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Biomedical subjects

T Yamaguchi

Publications and source records attributed to T Yamaguchi.

At least 523 records · Page 29Linked to original sources
PubMed1999

Effect of a ligand selective for peripheral benzodiazepine receptors on the expression of rat hepatic P-450 cytochromes: assessment of the effect in vivo and in a hepatocyte culture system.

The peripheral benzodiazepine receptor plays a role in the translocation of cholesterol into mitochondria where steroidogenesis occurs. Sterols have been suggested to be involved in the regulation of the cytochrome P-450 (CYP)2B subfamily as the endogenous suppressor of this CYP. To investigate the role of cholesterol metabolites on the expression of CYPs, the effect of PK11195, a specific ligand of the peripheral benzodiazepine receptor and a stimulator of cholesterol transportation, on CYP expression was examined in rats in vivo and in cultured hepatocytes. As judged by the change in testosterone metabolic activity catalyzed by liver microsomes, i.p. injection of PK11195 into rats increased the CYP2B subfamily significantly. A trend in the induction of the CYP2A1, 2C11, and 3A isozymes was also observed. When PK11195 was given to rats together with phenobarbital, an additive effect of these compounds on testosterone metabolic activity was observed. In cultured hepatocytes, PK11195 exhibited the same effect on CYP expression as seen in vivo, but the magnitude of the effect was much greater than that observed in vivo. The inductive effect of PK11195 toward the CYP2B and 3A subfamilies was 2.3- and 6.5-fold greater, respectively, than that with phenobarbital. The inductive effect of PK11195 was confirmed by immunoblotting with antibodies against CYP2A, 2B, 2C, and 3A proteins. These results indicate that PK11195 has an inductive effect on several subfamilies of CYPs by directly acting on liver cells and has no ability to suppress the expression of these CYPs. This observation suggests that, if certain sterols play a role in the suppressive control of the CYP2B subfamily, they are produced in organelles other than the mitochondria.

Animals↗
PubMed1999

[Biliverdin].

Explore the source record for details and available documents.

Biliverdine↗
PubMed1999

[Homolateral ataxia and crural paresis following anterior cerebral artery territory infarction].

Homolateral ataxia and crural paresis (HACP) is defined as predominantly crural paresis with ipsilateral ataxia, a variant of ataxic hemiparesis (AH), by Fisher and his colleagues. HACP usually resulted from lacunar infarction in the basis pontis at the junction of the upper one-third and inferior two-third of the pons, or in the posterior limb of the internal capsule. We reported a patient with HACP which was caused by an infarct in the paracentral gyrus irrigated by the anterior cerebral artery (ACA). He had had no cerebellar signs before the onset of HACP, although he had old small infarcts in the right pons, right thalamus and left cerebellar hemisphere. Neuroimaging and other clinical studies suggested that the mechanism of the present infarction was the most-likely embolic, but not lacunar. As far as we know, there has been only one abstract presentation of a patient with HACP due to ACA territory infarction in Japan, although five such cases were recently reported by Bogousslavsky and others.

Aged↗
PubMed1999

[Clinical evaluation of weekly hepatic arterial infusion chemotherapy in patients with unresectable metastatic liver cancer].

Twenty-five cases with unresectable metastatic liver cancers were experienced in our hospital over the past five years who underwent weekly 24-hour continuous hepatic arterial infusion chemotherapy using 5-FU and CBDCA. The response rate was 20%, the median survival was 23 months, and the one/two year overall survival rates averaged 81.3/45.5%. In 77% of patients, this therapy prevented death from hepatic metastases. Moreover, since adverse effects were limited compared with bolus infusion, weekly 24-hour continuous hepatic arterial infusion chemotherapy was thought to be a favorable method.

Adult↗
PubMed1999

[Long-term outcome of coronary events in hemodialysis patients younger and older than 65 years of age].

BACKGROUND AND AIM: It has been reported that a coronary event is the leading cause of mortality in HD patients. The aim of this study was to examine and compare prospectively the effect of aging in relation to the in-hospital and the long-term outcome in HD patients with or without revascularization therapy who had experienced a coronary event. STUDY PATIENTS AND METHODS: Seventy consecutive HD patients with coronary events (9 AMI, 48 AP, and 13 CHF) were registered in this study and 69 patients underwent CAG. Patients were classified into elderly (> or = 65, n = 33) and younger (< 65, n = 37) groups based on their ages at the time of the events. Forty-six patients (21 vs 25) underwent initial coronary revascularization therapy. We followed 70 HD patients with coronary events for a mean period of 31 +/- 21 months (range: 1 day to 77 months). RESULTS: A level of 64% of the elderly group and 41% of the younger group experienced coronary events within the first year of HD. The diseased vessels (2.2 vs 1.9 per patient) and stenotic lesions (2.8 vs 2.5 pre patients) were not significantly different between the two groups. The 70-month survival rate was significantly lower (21% vs 65%, p = 0.0423) in the elderly group than in the younger group. The complicated rate of stroke after a major event was significantly higher (14 vs 4, p = 0.0025) in the elderly group than in the younger group. Moreover 21 elderly patients (11 cardiac death, 5 stroke, 4 cancer) and 9 younger patients (8 cardiac death, 1 stroke) died during the 70-month follow-up period. CONCLUSIONS: Coronary events were most frequent in the first year of HD. Long-term survival rate was significantly lower in elderly patients than in younger patients. Cardiac death was the most common cause of death in both groups regardless of performing coronary revascularization. Death due to stroke and cancer was also more common in elderly patients.

