Biomedical subjects

Y Tsuda

Publications and source records attributed to Y Tsuda.

At least 127 records · Page 7Linked to original sources

PubMed1996

Quantification of leucocyte elastase and cathepsin G in plasma by a simple method: effect of elastase in plasma levels of D-dimer and thrombomodulin.

The purpose of this study was to determine levels of leucocyte elastase and cathepsin G in the plasma of patients in various pathological states, in which plasma increases or decreases in coagulation and fibrinolytic factors were seen. Simple methods were developed to measure the leucocyte proteinases and the results were correlated with conventional assays of coagulation and fibrinolytic factors. The total number of patients and total number of plasma samples examined were 340 and 1292, respectively. No correlation was observed between the plasma levels of elastase and cathepsin G, and plasminogen, fibrinogen and leucocyte counts. There was a weak overall correlation, however, between the leucocyte proteinases and each of the four parameters: D-dimer, thrombomodulin, antithrombin III and platelet count. There was a strong correlation between leucocyte proteinases and D-dimer and thrombomodulin in those patients with plasminogen levels within the normal range. Increased D-dimer levels, as well as plasmin, may suggest that elevated leucocyte proteinases contribute to elevated fibrinolytic mechanisms in these instances.

Biological Assay↗

PubMed1996

Urinary excretion profile of torasemide and its diuretic action in dogs.

The plasma concentration profile, urinary excretion rate and diuretic response were studied in anaesthetized dogs after an intravenous administration of torasemide or furosemide. The urinary excretion rate of furosemide decreased rapidly after administration. The plasma concentration, which is related to the urinary excretion profile, also decreased rapidly. The diuretic response, which reflected the excretion rate, occurred rapidly after administration but lasted for a short time. The urinary excretion rate of torasemide was much lower than that of furosemide and decreased slowly after administration. The plasma concentration also decreased slowly. The diuretic response to torasemide occurred more slowly but lasted longer than the response to furosemide. These results suggest that the diuretic response profile of either diuretic depends on their urinary excretion rate, and that the difference in the diuretic response between torasemide and furosemide may be explained by the different transfer rate of the drugs from the plasma to the nephron.

Animals↗

PubMed1996

Effects of defibrination on hemorheology, cerebral blood flow velocity, and CO2 reactivity during hypocapnia in normal subjects.

BACKGROUND AND PURPOSE: Plasma fibrinogen is reported to be an independent risk factor for stroke and cardiovascular diseases. The effects of defibrination on hemorheology, middle cerebral artery (MCA) blood flow velocity, and CO2 reactivity during hypocapnia were evaluated in normal subjects. METHODS: Twenty-five healthy subjects (mean age, 31.8 +/- 5.7 years) were included in the study. Measurements were done at rest and repeated 24 hours after administration of 10 batroxobin units. Plasma fibrinogen, plasma viscosity, and whole blood viscosity were measured as hemorheological factors. MCA blood flow velocity was measured with a transcranial Doppler flowmeter. Blood flow velocity was corrected to 40 mm Hg of end-tidal CO2 partial pressure (PETCO2), and expressed as CV40. CO2 reactivity was measured as percent change in mean blood flow velocity per millimeter of mercury PETCO2. RESULTS: Plasma fibrinogen (from 7.04 to 2.29 mumol/L; P < .001), whole blood viscosity, and plasma viscosity decreased after administration of batroxobin. Mean MCA blood flow velocity at rest, CV40. and CO2 reactivity during hypocapnia increased significantly (from 67.4 to 73.6 cm/s, from 71.7 to 77.7 cm/s, and from 2.9%/mm Hg to 3.2%/mm Hg, respectively; P < .01) after defibrination. Mean arterial blood pressure and PETCO2 at rest were constant before and 24 hours after administration of batroxobin. There was a significant positive correlation between CV40 and CO2 reactivity (r = .623, P < .0001). CONCLUSIONS: The increase in MCA blood flow velocity was associated with improved CO2 reactivity and reduced blood viscosity after defibrination. The data may suggest that defibrination increases cerebral blood flow by reducing blood viscosity.

