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Biomedical subjects

P J O'Brien

Publications and source records attributed to P J O'Brien.

At least 235 records · Page 13Linked to original sources
PubMed1985

Peroxidase catalysed oxygen activation by arylamine carcinogens and phenol.

Peroxidase catalysed the formation of active oxygen in the presence of NADH or GSH and traces of H2O2 and arylamine or phenolic substrates. Some oxygen activation occurred with some arylamines even in the absence of NADH or GSH. Oxygen consumption was proportional to the NADH oxidized or GSSG formed. Approximately 0.80 and 0.40 mol of oxygen were consumed per mole of NADH or GSH oxidized respectively. The requirement for trace amounts of hydrogen peroxide and arylamine or phenolic substrates suggest that redox cycling resulted in H2O2 formation. It is proposed that initially formed phenoxy radicals or arylamine cation radicals oxidize NADH or GSH to radicals which react with oxygen to form superoxide radicals and H2O2.

Amines↗
PubMed1985

Effects of ingestion of hibernia and Prudhoe Bay crude oils on hepatic and renal mixed function oxidase in nestling herring gulls (Larus argentatus).

Oral administration of Prudhoe Bay crude or Hibernia crude to nestling herring gulls increased the hepatic cytochrome P-450 content 4-fold. Concomitantly, there was an increase in various mixed-function oxidase and phase II enzyme activities. 7-Ethoxyresorufin O-deethylase was elevated 19-fold, benzo(a)pyrene 3-hydroxylase 6-fold, aniline hydroxylase 3-fold, and aminopyrine N-demethylase and uridine diphosphate glucuronyl transferase 2-fold. There was no change in reduced glutathione S-transferase activity. Renal mixed-function oxidase activities were also elevated. Herring gull livers contained very low levels of DT-diaphorase activity which was inducible 3- to 5-fold by oil administration.

Administration, Oral↗
PubMed1985

Biochemical and functional disturbances in red blood cells of herring gulls ingesting Prudhoe Bay crude oil.

Heinz body hemolytic anemia developed in Herring Gull (Larus argentatus) nestlings given oral doses of 10 ml of Prudhoe Bay crude oil per kilogram of body weight per day for 5 days. Associated disturbances in red blood cells were increased amounts of reduced glutathione (GSH), peroxidation of membrane lipids, an increase in membrane permeability, and a decrease in the oxygen-carrying capacity of cyanomethemoglobin-convertible hemoglobin. Among groups of gulls given different cumulative doses of oil over a 6-day period, significant covariance with dose and dependence on dose was demonstrated for packed cell volume, hemoglobin, and red cell GSH. Rapid defecation of oil by gulls indicated that the effective dose was substantially less than the administered dose. Pronounced damage to red cells occurred in some birds administered oil for only 2 days. These data imply that the toxic effects of ingested oil may contribute significantly to the morbidity and mortality of oil-contaminated birds.

Animals↗
PubMed1985

Peroxidase-catalyzed benzidine binding to DNA and other macromolecules.

[14C]Benzidine is rapidly oxidized by a peroxidase/H2O2 system to products which bind irreversibly to DNA. The presence of exogenous DNA also prevented benzidine polymerization to 'benzidine brown' and azobenzidine. Two molar equivalents of H2O2 were required to oxidize the benzidine and achieve maximal DNA binding. Furthermore, 95% of the benzidine was trapped and 36 nmol benzidine was bound per mg DNA. Polyriboguanylic acid was as effective as DNA in binding benzidine, but polyriboadenylic acid, polyribouridylic acid and polyribocytidylic acid were much less effective. Binding of [14C]benzidine correlated well with the absorbance at 295 nm and 390 nm of the modified DNA or various synthetic homopolymers of ribonucleotides isolated from the reaction mixture. The peroxidase/H2O2 system also catalyzed the binding of dichlorobenzidine, o-tolidine and o-dianisidine to DNA but 3,5,3',5'-tetramethylbenzidine, a non-carcinogen, did not bind. The binding could be prevented by various biological hydrogen donors, thiols, or phenolic antioxidants. The mechanisms for DNA protection were investigated; the oxidized benzidine species involved in binding can be reduced with ascorbate, NADPH, or thiols, and trapped by thiols or phenolic antioxidants to form conjugates or adducts.

