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Biomedical subjects

J M Rau

Publications and source records attributed to J M Rau.

10 recordsLinked to original sources
PubMed1996

Referring and reporting research participants at risk: views from urban adolescents.

Researching developmental risks of urban youth raises ethical concerns when an investigator discovers a participant is in jeopardy. This study collected data on 147 seventh, ninth, and eleventh graders' views of 3 investigator options: (1) taking no action and maintaining confidentiality, (2) reporting the problem to a concerned parent or adult, and (3) facilitating adolescent self-referrals. Participants judged these options within the context of 5 risk domains: substance abuse, child maltreatment, life-threatening behaviors, delinquency, and shyness. Judgments of reporting options were related to grade and ratings of risk severity, but not to moral reasoning. Confidentiality was viewed favorably for risk behaviors of low perceived severity or for which the consequences of adult discovery might introduce greater risk. Confidentiality was viewed unfavorably and reporting to adults favorably for child maltreatment and threats of suicide. Self-referral was viewed favorably across all grades and risk behaviors. Implications of adolescent perspectives for research ethics are discussed.

Adolescent↗
PubMed1995

Inorganic phosphate promotes redox cycling of iron in liver microsomes: effects on free radical reactions.

The phosphate buffer concentration used in spin trapping experiments with liver microsomes markedly influenced rates of free radical formation from ethanol and dimethylsulfoxide, but not from carbon tetrachloride. Effects of phosphate concentration on ethanol radical formation were abolished by addition of deferoxamine or bathophenanthrolene, indicating that an iron-phosphate complex might be involved. High concentrations of phosphate stimulated rates of microsomal Fe+3 reduction and facilitated the mobilization of microsomal nonheme iron, but had little effect on a variety of microsomal monooxygenase enzyme activities. Although microsomal oxygen utilization and superoxide production were relatively unaffected by phosphate, hydrogen peroxide concentrations were markedly decreased in the presence of high concentrations of phosphate. Taken together, the data suggest that a ferric-phosphate complex may be enzymatically reduced by microsomal enzymes and NADPH. Reoxidation of ferrous ion is nonenzymatically promoted by phosphate and/or H2O2 produced by the microsomes. During the process of reoxidation, one or more oxidizing intermediates may be formed which initiate secondary free radical reactions. Although the reactivity of the intermediate(s) is similar to that of the hydroxyl radical, no spin trapping evidence was obtained to support this assignment.

Animals↗
PubMed1994

Characteristics of an oxidant formed during iron (II) autoxidation.

When ethanol (100 mM) and the spin trapping agent DMPO were added to a solution of FeSO4 (0.1 mM) in phosphate buffer (40 mM), pH 7.4, the spectrum of the 1-hydroxyethyl radical spin adduct of DMPO could be detected by ESR spectroscopy. The ESR signal intensity of the 1-hydroxyethyl radical increased with higher concentrations of phosphate. Under these conditions, hydroxyl radical adducts could not be detected. However, if H2O2 (0.1 mM) was also added, the ESR spectra contained signals from both the hydroxyl and 1-hydroxyethyl radical adducts of DMPO. When ethanol was replaced with azide (100 mM) in these experiments, strong ESR signals from the azidyl radical adduct of DMPO were observed only in the Fenton system. The absence of hydroxyl radical adduct signals in the Fe(2+)-PO4 reaction could not be explained by instability of the hydroxyl radical adduct in the presence of Fe2+ or superoxide. Experiments with oxygen radical scavengers indicated that the oxidant formed during Fe2+ autoxidation was less reactive to benzoate, DMSO and tert-butanol than the hydroxyl radical. The available data indicate that the primary oxidant formed during Fe2+ autoxidation in phosphate buffer is not the hydroxyl radical, but may be an iron-oxygen complex such as a ferryl species.

Cyclic N-Oxides↗
PubMed1994

Oxygen radical formation in well-washed rat liver microsomes: spin trapping studies.

The generation of hydroxyl radicals by rat liver microsomes was monitored by spin trapping with 5,5-dimethylpyrroline N-oxide (DMPO). The results confirm and extend previous data which demonstrated that hydroxyl radicals are produced by microsomes in the presence of NADPH and O2, and without the exogenous addition of iron. No EPR signals could be detected unless catalase activity which was associated with the microsomes could be substantially diminished. Addition of azide was the most effective means of eliminating catalase activity, but azide also reacted rapidly with hydroxyl radicals, forming azidyl radicals which were in turn trapped by DMPO. Extensive washing and preincubation of microsomes with 3-amino-1,2,4-triazole in the presence of H2O2 were evaluated as alternative methods of decreasing the catalase contamination of microsomes. Although neither method completely eliminated microsomal catalase activity, addition of azide was no longer necessary for hydroxyl radical detection with DMPO. When highly washed microsomal preparations were tested, weak signals of the superoxide radical adduct of DMPO could also be detected. These data indicate that the sensitivity of spin trapping in microsomal systems can be improved substantially when care is taken to eliminate cytosolic contaminants such as catalase.

