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Biomedical subjects

T Yamaguchi

Publications and source records attributed to T Yamaguchi.

At least 685 records · Page 38Linked to original sources
PubMed1998

[Long-term administration study of propiverine hydrochloride (BUP-4 tablets) in pollakiuria and urinary incontinence].

The safety and efficacy of one-year administration of propiverine hydrochloride (BUP-4 tablets) were assessed in facilities affiliated with the Department of Urology of Yokohama City University School of Medicine. Changes in subjective symptoms showed significant improvement in mean frequency of urination in the daytime from 10.3 +/- 4.0 times before administration to 7.1 +/- 2.9 times 1 year after the start of administration, in mean frequency of voiding at night from 4.2 +/- 1.7 times to 2.1 +/- 1.1 times and in mean incidence of urinary incontinence from 2.9 +/- 2.1 times to 0.7 +/- 1.0 times. The final degree of overall improvement rate was 82.0% (41/50 cases). Adverse effects were observed 26 times in 22 patients, the incidence being 15.6% (22/141 cases). They consisted of digestive symptoms in 9.9% (6 events of dry mouth, 4 of constipation, 2 of abdominal discomfort, 2 of diarrhea and 1 of gastritis), urinary tract symptoms in 3.5% (4 of dysuria and 1 of residual urine), abnormal laboratory findings in 1.4% (increase in glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase or lactate dehydrogenase levels) and others (1.4%). These results provide further evidence of the safety and efficacy of propiverine hydrochloride (BUP-4 tablets) even when administered for a long-term in the treatment of patients with pollakiuria and urinary incontinence.

Administration, Oral↗
PubMed1998

Neuroprotective efficacy of YM872, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, after permanent middle cerebral artery occlusion in rats.

The neuroprotective efficacy of YM872, a novel, highly water-soluble alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, was investigated in rats subjected to permanent occlusion of the left middle cerebral artery. The rats were assessed either histologically or neurologically 24 hr or 1 wk after ischemia. YM872 was intravenously infused for either 4 or 24 hr at dose rates of 0 to 20 mg/kg/hr starting 5 min after ischemia to examine the effect of prolonged treatment. YM872 was then infused at 20 mg/kg/hr beginning 0 to 4 hr after ischemia to determine the efficacy time window. Additionally, a 20 mg/kg/hr dose rate of YM872 was infused for 4 hr in single day- or 5-day repetitive-administrations to evaluate long-term benefits of the drug. YM872 significantly reduced infarct volume in both 4- and 24-hr treatment groups measured 24 hr after ischemia. No difference was observed in the degree of protection between length of infusion. Significant neuroprotection was maintained even when drug administration was delayed up to 2 hr after ischemia. A single YM872-administration significantly improved neurological deficit and reduced infarct volume (30%, P <.01) measured 1 wk after ischemia. YM872 treatment did not induce such adverse effects as physiological changes, serious behavioral abnormalities or nephrotoxicity. These data suggest that the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor plays a crucial role in the progression of neuronal damage in the early phase of ischemia and that YM872 may be useful in treating acute ischemic stroke.

Animals↗
PubMed1998

Extracellular calcium-sensing receptor in rat oligodendrocytes: expression and potential role in regulation of cellular proliferation and an outward K+ channel.

A G protein-coupled, extracellular calcium (Ca(0)2+)-sensing receptor (CaR) cloned from parathyroid, kidney, and brain plays crucial roles in systemic calcium metabolism. In brain, the CaR is located in nerve terminals as well as in fiber tracts, where it may be expressed in glia. Moreover, there is Ca2+- and K+-dependent communication between axons and oligodendroglia. To investigate further the potential role of the CaR in oligodendroglia, we studied expression of CaR mRNA and protein as well as the effects of CaR agonists on cellular proliferation and Ca2+-activated K+ channel activity in immature rat oligodendrocytes in primary culture. Reverse transcriptase polymerase chain reaction and sequencing of CaR transcripts from oligodendrocytes revealed >99% sequence identity with the rat kidney CaR. Northern analysis demonstrated 7.5 and 4.1 kb transcripts in oligodendrocytes, similar to those in rat parathyroid and kidney, while Western analysis and immunocytochemistry with CaR-specific antisera showed the presence of CaR protein. Immunocytochemically, the CaR was colocalized with galactocerebroside in the cultured oligodendrocytes. Raising Ca(0)2+ from 1.8 to 4.8 mM or addition of the polycationic CaR agonist neomycin (300 microM) modestly but significantly increased [3H]-thymidine incorporation into oligodendrocytes. Elevating Ca(0)2+ from 0.75 to 3.0 mM or addition of 100 microM neomycin also produced 2-2.5-fold increases in the open state probability (Po) of an outward K+ channel with a unitary conductance of 88+/-5 pS. Taken together, our data show that the CaR is expressed in immature oligodendrocytes and may be functionally linked to cellular proliferation and an outward K+ channel potentially contributing to local ionic homeostasis in the vicinity of oligodendroglia.

