Search PubMed⌕ Search

Biomedical subjects

M P Murphy

Publications and source records attributed to M P Murphy.

118 records · Page 7Linked to original sources
PubMed1982

Release of enzymes from adult rat heart myocytes.

The release of lactic dehydrogenase, creatine phosphokinase, and aspartate aminotransferase from initially viable, metabolically competent adult rat heart myocytes has been examined. Freshly isolated cells contain levels of total lactic dehydrogenase, creatine phosphokinase, and aspartate aminotransferase, as well as lactic dehydrogenase and creatine phosphokinase isoenzyme profiles that are quite comparable to those of intact heart tissue. When the cells are lysed with digitonin, 89% of total lactic dehydrogenase, but only 58% of creatine phosphokinase and 27% of aspartate aminotransferase are released. The retention of creatine phosphokinase by the digitonin-lysed cells is accounted for by complete retention of mitochondrial creatine phosphokinase and 20% of MM-creatine phosphokinase. When intact myocytes are incubated under anoxic, substrate-deprived conditions, there is a gradual loss of the three enzymes to the suspending medium and a parallel increase in the fraction of the cells permeable to trypan blue. The fraction of freely soluble cytoplasmic enzymes lost was equivalent to the fraction of the cells permeable to the dye over a wide range of viability (17-95% viable by dye exclusion criteria), but permeable cells retained mitochondrial creatine phosphokinase and particulate aspartate aminotransferase. These results suggest that simultaneous and complete release of soluble cytoplasmic enzymes occurs as each individual cell sustains sarcolemmal damage.

Animals↗
PubMed1979

Urinary excretion of dimethyltryptamine in liver disease.

The urinary excretion of N,N-dimethyltryptamine (DMT) was higher in patients with severe liver disease than in normal subjects. This difference remained significant when patients with all grades of hepatic encephalopathy were excluded. Patients with liver disease whose mental states were normal excreted amounts of DMT similar to those of patients with a hospital diagnosis of schizophrenia.

Acute Disease↗
PubMed1977

Factors affecting the urinary excretion of endogenously formed dimethyltryptamine in normal human subjects.

The hallucinogenic substance N',N'-dimethyltryptamine and its precursor N-methyltryptamine were found in 24-h specimens of urine from 19 normal human subjects; the mean excretion rates were 386 ng 24 h(-1) and 856 ng 24 h(-1) respectively. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal pattern observed. Rates for the mono and dimethylated compounds were not correlated. Diet and the intestinal flora were excluded as a source of urinary dimethyltryptamine. Administration to 4 subjects of sufficient ammonium chloride to increase the H ion concentration of the urine caused a transient increase in dimethyltryptamine excretion but no consistent increase in the rate for N-methyltryptamine. Acidification of the urine did not appear to be the determining factor in this result since in one subject the same drop in urinary pH was achieved by feeding methionine without any increase in dimethyltryptamine excretion.

Adult↗
PubMedDate not supplied

Effects of chronic oral administration of L-deprenyl in the dog.

Dogs were administered capsules containing L-deprenyl daily over 3 weeks at dose levels of 0, 0.1, 0.5, and 1.0 mg/kg. Spontaneous behavior was measured using a canine open field test, and was not significantly affected by L-deprenyl. Plasma levels of amphetamine showed a clear dose-dependent elevation 2 h and was not significantly affected by L-deprenyl. Plasma levels of amphetamine showed a clear dose-dependent elevation 2 h following treatment, but were markedly lower after 24 h, and were undetectable 5 days following the last treatment. Plasma levels of phenylethylamine were increased, but were highly variable. Animals sacrificed 1 day following the last treatment showed a dose-dependent inhibition of monoamine oxidase B in the brain, liver, and kidney, whereas monoamine oxidase A was unaffected in these tissues. L-Deprenyl also caused an increase in phenylethylamine in the striatum and hypothalamus, but not in the neocortex. Brain levels of DA, DOPAC, 3-MT, HVA, 5-HT, and 5-HIAA were unaffected. The pharmacological profile for the dog is distinct from that of other species in that long-term treatment did not produce any significant inhibition of MAO-A activity. The absence of an effect on biogenic amines or metabolites suggests that the metabolism of dopamine is mediated at least in part through pathways other than MAO-B in the normal adult dog.

Amphetamine↗
PubMedDate not supplied

Reduced effectiveness of Abeta1-42 immunization in APP transgenic mice with significant amyloid deposition.

