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E Chung

Publications and source records attributed to E Chung.

At least 55 records · Page 3Linked to original sources
PubMed1993

The NF-kappa B p65 promoter.

The promoter of the human gene encoding the p65 subunit of the transcription factor NF-kappa B was cloned and the nucleotide sequence determined. The p65 promoter lacks both TATA and CCAAT consensus sequences. The p65 promoter contains three consensus binding sites of the transcription factor SP1. In contrast to the promoter of the p50 subunit of NF-kappa B, no sequences predicted to bind NF-kappa B are present in the p65 promoter. Phorbol ester (PMA) and phytohemagglutinin (PHA) treatment of Jurkat cells did not activate the p65 promoter in transient transfection experiments. Using different deletion mutants of the p65 promoter, essential promoter elements were mapped.

Base Sequence↗
PubMed1992

Spontaneous intracerebral hemorrhage: a very late delayed effect of radiation therapy.

Cerebral necrosis is a well-known delayed sequela of radiation to the central nervous system. Delayed intracerebral hemorrhage occurring several years after radiation is rare; however, with increased survival, this complication will become more common. We report a child who developed a brain-stem hemorrhage 4.5 years following radiation therapy for brainstem tumor. The possible pathogenesis for the spontaneous hemorrhage is discussed. The onset of the neurologic symptoms in this setting occurs later than the usual symptoms of radiation necrosis. It is important to recognize this entity as a late delayed complication of radiation therapy and not to mistake it for tumor recurrence.

Brain Neoplasms↗
PubMed1991

Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates.

Acetyl-levo-carnitine (ALC) protects against 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the nonhuman primate. ALC pretreated monkeys do not show signs of parkinsonism or electroretinographic changes typical of dopaminergic deficiency when given MPTP. In addition, pilot neurochemical and morphological data confirm a partial protection effect. While MAO-B inhibitors, like L-Deprenyl, are thought to protect dopaminergic neurons from MPTP-induced cell death by preventing the conversion of MPTP to its toxic metabolite MPP+, ALC is not known to have MAO-B affinity. Converging evidence suggests that ALC may affect directly mitochondrial respiration, which is known to be the target of MPP+ and affected in human neurodegenerative diseases, including Parkinson's disease. The results of this study point to new therapeutic avenues for the treatment of these nosologic entities.

Acetylcarnitine↗
PubMed1989

Age-dependent changes in brain glycine concentration and strychnine-induced seizures in the rat.

Glycine levels and receptor binding were measured in the medulla and spinal cord of 2-month, 10-month, and 24-month-old Fischer 344 rats. The behavioral response to the administration of the glycine antagonist, strychnine, was also evaluated in 2- and 24-month-old animals to investigate the relevance of these parameters to the susceptibility to seizures. Significant reductions in glycine in both the spinal cord and medulla occurred from 2 to 24 months of age. The glycine precursors, serine and threonine, were decreased only in the spinal cord. [3H]Strychnine binding was also decreased by 38% and 34% in the medulla and spinal cord, respectively, of 24-month-old rats compared to 2-month-olds. [3H]GABA binding was similarly reduced while no age-related changes in [3H]diazepam binding in the spinal cord were detected. Comparison of 2- and 24-month-old animals after systemic injection of 1.75 mg/kg strychnine showed that senescent animals have a higher incidence of seizures and mortality compared to young animals. Decreases in glycinergic neurotransmission may lower strychnine seizure threshold in the aged animal.

Aging↗
PubMed1989

Platelet monoamine oxidase in Parkinson patients: effect of L-deprenyl therapy.

Platelet MAO activity was measured in 79 Parkinson patients (56 males and 23 females) before and during L-deprenyl therapy. Baseline platelet MAO activity was higher in females than in males with no age dependent differences. During chronic L-deprenyl therapy, MAO activity was inhibited greater than 98%. Four hours after the oral administration of the first 5 mg dose of L-deprenyl, platelet MAO activity was inhibited by 86%. By 24 hours, greater than 98% inhibition was achieved and this degree of inhibition was maintained during continuous L-deprenyl administration. Following oral administration of 10 mg L-deprenyl once a day versus 5 mg L-deprenyl twice a day, the time course of platelet MAO inhibition was similar. Five days after the termination of chronic L-deprenyl therapy, platelet MAO activity was still inhibited by 96%. MAO activity returned to normal by 2 weeks after stopping L-deprenyl. Platelet MAO activity is a useful method of monitoring bioavailability, compliance, dose-response relationship and optimal dosage schedules for L-deprenyl in Parkinson patients.

Adult↗
PubMed1989

Regional distribution of calcium/calmodulin-dependent phosphatase activity of calcineurin in rat brain.