Animals↗
PubMed1998

Disposition and metabolism of the new hypocholesterolemic compound S-8921 in rats and dogs.

S-8921 (methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)-4-hydroxy-6,7,8-trimeth oxy-2- naphthoate, CAS 151165-96-7) is a novel hypocholesterolemic agent which was found to inhibit ileal Na+/bile acid cotransporter. In this report, the pharmacokinetic profile of S-8921 was studied in rats and dogs. After dosing of 14C-S-8921 to rats at 1 to 25 mg/kg as 0.5% methylcellulose (MC) suspension, tmax was observed during 5-6 h, and AUCs increased with the dose, but not proportionally. The elimination half-lives were around 38-41 h for the doses examined. The apparent absorption ratio of 5 mg/kg of 14C-S-8921 as MC suspension was about 14%. Most of the radioactivity (98% of dose) was excreted into the feces and only 1-2% into the urine. Biliary excretion of radioactivity after dosing of 1, 5 or 25 mg/kg was 22, 20, 15%, respectively. Saturation of the absorption process was suggested. Even in case of intravenous dosing, about 88% was excreted into the bile. Enterohepatic circulation of biliary metabolites was also observed in rat. Its extent was small (6%), but, it may be contribute to the slow elimination of S-8921 from rat. The highest radioactivity was observed in the liver, with other tissues showing similar radioactivity profiles to that of plasma. The elimination half-lives of radioactivity from tissues were very long, e.g. 68 h for the liver and 58 h for the kidney. After 14 days multiple dosing, most tissues showed about two times higher radioactivity than that after a single dose. The simulation curves of liver and plasma showed a good fit with those of the observed values. These results suggested that there is no serious accumulation of radioactivity in tissues by multiple dosing of 14C-S-8921 in rats. The plasma radioactivity after oral dosing of 5 mg/kg of 14C-S-8921 to dogs as an MC suspension reached maximum concentration (c.a. 33 ng/ml) at 2 h, then decreased very slowly with a half-life of 169 h. The apparent absorption ratio was 4.6% for MC suspension. The excretion of radioactivity into bile, feces and urine after oral dosing of 14C-S-8921 at 5 mg/kg as an MC suspension were 3.0%, 94.6% and 0.3%, respectively. Even in the case of intravenous dosing, urinary excretion was very small (2.2%) and most of the radioactivity was excreted very slowly into the feces. The major metabolite of S-8921 in rat bile was its glucuronide. Other minor metabolites identified were the demethylated forms of 7-methoxy and 4'-methoxy moieties of S-8921. They were also excreted into bile as their glucuronides.

Administration, Oral↗
PubMed1998

[Radiological evidence of involvement of dust exposure in pathogenesis of pulmonary alveolar proteinosis].

A 52-year-old man was admitted because of increasing dyspnea on exersion and presence of pulmonary infiltrates. The patient had pulmonary tuberculosis at the age of 31, which resulted in volume loss and calcified foci in the upper lobe of his left lung. As a construction worker for more than 20 years, he had been exposed to inorganic dusts. Chest radiographs showed a symmetrical consolidation of infiltrates in both lungs with the exception of the left upper lobe, where no apparent infiltrates were shown. A computed tomographic scan of the chest revealed widely panlobular consolidation with the exception of the left upper lobe. A diagnosis of pulmonary alveolar proteinosis (PAP) was established by analysis of bronchoalveolar lavage fluid. Although the patient underwent segmental bronchoalveolar lavage four times under general anesthesia, he suffered frequent pulmonary infection and died two years after the onset his symptoms. Interestingly, the patient had a markedly narrowed orifice in the left upper lobe, as demonstrated by fiberoptic bronchoscopy. Chest radiographs of this lung field revealed no infiltrative shadows. These results suggest that some inhalative agent was involved in the pathogenesis of PAP in this case. In addition, significantly increased levels of KL-6 detected in both serum and bronchoalveolar lavage fluid were attributable to overproduction of KL-6 by Type II pneumocytes that had been stimulated or damaged by PAP.

