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Biomedical subjects

X M Li

Publications and source records attributed to X M Li.

At least 145 records · Page 8Linked to original sources

Chronic haloperidol treatment leads to an increase in the intramembrane interaction between adenosine A2 and dopamine D2 receptors in the neostriatum.

Stimulation of adenosine A2 receptors (with the selective adenosine A2 agonist CGS 21680) in rat striatal membrane preparations, produces a decrease in both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G protein. This intramembrane A2-D2 interaction might be responsible for the behavioural depressant effects of adenosine agonists and for the behavioural stimulant effects of adenosine antagonists such as caffeine and theophylline. Dopamine denervation induces an increase in the intramembrane A2-D2 interaction, which may underlie the observed higher sensitivity to the behavioural effects induced by adenosine antagonists found in these animals. The present study was designed to examine if chronic treatment with haloperidol, which also produces dopamine receptor supersensitivity, is also associated with an increase in the intramembrane A2-D2 interaction in the neostriatum and with a higher sensitivity to the behavioural effects induced by adenosine antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

The significance of anatomical variations of hepatic artery and multiple arterial supplies in embolization of liver tumors.

A new therapeutic measure-step by step-embolization of every feeding vessel in dealing with liver cancer has been proposed on the base of the following criteria after reviewing the coeliac and superior mesenteric arteriographies in 100 cases of liver cancer. The emphasis is put on: 1. Anatomic variation of hepatic arteries. 2. Multiple feeding vessels, and 3. The importance of the presence of stenosis after embolization and the formation of collateral circulation.

Adult↗

Receptor binding and degradation of urokinase-type plasminogen activator by human mesangial cells.

The binding of [125I] labeled urokinase-type plasminogen activator (u-PA) was studied on human mesangial cells (MC) in culture. The binding of active [125I]u-PA at 37 degrees C reached a plateau after 30 minutes of incubation and remained stable for at least four hours. When the supernatant was analyzed with trichloracetic acid (TCA), TCA soluble radioactive material could be detected after a lag phase of 30 minutes, and then increased linearly for four hours. Analysis by electrophoresis on SDS PAGE and autoradiography of the cell associated radioactivity and of the intracellular content showed that active u-PA and u-PA complexed to plasminogen activator inhibitor type-1 (PAI-1) were bound to the cell surface, but only u-PA/PAI-1 complexes were internalized and degraded. Therefore, the Kd and the number of binding sites were determined by competitive inhibition curves at 4 degrees C using diisopropyl-fluorophosphate (DFP) u-PA. Scatchard plots showed a Kd = 400 +/- 30 pM, and Bmax = 240,000 +/- 25,000 sites/cell. Excess of the amino terminal fragment of u-PA (ATF) completely blocked the specific binding of [125I]u-PA, confirming that the binding of u-PA was independent of the presence of the active site and/or of the formation of complexes with PAI-1. 3H thymidine incorporation by mesangial cells after stimulation with 100 nM active u-PA showed that u-PA had a moderate but significant mitogenic effect, in contrast to inactive u-PA and ATF. However, this mitogenic effect was not accompanied by a proliferative effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Percutaneous balloon mitral valvuloplasty. An observation of 50 patients.

Percutaneous balloon mitral valvuloplasty (PBMV) was successfully performed in 50 selected patients with mitral stenosis by using Inoue pillow-shaped balloon and Inoue technique. The average diameter of balloon used was 26.9 +/- 0.9 mm. 90% (45/50) of cases had either double or single mitral commissura split. Of the rest 5 cases, 1 had a mitral score 13 and 4 had a history of mitral valve commissurotomy. Totally they had a mean mitral valve area increase from 1.13 +/- 0.32 to 2.21 +/- 0.43 cm2, left atrial pressure decrease from 31.8 +/- 9.3 to 14.7 +/- 5.6 mmHg, left atrial diameter reduction from 44.9 +/- 7.7 to 37.4 +/- 4.9 mm, and transmitral gradient decrease from 21.7 +/- 9.8 to 4.0 +/- 5.2 mmHg. Most patients had a obvious cardiac function improvement, especially in patients with mitral score of 8 or less. 30% patients (15/50) had a mild mitral regurgitation, but relieved 3-6 months after procedure. During one year of follow up, the majority of patients (16/20) were found in a good cardiac function, mitral area and the left atrial diameter, except in 4 patients with a high mitral score of more than 10. It is suggested that for patient with lower mitral morphological score and good general health, a larger diameter balloon might be suitable for effectively improving patient's symptom, but for patients with a previous surgical mitral commissurotomy, PBMV should not be selected.

Adult↗

[Quantitative study on DNA-adduct in normal lung tissues of smoking and non-smoking lung cancer patients].

Lung tissues from 32 cases of lung cancer with surgical operation, 22 smokers and 10 nonsmokers, were analyzed with P1-mediated modification of 32P-postlabelling technique. The level of lung DNA-adduct in cigarette smokers was higher that in nonsmokers with significant difference (P < 0.001). Autoradiogram showed a diagonal radioactive zone in smokers' lung tissues. Correlation analysis indicated DNA-adduct in lung tissues increased with the number of cigarettes smoked with a regression equation of Y = 0.411 X + 3.52, r = 0.74, P < 0.001.

