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Y Hong

Publications and source records attributed to Y Hong.

At least 235 records · Page 13Linked to original sources

Phaclofen-reversible effects of GABA in the spinal cord of the rat.

Our earlier observation that intrathecal administration of L- and D-baclofen had different effects on sympathetic output regulating arterial pressure and heart rate in the rat prompted the present study which was designed to determine whether intrathecal administration of GABA elicits a phaclofen-reversible effect on arterial pressure and/or heart rate and whether this effect mimics that of L-baclofen or that of D-baclofen. Following intrathecal administration of the GABAA antagonist, bicuculline (10 nmol), at the T9 level, administration of GABA at a dose of 5 mumol (n = 8) decreased arterial pressure and heart rate by about 25 mm Hg and 45 bpm, respectively. The responses started at 1-2 min and lasted 3-20 min; comparison was made with rats given NaCl (5 mumol; n = 5), which was without effect on arterial pressure and heart rate. In rats pretreated with both bicuculline and the GABAB antagonist, phaclofen (5 mumol intrathecally; n = 9), the effect of GABA on arterial pressure was attenuated and the effect of GABA on heart rate was absent; comparisons were made with rats given bicuculline, phaclofen and NaCl (n = 5) and with rats given bicuculline, NaCl and GABA (n = 6). These data suggest that there is a phaclofen-reversible effect of GABA in spinal pathways regulating sympathetic output and that this effect of GABA resembles that L-baclofen reported in our earlier study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A redox switch and phosphorylation are involved in the post-translational up-regulation of the adenosine-uridine binding factor by phorbol ester and ionophore.

Messenger RNAs coding for cytokines and lymphokines are extremely unstable due to an AU-rich cis element located in their 3'-untranslated region. Cell activation with phorbol ester 12-O-tetradecanoylphorbol-13-acetate or calcium ionophore has been shown to markedly stabilize these normally labile messages. We have recently described a cytoplasmic protein, denoted the adenosine-uridine binding factor (AUBF) which complexes in vitro to a variety of labile RNAs containing multiple reiterations of the pentamer AUUUA. In order to determine if AUBF plays a role in the stabilization of cytokine and lymphokine mRNAs, we have investigated the mechanisms which control AUBF activity in peripheral blood mononuclear cells as well as Jurkat cells. AUBF is inactive in resting peripheral blood mononuclear cells but can be activated by brief treatment with 12-O-tetradecanoylphorbol-13-acetate or ionophore. Up-regulation is independent of protein synthesis or RNA transcription, suggesting pre-existing AUBF is subject to post-translational modification. AUBF activity can be reversibly blocked by diamide but irreversibly inhibited by n-ethylmaleimide, suggesting that AUBF contains a redox switch as described for other RNA-binding proteins. Finally, AUBF activity is abolished by potato acid phosphatase, demonstrating that AUBF is a phosphoprotein. These data demonstrate that AUBF activity is subject to at least two levels of post-translational regulation and is enhanced by mitogens previously shown to induce the stabilization of AUUUA mRNAs. Based upon these data, we propose that AUBF binding may mediate 12-O-tetradecanoylphorbol-13-acetate and ionophore-mediated labile message stabilization.

Adenosine↗

Cardiovascular responses to intrathecal administration of L- and D-baclofen in the rat.

