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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 595 records · Page 33Linked to original sources
PubMed1989

Characterization of acute N-ethyl-3,4-methylenedioxyamphetamine (MDE) action on the central serotonergic system.

The effect of N-ethyl-3,4-methylenedioxyamphetamine (MDE) on the central serotonergic system was studied. Within 1 hr after administration of MDE (10 mg/kg), the concentration of 5-hydroxytryptamine (5-HT) and the activity of tryptophan hydroxylase (TPH) had declined significantly in the hippocampus but returned to control within 12 hr. Hippocampal 5-hydroxyindoleacetic acid (5-HIAA) content decreased within 2 hr, rebounded to 22% above control by 12 hr, and returned to control by 24 hr. Blockade of the 5-HT uptake carrier with fluoxetine (10 mg/kg) prevented or attenuated the MDE-induced changes in 5-HT content and TPH activity, except for neostriatal TPH activity which remained unresponsive to the fluoxetine treatment. The MDE-induced decline in TPH activity could be reversed by incubating the TPH preparation with dithiothreitol and Fe2+ under nitrogen for 24 hr. This suggests that the loss in TPH activity induced by MDE results from an alteration of the oxidation-reduction state of a sulfhydryl group located on the enzyme. The inhibition of monoamine oxidase (MAO) by the administration of pargyline (75 mg/kg) failed to protect the neostriatal TPH activity from the MDE-induced decline while potentiating the MDE-induced decrease in cortical TPH activity. This suggests that H2O2 generated by MAO in vivo is not responsible for oxidation of the sulfhydryl site located on TPH during the MDE treatment.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Distribution of [3H]MK801 binding in the normal aged human hippocampus.

The distribution of NMDA receptors in the normal human hippocampus has been investigated using the non-competitive channel blocking agent, MK801. The pattern of specific [3H]MK801 binding was broadly similar to that previously described for agonist binding although differences included equal densities in h1 and h2 regions where binding was mainly confined to the pyramidal layer and stratum radiatum.

Aged↗
PubMed1989

Protein engineering and design.

Rapid advances in site-directed mutagenesis and total gene synthesis combined with new expression systems in prokaryotic and eukaryotic cells have provided the molecular biologist with tools for modification of existing proteins to improve catalytic activity, stability and selectivity, for construction of chimeric molecules and for synthesis of completely novel molecules that may be endowed with some useful activity. Such protein engineering can be seen as a cycle in which the structures of engineered molecules are studied by X-ray analysis and two-dimensional nuclear magnetic resonance. The results are used in the improvement of the design by using knowledge-based procedures that exploit facts, rules and observations about proteins of known three-dimensional structure.

Amino Acid Sequence↗
PubMed1989

Effect of MK-801 on the decrease in tryptophan hydroxylase induced by methamphetamine and its methylenedioxy analog.

The role of N-methyl-D-aspartate (NMDA) receptors in the decrease in neostriatal tryptophan hydroxylase (TPH) activity induced by repeated high doses of methamphetamine or 3,4-methylenedioxymethamphetamine (MDMA) was evaluated. Rats received 4 injections of methamphetamine (15 mg/kg) or MDMA (10 mg/kg) at 6 h intervals, and were killed 18-20 h after the last administration. These treatments with methamphetamine or MDMA reduced neostriatal TPH activity to 26 and 34% of control, respectively. Coadministration of MK-801 (2.5 mg/kg) significantly attenuated the methamphetamine-induced decrease in TPH activity (66% of control), but did not alter the effect of MDMA. This study suggests that excitatory amino acids may participate in the methamphetamine-induced decline in central TPH activity, and that the mechanism by which MDMA and methamphetamine decreases TPH activity may differ.

3,4-Methylenedioxyamphetamine↗
PubMed1989

[Acyclovir creme in recurrent herpes genitalis].

A multicenter clinical, double-blind crossover trial was conducted in 65 men and 31 women experiencing recurrent episodes of genital herpes in order to compare the effect of acyclovir in propylenglycol (40% cream) with that of cream alone (placebo). 59.4 of the patients on acyclovir experienced a beneficial effect in relation to the usual clinical course of their herpetic eruptions. The corresponding figure for placebo was 34.4%. These percentages were 76.6 and 33.3 respectively if the treatment started within four hours after appearance of symptoms or skin lesions. Pain and burning lasted less than four days in 70.8% of the patients on acyclovir and in 36.4% of those on placebo cream (p less than 0.001). The average duration until complete healing of all skin lesions was 32 hours shorter for patients on acyclovir. In 42 patients on acyclovir and 31 patients on placebo (p less than 0.001) it was less than four days. As regards duration of symptoms and skin lesions, the effect was significantly better if treatment was started early (e.g. less than 4 h). Slight to moderate side-effects were reported in 13.5% of the patients on both treatment regimens.

