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Biomedical subjects

Y Goda

Publications and source records attributed to Y Goda.

At least 19 recordsLinked to original sources

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

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

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

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

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

[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

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

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

Antibodies to clathrin inhibit endocytosis but not recycling to the trans Golgi network in vitro.

Mannose 6-phosphate receptors carry newly synthesized lysosomal enzymes from the trans Golgi network (TGN) to prelysosomes and then return to the TGN to carry out another round of lysosomal enzyme delivery. Although clathrin-coated vesicles mediate the export of mannose 6-phosphate receptors from the TGN, nothing is known about the transport vesicles used to carry these receptors back to the TGN. Two different in vitro assays used in this study show that an antibody that interferes with clathrin assembly blocks receptor-mediated endocytosis of transferrin, but has no effect on the recycling of the 300-kilodalton mannose 6-phosphate receptor from prelysosomes to the TGN. These results suggest that the transport of mannose 6-phosphate receptors from prelysosomes to the TGN does not involve clathrin.

Animals

[Increased fibrinolytic activity during surgery with cardiopulmonary bypass].

We studied blood coagulation and fibrinolysis in 19 patients during surgery with cardiopulmonary bypass (CPB). CPB was performed with a rotating pump and a membrane oxygenator. Heparinization was achieved with heparin 3 mg.kg-1 and the ACT value was kept above 400 seconds throughout the CPB. Heparin was neutralized by protamine at a ratio of 1:1-1.5 of the total amount of heparin. Blood was collected four times from an indwelling arterial line. We obtained the first sample immediately after induction of anesthesia, the second sample before heparinization, the third sample before protamine administration, and the fourth sample at the end of the operation. FPA, FPB beta 15-42, alpha 2PI-Pl-C, D-dimer, and the t-PA activity were measured. A statistically significant elevation of FPA was observed during the operation. FPB beta 15-42, alpha 2PI-Pl-C, and the D-dimer rose significantly immediately after the beginning of the CPB and these elevations continued until the end of the operation. The t-PA activity was elevated significantly only during the CPB. In conclusion, the t-PA is released from the endothelial cells during CPB by some undetermined mechanism (primary fibrinolysis). Then, plasmin is generated by the t-PA and this dissolves the fibrin clots formed by thrombin before the beginning of the CPB (secondary fibrinolysis). Enhanced fibrinolytic activity before and after the CPB is physiological secondary fibrinolysis.

Cardiopulmonary Bypass

Cell-free systems to study vesicular transport along the secretory and endocytic pathways.

Proteins bound for the cell surface, lysosomes, and secretory storage granules share a common pathway of intracellular transport. After their synthesis and translocation into the endoplasmic reticulum, these proteins traverse the secretory pathway by a series of vesicular transfers. Similarly, nutrient and signaling molecules enter cells by endocytosis, and move through the endocytic pathway by passage from one membrane-bound compartment to another. Little is known about the mechanisms by which proteins are collected into transport vesicles, or how these vesicles form, identify their targets, and subsequently fuse with their target membranes. An important advance toward our understanding these processes has come from the establishment of cell-free systems that reconstitute vesicular transfers in vitro. It is now possible to measure, in vitro, the transport of proteins from the endoplasmic reticulum to the Golgi, between Golgi cisternae, and the formation of transport vesicles en route from the trans Golgi network to the cell surface. Along the endocytic pathway, cell-free systems are available to study clathrin-coated vesicle formation, early endosome fusion, and the fusion of late endosomes with lysosomes. Moreover, the selective movement of receptors between late endosomes and the trans Golgi network has also been reconstituted. The molecular mechanisms of vesicular transport are now amenable to elucidation.

Animals

[Power spectral analysis of heart rate and peripheral blood flow variations during total spinal anesthesia].