Animals↗
PubMed1985

Free-radical-mediated DNA binding.

Free-radical metabolites can be generated metabolically by a one-electron reductase-catalyzed reaction or a "peroxidase" catalyzed oxidation or by photoactivation of a wide variety of aromatic xenobiotics. Radicals may also be generated during lipid peroxidation. Some radicals can react with DNA or bind covalently or noncovalently as a dismutation product or as a dimer, trimer or polymeric product. Modification to the DNA can result in single-strand breaks, loss of template activity, and crosslinking. The binding can prevent enzymic digestion. In some cases, the radicals react with oxygen, resulting before conversion to DNA reactive oxygen species. Most radicals probably do not interact with DNA.

Animals↗
PubMed1985

Peroxidase-catalysed binding of [U-14C]phenol to DNA.

14C-Phenol binds irreversibly to calf-thymus DNA in the presence of horseradish peroxidase and hydrogen peroxide, approximately 65% of the added phenol was bound to DNA. Binding was maximal at an equimolar concentration of hydrogen peroxide. Binding also occurred to homopolyribonucleotides polyadenylic acid, polyguanylic acid, polycytidylic acid and polyuridylic acid, and suggests that binding is relatively non-specific with respect to the nucleotide bases. p,p'-Biphenol, p,p'-biphenoquinone, o,o'-biphenol and two unidentified products were formed by the oxidation of phenol, in the presence and in absence of DNA. DNA accelerated phenol oxidation four fold and prevented the polymerization of oxidized phenol products, but was found to have no effect on the range of ethyl acetate-extractable products. Phenol accelerated the metabolism of o,o'-biphenol but had no effect on p,p'-biphenol metabolism. The mechanism of phenol activation is not clear, but p,p'-biphenoquinone binds to protein and not to DNA. DNA binding was prevented by glutathione, N-acetyl-cysteine and ascorbate, and the mechanism was shown to involve reduction of the activated phenol intermediates and the formation of conjugates with glutathione and N-acetyl-cysteine. DNA binding was not inhibited by lysine and proline.

Bone Marrow↗
PubMed1985

Phenol oxidation product(s), formed by a peroxidase reaction, that bind to DNA.

Phenol oxidation by horseradish peroxidase/H2O2 initially results in p,p'-biphenol and o.o'-biphenol formation and subsequently results in polymer formation. o,o'-Biphenol is the major product formed, but it is rapidly oxidized to the polymer, particularly in the presence of phenol. p,p'-Biphenol is very rapidly oxidized to p,p'-biphenoquinone which can also be involved in polymer formation. Extensive binding of 14C-phenol oxidation products to DNA occurs if the DNA is present in the reaction mixture. However, enzymic hydrolysis of DNA releases the bound polymers. p,p'-Biphenol, however, did not bind to DNA following peroxidase-catalysed oxidation, but o,o'-biphenol readily binds to DNA following peroxidase-catalysed oxidation. Enzymic hydrolysis of the oxidized o,o'-biphenol-bound DNA also resulted in the release of the polymers.

Carbon Radioisotopes↗
PubMed1985

Proton release by polymorphonuclear leukocytes during phagocytosis or activation by digitonin or fluoride.

The stimulation of polymorphonuclear leukocytes with bacteria or digitonin causes protons to be released into the reaction medium at the same time as the respiratory burst. Although lactic acid is released from the cells due to the stimulated metabolic activity, proton release was not due to lactic acid accumulation as fluoride markedly inhibited lactic acid accumulation in untreated cells within 5 minutes of incubation and a rapid proton release and superoxide anion production occurred after lactate production had ceased. The proton releasing mechanism, however, is closely linked with the activation of the plasma membrane NAD(P)H oxidase since the proton release is depressed only when the activation mechanism and/or the oxidase is inhibited.

Animals↗
PubMed1985

Porcine malignant hyperthermia susceptibility: erythrocytic osmotic fragility.

