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Biomedical subjects

C Tsai

Publications and source records attributed to C Tsai.

At least 55 records · Page 3Linked to original sources
PubMed1988

Homocysteic acid as a putative excitatory amino acid neurotransmitter: I. Postsynaptic characteristics at N-methyl-D-aspartate-type receptors on striatal cholinergic interneurons.

The actions of the stereoisomers of homocysteic acid (HCA) were characterized at N-methyl-D-aspartate (NMDA)-type receptors which mediate excitatory amino acid-evoked [3H]acetylcholine ([3H]ACh) release from striatal cholinergic interneurons. Like NMDA, L-HCA and D-HCA evoked the release of [3H]ACh formed from [3H]choline in striatal slices. The concentration-response curve for L-HCA was virtually superimposable on that for NMDA, yielding an equal EC50 value (56.1 microM) and maximal response. However, D-HCA was weaker, with an EC50 value of 81.1 microM, and an apparently smaller maximal response. L-HCA-evoked [3H]ACh release was inhibited by the same categories of compounds which inhibit NMDA-evoked [3H]ACh release: the divalent ion Mg2+ (IC50 = 25.8 microM); competitive NMDA antagonists 2-amino-7-phosphonoheptanoate (IC50 = 51.2 microM) and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (IC50 = 20.1 microM); and the dissociative anesthetics tiletamine (IC50 = 0.59 microM) and MK-801 (IC50 = 0.087 microM). Like NMDA, L-HCA produced a tachyphylaxis in this system. Tachyphylaxis to NMDA resulted in a decrease response to L-HCA, and conversely, tachyphylaxis to L-HCA resulted in a decrease response to NMDA. The results suggest that L-HCA is an agonist at the NMDA-type receptor and may represent an endogenous ligand for this excitatory amino acid receptor.

2-Amino-5-phosphonovalerate↗
PubMed1988

Sodium fluxes modulating neuronal glutamate uptake: differential effects of local anesthetic and anticonvulsant drugs.

Local anesthetics and anticonvulsant drugs were differentiated biochemically by quantitating their effects on aconitine- and ouabain-induced inhibition of L-[3H]glutamate uptake in synaptosomes. Amine local anesthetics reversed the inhibition by both compounds whereas the anticonvulsant drugs such as carbamazepine and diphenylhydantoin reversed the effects of aconitine but not ouabain. These results support the concept that carbamazepine and diphenylhydantoin interact with voltage-sensitive Na channels to block Na conductance whereas the amine local anesthetics are less specific in their actions.

Aconitine↗
PubMed1988

CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist.

CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid) was found to be a potent, stereospecific inhibitor of N-methyl-D-aspartate (NMDA)-evoked, but not KCl-evoked, [3H] acetylcholine release from slices of the rat striatum. The concentration-response curve to NMDA was shifted to the right by CGS 19755 (pA2 = 5.94), suggesting a competitive interaction with NMDA-type receptors. CGS 19755 inhibited the binding of [3H]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to NMDA-type receptors with an IC50 of 50 nM, making it the most potent NMDA-type receptor antagonist reported to date. CGS 19755 failed to interact with 23 other receptor types as assessed by receptor binding, including the quisqualate- and kainate-type excitatory amino acid receptors. In crude P2 fractions, no evidence was obtained to suggest that CGS 19755 is taken up by an active transport system. Furthermore, CGS 19755 failed to affect the uptake of L-[3H]glutamate, or to interact with aconitine-induced inhibition of L-[3H]glutamate uptake, the latter finding suggesting a lack of membrane-stabilizing or local anesthetic properties. CGS 19755 selectively antagonized the excitatory effect of iontophoretically applied NMDA in the red nucleus of the rat without affecting the excitatory effects of quisqualate. CGS 19755 blocked the harmaline-induced increase in cerebellar cyclic GMP levels at a dose of 4 mg/kg i.p. with a duration of action exceeding 2 hr. CGS 19755 inhibited convulsions elicited by maximal electroshock in rat (ED50 = 3.8 mg/kg i.p. 1 hr after administration) and in mouse (ED50 = 2.0 mg/kg i.p. 0.5 hr after administration). Likewise, convulsions elicited by picrotoxin were inhibited by CGS 19755, whereas the compound was relatively weak in protecting against convulsions elicited by pentylenetetrazole or strychnine. CGS 19755 produced retention performance deficits in a dark avoidance task. However, CGS 19755 did not show a unique propensity for learning and memory disruption compared to other anticonvulsants.