The regional distribution of calcineurin activity (measured using p-nitrophenyl-phosphate which detects the phospho-tyrosylphosphatase activity of calcineurin) shows that the striatum, hippocampus and cerebral cortex contains high calcineurin activity. Within the striatum, calcineurin activity does not appear to be present in dopaminergic terminals, since lesions of the nigro-striatal dopaminergic pathway (which reduce striatal dopamine levels by 97%) had no effect on calcineurin activity. On the other hand, kainic acid, which destroys neurons whose perikarya are in the striatum, reduced calcineurin activity by 86% indicating that calcineurin activity is localized in striatal intrinsic neurons. Calcineurin apparently does not exist in glia, since glial cells actually proliferate in kainic acid lesioned striatal tissues.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Strychnine seizure potentiation by azaspirodecanedione anxiolytics in rats.

Buspirone, gepirone and ipsaperone administered intraperitoneally (40 mg/kg) to naive rats were found to be proconvulsive for strychnine-induced seizures. The dose of strychnine required to induce seizures in 50% of test animals (CD50) was 2.18 mg/kg in naive rats, while CD50s for rats treated with the azaspirodecanediones ipsaperone, gepirone and buspirone were 1.65, 0.97 and 0.70 mg/kg respectively. Azaspirodecanediones have high affinity for the 5-HT1A serotonin receptor, however, the specific 5-HT1A agonist, 8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT) had no effect on strychnine seizure in naive rats (CD50 = 2.0 mg/kg). The strychnine specific proconvulsive effects of inferior olive lesions and buspirone were additive, resulting in a CD50 of 0.1 mg/kg. This observation indicates that the buspirone-induced decrease in strychnine seizure threshold does not require intact inferior olive-climbing fiber pathways. Cerebellar sites for possible azaspirodecanedione action are discussed.

Animals↗
PubMed1988

Systemic 1-methyl,4-phenyl,1-2-3-6-tetrahydropyridine (MPTP) administration decreases retinal dopamine content in primates.

Following MPTP administration, 4 Cynomolgus monkeys developed a parkinsonian syndrome, accompanied by specific changes of both pattern visual evoked potential and electroretinogram. Retinal dopamine and dihydroxyphenylacetic acid contents were measured in the 4 MPTP-treated monkeys and in 3 normal monkeys. Dopamine and dihydroxyphenylacetic acid levels were significantly lower in the retinas of the MPTP-treated animals (p less than 0.001), suggesting that dopamine has a specific function in the visual system of primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Ca2+/calmodulin-dependent phosphoprotein phosphatase activity of calcineurin in rat striatum: effect of kainic acid lesions.

Calcineurin, a Ca2+ and calmodulin (CM)-dependent phosphatase, has been shown to be present in high concentrations in the striatum. Using inhibitor-1(phosphorylated by cAMP-dependent protein kinase) as a substrate, we found Ca2+/CM-dependent phosphatase (calcineurin) to be more than 2-fold higher than non-Ca2+/CM-dependent phosphatase in the rat striatum. In order to determine the cellular localization of calcineurin, striatal kainic acid injections were used to destroy neurons whose cell bodies are present at the site of injection. Glutamic acid decarboxylase (GAD) activity was measured as an indicator of destruction of striatal GABA-ergic neurons. After intrastriatal injection of 1 and 2 ug of kainic acid, there was a significant decrease of both calcineurin and GAD. However, injection of 0.5 ug kainic acid into the striatum reduced GAD activity by 81%, but had no effect on calcineurin phosphatase activity. Thus calcineurin does not appear to be equally distributed among all types of striatal neurons, but rather may be concentrated in neurons that are less sensitive to kainic acid than the GABA-ergic neuron.

Animals↗
PubMed1985

Urea-induced myoclonus: medullary glycine antagonism as mechanism of action.

Stimulus sensitive myoclonus is a prominent symptom of uremia in both man and animals. Intravenous injection of urea into cats had been previously reported to produce spike and sharp wave electrical discharges in the medullary reticular formation which correlated with the myoclonic movements. In the present investigations, intraperitoneal injections of 2 g/kg urea every 15 minutes for 4 injections produced myoclonus in rats accompanied by brain urea concentrations of 6.8 X 10(-2)M, which is sevenfold higher than normal. 10(-2) and 10(-1) M urea significantly reduced 3H-strychnine binding to rat medulla membranes by 30% and 43% respectively. Urea inhibition of 3H-strychnine binding was reversible and binding kinetics revealed that 10(-1)M urea decreased Bmax by 65% with no effect on the affinity. Brain glycine levels did not change after urea injections and urea had no effect on synaptosomal uptake of 3H-glycine. Urea did not alter 3H-GABA, 3H-glutamate and 3H-QNB receptor binding but decreased 3H-diazepam receptor binding in the medulla. Mannitol also reduced 3H-diazepam binding but had no effect on 3H-strychnine binding. Stereotaxic injection of the glycine receptor antagonist, strychnine, into the rat medullary reticular formation produced myoclonus, whereas Ro 15-1788, a benzodiazepine antagonist, had no effect. Urea may produce myoclonus by blockade of glycine receptors in the medullary reticular formation.

