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Biomedical subjects

Y Goda

Publications and source records attributed to Y Goda.

At least 73 records · Page 4Linked to original sources
PubMed1994

Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse.

Mice carrying a mutation in the synaptotagmin I gene were generated by homologous recombination. Mutant mice are phenotypically normal as heterozygotes, but die within 48 hr after birth as homozygotes. Studies of hippocampal neurons cultured from homozygous mutant mice reveal that synaptic transmission is severely impaired. The synchronous, fast component of Ca(2+)-dependent neurotransmitter release is decreased, whereas asynchronous release processes, including spontaneous synaptic activity (miniature excitatory postsynaptic current frequency) and release triggered by hypertonic solution or alpha-latrotoxin, are unaffected. Our findings demonstrate that synaptotagmin I function is required for Ca2+ triggering of synchronous neurotransmitter release, but is not essential for asynchronous or Ca(2+)-independent release. We propose that synaptotagmin I is the major low affinity Ca2+ sensor mediating Ca2+ regulation of synchronous neurotransmitter release in hippocampal neurons.

Animals↗
PubMed1994

Involvement of 5-HT3 receptors in the initiation of pharyngeal reflex.

Activation of peripheral serotonin (5-HT) receptors, classified as 5-HT3, was shown to elicit the pharyngeal reflex in anesthetized rats. Intravenous bolus injection of 5-HT (6.25-50 micrograms/kg) evoked rhythmic bursts in the efferent pharyngeal branch of the vagus nerve in a dose-related manner, whereas afferent superior laryngeal nerve activity was not altered by even a high dose of 5-HT. The pharyngeal branch response was blocked by pretreatment with a selective 5-HT3-receptor antagonist YM060 (1 and 10 micrograms/kg). A 5-HT3-receptor agonist, 2-methyl-5-HT, also produced a rhythmic burst in the pharyngeal branch, and this effect was blocked by YM060. Intrapharyngeal pressure was rhythmically increased by both 5-HT (12.5-50 micrograms/kg) and 2-methyl-5-HT (6.25-50 micrograms/kg) in a dose-related manner. Both of these effects were antagonized by YM060 (10 micrograms/kg). In addition, a neuromuscular blocking agent vecuronium (1 mg/kg iv) completely inhibited the 5-HT-induced increase in pharyngeal pressure. After a bilateral vagotomy was performed below the nodose ganglia, the 5-HT-induced increase in pharyngeal branch activity was abolished, whereas a bilateral sectioning of the superior laryngeal nerve did not alter the 5-HT-induced increase in pharyngeal branch activity. Retrograde tracing with fluorescent dye (fast blue) was used to identify the cell bodies of the pharyngeal branch. Pharyngeal motoneuron cell bodies were distributed along the entire length of the nucleus ambiguus. Our results suggest that exogenous 5-HT-induced increases in pharyngeal branch activity and intrapharyngeal pressure may be initiated by the peripheral 5-HT3-receptors of the vagal nervous system and that this may be a viscerosomatic reflex.

Animals↗
PubMed1994

Identification of adducts formed by reaction of purine bases with a mutagenic anthraquinone, lucidin: mechanism of mutagenicity by anthraquinones occurring in rubiaceae plants.

A mutagenic anthraquinone, lucidin (1), occurring in Rubiaceae plants, reacted with nucleic bases under physiological conditions to form adducts. The order of the reactivity is as follows: adenine > guanine >> pyrimidine bases approximately 0. By spectroscopic analyses, the isolated purine base adducts were identified as condensed reactants at the benzylic position of 1 with a nitrogen atom of a purine base. The results indicate a strong possibility of the formation of an exomethylenic compound as an electrophile intermediate.

Anthraquinones↗
PubMed1994

[Increased fibrinolytic activity during cardiopulmonary bypass is caused by activated protein C system].

To examine the hypothesis that activated protein C system during cardiopulmonary bypass surgery may increase fibrinolytic activity during cardiopulmonary bypass, protein C activity, protein C antigen and thrombomodulin of sixteen patients undergoing elective cardiopulmonary bypass surgery were investigated after induction of anesthesia, before and after cardiopulmonary bypass, and at the end of operation. Protein C activity decreased and thrombomodulin increased significantly after the cardiopulmonary bypass. There were no significant correlations of thrombomodulin with protein C activity and protein C antigen. In conclusion, we have demonstrated that protein C system is activated and circulating thrombomodulin appears in the systemic circulation during cardiopulmonary bypass surgery and this enhanced activation of protein C system is possibly related to the reported increase of fibrinolytic activity during cardiopulmonary bypass.

Anesthesia↗
PubMed1993

Modified hippocampal long-term potentiation in PKC gamma-mutant mice.

