical subjects

A Wiseman

Publications and source records attributed to A Wiseman.

At least 55 records · Page 3Linked to original sources

Cytochrome P-450 and oxidative metabolism in molluscs.

1. Cytochrome P-450 and the associated components and oxidative activities of a mixed-function oxidase (MFO) system are localized primarily in the microsomes of the digestive gland of molluscs. 2. Cytochrome P-450 and putative cytochrome P-450-catalysed oxidative activities, measured in vitro and/or in vivo, have variously been detected in 23 species of mollusc. 3. Cytochrome P-450 and other MFO components and activities may be increased by exposure to xenobiotics, but the results are variable and no correlation is obvious between changes in cytochrome P-450 content and measured MFO activities (benzo[a]pyrene hydroxylase (BPH) and 7-ethoxycoumarin O-deethylase (ECOD)). 4. Type II binding compounds (clotrimazole, miconazole, ketoconazole, metyrapone and pyridine) give type II difference spectra with mussel digestive gland microsomal P-450, whereas type I binding compounds (testosterone, 7-ethoxycoumarin, alpha-naphthoflavone, SKF525-A) give apparent reverse type I difference spectra. 5. The existence of multiple or particular forms (P450 IVA or LAw) of cytochrome P-450 is indicated from enzyme kinetics and inhibition studies, seasonality, purification studies and cDNA probes. 6. Microsomal MFO activities are observed even in the absence of added or generated NADPH, and the NADPH-independent BPH, ECOD and N,N-dimethylaniline N-demethylase activities are inhibited by reducing agents, including NADPH. 7. The major metabolites of microsomal benzo[a]pyrene metabolism are quinones. 8. One-electron oxidation is considered to be one possible mechanism of molluscan cytochrome P-450 catalytic action.

Animals↗

Acute phase response in calves following infection with Pasteurella haemolytica, Ostertagia ostertagi and endotoxin administration.

The concentrations of bovine acute phase proteins were monitored in plasma following experimental infection with Pasteurella haemolytica and Ostertagia ostertagi and after endotoxin administration. Raised levels of haptoglobin, alpha 1 proteinase inhibitor and seromucoid were detected after pasteurella infection and endotoxin administration. Ceruloplasmin levels increased after endotoxin administration but not during pasteurella infection. Raised levels of the four acute phase proteins were found in eight of 19 calves infected with ostertagia but showed a variable pattern and did not correlate with plasma pepsinogen increases. Bovine alpha 1 antichymotrypsin and alpha 2 macroglobulin were identified as acute phase reactants.

Acute-Phase Proteins↗

Long-term prognosis after myocardial infarction in patients with previous coronary artery bypass surgery.

A group of 205 patients hospitalized with myocardial infarction 2 to 162 months (mean 66) after bypass surgery and 205 control patients with myocardial infarction were compared and followed up for 34 +/- 25 months after hospital discharge. At baseline the postbypass group contained more men (p less than 0.03) and more patients with previous myocardial infarction (p less than 0.06), but the groups were otherwise comparable. Indexes of infarct size were lower in postbypass patients: sum of ST elevation, QRS score, peak serum creatine kinase (CK) (1,115 +/- 994 versus 1,780 +/- 1,647 IU/liter) and peak MB CK (all p less than or equal to 0.001). Postmyocardial infarction ejection fraction was 45 +/- 15% in the postbypass group and 43 +/- 15% in the control group (p = NS); in-hospital mortality rate was 4 and 5%, respectively (p = NS). When patent grafts were taken into account, the two groups were comparable in extent of coronary artery disease. At 5 years after discharge, cumulative mortality was similar in the postbypass and control groups (30 versus 25%, respectively, p = NS). However, postbypass patients had more reinfarctions (40 versus 23%, p = 0.007), more admissions for unstable angina (23 versus 18%, p = 0.04) and more revascularization procedures (34 versus 20%, p = 0.04) than did control patients. The total for these events at 5 years was 70% in the postbypass group and 49% in the control group (p = 0.001). Thus, although patients with previous bypass surgery who develop acute myocardial infarction have a smaller infarct, their subsequent survival is no better than that of other patients with acute myocardial infarction. They experience more reinfarctions and unstable angina. Previous bypass surgery is an important clinical marker for recurrent cardiac events after myocardial infarction.

Angiography↗

Bovine acute phase response following turpentine injection.

The serum levels of five proteins, alpha 1 antitrypsin, ceruloplasmin, fibrinogen, haptoglobin and seromucoid, were measured daily in calves after the subcutaneous injection of oil of turpentine. Raised concentrations were detected on the second and third days after injection with peak levels occurring on the fourth to seventh days and returning to normal by the 17th day. Levels of four of these proteins, alpha 1 antitrypsin, ceruloplasmin, haptoglobin and seromucoid were compared in the same calves following three different doses of turpentine. Levels of haptoglobin and seromucoid varied with the dose whereas ceruloplasmin and alpha 1 antitrypsin levels did not.

Acute-Phase Proteins↗

Cytochrome P-450 accumulation and loss as controlled by growth phase of Saccharomyces cerevisiae: relationship to oxygen, glucose and ethanol concentrations.

