Biomedical subjects

T Yamaguchi

Publications and source records attributed to T Yamaguchi.

At least 631 records · Page 35Linked to original sources

PubMed1998

Effect of acetazolamide reactivity on [corrected] long-term outcome in patients with major cerebral artery occlusive diseases.

BACKGROUND AND PURPOSE: It remains unclear whether hemodynamic insufficiency plays a major role in ischemic events. We performed a prospective follow-up study in ischemic stroke patients with occlusive large-artery diseases to determine whether stroke recurrence is related to reduced vasodilatory capacity, judged with single-photon emission CT and acetazolamide (ACZ) challenge. METHODS: During the period from 1987 to 1995, we examined cerebral vasodilatory capacity with single-photon emission CT and an ACZ challenge in 105 consecutive stroke patients with severe stenosis (> 75% in diameter) or occlusion of the internal carotid artery or the trunk of the middle cerebral artery who had no or minimal infarcts on CT. According to criteria reported earlier, the patients were divided into two groups: normal (negative ACZ, n = 50) or reduced ACZ reactivity (positive ACZ, n = 55). They were prospectively followed at regular intervals for a median period of 2.7 years. RESULTS: The Kaplan-Meier analysis revealed no difference in cumulative recurrence-free survival rate between the two groups. The multivariate analysis with Cox proportional hazards model demonstrated that a high systolic blood pressure at entry into the study significantly increased stroke recurrence (coefficient = .0466; hazard ratio = 1.0477; 95% confidence interval = 1.0017 to 1.0957; P = .04), whereas antihypertensive medication significantly reduced stroke recurrence (coefficient = -1.527; hazard ratio = 0.217; 95% confidence interval = 0.0612 to 0.771; P = .02), but no other variables including ACZ reactivity affected stroke recurrence rate. CONCLUSIONS: The present results demonstrate that reduced vasodilatory capacity does not play a major role in stroke recurrence. Antihypertensive therapy appears to reduce stroke recurrence even in patients with hemodynamically significant arterial diseases.

Acetazolamide↗

PubMed1998

Transoral carotid ultrasonography.

BACKGROUND AND PURPOSE: We attempted ultrasonographic evaluation of the distal extracranial internal carotid artery (ICA) using the transoral method (transoral carotid ultrasonography [TOCU]). METHODS: The subjects consisted of five healthy volunteers and seven stroke patients. Examinations were performed with a color Doppler flow imaging system equipped with convex array transducers (7 or 9.5 MHz), originally designed for transrectal use. After local anesthesia of the pharynx, we inserted a probe covered with thin gum transorally, touching the tip to the pharyngeal posterolateral wall. We then attempted to detect the ICA and measure flow velocity of the distal extracranial ICA using principal images obtained by TOCU. RESULTS: TOCU was successfully performed in all subjects without any difficulty. In the healthy volunteers, the ICA was identified at a depth of 2.2+/-0.6 cm and visualized as a vertical linear vessel 2.9+/-0.3 cm in length and bent slightly backward. The diameter and mean flow velocity of the distal extracranial ICA were 4.7+/-0.2 mm and 50+/-7 cm/s, respectively. In the stroke patients, some remarkable findings were obtained, including a narrow ICA with low flow velocity in a patient with possible ICA dissection, a lucent echo without flow signal in a patient with acute cardioembolic ICA occlusion, and decreased ICA flow velocity in a patient with ipsilateral MCA stenosis. CONCLUSIONS: These preliminary data demonstrate the potential applicability of TOCU to the evaluation of flow in the far distal extracranial ICA. TOCU definitely warrants further investigation in patients with carotid artery disease.

Adult↗

PubMed1998

Allergen exposure induces the expression of endothelial adhesion molecules in passively sensitized human bronchus: time course and the role of cytokines.

To study the mechanisms contributing to the recruitment of a selective leukocyte subset in allergic inflammation involving the airways as may occur in asthma, we examined whether allergic exposure induces the expression of cell adhesion molecules (CAMs) on the bronchial endothelium of passively sensitized human bronchi. Human bronchial tissue obtained from patients undergoing lung cancer surgery was passively sensitized with serum from patients with atopic asthma who were sensitive to house dust mite. We incubated the tissues for 30, 120, 240, and 480 min in the presence or absence of the dust mite allergen. The tissues were stained immunohistochemically for intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1). ICAM-1 was constitutively expressed in both the epithelium and endothelium in all tissues but after allergen stimulation significantly increased at 240 and 480 min. E-selectin expression also existed constitutively and increased significantly at 120 and 240 min with allergen exposure. The constitutive expression of VCAM-1 was less than that of ICAM-1 and E-selectin. Following allergen exposure, VCAM-1 expression increased significantly at 30, 120, 240, and 480 min, and at 480 min reached an almost 3.5-fold increase from baseline expression. The TNF-alpha level in the supernatants significantly increased at 120 min after allergen stimulation, and the interleukin (IL)-1beta level increased in 4 of 15 samples. We also examined the induction of CAMs by TNF-alpha, IL-1beta, and IL-4 on human bronchial tissue. TNF-alpha and IL-1beta increased the expression of ICAM-1, E-selectin, and VCAM-1, whereas IL-4 induced only that of VCAM-1. In addition, neutralizing antibody against TNF-alpha and IL-1beta partially blocked the upregulation of CAMs on passively sensitized bronchial tissue after allergen exposure. Thus, both an IgE-dependent allergic response and selected cytokines are able to upregulate endothelial CAMs in human bronchial tissue. These observations provide further evidence that leukocyte infiltration into the site of allergic inflammation as occurs in atopic asthma is in part regulated by the expression of ICAM-1, VCAM-1, and E-selectin.