Acyclovir↗
PubMed1989

Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves the oxidation of sulfhydryl sites.

The activity of rat hippocampal tryptophan hydroxylase was reduced from 30-60% 3 h after the administration of a 10-15 mg/kg dose of either fenfluramine, methamphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Tryptophan hydroxylase inactivated by these drug treatments could be reconstituted by a prolonged anaerobic incubation in the presence of 5 mM dithiothreitol and 50 microM Fe2+. Drug-inactivated enzyme obtained from rats killed 18 h after multiple doses of either D(+)- or L(-)-MDMA could not be similarly restored. These observations suggest that the rapid decrease in central tryptophan hydroxylase activity induced by amphetamine analogs results from the reversible oxidation of a sulfhydryl site(s) within the enzyme molecule, whereas the irreversible decrease in enzymatic activity measured 18 h after multiple-dose MDMA treatment may reflect serotonergic toxicity.

Amphetamines↗
PubMed1989

Glucocorticoids and 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity.

The present study was carried out in order to explore the role of glucocorticoids in 3,4-methylenedio-xymethamphetamine (MDMA)-induced neurotoxicity of the central serotonergic system. The activity of tryptophan hydroxylase (TPH) was used as an index of this drug-induced neuronal degeneration. One week after a single high dose of MDMA (20 mg/kg), a significant decrease in the enzyme activity was measured in both the frontal cortex and hippocampus. Adrenalectomy (ADX) attenuated or blocked this decrease in TPH activity in the hippocampus but not in the frontal cortex. This protective effect of ADX on hippocampal serotonergic neurons disappeared with concurrent administration of corticosterone (CORT) and MDMA administration. The long-term MDMA-induced decreases in hippocampal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were similarly affected by CORT replacement. However, ADX did not alter the short-term decline in hippocampal TPH activity and 5-HT concentrations measured 3 h after a single dose of MDMA (10 mg/kg s.c.). This study suggests that CORT play a role in the development of neurotoxicity induced by MDMA in the hippocampal serotonergic system, but may be less important in other brain structures.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Response by the neurotensin systems of the basal ganglia to cocaine treatment.

Multiple administrations of high doses of cocaine had profound effects on the neurotensin (NT) systems of the basal ganglia. Approximately 200-300% increases in striatal content of neurotensin-like immunoreactivity (NTLI) were observed 1-8 h following five doses of 30 mg/kg per dose of cocaine. The effect subsided by 48 h after treatment. Significant changes in striatal NTLI levels were not observed after a single dose of this stimulant. The nigral NT systems appeared to be even more sensitive to cocaine administration. Compared to striatal changes, increases in nigral NTLI content were greater (as much as 455% of control), required lower cocaine doses (20 mg/kg per dose), lasted longer (still elevated to 200% of control after 48 h) and were significant following a single cocaine exposure. The response of the striatal NT systems to cocaine appeared to be mediated principally by dopamine D-1 receptors, while both D-1 and D-2 receptors contributed to the response by the nigral NT projections. Specific dopamine, but not serotonin, uptake blockers caused increases in striatal and nigral NTLI concentrations similar to that seen with cocaine treatments, suggesting that interference with the dopamine uptake carrier complex by cocaine was responsible for its actions on extrapyramidal NT systems.

Animals↗
PubMed1989

Cholestatic hepatitis due to antibacterial combination of amoxicillin and clavulanic acid (augmentin)

Five case histories are presented of patients developing cholestatic hepatitis associated with the intake of the antibiotic combination agent amoxicillin and clavulanic acid (Augmentin). In two of these cases, signs of hepatic injury recurred after readministration of this combination but not after the intake of amoxicillin alone. In none of the patients was another cause for cholestatic hepatitis found and extrahepatic causes were excluded by ultrasonography, CT scanning, or ERCP. Most viral causes of hepatic injury were excluded in these patients. With the exception of one patient, who developed a transient rash, no immunoallergic signs were present. Biopsy in two patients showed extensive cholestasis without significant necrosis. Clavulanic acid seems to be responsible for this adverse effect.

Aged↗