Animals↗
PubMed1984

DDT myoclonus: sites and mechanism of action.

Intragastric injection of the insecticide DDT produces a stimulus-sensitive myoclonus in mice and rats. Unilateral stereotaxic infusions of DDT into rat medullary reticular formation also induced generalized myoclonus, identical to that produced by systemic administration. Similar myoclonus, but of lesser intensity, occurred when DDT was injected into cerebellar nuclei, red nucleus, and the inferior olive. Multiple other regions of the brain were resistant to the myoclonic action of locally infused DDT. Direct infusions into the medullary reticular formation of allethrin, which has a similar action on neuronal membranes as DDT, or the glycine receptor antagonist, strychnine, also elicited myoclonus.

Allethrins↗
PubMed1983

Fluoxetine in the treatment of intention myoclonus.

Some types of intention myoclonus respond to serotonin precursor therapy (e.g., L-5-hydroxytryptophan, L-5HTP). Fluoxetine, a specific serotonin (5HT) uptake blocker, was found to have no antimyoclonic effect when administered by itself to four patients with intention myoclonus. However, in two patients with intention myoclonus responsive to L-5HTP and carbidopa, fluoxetine reduced the required dose of L-5HTP to approximately one-third, with greater antimyoclonic activity, decreased side effects, and reduction in platelet 5HT and plasma 5-hydroxyindoleacetic acid and L-5HTP concentrations. These findings further support the hypothesis that some forms of intention myoclonus are caused by a deficiency of brain 5HT, and suggest that the addition of fluoxetine to L-5HTP and carbidopa may improve antimyoclonic therapy.

5-Hydroxytryptophan↗
PubMed1983

Cerebellar cyclic GMP in p,p'-DDT myoclonus: effects of antimyoclonic agents.

The relationship of DDT myoclonus and antimyoclonic agents to the concentration of cGMP in the cerebellum was investigated. Intragastric administration of 600 mg/kg DDT increased mouse cerebellar cGMP levels about 4 fold. Antimyoclonic agents, such as L-5HTP plus fluoxetine, clonazepam, phenoxybenzamine, prostaglandin E2 and harmaline, all counteracted the elevation of cerebellar cGMP induced by DDT. Cinnanserin, a 5-HT receptor blocker, did not counteract the reduction of cerebellar cGMP produced by L-5HTP plus fluoxetine, clonazepam, and phenoxybenzamine, although cinnanserin abolished the antimyoclonic actions of these agents. Destruction of the inferior olive-climbing fiber pathway by 3-acetylpyridine in rats did not prevent the elevation of cerebellar cGMP levels by DDT. L-5HTP, clonazepam and phenoxybenzamine still significantly counteracted DDT-induced elevation of cerebellar cGMP levels in the inferior olive lesioned rats, although these agents no longer had any antimyoclonic action in these animals. These data indicate that 1) DDT-induced elevation of cerebellar cGMP and DDT-induced myoclonus are not related, and 2) antimyoclonic agents counteract DDT-induced elevation of cerebellar cGMP levels via pathways other than the olivo-cerebellar tract.

Animals↗
PubMed1976

Cleavage of Type II and III collagens with mammalian collagenase: site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens.

Collagenase cleavage of human Type II and III collagens has been studied using a highly purified preparation of rabbit tumor collagenase. Progress of the reactions in solution was followed by viscometry and the results indicated that under the conditions employed Type III collagen molecules were cleaved at approximately five times the rate of Type II molecules. Cleavage products of the reactions were isolated in denatured form by agarose molecular sieve chromatography. The molecular weights and amino acid compositions of the products demonstrated that Type II and III molecules had been cleaved at the characteristic three-quarter, one-quarter locus, giving rise to a large fragment derived from the NH2-terminal portion of the molecule and a smaller fragment representing the COOH-terminal region. The amino acid sequence at the NH2-terminal portion of the smaller fragment derived from Type II collagen was determined to be Ile-Ala-Gly-Gln-Arg, and the corresponding region from Type III collagen was found to have the sequence Leu-Ala Gly-Leu-Arg. These sequences for alpha1(II) and alpha1(III) chains adjacent to the site of collagenase cleavage along with previous data for alpha1(I) and alpha2 chains indicate that the minimum specific sequence required for collagenase cleavage is Gly-Ile-Ala or Gly-Leu-Ala. Inspection of the available sequence data for collagen alpha chains indicates that the latter sequences are found in at least three additional locations at which collagenase cleavage does not occur. Each of the sequences which are apparently not substrates for collagenase, however, are followed by a Gly-X-Hyp sequence. We suggest, then, that a minimum of five residues in collagen alpha chains COOH-terminal to the cleavage site comprise the substrate recognition site.

Amino Acid Sequence↗