Construction Materials↗
PubMed1997

Molecular evolution of amphioxus fructose-1,6-bisphosphate aldolase.

The cDNA for amphioxus fructose-1,6-bisphosphate (FBP)-aldolase was isolated and its nucleotide sequence was determined. In the cDNA, there existed a probable open reading frame comprising 1080 bp; hence, 359 amino acid residues were deduced. The amino acid sequence indicates the deletion of 4 residues from N-terminus, in comparison with the sequence of FBP-aldolase isozymes from other sources. There was only one FBP-aldolase gene, and one enzyme species corresponding, in the amphioxus; this is the first report of the existence of a single FBP-aldolase species in animals. Enzymatic studies of both native and the recombinant FBP-aldolase suggest that the amphioxus enzyme belongs to an ancestral class I type which is not discovered among vertebrate aldolase isozymes.

Amino Acid Sequence↗
PubMed1997

Mechanisms of limited maximum coronary flow in severe single-vessel coronary artery disease in humans due to vertical steal.

We evaluated the usefulness of a decrease in the average peak velocity from 4 to 10 minutes after infusion of dipyridamole for detecting myocardial ischemia in 50 patients, including patients with a prior myocardial infarction. The decrease in the average peak velocity from 4 to 10 minutes associated with vertical steal and combined with a coronary flow reserve of < 1.6 had a high predictive value for myocardial ischemia in patients with or without prior myocardial infarction.

Aged↗
PubMed1997

Reduced blood accumulation of biotinylated monoclonal antibody A7 after the subsequent administration of avidin.

Clear immunoscintigraphy with radiolabeled monoclonal antibodies (MAbs) requires a high tumor tissue/blood ratio of radioactivity. In this study, we attempted to obtain a high tumor tissue/blood ratio by the active removal of radiolabeled MAb from the circulation, using the avidin-biotin system. Biotinylated 125I-labeled MAb A7 was injected intravenously into nude mice bearing a human colon cancer (WiDr) xenograft. Avidin was injected 24 h later. The tumor tissue/blood ratio of radioactivity was almost four times that of controls. These results suggest that biotinylated 125I-labeled MAb A7 and avidin are potentially useful for the rapid immunodetection of human colon cancer.

Animals↗
PubMed1997

Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene.

In mice lacking the nociceptin (or orphanin FQ) receptor gene, when 10 mg/kg of morphine was subcutaneously given, a potent analgesia in the tail pinch test was observed. The analgesic effect of morphine was equivalent among wild-type, heterozygous and homozygous mutant mice. When morphine was given to such mice in a dose of 10 mg/kg once per day for 5 days, wild-type and heterozygous mice showed marked tolerance or reduction in the morphine analgesia on the 5th day, while homozygous mice showed only 50% reduction in the peripheral analgesia of morphine. These findings suggest that nociceptin or its receptor plays important roles in the in vivo mechanism for the development of morphine tolerance.

Analgesics, Opioid↗
PubMed1997

A new method for studying the binding of human IgE to CD23 and the inhibition of this binding.

CD23, a low-affinity receptor for IgE (Fc epsilonRII), is a type II membrane-bound glycoprotein expressed on many hematopoietic cells, particularly activated B-cells. CD23 binds to IgE at a domain homologous to Ca2+-dependent (C-type) animal lectin. This paper describes a binding assay by which only the specific binding of IgE to CD23 expressed on Epstein-Barr virus (EBV)-transformed B-cell line, L-KT9 cells, can be detected. This assay is useful in the search for CD23 ligands among many chemical compounds, because it is easily carried out and does not require the use of any radiolabeled reagents. Using the assay, we investigated the inhibition of IgE binding to CD23 by fucose-1-phosphate which has been reported to inhibit the binding of sCD23 to IgE [Delespesse, G., Sarfati, M., Wu, C.Y., Fournier, S., Letellier, M., 1992. The low affinity receptor for IgE. Immunol. Rev. 125, 77.] and the binding of CD23 to CD21 [Pochon, S., Graber, P., Yeager, M., Jansen, K., Bernard, A.R., Aubry, T.-P., Bonnefoy, J.-Y., 1992. Demonstration of second ligand for the low affinity receptor for immunoglobulin E (CD23) using recombinant CD23 reconstituted into flourescent liposomes. J. Exp. Med. 176, 389.]. Although both alpha- and beta-L-fucose-l-phosphate/di(cyclohexylammonium) salt decreased the extent of IgE binding to CD23, the inhibitory effects were not due to alpha- or beta-L-fucose-1-phosphate but to cyclohexylamine. The inhibitory effect of cyclohexylamine was dose dependent and the effect was decreased when inhibition tests were carried out in the presence of a 10-fold excess of IgE. These results suggest that cyclohexylamine specifically interacts with the binding of CD23 and IgE.