Ethanol induced small amounts of cytochrome P-450 in Saccharomyces cerevisiae NCYC 754 under conditions in which it is not normally detectable. Moreover, in non-growing yeast the existing cytochrome P-450 content was increased by 50% at a limited range of glucose concentrations (8-12% in 0.1 M-potassium phosphate buffer, pH 7.0), in which ethanol is produced by fermentation, possibly at an optimum concentration for induction of cytochrome P-450. Added alkanols, other than ethanol, caused rapid degradation of cytochrome P-450 in non-growing yeast; the rate of loss was directly related to the lipid solubility of the alkanol. Ethanol therefore favoured the accumulation of cytochrome P-450 in yeast; this may be related to an important putative role of one of the isoenzymes in ethanol-tolerance of the yeast, by the oxidative removal of ethanol from the endoplasmic reticulum of the cell. It is the accumulation of dissolved oxygen, rather than ethanol, that occurs on cessation of yeast growth that is likely to trigger the rapid disappearance of cytochrome P-450 observed at this time.

Cytochrome P-450 Enzyme System↗

Pasteurella species isolated from the bovine respiratory tract and their antimicrobial sensitivity patterns.

Pasteurella haemolytica biotype A, serotype 1 (P haemolytica A1) was the most commonly isolated Pasteurella species from 80 calves examined at necropsy from 40 outbreaks of respiratory disease, the majority of which were pathologically confirmed as bovine pneumonic pasteurellosis (transit fever; shipping fever). Similarly, nasopharyngeal swabs from in-contact and apparently healthy calves indicated the widespread presence of P haemolytica A1. Pasteurella multocida and other serotypes of P haemolytica A1 were found including six isolations of P haemolytica T10, a fairly common pathogen in sheep. Approximately two-thirds of the isolates were tested for their antimicrobial sensitivity patterns and the degree of sensitivity for P haemolytica A1, the most frequently isolated serotype, was chloramphenicol (100 per cent), sulphamethoxazole trimethoprim (98 per cent), oxytetracycline (80 per cent), ampicillin (85 per cent), penicillin (82 per cent), streptomycin (3 per cent) and lincomycin (1 per cent).

Animals↗

Sequential lesions of experimental bovine pneumonic pasteurellosis.

A strain of Pasteurella haemolytica biotype A serotype 1, which had been isolated from a pathologically-confirmed outbreak of bovine pneumonic pasteurellosis, was used successfully to reproduce the disease in conventional calves. The development of the various pathological features was studied at regular intervals following infection. The acute inflammatory reaction which had developed by day 2 after initial infection was characterised by flooding of the alveoli by oedema and neutrophils together with a mild degree of bronchiolar epithelial necrosis. This progressed to an acute exudative fibrinous pneumonia with extensive involvement of the interlobular septa and often with pleurisy. Subsequently, these pulmonary lesions became walled off by fibrous tissue which became infiltrated by plasma cells and lymphocytes. At this stage organisms could be demonstrated only within these nodules in the lung tissue.

Animals↗

Differences in the cytochrome P-450 enzymes of sterol C-14 demethylase mutants of Saccharomyces cerevisiae.

A number of nystatin-resistant strains of S. cerevisiae have been isolated which are defective in lanosterol C-14 demethylation, a reaction normally catalysed by cytochrome P-450. In this paper two of these strains have been compared and found to have differences in their reduced-CO difference spectra indicating different distortions in the enzyme molecule. Nystatin resistance in the C-14 demethylation deficient SG1 in shown to be determined by a single gene, and a sterol 5,6-desaturase defect does not appear to be required for viability of SG1, was reported for the C-14 demethylase deficient isolate JR4 by Taylor et al. (1983). There are at least two discernable mutant phenotypes for the yeast cytochrome P-450 structural gene which give a C-14 demethylase defect.

Cytochrome P-450 Enzyme System↗

Human cell variants resistant to rhodamine 6G.

Two variants have been isolated from the cultured human cell line VA2-B which are resistant in vivo to the mitochondrial-specific fluorescent dyes rhodamine 6G and rhodamine 123. Both mutants are cross-resistant to ethidium bromide but are sensitive to both colchicine and chloramphenicol. When either mutant is treated with low levels of rhodamine 6G, mitochondrial-associated fluorescence is significantly lower than in wild-type cells. Furthermore, when cell cultures are treated with high concentrations of either rhodamine 123 or 6G, and then washed free of the dye, mitochondrial-associated rhodamine fluorescence rapidly diminishes in the parental cell line. In hybrid cell fusions between resistant and sensitive cell lines, rhodamine resistance is gradually expressed, reaching maximal expression approximately 11 days after fusion. Cytoplasmic transmission of rhodamine resistance has not been clearly demonstrated in cytoplast-cell fusions, and thus resistance is probably due to a mutation of a nuclear, rather than mitochondrial DNA gene(s). These observations indicate that mitochondria of both rhodamine-resistant variants, unlike wild type, have a significantly decreased ability to bind and retain rhodamine, and thus their mitochondrial tramsmembrane electrical potential may be significantly reduced.

Cell Division↗

Interaction between yeast cytochrome P-450 and chemical carcinogens.

The binding of various chemical carcinogens to the glucose-inducible form of cytochrome (cyt.) P-450 in Saccharomyces cerevisiae was examined with reference to known metabolism in mammalian systems. All the carcinogens examined gave spectral interactions with the yeast cytochrome. The carcinogens benzo[a]pyrene and cyclophosphamide gave Type I binding, while benzidine and 2-naphthylamine gave Type II binding spectra indicating binding at the haem group. Dimethylnitrosamine gave undetectable binding in yeast microsomal fractions, but a Type I binding spectrum was seen with purified cyt. P-450 preparations. The demonstration that these carcinogens bind to yeast cyt. P-450 is discussed in the light of their genotoxicity.

2-Naphthylamine↗