D- and L-baclofen were given intrathecally at the T2 spinal level in the anaesthetized rat. D-Baclofen, in doses of 7, 35 and 70 nmol produced graded increases in arterial pressure but heart rate remained unaffected. Responses appeared within 30 s, peaked at 2 min and decayed over the next 5 min. Injection i.v. of 70 nmol of D-baclofen failed to alter arterial pressure or heart rate. In contrast, intrathecal administration of L-baclofen decreased both arterial pressure and heart rate. The amplitude and time course of the effects depended on the dose used; 700 nmol of L-baclofen had stronger and longer effects than those induced by 70 nmol, while 7 nmol had no effect. (I.v. injection of 70 nmol of L-baclofen had similar effects to intrathecal administration but with different time course and amplitude.) When given at the T9 level at doses of 70 nmol, D- and L-baclofen had effects similar to those observed at the second thoracic level. Effects of intrathecal administration of D- and L-baclofen at T2 were prevented by pretreatment with either hexamethonium (10 mg/kg i.v.) or lidocaine (25 microliters of a 1% solution, intrathecally). The results suggest that D- and L-baclofen-sensitive receptors in the spinal cord are involved in regulating sympathetic output in pathways to the vessels and/or to the heart. In addition, our results suggest that D- or L-baclofen may not act via classical GABAB receptors or that two types of GABAB receptor exist in spinal sympathetic pathways.

Anesthesia, Local↗

Complement component C1q and its receptor are involved in the interaction of human sperm with zona-free hamster eggs.

C1q is a component of the classical complement pathway that can react with the Fc-fragment of immunoglobulins and with other proteins, such as fibronectin, laminin, and a specific C1q receptor present on several cell types. Given its role in many adhesion systems, mainly related to phagocytosis, we tested the effects of C1q on the interaction between human spermatozoa and zona-free hamster eggs. The presence of C1q in the medium used for gamete coincubation resulted in promotion of sperm-oolemma adhesion and an inhibition of penetration. The number of adherent sperm per egg at 5 micrograms/ml concentration was 90 +/- 35 vs. 29 +/- 7 for the control (P less than 0.001). At 1 microgram/ml, the lower concentration at which C1q had an effect, the number of penetrating sperm/egg was 0.6 vs. 1.7 for the control without C1q (P less than 0.01), and the percent of penetrated eggs was 28% vs. 85%. At 50 micrograms/ml, the percent of penetrated eggs was 7%, with a penetration index of 0.07. The addition of C1q to the medium resulted in sperm agglutination, which varied between sperm donors. The presence of C1q receptors, as detected by anti-C1qR monoclonal antibodies (Mabs), was demonstrated both on zona-free hamster eggs by immunobead rosetting and on human spermatozoa by immunobead binding and indirect immunofluorescence. Mabs directed against different epitopes of C1qR had different effects on gamete interaction, with a partial inhibition of penetration mediated by some of them. The binding of C1q to antibody-free human spermatozoa was also demonstrated both by means of indirect immunofluorescence and utilizing 125I-C1q.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Studies on DNA sequence specific binding proteins for 5' flanking upstream region of CPSI gene.

Two specific carbamyl phosphate synthetase I gene binding nuclear proteins (M. W. 109 kD and 74 kD) have been determined in the rat liver by the protein blotting technique (Southwestern blot assay). The result shows that they are not present in the normal rat spleen and F-26 rat hepatoma cell. The Bal31 nuclease deletion in the CPSI gene 5' upstream region proves that the binding sites for 109 kD and 74 kD are respectively located in the regions of -38 bp to -4 bp and -113 bp to -38 bp. The binding proteins may be the liver-specific ones of the CPSI gene, which are related to hepatocyte differentiation and hepatocarcinogenesis.

Animals↗

Spinal mediation of the increases in arterial pressure and heart rate in response to intrathecal administration of bicuculline.

The present experiments were designed to determine the mechanisms by which the intrathecal administration of the GABAA antagonist, bicuculline (2.2 and 8.8 nmol), at the second thoracic spinal segment (T2) affects cardiovascular function in the anaesthetized rat. Bicuculline produced a dose-related, transient increase in arterial pressure and heart rate which peaked at 5-7 min and persisted for 30 min or more, depending on dose. There was a mutually reversible interaction between bicuculline and intrathecal administration of the GABAA agonist, muscimol (8.8 nmol), which alone decreased arterial pressure and heart rate. Bicuculline was given intrathecally at the third lumbar spinal level (8.8 nmol) and intravenously (8.8 nmol), but in these cases it failed to affect these cardiovascular parameters. Pretreatment with intrathecal infusion of 15 microliters of 1% lidocaine or with intravenous injection of hexemathonium (10 mg/kg) prevented the responses to intrathecal administration of 8.8 nmol of bicuculline at T2. These results demonstrate that the effects of bicuculline on arterial pressure and heart rate are due to an action in the spinal cord on GABAA receptors, and the data may be interpreted as indicating that there is a tonic GABAergic inhibition of sympathetic outflow at the spinal level.