Calcium-phospholipid-dependent protein kinase (PKC) has long been suggested to play an important role in modulating synaptic efficacy. We have created a strain of mice that lacks the gamma subtype of PKC to evaluate the significance of this brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable, develop normally, and have synaptic transmission that is indistinguishable from wild-type mice. Long-term potentiation (LTP), however, is greatly diminished in mutant animals, while two other forms of synaptic plasticity, long-term depression and paired-pulse facilitation, are normal. Surprisingly, when tetanus to evoke LTP was preceded by a low frequency stimulation, mutant animals displayed apparently normal LTP. We propose that PKC gamma is not part of the molecular machinery that produces LTP but is a key regulatory component.

Animals↗
PubMed1993

Rab9 functions in transport between late endosomes and the trans Golgi network.

Rab proteins represent a large family of ras-like GTPases that regulate distinct vesicular transport events at the level of membrane targeting and/or fusion. We report here the primary sequence, subcellular localization and functional activity of a new member of the rab protein family, rab9. The majority of rab9 appears to be located on the surface of late endosomes. Rab9, purified from Escherichia coli strains expressing this protein, could be prenylated in vitro in the presence of cytosolic proteins and geranylgeranyl diphosphate. In vitro-prenylated rab9 protein, but not C-terminally truncated rab9, stimulated the transport of mannose 6-phosphate receptors from late endosomes to the trans Golgi network in a cell-free system that reconstitutes this transport step. Rab7, a related rab protein that is also localized to late endosomes, was inactive in the in vitro transport assay, despite its efficient prenylation and capacity to bind and hydrolyze GTP. These results strongly suggest that rab9 functions in the transport of mannose 6-phosphate receptors between late endosomes and the trans Golgi network. Moreover, our results confirm the observation that a given organelle may bear multiple rab proteins with different biological functions.

Amino Acid Sequence↗
PubMed1993

[Pharmacodynamics of vecuronium in the kidney transplant recipient and the patient with normal renal function].

Pharmacodynamics of vecuronium were evaluated in seven kidney transplant recipients and compared with seven patients with normal renal function. Vecuronium 0.12 mg.kg-1 was used for the initial dose and 0.03 mg.kg-1 for the second dose for each patient under general anesthesia with either isoflurane, sevoflurane or halothane plus nitrous oxide after induction by thiamylal. The effect of vecuronium was evaluated by a muscle relaxation monitor. The time to the maximum blockade (onset time) and the time of 25% recovery of the first twitch height (duration time) were measured after each administration of vecuronium in patients of both groups. The onset times after the initial and second doses were similar in both groups (180.0 +/- 15.5 sec for recipients versus 185.7 +/- 14.9 sec for patients of normal renal function). However, duration was significantly longer in recipients than in patients of normal renal function. Durations after the initial and second doses were 130 +/- 19 min for the initial dose and 86 +/- 12 min for the second dose in recipients, whereas they were 51 +/- 5 min and 37 +/- 5 min in patients of normal renal function. The prolonged durations of vecuronium in the kidney transplant recipient were speculated to be mainly due to delayed elimination of the drug and effect of cyclosporin, an immunosuppressive agent in the recipients. These results suggest that the titrated administration of vecuronium by keen monitoring of muscle relaxation is needed in the kidney transplant recipient to avoid unnecessary prolongation in duration of action.

Adolescent↗
PubMed1993

[Ventilatory mechanical analysis of respiratory depression induced by serotonin].

This study was aimed to prove the pharmacological characteristics of 5-hydroxytryptamine (5-HT)-induced respiratory depression, especially apnea. Effects of 5-HT-receptor agonists and antagonists on respiratory parameters were examined using anesthetized and spontaneously breathing rats. A bolus intravenous administration of 5-HT (3.125-25 micrograms/kg) immediately produced an apnea, the duration of which increased in a dose-related manner. This response was antagonized by a selective 5-HT3-receptor antagonist, GR38032F (10 and 100 micrograms/kg). Ketanserin, a 5-HT2-receptor antagonist, 100 micrograms/kg also inhibited the 5-HT-induced apnea. In addition, the effect of 5-HT-induced apnea mimicked by 2-methyl-5-HT (3.125-50 micrograms/kg), a 5-HT3-receptor agonist, and by alpha-methyl-5-HT (3.125-25 micrograms/kg), a 5-HT2-receptor agonist. On the other hand, 5-HT produced a decrease in lung compliance and an increase in lung resistance in a dose-related manner. The 5-HT-induced changes in lung compliance and lung resistance were antagonized by ketanserin (100 micrograms/kg), but not by GR38032F (100 micrograms/kg). Furthermore, alpha-methyl-5-HT caused bronchoconstriction as did 5-HT, but 2-methyl-5-HT did not. Although bilateral vagotomy at the supra-nodose ganglia completely prevented 5-HT-induced apnea, cervical vagotomy below the superior laryngeal nerve did not prevent this change. On the other hand, cervical vagotomy almost prevented bronchoconstrictive responses, and completely blocked alpha-methyl-5-HT-induced apnea. These results suggest that 5-HT-induced apnea might be mediated through 5-HT3-receptor mechanisms of the vagal afferent system including the nodose ganglia, and that 5-HT2-receptor mechanisms also contribute to the apnea via the afferent cervical vagus nerves. Direct and indirect bronchoconstriction might also be partly involved in 5-HT-induced apnea.