Acetylcholine↗
PubMed1987

CPP, a selective N-methyl-D-aspartate (NMDA)-type receptor antagonist: characterization in vitro and in vivo.

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) was synthesized as a rigid analog of 2-amino-7-phosphonoheptanoate, a previously known antagonist at the N-methyl-D-aspartate (NMDA) preferring, or NMDA-type, of excitatory amino acid receptor. CPP was found to be a potent, selective and competitive antagonist of NMDA-type receptors. CPP antagonized with an IC50 of 8 muM [3H]ACh release which was evoked from rat striatal brain slices by NMDA (50 muM). In contrast, the release of [3H]ACh evoked by elevated KCI was not inhibited by CPP even at a concentration of 100 muM. The antagonism by CPP of NMDA-evoked [3H]ACh release was competitive, with a pA2 of 5.66 for CPP, compared with a pA2 value of 5.22 for 2-amino-7-phosphonoheptanoate. CPP affected neither the uptake of L-[3H]glutamate nor the inhibition by aconitine of L-[3H]glutamate uptake, suggesting a lack of membrane-stabilizing or local anesthetic effects, and also suggesting that CPP itself may not be taken up through the L-glutamate membrane transporter. Moreover, [3H] CPP was not accumulated by synaptosomes (P2 fraction) which avidly accumulate L-[3H]glutamate, supporting the concept that this NMDA-type receptor antagonist acts at an NMDA-type receptor on the external surface of the plasma membrane. CPP (10 muM) failed to interact with any of 21 other putative neurotransmitter receptors including alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding (quisqualate-type receptor) and [3H]kainate binding (kainate-type receptor). Audiogenic convulsions in DBA/2 mice were blocked by CPP (ED50 = 1.5 mg/kg i.p.) as were NMDA-induced seizures in CF-1 mice (ED50 = 1.9 mg/kg i.p.). In both strains, CPP impaired the traction reflex at higher doses (ED50 = 6.8 mg/kg and 6.1 mg/kg and 6.1 mg/kg i.p. for DBA/2 and CF-1, respectively). The traction reflex impairment by CPP may be due to muscle relaxant effects of the compound, an explanation supported by the finding that CPP reduced muscle tone as assessed by electromyogram measurement in animals whose muscle tone had been increased by opiate administration. Finally, cerebellar cyclic GMP levels, known to be sensitive to neurotransmission via NMDA-type receptors, were decreased by CPP (ED50 = 4.7 mg/kg i.p.) in mice. In conclusion, based upon the competitive antagonism by CPP of NMDA-evoked [3H] ACh release in vitro and the antagonism of NMDA-induced convulsions in vivo, the data presented are consistent with competitive antagonism of NMDA-type receptors.

Acetylcholine↗
PubMed1986

Immunochemistry of urinary calcium oxalate crystal growth inhibitor (CGI).

Calcium oxalate crystal growth inhibitor (CGI) was isolated from human urine in monomeric form (14,000 daltons). Antibody was elicited and purified to monospecificity by affinity chromatography. Tamm-Horsfall protein was isolated from human urine and an antibody to Tamm-Horsfall protein compared to anti-CGI. The anti-CGI reacted with its antigen on immunodiffusion, by ELISA and by Western Blotting of polyacrylamide gel electrophoresis-separated antigen. Immunofluorescent localization of CGI was found in distal renal tubules. This was precisely the localization of Tamm-Horsfall protein. Isolated Tamm-Horsfall protein was found to bind CGI which could only be partially removed with EDTA. While anti-CGI is suitable to assay CGI in human urine by ELISA techniques, it will also detect CGI that is complexed to THP. While the CGI found in human urine possesses 90% of the urinary macromolecular crystal growth inhibitor activity, THP is without effect on crystal growth, in spite of bound CGI. The balance between free CGI and that bound to Tamm-Horsfall protein may be important in the overall balance of urinary macromolecules that affect calcium oxalate nephrolithiasis.