Adult↗

PubMed1996

[Pharmacokinetics of propofol during liver transplantation in small pigs].

A study using 14C propofol showed that the liver is the main eliminating organ for the agent. The current study was designed to clarify pharmacokinetics of propofol during liver transplantation in pigs. Five small pigs weighing 25.4 +/- 2.5 kg were anesthetized with isoflurane (0.5-1.5%) and mechanically ventilated under muscle paralysis with pancuronium. In the anhepatic phase, veno-veno bypass was placed from the inferior vena cava and portal vein to the superior vena cava. We studied pharmacokinetic parameters following an intravenous bolus injection of propofol at 2 mg.kg-1 in each phase, i.e. the pre-anhepatic, anhepatic and post-anhepatic phase during liver transplantation. Pharmacokinetic analysis showed that total plasma clearance of propofol in the anhepatic phase was significantly lower than that in the post-anhepatic phase. The results suggest that propofol may be metabolized extrahepatically and can be used at reduced doses in the anhepatic phase during liver transplantation.

Anesthetics, Intravenous↗

PubMed1996

Genetic differentiation among three populations of Anopheles minimus of Guangxi and Yunnan Provinces in the People's Republic of China.

Electrophoretic studies were carried out on isozymes of 3 populations of Anopheles minimus collected from Guangxi and Yunnan Provinces of the People's Republic of China in 1993. Eight proteins were analyzed by 5% polyacrylamide gel electrophoresis. The most variable population, Y-F, was highly polymorphic at 14 of 20 loci (P=0.700) with an average heterozygosity H of 0.340. P values of 0.500 and 0.700, and H values of 0.220 and 0.210 were obtained for each from 'Guangxi-Lab' (GX-L) and 'Yunnan-Lab' (Y-L), respectively. Nei's genetic distances (D) between Y-L and GX-L, Y-F and GX-L, and Y-F and Y-L were 0.1131, 0.1946 and 0.1069, respectively. These results suggest that GX-L is distant from the 2 other populations, Y-L and Y-F, and that this genetic differentiation between the 2 populations of Yunnan and Guangxi Provinces corresponds to the forms A and B, which were morphologically classified by Xu et al (unpublished).

Alleles↗

PubMed1995

Calculation of relative binding free energies and configurational entropies: a structural and thermodynamic analysis of the nature of non-polar binding of thrombin inhibitors based on hirudin55-65.

Free energy calculations were carried out on a series of exosite-binding inhibitors of thrombin. These inhibitors are based on the C-terminal fragment of hirudin and have the sequence Phe-Glu-Glu-IleH59-Pro-Glu-Glu-Tyr- Leu, where the superscript over Ile indicates its relative position in the natural sequence of hirudin. In this study, the effect of replacing IleH59 with ten other non-polar amino acids was examined. Three preferred interaction sites for methyl/methylene groups for the various XaaH59 side-chains in the complex were identified from conformational search calculations. The corresponding thermodynamic changes were determined using a combination of systematic search and energy minimization in a manner that locates the local minima in the system and in the process simultaneously builds up the partition function. The free energy, internal energy and entropic contributions are readily calculated from the partition function. Very good agreement in the resulting relative binding free energies was obtained between theory and experiment. The calculations allowed us to dissect out the enthalpic, entropic and solvation contributions to delta delta G. The contribution from desolvation was found to be relatively weak. The binding of these non-polar side-chains to thrombin is found to be driven mainly by favorable protein-ligand interactions rather than by the desire for non-polar groups to be desolvated. We also find that the configurational entropy contributes about 0.48 kcal/mol (0.81 kappa T) in average for each torsional angle "frozen" in binding.

Algorithms↗

PubMed1995

Design of noncovalent trypsin inhibitor based on the X-ray crystal structure of the complex.