Aged↗
PubMed1999

[Nitric oxide inhalation as an effective therapy for acute respiratory distress syndrome due to near-drowning: a case report].

A 16-year-old boy with acute respiratory distress syndrome (ARDS) due to near-drowning was admitted to our hospital. ARDS was treated with low-level nitric oxide (NO) inhalation (ranging from 4 ppm to 1 ppm) for 24 days. Oxygenation was improved and pulmonary hypertension was reduced after NO inhalation, but systemic blood pressure, heart rate, and cardiac output were not affected. PaO2 improved from 153 Torr to 354 Torr under identical ventilating conditions (F1O2 1.0), and mean pulmonary arterial pressure fell from 40 mm Hg to 27 mmHg. It has been reported that NO inhalation alleviates ventilation-flow mismatch and pulmonary hypertension. It is unclear, however, whether this therapy improves the prognosis for ARDS. In our patient, NO inhalation was effective in alleviating the oxygenation impairment and pulmonary hypertension associated with ARDS.

Acute Disease↗
PubMed1999

Effect of saliva on the growth of Helicobacter pylori.

The effect of saliva mixed in culture media from young healthy volunteers on the growth of Helicobacter pylori (H. pylori) was investigated. Saliva was centrifuged at 15,000 rpm for 10 min and the supernatant was mixed with the reference strain of standard H. pylori which was suspended in sterilized physiological saline. The mixture was inoculated onto agar plate and incubated for 3 days. The numbers of colonies were counted. Saliva from a young male volunteer stimulated the growth of H. pylori significantly compared with the control. This result indicates that there may be such individuals who have saliva increasing the growth of H. pylori. But this is the preliminary report and more studies are needed to know what factors in saliva may affect the growth of H. pylori.

Adult↗
PubMed1999

Computer modeling of fluid dynamics related to a myocardial bridge in a coronary artery.

Fluid mechanics associated with blood flows induced by the so-called myocardial bridge (MB) has been studied systematically using a computational fluid dynamic modeling of the Newtonian, incompressible, two-dimensional, unsteady flow in a channel with a time-dependently flushing in/out indentation. During each cycle, a train of vortex wave flow was observed downstream of the phasic stenosis and both upper and lower walls suffer severely from consistently high, oscillating wall shear stresses (WSS). Extensive studies were conducted on the influence of the Reynolds number, the geometry and the Strouhal number of the MB movement on the nature of the vortex flow and the time-dependent wall shear stress distribution. Special attention was drawn to the relationship between the vortex wave and the pressure distribution. It was found that the pressure gradient changed markedly during one cycle, which was apparently dominated by the dynamics of the indentation. A steep, adverse pressure gradient was observed when the indentation was flushing out, which corresponded to the existence of the most developing vortices. It implies the possibility that the MB in a coronary artery can produce an extremely low pressure region immediately downstream of the phasic stenosis, where elastic choking or collapse of the coronary artery might occur.

Computational Biology↗
PubMed1998

ADP-ribosylation factor-1 is sensitive to N-ethylmaleimide.

The treatment of normal rat kidney cells with N-ethylmaleimide caused the release of beta-COP, a component of coatomer, from the Golgi apparatus without causing disassembly of the organelle. The release of beta-COP, which was not due to depolymerization of microtubules, was markedly blocked by the activation of GTP-binding proteins by aluminum fluoride or a nonhydrolyzable analogue of GTP. To determine which component is N-ethylmaleimide-sensitive, we reconstituted the recruitment of coatomer from the bovine brain cytosol onto the Golgi apparatus in digitonin-permeabilized cells. In cells treated with N-ethylmaleimide before permeabilization, beta-COP was still recruited onto the Golgi apparatus. In contrast, beta-COP was not recruited when N-ethylmaleimide-treated bovine brain cytosol was used. These results suggest that the N-ethylmaleimide-sensitive factor(s) are present in the cytosol. It is known that coatomer and ADP-ribosylation factor-1 (ARF1) are the only cytoplasmic proteins needed for the assembly of Golgi-derived coated vesicles. N-Ethylmaleimide treatment of a coatomer-rich fraction did not affect the binding of beta-COP to the Golgi apparatus, whereas the same treatment of an ARF-rich fraction abolished beta-COP binding. Similar results were obtained using purified recombinant ARF1. Concomitant with inactivation, 0.85 mol of N-ethylmaleimide was incorporated into 1 mol of ARF1. ARF1 contains only one cysteine residue (Cys-159), which is located near the base moiety of the bound guanine nucleotide.