Erythrocyte osmotic fragility was determined in 27 Pietrain swine which were susceptible to malignant hyperthermia (MH), 29 Yorkshire swine which were resistant to MH (controls), and 50 crossbred swine (Pietrain x Yorkshire), half of which were MH susceptible. Halothane challenge tests and blood creatine kinase activity were used as criteria for determining MH susceptibility. Mean values for osmotic fragility of erythrocytes in concentrations of NaCl between 60 and 120 mM were significantly different for the 3 groups (P less than 0.001). Hemolysis (50%) of erythrocytes occurred at NaCl concentrations of 90 mM for Pietrains, 85 mM for crossbreds, and 78 mM for controls. Increased fragility values occurred in 96% of the Pietrains, 3% of the controls, and 42% of crossbred swine that were halothane test-positive, and 58% of halothane test-negative crossbreds (P less than 0.05). The mean time of onset of signs of MH in response to halothane challenge testing was twice as long in the crossbreds as in Pietrains (P less than 0.01). Reticulocyte counts were moderately high in blood samples from both the Pietrains (P less than 0.001) and the crossbreds (P less than 0.05). Of the swine which were tested for erythrocyte selenium-dependent glutathione peroxidase activity, values were within acceptable laboratory limits in 18 of 20 Pietrains, 14 of 14 halothane test-negative crossbreds, and 8 of 8 halothane test-positive crossbreds. In 2 of 20 Pietrains, a 35% deficiency of this enzyme was found. Heinz bodies were not detected in erythrocytes examined from 21 Pietrains, 20 crossbred swine (8 halothane test positives), and 12 controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Acylation of bovine rhodopsin by [3H]palmitic acid.

Bovine retinas or preparations of rod outer segments incorporate [3H]palmitic acid into rhodopsin. The incorporation is both time- and temperature-dependent. The major product retains the chromatographic and electrophoretic properties of rhodopsin and remains photosensitive as demonstrated by alteration of its chromatographic behavior upon exposure to light. The incorporated radioactivity resists extraction with organic solvents and is not dissociated from the protein by detergents or under the denaturing conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Radioactive free fatty acid can, however, be released by alkaline hydrolysis. Hydroxylamine treatment yields a mixture of the free fatty acid and the fatty acyl hydroxamate. These results demonstrate the formation of an ester bond between [3H]palmitic acid and rhodopsin. Cycloheximide fails to inhibit the incorporation. This finding along with the ability of rod outer segments to support the incorporation point to the acylation of rhodopsin as a late post-translational event.

Acylation↗
PubMed1984

Synthesis of interphotoreceptor retinoid-binding protein (IRBP) by monkey retina in organ culture: effect of monensin.

Whole monkey retinas were incubated in short-term organ culture with either radiolabeled amino acids or glucosamine. Soluble retinal proteins and proteins in the culture medium were analyzed by SDS-poly-acrylamide gel electrophoresis. Fluorography showed that the interphotoreceptor retinoid-binding protein (IRBP), a 146,000 Mr glycoprotein localized in the extracellular matrix, is synthesized by the neural retina and rapidly secreted into the medium. Secretion is blocked by 10-5M monensin. No significant IRBP synthesis was observed in the pigment-epithelium-choroid complex. IRBP is thus the major component synthesized and secreted by the neural retina into the interphotoreceptor space. This, and its affinity for retinoid makes it a prime candidate for an extracellular retinoid transport vehicle.

Animals↗
PubMed1984

The role of parental attitudes in the development of temperament in twins at home, school and in test situations.

In the La Trobe Twin Study, data are collected on temperament and social development in 3-15 year old twins and singletons from four different sources: questionnaires to parents covering development from birth to the present plus the Bristol Social Adjustment Guide completed by the teacher, Sattler's Behavior and Attitude Checklist completed by the tester, and the Qualitative Score on the Porteus Maze Test. Particular stresses are identified which the parents perceive as distinguishing a multiple from a singleton birth. Whereas they perceive no differences between the first and second-born in birth complications, the second-born is judged less favourably particularly in MZ pairs. The distinction continues in the later assessments by the teacher and tester, where in addition the male twins are seen as being different from other children both in cognition and in temperament. It is proposed that social and cognitive development of twins are interrelated and have two unique components, one related to the greater problems accompanying a multiple birth and the other to comparisons between cotwins.

Adolescent↗
PubMed1984

The high incidence of reading disability in twin boys and its implications for genetic analyses.