B-Lymphocytes↗
PubMed1997

Evidence for 5-HT4 receptor involvement in the enhancement of acetylcholine release by p-chloroamphetamine in rat frontal cortex.

The roles of endogenous serotonin (5-HT) and 5-HT receptor subtypes in regulation of acetylcholine (ACh) release in frontal cortex of conscious rats were examined using a microdialysis technique. Systemic administration (1 and 3 mg/kg, i.p.) of the 5-HT-releasing agent p-chloroamphetamine (PCA) elevated ACh output in a dose-dependent manner. Depletion of endogenous 5-HT by p-chlorophenylalanine significantly attenuated the facilitatory effect of PCA on ACh release. The PCA (3 mg/kg)-induced increase in ACh release was significantly inhibited by local application of the 5-HT4 receptor antagonists RS23597 (50 microM) and GR113803 (1 microM), while the 5-HT1A antagonist WAY-100135 (10 mg/kg, i.p.; 100 microM), 5-HT(1A/1B)/beta-adrenoceptor antagonists (-)-pindolol (8 mg/kg, i.p.) and (-)-propranolol (150 microM), 5-HT(2A/2C) antagonist ritanserin (1 mg/kg, i.p.; 10 microM) and 5-HT3 antagonist ondansetron (1 mg/kg, i.p.; 10 microM) failed to significantly modify the effect of PCA. These results suggest that PCA-induced enhancement of 5-HT transmission facilitates ACh release from rat frontal cortex at least in part through 5-HT4 receptors.

Acetylcholine↗
PubMed1997

Serum leptin levels are associated with hyperinsulinemia independent of body mass index but not with visceral obesity.

To examine the relationship between leptin levels and visceral obesity or plasma insulin levels, we studied serum leptin levels, fat distribution assessed by CT scan, and plasma insulin levels during 75 g oral glucose load in 100 Japanese men. Regression analysis adjusted by age and body mass index (BMI) showed leptin levels to be associated with visceral fat area(V)(p = 0.003), subcutaneous fat area(S)(p < 0.0001), and V + S(p < 0.0001), but not with V/S ratio(p = 0.897). By regression analysis adjusted by age, BMI, and V + S, serum leptin levels were still highly and positively correlated with plasma insulin levels during 75 g oral glucose load (p < 0.001), insulin resistance index(p < 0.001), and beta cell function index(p = 0.009) in homeostasis model assessment. These data suggest that hyperinsulinemia, but not visceral obesity, may be regulators of serum leptin levels independent of BMI.

Adult↗
PubMed1997

Chiral discrimination of 2'-deoxy-L-cytidine and L-nucleotides by mouse deoxycytidine kinase: low stereospecificities for substrates and effectors.

The effects of four kinds of 2'-deoxy-L-nucleoside 5'-triphosphates and L-ATP, which are enantiomers of natural D-dNTPs and D-ATP, on deoxycytidine kinase (dCK) partially purified from mouse leukemic P388 cells were investigated. Only L-dCTP did not act as a phosphate donor while other L-dNTPs and L-ATP showed 15-30% of the activity of the corresponding D-dNTP or D-ATP. L-dCTP inhibited dCK non-competitively with 2'-deoxycytidine (D-dCyd) and competitively with phosphate donor D-ATP. These inhibitory effects of L-dCTP on dCK were similar to the results of earlier studies using D-dCTP. Thus, L-dCTP was shown to be capable of serving as a feedback inhibitor for dCK instead of D-dCTP. Mouse dCK was also able to phosphorylate L-dCyd, as demonstrated in the case of human dCK. The present results suggest that the chirality of not only dCyd as the substrate but also nucleotides as the substrate or effector is not strictly discriminated by dCK.