Animals↗
PubMed1992

Hydroxyl radicals are generated by hepatic microsomes during NADPH oxidation: relationship to ethanol metabolism.

Ethanol is metabolized to acetaldehyde by hepatic microsomes in a reaction that requires cytochrome P-450, and a role for hydroxyl radicals has been implicated in this process. However, previous spin trapping experiments have failed to demonstrate the production of hydroxyl radicals by liver microsomes unless iron or other metal catalysts have been added. The spin trapping experiments described in this report provide unambiguous evidence that liver microsomes form hydroxyl radicals during oxidation of NADPH, that the addition of exogenous iron is unnecessary for this process, and that hydroxyl radicals participate in the metabolism of ethanol. Liver microsomes are known to metabolize ethanol to the 1-hydroxyethyl radical, and our experimental data support the conclusion that a significant part of the production of the 1-hydroxethyl radical occurs as a consequence of hydroxyl radical attack on ethanol. Lack of previous observation of microsomal hydroxyl radical production in spin trapping experiments is shown to be related to the contamination of the microsomes with catalase.

Animals↗
PubMed1990

Direct observation of spin-trapped carbon dioxide radicals in hepatocytes exposed to carbon tetrachloride.

Carbon dioxide radical adducts of the spin trapping agent, alpha-phenyl N-t-butyl nitrone (PBN), have been observed to occur in the urine and bile of rats exposed to carbon tetrachloride as well as in perfusates of liver in which the perfusion medium contained carbon tetrachloride (Connor et al., J. Biol. Chem., 261, 4542, (1986]. The carbon dioxide adduct was proven to be derived from CCl4 by use of 13-C-labelled compound. These adducts were not observed in the liver itself suggesting that they might be rapidly secreted from the liver. However, using isolated hepatocytes, we have demonstrated that the carbon dioxide radical adduct can be observed directly in the liver cells as it is formed. Since this water-soluble adduct cannot be extracted by non-aqueous solvents such as chloroform or toluene, its formation in liver in vivo or in perfused livers was not detected. Lowering the oxygen tension in the system diminished the intensity of production of the carbon dioxide adduct, consistent with the adduct being produced as a result of .OOCCl3 generation. It is not clear the extent to which this adduct is formed as a result of the .CO2 radical or is produced by metabolic oxidation of the trichloromethyl radical adduct of PBN per se to the carbon dioxide radical adduct. The intensity of the signal of the carbon dioxide radical adduct suggests that adduct conversion may be the route of formation since it seems unlikely that a sufficient amount of the halocarbon could be metabolized to .COCl or .CO2 radicals to generate a signal of the magnitude involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Possible roles of free radicals in alcoholic tissue damage.

Hepatic microsomes metabolize ethanol to a free radical metabolite which forms adducts with the spin trapping agents PBN (phenyl-N-t-butylnitrone) and DMPO (5,5-dimethyl-l-pyrroline N-oxide). This ethanol radical has been identified as the l-hydroxyethyl radical through the use of 13C-labelled ethanol. A role of the cytochrome P-450 enzymes in the generation of the l-hydroxyethyl radical was suggested by requirements for oxygen and NADPH, as well as inhibition in the presence of SKF 525-A and imidazole. In contrast, the ESR signal intensity of the l-hydroxyethyl radical was diminished when either catalase, or the iron chelating agent deferoxamine, was added to the microsomal incubations, and was increased by the addition of ADP-Fe. These observations suggest that the ethanol radicals may arise secondary to iron-catalyzed formation of hydroxyl radicals from hydrogen peroxide. This possibility was supported by enhanced rates of l-hydroxyethyl radical formation when microsomal catalase activity was inhibited by the addition of sodium azide, or by pretreatment of rats with aminotriazole. However, the reaction was relatively insensitive to scavengers of the hydroxyl radical. Thus, the mechanism of l-hydroxyethyl radical formation could involve two cytochrome P-450-dependent pathways: generation of hydrogen peroxide required for a Fenton reaction, as well as direct catalytic formation of the ethanol radical.

Animals↗
PubMed1980

Primary cutaneous histoplasmosis: a new presentation.

A fifty-one year old man on chronic steroid therapy presented with a cellulitis-erysipelas-like eruption which proved to be histoplasmosis without demonstrable systemic involvement. This presentation deviates from the five previously reported cases, two nodular and three noduloulcerative, all of which presented as a self-limited, minimally tender lesion.

Asthma↗
PubMed1976

Purpura fulminans.

Purpura fulminans is a rare disease characterized by cutaneous ecchymosis, hypotension and fever associated with disseminated intravascular coagulation. It usually follows a preparatory infectious illness. A case in a 55 year old woman challenges the concept that this disease is limited to childhood. A review of 100 case reports is presented in which the often quoted high mortality of 90 per cent is found to be no longer tenable.

Age Factors↗