The inhibitory mechanism of trans-4-aminomethylcyclohexanecarbonyl-L-phenyl-alanine-4-carbo xymethylanilide (1), a noncovalent serine protease inhibitor synthesized based on previous structure-activity studies, was clarified based on the X-ray crystal structure of the complex (2.2 A resolution, R = 0.175), where the amino group of the aminomethylcyclohexane moiety was bifurcately hydrogen-bonded to the carboxyl oxygens of Asp 189 side group (specificity pocket), and the hydrogen bonds of the cyclohexanecarbonyl oxygen to NHs of Gly 193 and Ser 195 residues (oxyanion hole) and of Phe NH to Ser 195 O gamma atom (catalytic triad) were observed. In contrast, the Phe benzene moiety and terminal carboxymethylanilide of 1 were not well located on the electron density map, suggesting the conformational freedom of these P1' and P2' sites at the binding pocket. Based on these insights, trans-4-aminomethylcyclohexanecarbonyl-4-nitro-L-phenylalanine-4-+ ++benzoylanilide (2) was designed, in which the P1' and P2' sites were modified so as to effectively interact with the amino acid residues of trypsin binding pocket via hydrogen bonding and van der Waals interactions, respectively. Consequently, 2 showed 40 times higher inhibitory activity against trypsin than 1.

Crystallization↗

PubMed1995

Interactions of hirudin-based inhibitor with thrombin: critical role of the IleH59 side chain of the inhibitor.

Hirudin is the most potent and specific thrombin inhibitor from medicinal leech with a Ki value of 2.2 x 10(-14) M. It consists of an active site inhibitor segment, hirudin1-48, a fibrinogen-recognition exosite inhibitor segment, hirudin55-65, and a linker, hirudin49-54, connecting these inhibitor segments. The role of the side chain of the hirudin 59th residue, Ile, is studied by using a series of synthetic bivalent thrombin inhibitors, which mimic the binding mode of hirudin. The synthetic inhibitors based on the hirudin sequence have a general sequence of Ac-(D-Phe)-Pro-Arg-Pro-(4-aminobutyric acid)-(7-amino-heptanoic acid)-Asp-Phe-Glu-Glu-Xaa-Pro-Glu-Glu-Tyr-Leu-Gln-OH, in which the 59th residue, Xaa, is substituted by various natural and unnatural L-amino acids. For example, substitution of IleH59 by Val, which is equivalent to removing the delta-methyl group of IleH59, reduces the affinity of the inhibitor 5.7-fold (delta delta G0 = 1.0 kcal/mol) to a Ki value of 4.7 nM compared to that (Ki = 0.82 nM) of the corresponding inhibitor with IleH59. Removal of the entire side chain of IleH59, i.e., a substitution of IleH59 by Gly, reduces the affinity of the inhibitor 6300-fold, revealing the critical role of the IleH59 side chain in the inhibitor binding. Theoretical free energy calculation successfully reproduces the binding free energy of most of the analogs. It suggests that intra- and intermolecular van der Waals interactions of delta-CH3, gamma-CH3, and gamma-CH2 of IleH59 play the major role in the binding affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

Cerebellar diaschisis in pontine infarctions: a report of five cases.

We evaluate regional cerebral and cerebellar perfusion to prove the occurrence and follow the persistence of crossed cerebellar diaschisis in infratentorial pontine infarction. Six consecutive patients exhibiting mild hemiparetic symptoms or a heavy feeling in the head (mean age 65 years; four women, two men) and diagnosed as having pontine infarction by magnetic resonance imaging were subjected to evaluation. Lesions due to infarction were located at the upper basis pontis in five patients and the upper tegmentum pontis in one, and medially at the paramedian portion in four and laterally in two. Regional cerebral and cerebellar perfusion was evaluated semiquantitatively by iodine-123 N-isopropyl-p-iodoamphetamine (IMP) single-photon emission tomography (SPET); this was done during the acute stage in five cases (mean time after onset: 0.7 months) and during the chronic stage in three (mean time after onset: 14.8 months). Four patients had two examinations during their clinical courses. For semiquantitative evaluation of perfusion, an asymmetry index was calculated for each region of interest, set symmetrically in regions of the cerebral cortex and cerebellum in both hemispheres. Significant asymmetry (P < 0.01) in cerebellar perfusion, which was reduced in the contralateral (n = 4) or ipsilateral (n = 1) cerebellar hemisphere, was demonstrated semiquantitatively in four cases during the acute stage and in one during the chronic stage, as compared with normal controls (n = 5, mean age 61 years). This asymmetry continued to the chronic stage (6.5 and 33.0 months) in two cases, while no patient showed any significant asymmetries in cerebral perfusion in any region of interest in either SPET study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Characterization of two Japanese encephalitis virus strains isolated in Thailand.

