Search PubMed⌕ Search

Biomedical subjects

L L Hsu

Publications and source records attributed to L L Hsu.

At least 37 records · Page 2Linked to original sources
PubMed1984

Brain irradiation: effects on regional MAO and COMT activity in the brain of the squirrel monkey and on the incorporation of [14C]tyrosine into catecholamines.

The effects of brain irradiation on the enzyme activity of monoamine oxidase (MAO) and catecholamine O-methyltransferase (COMT), as well as on the rate of incorporation of [14C]tyrosine into catecholamines (CAs), were examined in brain regions of the squirrel monkey (Saimiri sciureus). Results indicated that proton irradiation of the striate visual cortex at either 10,000 or 20,000 rad drastically affected the MAO activity, moderately affected the COMT activity, and significantly altered the incorporation of [14C]tyrosine into CAs in several brain regions. After 10,000 rad, MAO activity was increased in caudate nucleus (by 135%) and cerebellum (by 41%); significantly decreased in putamen (by 49%), gray matter (by 19%), and hippocampus (by 18%); and unchanged in brainstem. After 20,000 rad, MAO activity was markedly increased in caudate nucleus (by 114%), but decreased in cerebellum (by 24%), putamen (by 38%), gray matter (by 30%), and hippocampus (by 36%), and unchanged in brainstem. After 10,000 rad, COMT activity was significantly decreased in putamen (by 27%) and brainstem (28%). After 20,000 rad, COMT activity was significantly decreased in putamen (by 22%) and cortical gray matter (by 37%) but unchanged in the other brain regions examined. The 10,000 rad significantly increased the rate of incorporation of [14C]tyrosine into CAs in both the cerebellum (by 68%) and hypothalamus (by 26%), but 20,000 rad increased the rate only in hypothalamus (by 17%) and decreased the rate in hippocampus (by 24%). The whole-brain weights were significantly decreased after both 10,000 or 20,000 rad, by 17% and 11%, respectively. The only significant change in regional tissue weight was observed in putamen after 20,000 rad (a decrease by 17%). The protein concentration was significantly increased in hippocampus at both 10,000 (by 13%) and 20,000 (by 30%) but not affected in other brain regions examined. These data support our previous conclusion that a sustained chemical change occurs at the irradiated site and that the effect was transmitted to nonirradiated brain regions. Results also suggest that catecholaminergic pathways may exist between striate visual cortex and other cortical or subcortical brain areas where chemical changes were observed after visual cortical lesion by proton irradiation at various doses.

Animals↗
PubMed1984

Fenfluramine treatment in infantile autism. Neurochemical, electrophysiological, and behavioral effects.

As part of a multicenter, collaborative project, response to fenfluramine was assessed in 10 autistic outpatients. After 4 months of treatment, blood serotonin concentrations decreased an average of 60 per cent and returned to pretreatment levels after 2 months on placebo. This reduction was accompanied by a decrease in certain behavioral symptoms, including motor activity, distractibility, and mood disturbances. Baseline evoked potential recordings indicated that autistic patients tended to have a larger amplitude of the P3 component to frequent tones as compared to age-matched controls. A tendency toward "normalization" of the P3 effect was observed during the medication trial and during the final placebo period. Treatment response was not related to initial serotonin levels, and no major clinical side effects were associated with fenfluramine.

Adolescent↗
PubMed1984

Pineal aryl acylamidase: effects of melatonin, serotonin-related compounds, beta-carbolines, RO4-4602 and antidepressants.

The pineal aryl acylamidase (AAA) activity has been demonstrated and characterized for the first time using ONAc as a substrate. The pineal AAA activity in the presence of 0.05% Triton X-100 was linear with protein concentration up to 1 mg and with incubation time up to 1 hour. Both the rat and bovine pineal showed a pH optimum at 5.0. The in vitro and in vivo effects of several classes of drugs on the pineal AAA activity were examined. At 0.1 mM, 5-HT, N-acetyl-5HT, melatonin, d-LSD, l-LSD, methiothepin, DA, chlorimipramine, imipramine, pargyline, TH C and harmaline significantly inhibited the rat pineal AAA activity by 19-51%. N-Acetyl-5-HT was the most potent in vitro inhibitor. However, at the same concentration, NE, 6-MeO-harman and eserine did not show any effect on the enzyme activity. Lineweaver-Burk plot indicated a competitive type of in vitro inhibition of the pineal AAA activity by melatonin. Acute subcutaneous injection of low doses (25-50 mg/kg) THBC harmaline, desipramine and protriptyline markedly inhibited the rat pineal AAA activity but at higher doses (75-100 mg/kg) the inhibition was reduced. On the contrary, RO4-4602 (200-800 mg/kg) greatly enhanced (1.5-2.3 fold) the enzyme activity, inversely proportional to the doses given. In view of the differential effects of these drugs on the brain and pineal AAA, it seems unlikely that they would be the same enzyme.

Amidohydrolases↗
PubMed1982

Choline acetyltransferase: further studies on the reverse reaction.