Airway Resistance↗
PubMed1992

Regional differences in skin blood flow and temperature during total spinal anaesthesia.

Three patients were studied to determine the changes in regional skin temperature and blood flow during extensive sympathetic blockade following total spinal anaesthesia (TSA). Skin temperature was measured at the right upper arm, the right anterior chest at the nipple level, the right hand and the foot, using infrared thermography. Skin blood flow of the right upper arm (C6 area) was measured with a laser Doppler flowmeter. The temperature of the truncal area, arm and leg decreased by 1 degree C following TSA, whereas the temperature of the hand and foot increased by 3 degrees C. The mean blood flow in three patients decreased to 26.1, 61.4, 51.7% of the control values 15 min after TSA. Our results indicate that extensive sympathetic nervous blockade during total spinal anaesthesia induces regional different changes in skin temperature and decrease in truncal skin blood flow.

Anesthesia, Spinal↗
PubMed1992

The mutagenic constituents of Rubia tinctorum.

Twenty compounds were isolated from the roots of Rubia tinctorum which are used as a commercial source of madder color. Among these compounds, mollugin (1), 1-hydroxy-2-methylanthraquinone (2), 2-ethoxymethylanthraquinone(11), rubiadin (13), 1,3-dihydroxyanthraqunone (14), 7-hydroxy-2-methylanthraquinone (16), lucidin (17), 1-methoxymethylanthraquinone (18) and lucidin-3-O-primeveroside (19) showed mutagenicity with Salmonella typhimurium TA 100 and/or TA 98. Since the mutagenic compounds isolated are anthraquinone derivatives with the exception of compound 1, structure-mutagenicity relationships of the anthraquinones were also studied. The results suggested that the greatest activity is exhibited by 1,3-dihydroxyanthraquinones possessing methyl or hydroxylmethyl group on carbon 2.

Anthraquinones↗
PubMed1992

3-anilino-L-alanine, structural determination of UV-5, a contaminant in EMS-associated L-tryptophan samples.

An aniline derivative which corresponds to UV-5 in the preceding paper was isolated from the case L-tryptophan sample associated with eosinophilia-myalgia syndrome (EMS). By spectroscopic analyses, the structure was identified as 3-anilinoalanine. The compound was optically active, and the stereochemistry of alanine moiety was determined as L, by comparing the specific rotation with a synthesized 3-anilino-L-alanine.

Alanine↗
PubMed1992

Inhibitors of prostaglandin biosynthesis from Dalbergia odorifera.

The root heartwood of Dalbergia odorifera T. Chen (Leguminosae) is a Chinese medicinal drug (Japanese name koshinko) used for a stagnant blood syndrome (stagnation of disordered blood; Japanese, oketsu). In addition to 10 known compounds, five new phenolic compounds, isomucronustyrene and hydroxyobtustyrene (cinnamylphenols), (+)-isoduartin (isoflavan), odoriflavene (isoflav-3-ene) and (-)-odoricarpan (pterocarpan) were isolated and their structures were elucidated on the basis of chemical and spectroscopic methods. Of the fifteen compounds isolated, cinnamylphenols, isoflavans, isoflavene and benzoic acid derivative significantly inhibited prostaglandin biosynthesis as well as platelet aggregation induced by arachidonic acid.

Cyclooxygenase Inhibitors↗
PubMed1992

Pharmacological characterization of 5-hydroxytryptamine-induced apnea in the rat.

To improve the pharmacological characterization of the receptors mediating 5-hydroxytryptamine (5-HT)-induced apnea the inhibitory effects of exogenous 5-HT on respiration and phrenic nerve activity (PNA) were studied in anesthetized rats. The effects of putative 5-HT receptor agonists and antagonists on respiratory parameters were examined. During spontaneous respiration the bolus i.v. injection of 5-HT (3.125-25 micrograms/kg) produced a transient apnea, the duration of which increased in a dose-related manner. In addition, during artificial respiration 5-HT produced a silent response of PNA, the duration of which increased dose-dependently. These responses were significantly antagonized by GR38032F, a selective 5-HT3 receptor antagonist. Ketanserin (100 micrograms/kg) and methysergide (100 micrograms/kg), 5-HT2 receptor antagonists, also inhibited the 5-HT-induced apnea. These effects of 5-HT on respiration were mimicked by 2-methyl-5-HT (3.125-25 micrograms/kg), a selective 5-HT3 receptor agonist, and by a high dose of alpha-methyl-5-HT, a 5-HT2 receptor agonist, but not by 5-carboxamidotryptamine, a 5-HT1-like receptor agonist. Lung compliance was greatly reduced and lung resistance greatly increased by 5-HT (3.125-25 micrograms/kg). The 5-HT-induced changes in lung compliance and lung resistance were antagonized markedly by both ketanserin (100 micrograms/kg) and methysergide (100 micrograms/kg), but not by GR38032F (100 micrograms/kg). Bilateral vagotomy above the nodose ganglia completely prevented both the changes in PNA and the apnea induced by 5-HT. These actions of 5-HT were not prevented, however, by cervical vagotomy below the level of the nodose ganglion. On the other hand, this cervical vagotomy completely blocked the alpha-methyl-5-HT-induced apnea.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1992