ADP-Ribosylation Factor 1↗
PubMed1998

Neuroprotective effect of the novel glutamate AMPA receptor antagonist YM872 assessed with in vivo MR imaging of rat MCA occlusion.

The neuroprotective effect of post-ischemic treatment with the novel, highly water-soluble, glutamate AMPA receptor antagonist YM872 was evaluated by using MR imaging and histopathology of rats subjected to permanent MCA occlusion. Two treatment groups with continuous i.v. infusion of 20 mg kg-1 h-1 YM872 during either the first 4 h or first 24 h after MCA occlusion, called 4 h YM872 treatment group (n=9) and 24 h YM872 treatment group (n=8) respectively, were compared to a control group (n=8). The main end-point was T2 weighted MR imaging and histopathology 24 h after MCA occlusion. Also the time evolution of the ischemic tissue damage was studied by diffusion weighted MR imaging 412 and 24 h after MCA occlusion. The volume of ischemic tissue damage as assessed by diffusion weighted MR imaging 412 h after MCA occlusion was significantly smaller in both YM872 treatment groups (99+/-52 mm3 and 102+/-44 mm3 compared to 186+/-72 mm3 in the control group, +/-S.D. and p=0.008). The infarct volume as assessed by T2 weighted MR imaging 24 h after MCA occlusion was significantly smaller only in the 24 h YM872 treatment group (262+/-57 mm3 compared to 366+/-49 mm3 in the control group, +/-S.D. and p=0.01) while the infarct volume in the 4 h YM872 treatment group (357+/-88 mm3) was similar to the control group. YM872 treatment significantly reduced the infarct volume 24 h after MCA occlusion when the drug was administered as continuous infusion during the 24-h observation period.

Animals↗
PubMed1998

Effects of YM872 on atrophy of substantia nigra reticulata after focal ischemia in rats.

Middle cerebral artery (MCA) occlusion causes atrophy in the ipsilateral substantia nigra reticulata (SNR). The effects of glutamate AMPA receptor antagonism on SNR atrophy, which is supposed to inhibit excitatory inputs from the subthalamic nucleus to the SNR, was investigated in rats with permanent MCA occlusions. Histological examination revealed marked atrophy two weeks after MCA occlusion in the saline-treated control group. However, constant i.v. infusion of YM872, a selective AMPA receptor antagonist, for 2 weeks significantly reduced SNR atrophy; neurological deficits also decreased. These results suggest that the AMPA receptor may be involved in the pathogenesis of SNR atrophy during the subacute phase of focal cerebral ischemia.

Animals↗
PubMed1998

Variation in CD4+ T and CD8+ T lymphocyte subpopulations in bovine mammary gland secretions during lactating and non-lactating periods.

Mammary gland secretions (MGS) of dairy cows at different stages of lactation were studied by immunofluorescence cytometry for T lymphocyte subpopulations using monoclonal antibodies. During early and late lactation, the mean ratio of CD4+/CD8+ T lymphocytes in the MGS was 0.5 and 0.8, respectively. A large proportion of the CD8+ cells coexpressed the activation molecule, ACT2. These results indicate that CD8+ ACT2+ cells constituted the major phenotype in the T lymphocytes throughout lactation. In the mammary gland of cows in which drying off was induced, however, the proportion of CD8+ ACT2+ cells decreased, resulting in the increase of the CD4+/ CD8+ ratio in the MGS. At the late non-lactation stage, the ratio reached a maximal level of 2.5-4.0, which was similar to or higher than that found in the peripheral blood. This selective increase of CD4+/CD8+ cell ratio correlated with an increase in the concentrations of total cells in the MGS. This high CD4+/CD8+ cell ratio during the drying off stage rapidly decreased just before parturition, correlating with the decrease in concentrations of total cells in the MGS, reaching the lowest level at early lactation. The cells isolated at the non-lactation stage produced the cytokines IL-2 and IL-4 at a level much higher than those of cells isolated at lactation stages, and the increases were correlated with the CD4+ T lymphocyte proportions.

Animals↗
PubMed1998

Strong promoting activity of phenylethyl isothiocyanate and benzyl isothiocyanate on urinary bladder carcinogenesis in F344 male rats.