In 1975 the Australian Council of Educational Research (ACER) conducted a nationwide survey of literacy and numeracy in 10- to 14-year olds. A total of 297 of the 12875 children involved were twins. By age 14, only 42% of the twin boys achieved adequate standards of literacy compared with 71% of single-born boys. The deficit in twin girls was much less and twins of both sexes were only moderately behind in numeracy. A survey of 9-13-year-old twin boys in the La Trobe Twin Study (LTS) produced similar results with 75% being below average in reading skills and 23% behind by 18 months or more, despite above average IQs. The ACER data are corroborated by teachers' reports obtained in the same survey, which indicate also how few of the twins with problems are receiving remediation and the high incidence of classroom problems in spelling and reading reversals. The pattern of mistakes twins make on specific items in the ACER survey can be explained as resulting either from specific cognitive deficits or from problems in concentration. The same factors influence performance on different tasks, so that literacy and numeracy are much more closely interrelated in twins than in singletons, and also correlate more with a measure of verbal intelligence. Implications for genetic analysis of scholastic achievement are examined, centering around the different factor structure of abilities in twins and common family environmental effects which are unique to twins.

Adolescent↗
PubMed1984

Orthopaedic aspects of the trismus pseudocamptodactyly syndrome.

The trismus pseudocamptodactyly syndrome is a relatively rare condition with autosomal dominant inheritance, characterized by decreased ability to open the mouth (trismus), interphalangeal flexion deformity with wrist extension (pseudocamptodactyly), various foot deformities, and slightly less than normal stature. Five affected individuals from one family are reviewed and the orthopaedic aspects are described. The presence of trismus is emphasized for the orthopaedic surgeon, as it may lead to anaesthetic complications during the treatment of the musculoskeletal problems.

Abnormalities, Multiple↗
PubMed1984

Canine malignant hyperthermia susceptibility: erythrocytic defects--osmotic fragility, glucose-6-phosphate dehydrogenase deficiency and abnormal Ca2+ homeostasis.

Two dogs were diagnosed as malignant hyperthermia susceptible based on increased susceptibility (P less than 0.001) of biopsied muscle to caffeine-induced contracture. Erythrocytes from malignant hyperthermia and normal dogs were then examined for an antioxidant system deficiency. Values for serum muscle enzymes, reticulocytes and corpuscular hemoglobin were mildly elevated. Osmotic fragility was increased: hemolysis occurred at a NaCl concentration 10 mM higher than for normal dogs (P less than 0.001). A 35% glucose-6-phosphate dehydrogenase deficiency (P less than 0.001) with a 40% compensatory increase (P less than 0.01) in 6-phosphogluconate dehydrogenase activity was found. The membrane Ca2+-activated ATPase activity was abnormal: 100% increased with a 40% decreased Arrhenius activation energy (P less than 0.005) and increased thermostability. A 40% increased intracellular accumulation of total Ca2+ occurred in response to in vitro energy depletion in erythrocytes from one malignant hyperthermia dog (P less than 0.01). The multifactorial pattern of inheritance and the broad spectrum of malignant hyperthermia susceptibility are proposed to result from an antioxidant system deficit unmasking or aggravating an intrinsic muscle membrane anomaly. An individual from a family with a history of malignant hyperthermia or unexplained anesthetic death should be considered malignant hyperthermia susceptible if erythrocyte osmotic fragility is abnormal and there is a mild, unexplained elevation in serum creatine kinase.

Adenosine Triphosphatases↗
PubMed1983

Oxidation of glutathione by free radical intermediates formed during peroxidase-catalyzed N-demethylation reactions.

Horseradish peroxidase-catalyzed N-demethylation of aminopyrine and dimethylaniline results in generation of free radical intermediates which can interact with glutathione (GSH) to form a glutathione radical. This can either dimerize to yield glutathione disulfide or react with O2 to form oxygenated products of glutathione. Ethylmorphine is not a substrate in the peroxidase-mediated reaction, and free radical intermediates which react with GSH, are not formed from aminopyrine and dimethylaniline when the horseradish peroxidase/H2O2 system is replaced by liver microsomes and NADPH. Therefore, it appears unlikely that formation of free radical intermediates can be responsible for the depletion of GSH observed during N-demethylation of several drugs in isolated liver cells.

Animals↗