We evaluated the effect of total spinal anesthesia (TSA) on the heart rate and peripheral blood flow variations to evaluate if TSA could influence these parameters as indicators of autonomic nervous function (ANF). Four patients with intractable pain were treated by TSA by administration of local anesthetics (lidocaine or mepivacaine) into the C7-Th1 vertebral interspace. Power spectrum of heart rate before TSA showed three peaks; low (LO-FR, 0.04-0.095 Hz), mid (MID-FR, 0.095-0.15Hz) and high frequency areas (HI-FR, 0.15-0.3Hz). Spectral peaks of LO-FR and MID-FR disappeared during TSA (P less than 0.001). HI-FR area decreased to 3.3% of the control level (P less than 0.001). Mean peripheral blood flow was changed to 59.9% of the control level (not significant). However, peripheral blood flow variations of LO-FR decreased to 11.3% of the control level (P less than 0.001) after TSA. Furthermore, the vagal discharge disappeared promptly after TSA in dog. These results suggest that TSA depresses the vagal activity as well as the sympathetic activity innervating the cardiovascular system and therefore, heart rate and peripheral blood flow variations are totally eliminated. Thus, we conclude that heart rate and peripheral blood flow variations can serve as valid markers of ANF activity.

Anesthesia, Spinal

[Studies on coloring constituents in commercial madder color].

Two main coloring constituents in the commercial madder color were isolated and identified as ruberthric acid and lucidin-3-O-primeveroside. On quantitative analysis by high-performance liquid chromatography, the contents of ruberthric acid and lucidin-3-O-primeveroside in commercial madder color were determined 0.07% and 0.04%, respectively.

Anthraquinones

[Distinction between sodium chlorite and sodium hypochlorite by ion-chromatography].

A new method to distinguish between sodium chlorite and sodium hypochlorite by ion-chromatography is described. Under the operating condition (TSK-gel DEAE-5PW glass column 8.0 mm ID x 7.5 cm with an aqueous solution containing 20 mM sodium carbonate, 10 mM sodium hydroxide and 4 mM ethylenediamine) and electrochemical detector (Toso EC-8000, -200 mV, Ag-electrode), chlorite and hypochlorite anions were clearly separated and detected and the retention times (tR) were 6.0 and 4.6 min, respectively.

Chlorides

Participation of microsomal aldehyde reductase in long-chain fatty alcohol synthesis in the rat brain.

The participation of microsomal aldehyde reductase in long-chain fatty alcohol synthesis in the rat brain was examined. A reaction mixture of [1-14C]hexadecanoic acid with brain microsomes and NADPH formed two radioactive products having the same mobilities as pure hexadecanal (RF 0.61) and hexadecanol (RF 0.22), respectively, on TLC plates. The product of the RF 0.61 spot was further identified as hexadecanal using gas-liquid chromatography after methylation and TLC of its reduced product with LiAlH4 and semicarbazide. The ratio of hexadecanal to hexadecanol varied from 0.4 to 1.2 under the present experimental conditions. When solubilized rat brain microsomes were applied to a Sepharose 4B column coupled with the rabbit antibody raised against rat liver microsomal NADPH-cytochrome-c reductase, which reacts with aldehyde reductase from rat brain, the eluted fraction ceased to form [14C]hexadecanol but continued to form [14C]hexadecanal from [14C]hexadecanoic acid. These results strongly indicate that hexadecanal is the intermediate in the synthesis of hexadecanol from hexadecanoic acid in rat brain microsomes with the participation of microsomal aldehyde reductase.

Alcohol Oxidoreductases

Selective recycling of the mannose 6-phosphate/IGF-II receptor to the trans Golgi network in vitro.

Mannose 6-phosphate receptors carry soluble lysosomal enzymes from the trans Golgi network (TGN) to prelysosomes, and then return to the TGN for another round of lysosomal enzyme sorting. We describe here a complementation scheme that detects the vesicular transport of the 300 kd mannose 6-phosphate/IGF-II receptor from prelysosomes to the TGN in cell extracts. In vitro transport displays the same selectivity observed in living cells in that the transferrin receptor traverses to the TGN at a much lower rate than mannose 6-phosphate receptors. Furthermore, recycling of mannose 6-phosphate/IGF-II receptors to the TGN requires GTP hydrolysis and can be distinguished biochemically from the constitutive transport of proteins between Golgi cisternae by its resistance to the weak base, primaquine.

Animals