Post-initiation effects of phenylethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC) on hepatocarcinogenesis and urinary bladder carcinogenesis were examined in rats pretreated with diethylnitrosamine (DEN) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Groups of 21 rats received a single intraperitoneal injection of 200 mg/kg body weight of DEN. Starting 2 days thereafter, they were administered 0.05% BBN in the drinking water for 4 weeks. Three days after completion of the carcinogen treatment, they were placed on a diet containing PEITC or BITC at a dose of 0.1%, or a basal diet alone for 32 weeks and then killed for autopsy. Further groups of 6 rats each were similarly treated with PEITC, BITC or basal diet alone for 32 weeks without prior DEN and BBN exposure. In the liver, although the incidences of liver tumors were not significantly affected, the multiplicity of foci larger than 0.5 cm in diameter was slightly increased by PEITC. In the urinary bladder, the incidences of papillary or nodular (PN) hyperplasias and carcinomas were significantly elevated by PEITC or BITC after DEN and BBN initiation. In the groups without initiation, PN hyperplasia was found in all rats of both PEITC and BITC groups, along with papillomas and carcinomas in some animals. Tumors and PN hyperplasias in the groups treated with PEITC and BITC are characterized by downward growth. Our results thus showed PEITC and BITC to be strong promoters of urinary bladder carcinogenesis with some complete carcinogenic potential.

Animals↗
PubMed1998

Oscillations of membrane potential across a polypeptide membrane, induced by an electrical current.

Oscillation of membrane potential across a tri-block copolypeptide membrane composed of (Glu)x-(Leu)y-(Glu)x (x = 0.18 and y = 0.64) was observed under an electrical current, when the membrane was placed between equimolar aqueous salt solutions. The amplitude of the oscillation was influenced by the type of cation and anion in the external salt solution, and the amplitude was in the sequence: K+ > Na+ > Cs+ > Ca2+ and Cl- > Br-. The frequencies of the oscillations were in the range 0.1 to 5 Hz, and were also slightly influenced by the type of cation and anion.

Anions↗
PubMed1998

A mushroom fruiting body-inducing substance inhibits activities of replicative DNA polymerases.

We found and isolated two natural products in the extract from a basidiomycete, Ganoderma lucidum, as eukaryotic DNA polymerase inhibitors. The compounds were identified as cerebrosides, (4E,8E)-N-D-2'-hydroxypalmitoyl- 1-O-beta-D-glucopyranosyl-9-methyl-4,8-sphingadienine and (4E,8E)-N-D-2'-hydroxystearoyl-1-O-beta-D-glucopyranos yl-9-methyl- 4,8-sphingadienine and were found to be identical to the mushroom fruiting body-inducing substances (FIS) reported. These cerebrosides selectively inhibited the activities of replicative DNA polymerases, especially the alpha-type, from phylogenetically broad eukaryotic species, whereas they hardly influenced the activities of DNA polymerase beta, prokaryotic DNA polymerases, terminal deoxynucleotidyl transferase, HIV reverse transcriptase, RNA polymerase, deoxyribonuclease I, and ATPase. The inhibition of another replicative polymerase, the delta-type, was moderate. The inhibitions of the replicative polymerases were dose-dependent, and the IC50 for animal or mushroom DNA polymerase alpha was achieved at approximately 12 micrograms/ml (16.2 microM) and for animal DNA polymerase delta at 57 micrograms/ml (77.2 microM). FIS is possibly a DNA polymerase inhibitor specific to the replicative enzyme group, and the fruiting body formation may be required for the suppression of the DNA replication or the vegetative growth of the mycelium.

Animals↗
PubMed1998

Synthesis and pharmacological characterization of novel 6-fluorochroman derivatives as potential 5-HT1A receptor antagonists.

A series of novel 6-fluorochroman derivatives was prepared and evaluated as antagonists for the 5-HT1A receptor. N-2-[[(6-Fluorochroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylami ne (3; J. Med. Chem. 1997, 40, 1252-1257) was chosen as a lead, and structural modifications were done on the aliphatic portion of the chroman ring, the tether linking the middle amine and the terminal aromatic ring, the aromatic ring, and lastly the amine. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT1A receptor, some of which were selective with respect to alpha1-adrenergic and D2-dopaminergic receptors. The antagonist activity of the compounds was assessed in the forskolin-stimulated adenylate cyclase assays in CHO cells expressing the human 5-HT1A receptors. Among the modifications attempted, introduction of an oxo or an optically active hydroxy moiety at the chroman C-4 position was effective in ameliorating the receptor selectivity. Six analogues were selected through the in vitro screens and further evaluated for their in vivo activities. A 4-oxochroman derivative (31n), having a terminal 1, 3-benzodioxole ring, demonstrated antagonist activities toward 8-OH-DPAT-induced behavioral and electrophysiological responses in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