Adenosine Triphosphate↗
PubMed1997

Possible involvement of heterotrimeric G proteins in the organization of the Golgi apparatus.

Nordihydroguaiaretic acid (NDGA) caused disassembly of the Golgi apparatus of NRK cells in a dose-, time-, and energy-dependent manner but not in a microtubule-dependent manner. In contrast to brefeldin A, NDGA did not cause release of beta-COP, a component of Golgi-derived vesicles. However, NDGA-induced disassembly was blocked by AlF4-, an activator of the heterotrimeric but not the small GTP-binding proteins. In digitonin-permeabilized cells, guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) as well as AlF4- blocked the NDGA-promoted disassembly of the Golgi apparatus, and Gbetagamma (betagamma subunits of heterotrimeric G proteins) reversed this effect. Our present results suggest the possible involvement of heterotrimeric G proteins in the organization of the Golgi apparatus.

Animals↗
PubMed1997

Self-sustained pH oscillations in a compartmentalized enzyme reactor system.

This work represents our continued effort toward fulfilling the need to discover a model system for experimental investigations of temporal oscillations in an enzyme-membrane system. In this paper, the regions in the parameter space where self-sustained pH oscillations can be induced for a compartmentalized enzyme reactor system, which consists of a well-stirred reactor, a reservoir and a membrane containing no enzyme, were determined via numerical simulation with two proteolytic enzymes: papain (EC 3.4.22.2) and alpha-chymotrypsin (EC 3.4.21.1). The sizes of the regions were qualitatively compared with those associated with enzymic membrane system. As a result, we found that the possibility of experimentally observing self-sustained oscillations in the compartmentalized papain reactor system, as well as in the papain-membrane system, is high. However, self-sustained pH oscillations are less likely in the compartmentalized alpha-chymotrypsin reactor system than in the alpha-chymotrypsin-membrane system.

Journal Article↗
PubMed1997

Prognostic value of slow resolution of ST-segment elevation following successful direct percutaneous transluminal coronary angioplasty for recovery of left ventricular function.

Our objective was to investigate the significance of the slow resolution of ST-segment elevation following a successful direct percutaneous transluminal coronary angioplasty (PTCA). ST-segment elevations were calculated from electrocardiograms recorded before PTCA and 1 hour after reperfusion. Forty-nine patients experiencing their first anterior acute myocardial infarction and who had undergone direct PTCA were classified into 3 groups: 17 patients with rapid ST resolution (group I), 23 patients with persistent ST elevation (group II), and 9 patients with ST reelevation (group III). Left ventricular function was evaluated by using single-plane cineventriculography performed in the acute stage, at discharge, and 4 months later. Peak creatine kinase activity was significantly increased: group III (4,046 +/- 634 IU), group II (3,336 +/- 772 IU), and group I (2,410 +/- 994 IU); p <0.05. Ejection fraction and regional wall motion in the acute stage were identical in each group. However, they were significantly higher in group I (67 +/- 6%, -1.01 +/- 0.30), followed by group II (56 +/- 6%, -1.90 +/- 0.41) and group III (38 +/- 7%, -2.79 +/- 0.46); p <0.01 4 months later. Multiple regression analysis revealed that the ST resolution was the only significant variable that indicated the recovery of regional wall motion. A good linear correlation was documented between the ST resolution and the recovery of regional wall motion. We concluded that a slow ST resolution after successful direct PTCA is a negative predictor of recovery of left ventricular function, especially when ST reelevation is evident.

Aged↗
PubMed1997

Effects of pyramidal tract stimulation on forelimb flexor motoneurons during fictive locomotion in cats.

To investigate spinal mechanisms of control of locomotion by the pyramidal system, we made intracellular recording from forelimb flexor motoneurons, and analyzed excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the medullary pyramid during forelimb fictive locomotion in immobilized, decerebrate cats. We observed that (1) pyramidal stimulation evoked disynaptic EPSPs, (2) which were much bigger in the locomotor state than in the resting state, and that (3) the pyramidal EPSPs were rhythmically modulated, so that the facilitation occurred in the flexor-active phase. Last-order neurons mediating pyramidal effects presumably receive rhythmic input from the spinal locomotor network.

Animals↗