Calcium Oxalate↗
PubMed1986

Effect of intrahepatic arterial infusion of 131I-labelled lipiodol on hepatocellular carcinoma of rat.

Intrahepatic arterial infusion of 131I-labelled lipiodol was performed to study the intrahepatic distribution of lipiodol and to determine the radiation effect on 3'-Methyl-4-Dimethylaminobenzene (DAB) induced hepatocellular carcinoma (HCC) in rats. From the findings of the softex films and scintigrams of the liver, according to the time course, lipiodol was found to accumulate in the tumour tissues parallel with the degree of perfusion, and it remained in the tumour tissues for an extended period probably due to the delay of the degradation of lipiodol compared to that in non tumour tissues. It was noticed that the lipiodol, accumulated and deposited selectively in the tumour tissues, existed mostly in the extracellular space but not in the intracellular space. In histological studies of the resected specimens of the tumours, complete necrosis of hepatocellular carcinoma was recognized 2 to 8 weeks after the infusion of 131I-labelled lipiodol, while there was none in the control group where cold lipiodol was employed. These results suggest that the most effect on hepatocellular carcinoma in this study is caused by the radiation effect of 131I-labelled lipiodol.

Animals↗
PubMed1984

Total lipid and cholesterol content in the blue crab, Callinectes sapidus Rathbun.

Total lipid and cholesterol concentrations in hepatopancreas, gonad and muscle were analyzed for 70 blue crabs. The concentrations were highest in hepatopancreas, then gonad, and muscle was the lowest. In male crabs, the concentrations decreased from the immature stage (feeding and growth stage) to the mature stage (breeding stage), and from August to September (breeding period) in mature males. In female crabs, the concentrations were comparatively high for peelers (pre-molting stage) and mature females in October (pre-spawning migration period). The total lipid and cholesterol concentrations were significantly, positively correlated in both sexes. The total lipid and cholesterol concentrations were independent of both body weight and tissue weight. Exceptions were the immature females whose concentrations in hepatopancreas were negatively correlated with both body weight and hepatopancreas weight, and the mature females whose concentrations in gonads were positively correlated with gonad weight.

Animals↗
PubMed1984

Monoclonal antibody to type IV collagen with selective basement membrane localization.

A monoclonal antibody (MCA IV-1) has been developed to a determinant of the high molecular weight fractions of human placental collagen, present also in bovine lens capsule and glomerular basement membrane type IV collagens. This unique determinant is pepsin and collagenase resistant and is apparently distinct from the alpha 1(IV) and alpha 2(IV) helical peptides. As part of the high molecular weight molecules, the determinant is located in a region additively deformable by reduction and sodium dodecyl sulfate denaturation. However, when a 20-kilodalton, largely collageneous, fragment containing this determinant is separated from the larger fraction by 37 degrees C collagenase treatment, the determinant is insensitive to reduction or sodium dodecyl sulfate denaturation. Immunohistologic analysis and comparison with a polyclonal antibody to type IV collagen shows a marked selectivity of localization in the glomerular basement membrane. MCA IV-1 reacts in the inner aspect of the glomerular basement membrane but primarily in the mesangium, where it selectively expands in diabetic nephropathy. Tissue selectivity is also evident in lens and corneal basement membrane.

Animals↗
PubMed1982

CGS 8216: receptor binding characteristics of a potent benzodiazepine antagonist.