Vaccinations with Abeta1-42 have been shown to reduce amyloid burden in transgenic models of Alzheimer's disease (AD). We have further tested the efficacy of Abeta1-42 immunization in the Tg2576 mouse model of AD by immunizing one group of mice with minimal Abeta deposition, one group of mice with modest Abeta deposition, and one group with significant Abeta deposition. The effects of immunization on Abeta deposition were examined using biochemical and immunohistochemical methods. In Tg2576 mice immunized prior to significant amyloid deposition, Abeta1-42 immunization was highly effective. Biochemically extracted Abeta40 and Abeta42 levels were significantly reduced and immunohistochemical plaque load was also reduced. Immunization of mice with modest amounts of pre-existing Abeta deposits selectively reduced Abeta42 without altering Abeta40, although plaque load was reduced. In contrast, in Tg2576 mice with significant pre-existing Abeta loads, Abeta1-42 immunization only minimally decreased Abeta42 levels, whereas no alteration in Abeta40 levels or in plaque load was observed. These results indicate that in Tg2576 mice, Abeta1-42 immunization is more effective at preventing additional Abeta accumulation and does not result in significant clearance of pre-existing Abeta deposits.

Age Factors↗
PubMedDate not supplied

Long-term treatment of male F344 rats with deprenyl: assessment of effects on longevity, behavior, and brain function.

L-Deprenyl (selegiline) was chronically administered to male Fischer 344 rats via their drinking water beginning at 54 weeks of age (estimated daily dose: 0.5 mg/kg/day). Beginning at 84 weeks of age, the rats were behaviorally evaluated using a sensorimotor battery, a motor-learning task, and the Morris water maze. At 118 weeks of age, cerebellar noradrenergic function was evaluated in the surviving rats using in vivo electrochemistry. The rats were then sacrificed to measure brain monoamine oxidase activity and perform quantitative autoradiography to evaluate the effect of chronic deprenyl treatment on beta-adrenergic receptors in the cerebellum, alpha 2-adrenergic receptors several brain regions, and D1 and D2 dopamine receptors in the striatum. Deprenyl treatment reduced brain monoamine oxidase B activity by 85%, but had no effect on brain monoamine oxidase A. A clear effect of chronic deprenyl treatment upon longevity was not observed. Several measures of CNS function were altered in the deprenyl-treated animals: 1) spatial learning in the Morris water maze was improved; 2) electrochemical signals recorded following local application of NE were reduced, and the responsiveness to the reuptake blocker nomifensine was enhanced, in the cerebellum; 3) beta-adrenergic receptor binding affinity was increased in the cerebellum; 4) alpha 2-adrenergic receptor density was increased in the inferior colliculus; and 5) striatal D1 dopamine receptor density was reduced but binding affinity was enhanced. In contrast, chronic deprenyl treatment did not cause changes in: 1) sensorimotor function, as evaluated by balance beam, inclined screen, or wire hang tasks; 2) motor learning; 3) alpha 2-adrenergic receptor density in any region examined except for the inferior colliculus, or binding affinity in any region examined; or 4) striatal D2 dopamine receptor number or affinity. Thus, long-term oral administration of deprenyl extended the functional life span of rats with respect to cognitive, but not motor, performance.

Animals↗
PubMedDate not supplied

Variable stoichiometry of proton pumping by the mitochondrial respiratory chain.

The proton/oxygen stoichiometry and the mechanism of the proton pumping respiratory complexes in the mitochondrial respiratory chain have been central issues in bioenergetics for several years. Recently, a number of disagreements about stoichiometry have been resolved, and H+/O ratios of 6 (refs 1-3) or perhaps 8 (refs 4 and 5) for succinate oxidation are now accepted. Suggestions that the stoichiometry in mitochondria is intrinsically variable ('slip' in the pumps) have been made but the evidence has been neither strong nor direct. We now show by direct measurement in steady-state conditions that the H+/O ratio (measured as the charge/O ratio) for isolated mitochondria respiring on succinate varies from 6 at low membrane potential to 2.5-3 at membrane potentials of about 170 mV.

Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone↗
PubMedDate not supplied

Punching the clock.

Explore the source record for details and available documents.

Employment↗
PubMedDate not supplied

Photochemotherapy in human heart transplant recipients at high risk for fatal rejection.

Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females generally form higher levels of panel reactive antibodies, which have been associated with fatal rejection episodes and accelerated graft atherosclerosis. In this study, two multiple transplant patients with preexistent high levels of panel reactive antibodies and two multiparous women who were considered at risk of sensitization were treated with a new form of immunotherapy termed photochemotherapy in addition to conventional immunosuppression. High levels of panel reactive antibodies have been reduced, and patients have suffered few rejection episodes and no infectious complications. This preliminary experience shows that the addition of photochemotherapy to conventional regimens may improve the clinical course of hypersensitized transplant patients without additional immunosuppressive risk.

Adult↗