In order to further characterize the reaction mechanism of brain ChAc in its purified form, we have investigated the reverse reaction of ChAc in terms of pH optimum, salt effects, and substrate kinetics using a radiochemical assay. We directly measured the reaction product acetylcoenzyme A which was separated from the substrate ACh by a cation exchange column. Dowex 50W-X8 (Na+ form). The reverse reaction of ChAc was linear with incubation time up to 40 minutes, and with enzyme protein concentration up to 5 micrograms. It had a pH optimum at 7.0. At 0.22 M the monovalent chloride and bromide salts activated the reverse ChAc activity by 23-47% but the fluoride and iodide salts inhibited the reverse enzyme activity by 10-30%. Kinetic studies in the absence of salt showed that KACh was 0.62 +/- 0.06 mM, KCoA . SH was 12.68 +/- 1.21 microM, and Vmax was 11.6 +/- 1.0 nmol AcCoA/mg protein/min. These data are in disagreement with the values reported on partially purified ChAc from bovine brain by Glover and Potter [1971] and Hersh [1980]. This indicates that further investigations are necessary to clarify or resolve these differences.

Animals↗
PubMed1982

Rat brain aryl acylamidase: further characterization of multiple forms.

1. Two fractions of aryl acylamidase (EC 3.5.1.13) were further separated from rat brain extracts at pH 7.5 by ammonium sulfate precipitation and Bio-Gel chromatography. 2. 1,2,3,4-Tetrahydro-beta-carboline competitively inhibited (67%) fraction-1 but slightly inhibited (13%) fraction-2. Tetrahydroharman, 6-hydroxy-tetrahydroharman and harminic acid slightly inhibited both fractions. Harmalol inhibited fraction-1 but enhanced fraction-2. 6-Methoxy-harman, 6-methoxy-harmalan and harmaline enhanced both fractions. 3. Pargyline did not affect either fraction. Methiothepin, cyproheptadine and chlorimipramine inhibited fraction-1 but stimulated fraction-2. 4. Neostigmine moderately (30%) inhibited AAA-2 but did not have any significant effect on AAA-1. 5. These results indicate that the beta-carboline compounds might play a role in regulating activity of AAA-1 and 2 in brain. 6. Both fractions might be related to serotonergic neurons but only AAA-2 might be associated with acetylcholinesterase.

Amidohydrolases↗
PubMed1982

Brain aryl acylamidase.

1. The serotonin (5-HT) sensitive brain aryl acylamidase (AAA) has received considerable attention due to its potential involvement in 5-HT action mechanism in CNS. 2. Multiple forms, AAA-1 and 2, have been separated by ammonium sulfate precipitation of brain extract and subsequent gel filtration. 3. Their chemical properties have been characterized and differentiated by effects of several classes of drugs including d-LSD, 5-HT, 5-HT related compounds and tetrahydro-beta-carbolines on their enzyme activities. 4. In the rat brain, AAA-1 shows highest specific activity in corpus striatum and lowest activity in cerebellum whereas AAA-2 shows highest specific activity in cerebellum and lowest activity in corpus striatum. 5. Subcellularly, AAA-1 exhibits highest specific activity in synaptosomal fraction of rat corpus striatum, lowest activity in mitochondrial fraction and no activity in nuclear fraction while AAA-2 exhibits highest specific activity in microsomal fraction and lowest activity in nuclear fraction. 6. Triton X-100 treatment altered the subcellular distribution pattern of both AAA-1 and AAA-2. 7. AAA-2 is possibly associated with true acetylcholinesterase (AChE) in brain based on its inhibition by neostigmine but its identity with AChE needs further elucidation. 8. To determine the physiological role(s) for brain AAA, naturally occurring aromatic alkylamines other than melatonin need to be tested as possible substrate(s) for the enzyme activity.

Acetylcholinesterase↗
PubMed1981

Aromatic alkylamine N-acetyltransferase in regional tissues in developing rat brain.

The specific activities of N-acetyltransferase (EC 2.3.1.5) were examined in several regions of rat brain of both sexes at various times after birth. The enzyme activity increased with development in whole brain, hippocampus, midbrain, cerebellum and the remainder of brain, peaking around 36 days of age. Lineweaver-Burk plots indicated linear kinetics for N-acetyltransferase in dialyzed supernatant and ammonium sulfate precipitates from the newborn rat brain, whereas enzyme preparation further purified by Bio Gel yielded biphasic kinetics. These data remain consistent with the possibility that there are two forms of N-acetyltransferase in rat brain even from birth.

Acetyltransferases↗
PubMed1976

Interactions between diverse proteinoids and microspheres in simulation of primordial evolution.

Experiments demonstrating an incorporation of different enzymelike activities into a single preparation of proteinoid microspheres provide a conceptual basis for the primitive lengthening of protometabolic pathways. An enhancement of one enzymelike activity by another proteinoid in the same microsphere has been found. This effect, plus the pathway-lengthening propensity of combinations of microspheres, indicates selective advantages contributing to adaptive protoselection. Data reported in this paper also bring into purview the concept of internally controlled variation. Inferences are derived for the origin of protosexuality in protocells. When allowance is made for a closer relationship to the environment than that needed in contemporary selection, the fundamental mechanistic requirements of protoevolution are regarded as met by the proteinoid microsphere.

Catalysis↗