CGS 8216 is a novel nonbenzodiazepine that inhibited 3H-flunitrazepam (3H-FLU) binding to rat synaptosomal membranes in vitro at subnanomolar concentrations. It prevented the in vivo labeling of brain benzodiazepine receptors by 3H-FLU with the same potency as diazepam when given orally to mice. Pharmacologic tests showed that it was devoid of benzodiazepine-like activity but it antagonized the actions of diazepam in these tests. It did not interact with alpha- or beta- adrenergic, H1-histaminergic or GABA receptors but it inhibited adenosine-activation of cyclic AMP formation. Studies with 3H-CGS 8216 demonstrated that it bound specifically and with high affinity to rat forebrain membranes and was displaced by drugs with an order of potencies similar to that observed when 3H-diazepam and 3H-FLU were used as radioligands. The regional distribution of 3H-CGS 8216 binding sites in the brain was also similar to that of 3H-FLU. Dissociation of 3H-CGS 8216 binding was slow at 0 degrees C but increased with temperature and was almost complete within 1 min at 37 degrees C. Scatchard analyses were linear, yielding KD values of 0.044, 0.11 and 0.18 nM at 0, 25 and 37 degrees C, respectively; the Bmax value did not change appreciably with temperature and was approximately 1000 fmoles/mg protein. Using 3H-FLU, the value for Bmax as well as for the KD increased with temperature. The total number of binding sites determined for 3H-FLU was greater than that for 3H-CGS 8216 at each temperature. CGS 8216 exhibited mixed-type inhibition of 3H-FLU binding. GABA did not stimulate 3H-CGS 8216 binding whereas it enhanced 3H-FLU binding. CGS 8216 may be a useful ligand for probing the antagonist properties of the benzodiazepine receptor and is likely to exhibit interesting therapeutic effects.

Animals↗
PubMed1980

Effect of thirty-two per cent dextran 70 on peritoneal adhesion formation and re-formation after lysis.

Thirty-two per cent dextran 70 in dextrose (Hyskon) has been reported effective in limiting adhesion formation following a peritoneal injury when employed in doses larger than that known to be safe for intraperitoneal use in humans. The effectiveness of a lower dosage believed to be safe for human use was investigated. Female rabbits received a standardized injury to their uterine horns and proximal fallopian tubes. Following the injury, Hyskon (2.5 ml/kg of body weight) was dripped over the sites of injury in the treatment group. Animals were reoperated upon 2 weeks later, and adhesions were scored. Hyskon significantly reduced adhesion formation. In a second experiment the effect of Hyskon on adhesion re-formation was evaluated. Adhesions were induced in the same manner. Two weeks later, the animals were reoperated upon, and adhesions were scored and lysed. Hyskon was instilled in the treatment group as in the first experiment. No significant difference was noted between adhesion scores in control and treatment groups after adhesion induction or when re-evaluated 2 weeks after lysis.

Animals↗
PubMed1976

Ultrastructure and biochemical studies of rat CNS and viscera after subcutaneous injection of chlorphentermine.

Ultrastructural and biochemical studies were carried out on three groups of experimental models which were induced by a single subcutaneous daily dose of 10 to 40 mg./kg. body weight of chlorphentermine hydrochloride. The first group consisted of 20 young adult rats which were sacrificed at intervals of from one to four weeks. The liver and lungs showed concentrically arranged memberanous bodies in the hepatocytes and alveolar cells during the first week after the first injection, while the CNS and pancreas showed no ultrastructural alterations. During the fourth week, the pancreas displayed abnormal cytoplasmic inclusion bodies in the A and B cells of the islets of Langerhans as well as in the exocrine portion. The brain showed various neuronal alterations at four weeks which consisted of irregular dense bodies to well-developed membranous structures which were similar to those of Tay-Sachs disease. Biochemically, thin layer chromatograms showed that the major ganglioside fraction in the brain at four weeks had an RF value similar to that of GM1-ganglioside. In an analysis of the total N-acetyl neuraminic acid the brains in the experimental group contained 90.9% GM1-gandlioside as compared with 44% in the controls. The total and fractions of phospholipids in the brains and livers of the experimental animals were within normal limits.

Animals↗