[Perioperative management for patients with hypertrophic cardiomyopathy undergoing noncardiac surgery].

We had two patients with hypertrophic cardiomyopathy for noncardiac surgeries. Case 1: A 74-year-old man for right nephrectomy received epidural lidocaine and nitrous oxide combined with 0.2-0.6% isoflurane. During the operation, heart rate and blood pressure were relatively unstable, but he woke up promptly after the operation. Early on the morning of the 2nd post-operative day, he was found dead on his bed. Case 2: A 52-year-old man for gastrectomy was anesthetized with nitrous oxide and halothane with continuous propranolol infusion. Through the operative period, heart rate and blood pressure were stable and postoperative course was uneventful. In these two patients, preoperative Holter ECG showed ventricular tachycardia, which may increase the risk of a sudden death. These cases demonstrate that general anesthesia with nitrous oxide combined with halothane, can be administered with a low risk in patients with HCM for noncardiac surgery and that postoperative intensive care unit monitoring is necessary for these patients for several days to prevent a sudden death.

Aged↗
PubMed1991

Identification of a novel, N-ethylmaleimide-sensitive cytosolic factor required for vesicular transport from endosomes to the trans-Golgi network in vitro.

We have recently described a cell-free system that reconstitutes the vesicular transport of 300-kD mannose 6-phosphate receptors from late endosomes to the trans-Golgi network (TGN). We report here that the endosome----TGN transport reaction was significantly inhibited by low concentrations of the alkylating agent, N-ethylmaleimide (NEM). Addition of fresh cytosol to NEM-inactivated reaction mixtures restored transport to at least 80% of control levels. Restorative activity was only present in cytosol fractions, and was sensitive to trypsin treatment or incubation at 100 degrees C. A variety of criteria demonstrated that the restorative activity was distinct from NSF, an NEM-sensitive protein that facilitates the transport of proteins from the ER to the Golgi complex and between Golgi cisternae. Cytosol fractions immunodepleted of greater than or equal to 90% of NSF protein, or heated to 37 degrees C to inactivate greater than or equal to 93% of NSF activity, were fully able to restore transport to NEM-treated reaction mixtures. The majority of restorative activity sedimented as a uniform species of 50-100 kD upon glycerol gradient centrifugation. We have termed this activity ETF-1, for endosome----TGN transport factor-1. Kinetic experiments showed that ETF-1 acts at a very early stage in vesicular transport, which may reflect a role for this factor in the formation of nascent transport vesicles. GTP hydrolysis appears to be required throughout the transport reaction. The ability of GTP gamma S to inhibit endosome----TGN transport required the presence of donor, endosome membranes, and cytosol, which may reflect a role for guanine nucleotides in vesicle budding. Finally, ETF-1 appears to act before a step that is blocked by GTP gamma S, during the process by which proteins are transported from endosomes to the TGN in vitro.

Animals↗
PubMed1991

In vitro effects of synthetic dyes on the syntheses of prostaglandin E2 (PGE2) and 5-hydroxyeicosatetraenoic acid (5-HETE).

The effects of thirty-one synthetic dyes (tar dyes in Japan), which are permitted in cosmetics, on three different enzymes were evaluated as an initial step in developing in vitro safety screens. The activities of the prostaglandin (PG)-synthetase from rabbit renal medulla and the lipoxygenases from potato tubers and guinea pig peritoneal polymorphonuclear leukocytes (PMN) were determined based on the biosyntheses of PGE2 and 5-hydroxyeicosatetraenoic acid (5-HETE), respectively. Xanthene dyes with halogen substituents exhibited marked inhibition on the PG-synthetase. Among the dyes which are permitted for any pharmaceutics and cosmetics, only the xanthene dyes exhibited inhibitory effects on the PG-synthetase at 2.5 mM. The xanthene dyes also showed inhibition and stimulation of potato lipoxygenase and PMN lipoxygenase, respectively.

Animals↗