Animals↗

The anatomical location of the transesophageal echocardiographic transducer during a short-axis view of the left ventricle.

This study was performed to clarify the location of a transesophageal echocardiographic (TEE) transducer when obtaining the short-axis view of the left ventricle (S-LV). The depth of the probe tip from the incisors when obtaining a S-LV, the relationship to the diaphragm, and the location of the cardia of the stomach using a gastroscope attached to the TEE probe were measured in 24 patients undergoing coronary artery bypass grafting. The location of the transducer relative to the cardia and diaphragm was determined. The study demonstrated that when obtaining a S-LV, the transducer was in the stomach in 72.7%, at the cardia in 13.6%, and in the esophagus in 13.6% of the patients. The predominantly intragastric position of the transducer suggests that gastric diseases should be included as contraindications to TEE. When the probe was advanced about 40 cm from the incisors, some resistance was often encountered by the TEE operator at about the level of the diaphragm. Careful manipulation is mandatory to avoid tissue damage by the probe. Visualization of the S-LV can be disturbed by gas in the stomach. This is a specific problem in anesthetized patients because gas is often pushed into the stomach at the time of induction.

Adult↗

Intraoperative monitoring of regional wall motion abnormalities for detecting myocardial ischemia by transesophageal echocardiography.

Transesophageal two-dimensional echocardiography has been used for intraoperative monitoring of regional wall motion of the left ventricle. Regional wall motion abnormality is a sensitive indicator of myocardial ischemia and the use of two-dimensional transesophageal echocardiography may have a substantial advantage for early detection of myocardial infarction and thus for initiating timely and appropriate therapy in preventing postoperative myocardial ischemia. With an expected increase in the use of intraoperative transesophageal echocardiography for monitoring regional wall motion, we described the practical aspects of transesophageal echocardiography: (1) insertion technique of transesophageal echocardiographic probe; (2) the technique for obtaining an optimal short-axis view of the left ventricle; and (3) the method for evaluating regional wall-motion abnormality and myocardial ischemia. Regional wall motion abnormality is best monitored at the mid-papillary muscle level where all three coronary arteries meet. In obtaining this view, the transesophageal echocardiographic probe was found to be predominantly located in the stomach. Failure in obtaining short-axis view of the left ventricle at this level occurred in patients with left ventricular dilatation or obesity. Because of the anatomical reason, the echocardiographic transducer cannot reach a proper plane. In anesthetized patients, air can be pushed into the stomach during induction and may disturb the visualization. The pitfalls in examining regional wall motion abnormalities include: (1) shifting of the center of left ventricular contraction; (2) inadequate direction of the scanning plane; and (3) paradoxical septal movement. Three cases are presented to demonstrate the usefulness of transesophageal echocardiography in managing coronary artery surgical patients.

Aged↗

The role of selenium-dependent and selenium-independent glutathione peroxidases in the formation of prostaglandin F2 alpha.