Adult↗

Decarboxylation of L-dopa by cultured mouse astrocytes.

Cultured astrocytes contain immunologically specific aromatic L-amino acid decarboxylase (AADC) protein and express the AADC gene. Following incubation with L-Dopa, glial cultures synthesize and metabolize dopamine. The addition of pyridoxal 5-phosphate did not change the rate of dopamine synthesis. The formation of dopamine was blocked by NSD-1015. These experiments show that mouse cultured astrocytes are capable to convert L-Dopa into dopamine in a dose-dependent fashion.

Animals↗

Three-step PCR mutagenesis for 'linker scanning'.

'Linker scanning' has been used as an efficient method for systematically surveying a segment of DNA for functional elements by mutagenesis. A three-step PCR method was developed to simplify this process. In this method, a set of 'mutation primers' was made with 6 to 8 base substitutions in the center of the primers. In the first PCR reaction, these 'mutation primers' are paired with an 3' primer from the opposite end of the analyzed sequences to form a 'ladder' of fragments containing the base pair substitutions. These are used as templates in the second PCR with the 3' primer as the only primer to generate single stranded sequences, which are used as primers in the third PCR paired with an 5' primer to complete the mutagenesis. We have tested the method in a mutation screen of the steroid sulfatase promoter. Its application to general site specific mutagenesis is discussed.

Arylsulfatases↗

Neuromedin N is a potent modulator of dopamine D2 receptor agonist binding in rat neostriatal membranes.

In the concentration range of 1-10 nM, neuromedin N produced a significant concentration-related increase in the Kd values of [3H]L-(-)-N-propylnorapomorphine binding sites in rat neostriatal membranes with a peak action at 10 nM (36% increase versus the control group mean value). The Bmax values were not affected by neuromedin N. Neurotensin at 10 nM induced an increase in the Kd values, which was not affected by a threshold concentration of neuromedin N (0.1 nM). In view of the higher potency of neuromedin N versus neurotensin to modulate neostriatal D2 receptors in contrast to the higher potency of neurotensin versus neuromedin N to bind to the cloned neurotensin receptors, it seems possible that the neuromedin N activated neostriatal neurotensin receptors controlling the D2 receptors represent a distinct subtype of neurotensin receptors.

Animals↗

The C-terminal neurotensin-(8-13) fragment potently modulates rat neostriatal dopamine D2 receptors.

The effects of neurotensin fragments and of neurotensin itself on the characteristics of neostriatal dopamine D2 agonist binding were studied in competition experiments with dopamine using the D2 antagonist, [3H]raclopride. The biologically active neurotensin-(8-13) fragment, but not the inactive neurotensin-(1-7) fragment, caused a concentration-related increase in the KH and KL values of dopamine with a maximal increase by 110 and 97%, respectively, at 1 nM, while neurotensin-(1-13) only induced such changes at 10 nM. In view of the higher potency and the increased ability of neurotensin-(8-13) versus neurotensin (1-13) to reduce the affinities of the high- and low-affinity states of the neostriatal D2 receptors, the C-terminal neurotensin fragments may be among the endogenous ligands of the neostriatal neurotensin receptors.

Animals↗

Persistent effects of subchronic toluene exposure on spatial learning and memory, dopamine-mediated locomotor activity and dopamine D2 agonist binding in the rat.

The effects of subchronic inhalation exposure to toluene (80 ppm, for 4 weeks, 5 days/week, 6 h/day) was studied on spatial learning (postexposure days 3-6) and memory (postexposure day 14) using a water maze, on spontaneous and apomorphine-induced (1 mg/kg, subcutaneously (s.c.)) locomotor activity (postexposure day 17) and on the binding parameters of the dopamine D2 agonist S(-)[N-propyl-3H(N)]propylnorapomorphine ([H]NPA) in membrane preparations of the neostriatum of the rat. Toluene treatment was found to cause a statistically significant impairment in acquisition and retention of the spatial learning task. Furthermore, toluene significantly increased (2-fold) apomorphine-induced locomotion and caused a trend for a 50-60% increase in motility without any significant effect on rearing. Spontaneous locomotion, motility and rearing were not affected by toluene. Toluene treatment produced a significant 30-40% increase in the Bmax values of [3H]NPA and a trend for a 20-30% increase in the KD values. These results indicate that subchronic exposure to toluene in low concentrations causes a slight but persistent deficit in spatial learning and memory, a persistent increase in dopamine-mediated locomotor activity and an increase in the number of dopamine D2 receptors in the rat.

Administration, Inhalation↗

Neurotensin and cholecystokinin octapeptide control synergistically dopamine release and dopamine D2 receptor affinity in rat neostriatum.