Two strains of Japanese encephalitis (JE) virus were isolated from a pool of Culex tritaeniorhynchus captured in 1992 and another pool of Cx. vishnui captured in 1993, in Chiang Mai Area, Northern Thailand. These two strains, ThCMAr44/92 and ThCMAr67/93, could not be identified either as Nakayama or JaGAr01 subtype by the hemagglutination-inhibition (HI) and the neutralization (N) tests using immune sera raised against these standard JE virus strains. Reverse transcription-polymerase chain reaction showed the presence of JE-specific conserved sequences in these strains. Sequencing of 240 nucleotides in their PrM gene region identified that these two strains belong to the genotype 1 of JE virus. Nucleotide and encoded amino acid sequences of their envelope glycoprotein gene revealed 98.8 and 99.8% identity, respectively. These two strains shared 77.8 to 87.7% homology in the nucleotide sequence and 90.0 to 98.8% homology in the amino acid sequence with other reported JE strains. Five strain-specific amino acid changes were noted in ThCMAr44/92 strain, while one in ThCMAr67/93. In addition, four common amino acid changes were found in both strains. Thus, the findings indicated that these two strains were structurally different from each other as well as different from all the reported strains which was in agreement with the serological tests by hemagglutination-inhibition and neutralization.

Animals↗

PubMed1995

A comparison of coronary arteries from Japanese and NZ subjects.

This paper describes a comparison of the anterior descending branch of the left coronary artery from 198 Japanese subjects of ages less than 60 yrs, with 301 New Zealand individuals of similar ages. The object of the study was to determine whether there were structural differences present which could be partially responsible for the low incidence of atherosclerosis in Japanese as well as the known low blood lipid levels. It was found that the internal elastic lamina of Japanese coronary arteries was less well formed at birth than that of NZ subjects. Intimal thickening was greater in Japanese coronary arteries from birth to the end of the first decade, but increased less rapidly with age, and was only about half as great as that of NZ vessels in the older age groups. The thickened intima of Japanese arteries was more uniform round the circumference of the vessel, the luminal surface was better formed with more stainable elastin present subjacent to the endothelial cells, and there was less evidence of mural thrombosis. NZ arteries showed pronounced eccentricity of the intima, more extensive lipid deposits, a poorly defined luminal surface, and frequent evidence of mural thrombosis.

Adolescent↗

PubMed1995

Mobility inhibition and nematocidal activity of asarone and related phenylpropanoids on second-stage larvae of Toxocara canis.

The in vitro effect of asarone, the nematocidal principle of the rhizome of Acorus calamus, on second-stage larvae of Toxocara canis is composed of two independent actions: one is a fast acting inhibition of the larval mobility and the other is a slow acting larvicidal action. Mobility of the larvae was rapidly inhibited when they were incubated with asarone. Dye exclusion assay revealed that larvae were alive at this stage, and their mobility was restored after the first inhibition, suggesting that this effect was temporary and reversible. However, when the mobility decreased again during prolonged incubation, the cellular viability of larvae disappeared, showing that they were killed by the compound. The above two-stage effect of asarone was almost identical in two geometrical isomers ((E)- and (Z)-asarone). Di- and tri-methoxypropenyl or propylbenzenes carrying two methoxy groups at a vicinal position on a benzene ring showed, more or less, a two-stage effect of this type. These two actions were suggested to be separable by an appropriate modification of the structure.

Allylbenzene Derivatives↗

PubMed1995

Amino acids and peptides. XXXIX. Synthesis of iNoc-Gln-Val-Val-Ala-Ala-pNA and its action on thiol proteinases.