In recent years, growing evidence suggests that glutathione peroxidases (GSH-Pxs), both selenium-dependent GSH-Px (Se-GSH-Px) and selenium-independent GSH-Px (non-Se-GSH-Px) play an important role in the biosynthesis of prostaglandins and leukotrienes and in the regulation of key enzymes associated with the arachidonic acid cascade. The precise nature of their involvement in eicosanoid metabolism, however, is not yet completely understood. In the study reported here, we have systematically determined the catalytic efficiencies of Se-GSH-Px and non-Se-GSH-Px toward prostaglandin (PG) G2 (PGG2) and PGH2. Se-GSH-Px exhibited high catalytic activity for the reduction of PGG2 as indicated by Km and Vmax values of 12 microM and 78 mumol/min/mg, respectively, whereas PGH2 was found to be a poor substrate, an indication that Se-GSH-Px reduces the hydroperoxide moiety but not the endoperoxide moiety of PGG2. The kinetic constants of Se-GSH-Px toward PGG2 were comparable to those determined for such classical substrates as H2O2 and cumene hydroperoxide. In contrast to Se-GSH-Px, non-Se-GSH-Px associated with cationic isozyme II of glutathione S-transferases (GSTs) from sheep lung cytosol was very active in the conversion of PGH2 to PGF2 alpha with a Vmax of 960 nmol/min/mg and a Km of 77 microM. This study shows that PGF2 alpha formation by non-Se-GSH-Px occurred in a GSH-dependent reduction of either PGG2 or PGH2. When PGG2 was used as the substrate for non-Se-GSH-Px, a novel intermediate compound appeared and was later identified by several methods of structural analysis as 15-hydroperoxy PGF2 alpha. Thus, the reductive cleavage of the endoperoxide occurs faster than the 15-hydroperoxide reduction allowing 15-hydroperoxy PGF2 alpha to accumulate briefly. A study of GSTs from several different tissues and species indicated that the transformation of PG endoperoxides to PGF2 alpha is catalyzed specifically by GST isozymes, which contain Ya size subunits. This specificity of GST isozymes in PG biosynthesis, coupled with their tissue-specific expression, may be a mechanism by which the body modulates the type of PGs produced in these tissues. Also, these results suggest a possible interaction of Se-GSH-Px and non-Se-GSH-Px in the biosynthesis of PGF2 alpha.

Animals↗

Serotonin blocks the facilitatory action of muscarinic and nicotinic agents in the hippocampus in vivo.

The inhibitory effect of serotonin, released iontophoretically, on acetylcholine-induced facilitation of population spikes evoked by fimbria-commissural stimulation was studied in the CA1 region of rat hippocampus in vivo. After serotonin was applied for 2.6 +/- 0.8 min, acetylcholine's action was inhibited in 39 cases out of 57 (68.4%), by 68.9 +/- 23.1%, irrespective of whether serotonin alone increased or reduced the population spike. Spiperone, used as a 5-hydroxytryptamine1A (5-HT1A) antagonist, suppressed the inhibitory action of serotonin in 14 of 21 tests. Serotonin had similar effects on population spike facilitations induced by acetyl-beta-methylcholine and dimethylphenylpiperazinium. Thus serotonin, probably acting on 5-HT1A receptors, blocks effectively but indiscriminately all cholinergic facilitations, whether mediated by nicotinic or muscarinic receptors.

Acetylcholine↗

Isozyme specificity of rat liver glutathione S-transferases in the formation of PGF2 alpha and PGE2 from PGH2.

When prostaglandin H2 (PGH2) was incubated with a mixture of glutathione S-transferases (GSTs) obtained from S-hexylglutathione affinity chromatography, as much as 40% of it was transformed into a prostanoid whose Rf value corresponded to that of the standard PGF2 alpha. The reaction product was identified as PGF2 alpha by cochromatography with a standard on TLC and HPLC. The stereochemistry of the hydroxyl groups on C-9 and C-11 of the cyclopentane ring was confirmed by mass-spectral analysis of the butylboronate derivative of the reaction product. Neither PGE2 nor PGD2 could substitute for PGH2 in the reaction mixture, indicating that the mechanism of formation of PGF2 alpha is a direct two-electron reduction of the endoperoxide moiety and not through a reduction of the keto group on PGE2 or PGD2. Individual GST isozymes exhibited distinct differences in their catalytic rates of formation of PGF2 alpha from PGH2. Among various GSTs, isozyme IV, a homodimer of Ya size subunit showed the highest activity with a Vmax value of approximately 6000 nmol.min-1.mg-1. In general, the isozymes containing Ya and Yc subunits exhibited relatively high activity toward PGH2, indicating that it is the non-selenium-dependent glutathione peroxidase activity associated with the GSTs that might be responsible for the reduction of PGH2 to PGF2 alpha. Interestingly, isozyme IV also exhibited the highest PGE2 forming activity with a Vmax value of approximately 3000 nmol.min-1.mg-1 followed by isozyme I, a homodimer of Yb subunit, which had a Vmax value of 420 nmol.min-1.mg-1. Based on these results, it appears that the GSTs play an important role in the biosynthesis of classical PGs. Therefore, it is conceivable that the tissue-specific formation of PGF2 alpha and PGE2 might, in part, be due to the relative distribution of these enzyme activities in a given tissue. Our results have not only confirmed the previously published reports (E. Christ-Hazelhof et al. (1976) Biochim. Biophys. Acta 450, 450-461), but also have characterized the specificity of GST isozymes in the formation of PGF2 alpha.