Combined perfusion of the neostriatum with 1 nM of cholecystokinin octapeptide (CCK-8) and 0.01, 0.1 or 1 nM of neurotensin was done in the halothane-anesthetized rat after systemic apomorphine treatment (0.05 mg/kg, s.c.). Neurotensin (1 nM) plus CCK-8 (1 nM) effectively counteracted the apomorphine-induced inhibition of neostriatal perfusate levels of dopamine (DA). With a constant concentration of CCK-8 (1 nM), the apomorphine-induced inhibition of DA release was counteracted dose relatedly by neurotensin in concentrations of 0.01, 0.1 and 1 nM. The results of binding experiments demonstrated that threshold concentrations of CCK-8 and neurotensin significantly increased the KD values of the high-affinity D2 receptors without significant alterations in the low-affinity D2 receptors or in the proportion of D2 receptors in the high-affinity state. Thus, neurotensin and CCK receptors may regulate synergistically, via intramembrane interactions with the D2 receptors, the binding characteristics and the signal transduction of D2 autoreceptors in the neostriatum. The combined presence of very low concentrations of CCK-8 and neurotensin in the extracellular fluid may be sufficient to regulate D2 receptor transduction, underlining the important role of these peptide receptor interactions with the D2 receptors.

3,4-Dihydroxyphenylacetic Acid↗

NSD-1015 alters the gene expression of aromatic L-amino acid decarboxylase in rat PC12 pheochromocytoma cells.

Aromatic L-amino acid decarboxylase (AADC) is involved in the synthesis of the putative neurotransmitters dopamine (DA), 5-hydroxytryptamine (5-HT), and trace amines some of which have been proposed as neuromodulators, such as 2-phenylethylamine and tryptamine. We report here that the gene expression of AADC can be regulated by the AADC inhibitor NSD-1015 in PC12 cells. The cells were treated with different doses of NSD-1015 (0.01-10 microM) for 3 days. Slot blot hybridization was performed to detect AADC mRNA and Western immunoblot to detect AADC protein. The cDNA probe for rat AADC was generated by reverse transcription from rat adrenal gland total RNA and was amplified by the polymerase chain reaction (PCR) method. The results demonstrated that NSD-1015 produced a concentration-dependent up-regulation in AADC mRNA levels which is followed by a stable increase in AADC protein. The results suggest that AADC is an enzyme that can be regulated at the level of gene expression. The finding may be of importance in the study of DA transmission and for an improved understanding of this enzyme.

Animals↗

Alterations in 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) mRNA accumulation induced by beta-adrenergic stimulation in cultured porcine granulosa cells.

1. In primary cultures of porcine granulosa cells incubation with isoproterenol (10(-7)-10(-5) M) produced a dose-dependent increase in 3 beta-HSD mRNA, 3 beta-HSD content and progesterone production which ranged from 1.5- to 5-fold. 2. These effects were completely blocked by alprenolol. Terbutaline (10(-6) M) increased 3 beta-HSD mRNA, 3 beta-HSD content and progesterone production (1.5- to 3-fold), an effect which could be prevented by alprenolol. 3. Treatment with dobutamine (10(-6) M) produced no significant change in 3 beta-HSD mRNA accumulation. 4. The results suggest that beta-adrenergic agonists have the capacity to regulate transcription and translation of 3 beta-HSD mRNA in granulosa cells and this effect is mediated by the beta 2 adrenergic receptor.

3-Hydroxysteroid Dehydrogenases↗

Prostaglandins alter the abundance of messenger ribonucleic acid for steroidogenic enzymes in cultured porcine granulosa cells.

The effects of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) on the accumulation of progesterone and mRNA for the steroidogenic enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and cytochrome P450 side-chain cleavage (P450scc) were determined in luteinized granulosa cells. These cells were aspirated from 3-5-mm follicles of prepubertal pigs and cultured 48 h with 10% serum and then 48 h under serum-free conditions. Cells were then incubated with medium (control), ovine LH (20 ng/ml), (bu)2cAMP (0.5 mM) and doses of PGF2 alpha (0.08-2.0 micrograms/ml) or PGE2 (0.1-1.0 micrograms/ml), or combinations of PGF2 alpha (0.1-1.0 micrograms/ml) or PGE2 (0.1-1.0 micrograms/ml) with and without 20 ng/ml LH. Cultures were terminated after 12 h of incubation, and the abundance of mRNA for 3 beta-HSD and P450scc was determined by hybridization with specific cDNA probes. Parallel cultures were terminated at 24 h for analysis of progesterone in the medium by RIA. The results demonstrated that LH and (bu)2cAMP elevated progesterone by 3- to 6-fold and the accumulation of mRNA for 3 beta-HSD by 1.5 to 3.5 or 4-fold and for P450scc by 2-4-fold. PGF2 alpha reduced the basal level of progesterone accumulation, as well as the steady-state concentrations of mRNA for both 3 beta-HSD and P450scc. PGF2 alpha interfered with LH and (bu)2cAMP induction of 3 beta-HSD and P450scc message, and this interference was dependent on the PGF2 alpha dose employed.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