Based on the results of X-ray analysis of the complex between Suc-Gln-Val-Val-Ala-Ala-pNA, a fairly potent thiol proteinase inhibitor, and papain, iNoc-Gln-Val-Val-Ala-Ala-pNA was designed and prepared and its inhibitory activity against thiol proteinases was examined. iNoc-Gln-Val-Val-Ala-Ala-pNA inhibited cathepsin L fairly specifically, although its potency is not high.

Amino Acid Sequence↗

PubMed1995

Effects of ajmaline on non-sodium ionic currents in guinea pig ventricular myocytes.

The lack of currently available data stimulated us to investigate the electrophysiological effects of ajmaline, a classical class Ia antiarrhythmic agent, on various currents responsible for the action potential plateau and repolarization phases. The whole cell patch clamp recording technique was applied to guinea pig ventricular myocytes. Ajmaline suppressed the Ca2+ current (Ica) in a dose-dependent manner (Kd = 1.2 x 10(-5) M) without affecting the steady-state inactivation kinetics and the voltage dependency of the current-voltage relationship. Ajmaline inhibited the inward portion of the inward rectifying K+ current (IKl). Ajmaline decreased the delayed rectifier K+ current (IK) without altering the activation or deactivation time courses. All these inhibitory effects of ajmaline prolonged the action potential duration in a dose dependent manner. The inhibitory actions of ajmaline on the action potential upstroke and various currents responsible for the plateau and repolarization may contribute to the observed suppression of depolarization-induced abnormal automaticities by this agent.

Action Potentials↗

PubMed1995

Coronary dilating effects of intracoronary nicorandil. Comparison with isosorbide dinitrate.

Although nicorandil, N-(2-hydroxyethyl) nicotinamide dinitrate, is a nitrate ester, its cardiovascular action differs from that of nitrate compounds in several aspects. In this quantitative angiographic study, the acute coronary dilating effect of intracoronary nicorandil (0.25, 0.50, 1.0 mg) was compared with that of isosorbide dinitrate (ISDN; 1.0 mg) in 46 patients with or without ischemic heart disease (IHD). Dose-dependent right coronary dilating action was observed by intracoronary administration of nicorandil without any adverse effects. The same degree of right coronary dilation was achieved by the intracoronary application of equivalent doses of ISDN. We conclude that intracoronary administration of nicorandil is beneficial for the supportive treatment of IHD during coronary artery investigation and intervention without the risk of severe systemic hypotension.

Angina Pectoris↗

PubMed1995

Mark-release-recapture experiments to estimate the efficiency of the light trap in collecting Japanese encephalitis vector mosquitoes.

Efficiency of the light trap in collecting females of Culex tritaeniorhynchus, the principal vector mosquito of Japanese encephalitis, was evaluated by mark-release-recapture experiments. Females collected with dry ice in the field were marked and released in a pigsty. The recapture rate of marked females by the light trap was so low as around 1% or lower. Owing to this low efficiency, it is not likely that the light trap can be a useful tool in the control of Japanese encephalitis.

Animals↗

PubMed1995

Facilitation in Anopheles and spontaneous disappearance of filariasis: has the concept been verified with sufficient evidence?

The validity of recently much argued phenomenon of facilitation in the transmission of filariasis was considered by examining previously published papers. It was concluded that there was no clear evidence to support the existence of facilitation and facilitation-based unstable equilibrium in relation to microfilaria prevalence and density in human population below which filariasis would spontaneously disappear, even when the vector was Anopheles mosquitoes. Instead, the existence of a critical level of man/mosquito contacts for the disappearance of filariasis was suggested.

Animals↗

PubMed1995

[A study of living response to artificially synthesized hydroxyapatite implant in the rabbit orbit].

We implanted artificially synthesized hydroxyapatite (a-HA) spheres into the orbits of sixteen rabbits after enucleation. The spheres were removed 1, 2, 3, and 6 months after implantation and examined by light and scanning electron microscopy. Tissue breakdown and exposure of a-HA implants were not observed in any case. As time passed, fibrovascular tissue gradually invaded the pores of the HA spheres deeper and deeper. Although the HA used was completely artificially, we observed a mild foreign body reaction around the a-HA sphere. HA spheres are appropriate for orbital implants after enucleation without scleral enveloping.

Animals↗