Animals↗

Retained intracardiac air. Transesophageal echocardiography for definition of incidence and monitoring removal by improved techniques.

Retained intracardiac air is a continuing hazard for cardiopulmonary bypass. M-mode transesophageal echocardiography of the left atrium, left ventricle, and aorta is a highly sensitive method for detecting retained intracardiac air bubbles. In 15 patients having valve operations and 18 having coronary bypass, M-mode transesophageal echocardiography was used to record air bubbles during and for 15 minutes after bypass. Routine air clearing methods were used: needle aspiration of the ascending aorta (combined coronary and valve operations) and left atrial, left ventricular, and aortic aspiration after careful passive chamber filling (valve operations). Air was detected in 12 of 15 (79%) patients having valve operations and two of 18 (11%) patients having coronary bypass. One with air in the aorta had visible right coronary air embolism. Three patients with positive echograms had transient central nervous system disturbances. In a further 11 patients having valve operations, an ascending aorta-venous shunt was created before bypass was discontinued, but air continued to be present in the left atrium. Finally, in seven patients, we added the following maneuvers to our routine: positive chamber filling with echocardiographic demonstration of left atrial stretching, vigorous chamber ballottement, specific echo-directed chamber aspiration, and maintenance of cardiopulmonary bypass until transesophageal echocardiography showed no retained air. Although small amounts of atrial air could still be detected for a minute or two in some patients, this technique appears finally to have eliminated significant retained air and its consequences. A sensitive technique for intracardiac air detection reveals retained air surprisingly often after cardiopulmonary bypass. There are both possible and probable adverse consequences of this air. After valve operations, it is most difficult to eliminate air from the left atrium. There are three essential elements of air removal: First is mobilization of the air; positive chamber filling, stretching of the atrial wall, and ballottement are critical. Second is removal of mobilized air; continuous ascending aorta-venous shunting and nonsuction venting of the left atrium are very important. Third is proof of elimination of air before cardiopulmonary bypass is terminated; transesophageal echocardiography is vital for this.

Adult↗

Protamine-induced circulatory changes.

The effects of rapid protamine administration via the left and right atria were compared. Preliminary studies first confirmed the safety of protamine administration via these routes, although decreases of up to 20 mm Hg were seen in the systolic blood pressure following protamine injection via the right atrium. Seventeen patients undergoing coronary artery bypass graft were studied, of whom nine received protamine via the right atrium and eight via the left atrium. Measurements of arterial pressure, left and right atrial pressure, cardiac output, and calculation of systemic vascular resistance and left ventricular stroke work index were made before and after protamine administration. Plasma histamine levels were measured in left atrial blood samples in 10 patients, before and after protamine injection. No significant change occurred after injection via the left atrial route, whereas a significant decrease in the systolic blood pressure and systemic vascular resistance with a transient increase in the cardiac index occurred after protamine administration via the right atrium. Plasma histamine levels were significantly higher after right atrial injection. It is concluded that histamine is released as protamine traverses the lungs following right atrial injection and produces peripheral vasodilation. Possible mechanisms for histamine release are discussed.

Aged↗