Adult↗

PubMed1998

Association of an insertion polymorphism of angiotensin-converting enzyme gene with the activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) shows various clinical manifestations, which are characterized by inflammation in many different organ systems. The cause of SLE is still unclear; however, the immunological abnormalities are considered to be responsible for the pathogenesis of SLE. As angiotensin I-converting enzyme (ACE) has been reported to be associated with various immunological phenomena, we investigated the correlation between insertion (I)/deletion (D) polymorphism of the ACE gene and the disease activity of SLE. Ninety-three patients with newly diagnosed SLE were enrolled in this study. ACE genotype was determined by the polymerase chain reaction (PCR). We measured serum levels of anti-double-stranded (ds) DNA antibody (Ab) and serum levels of total complements (CH50) as the parameter for lupus activity. Moreover, we evaluated the clinical disease activity by calculating SLE disease activity index (SLEDAI). Individuals with II genotype showed a significant increase in SLE activity. Patients with the ACE II genotype showed a higher serum level of anti-dsDNA Ab (14.3 IU/ml (5.475, 74.6, median (25th centile, 75th centile)) than those with the DD genotype (4.65IU/ml (4.05, 6.8)) (P<0.01). Moreover, patients with the 11 genotype also showed lower levels of serum CH50 than those with the DD genotype (P < 0.01). Patients with the II1 or DI genotype had significantly higher SLEDAI score than those with the DD genotype (P < 0.01). These results suggest that the ACE genotype could be associated with the disease activity of SLE. ACE insertion polymorphism might be used as one of predictive factors for the activity of lupus.

Adult↗

PubMed1998

Extracellular calcium (Ca2+(o))-sensing receptor in a murine bone marrow-derived stromal cell line (ST2): potential mediator of the actions of Ca2+(o) on the function of ST2 cells.

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+(o)) homeostasis by mediating the actions of Ca2+(o) on parathyroid gland and kidney. Bone marrow stromal cells support the formation of osteoclasts from their progenitors as well as the growth of hematopoietic stem cells by secreting humoral factors and through cell to cell contact. Stromal cells also have the capacity to differentiate into bone-forming osteoblasts. Bone resorption by osteoclasts probably produces substantial local increases in Ca2+(o) that could provide a signal for stromal cells in the immediate vicinity, leading us to determine whether such stromal cells express the CaR. In this study, we used the murine bone marrow-derived, stromal cell line, ST2. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in ST2 cells. We also identified CaR transcripts in ST2 cells by Northern analysis using a CaR-specific probe and by RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of ST2 cells to high Ca2+(o) (4.8 mM) or to the polycationic CaR agonists, neomycin (300 microM) or gadolinium (100 microM), stimulated both chemotaxis and DNA synthesis in ST2 cells. Therefore, taken together, our data strongly suggest that the bone marrow-derived stromal cell line, ST2, possesses both CaR protein and messenger RNA that are very similar if not identical to those in parathyroid and kidney. Furthermore, as ST2 cells have the potential to differentiate into osteoblasts, the CaR in stromal cells could participate in bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local, osteoclast-mediated release of Ca2+(o) and, thereafter, initiating bone formation after their differentiation into osteoblasts.

Amino Acid Sequence↗

PubMed1998

Effect of dexamethasone pretreatment on the dexamethasone-dependent induction of tyrosine aminotransferase activity in primary cultured rat hepatocytes.

The effect of dexamethasone (Dex) pretreatment on the Dex-dependent induction of tyrosine aminotransferase (TAT) activity was studied in primary cultured rat hepatocytes. The extent of the Dex-dependent induction of TAT activity decreased during culture in untreated cells. Dex pretreatment prevented this decrease. A Scatchard plot analysis of the results of a [3H]Dex binding assay showed that hepatocytes cultured for 2.5 h possessed both high and low affinity binding sites in their cytosols. The number of both high and low affinity binding sites decreased during culture for a further 24 h in untreated cells. Dex pretreatment partly prevented the decrease in low affinity binding sites but had no effect on the decrease in high affinity binding sites. These results show that Dex pretreatment counteracts the usual decrease in the inducibility of TAT activity, and suggest that this action of Dex may be due to the maintenance of low affinity binding sites. These results also suggest that low affinity binding sites could possibly mediate the biological response to Dex.

Animals↗

PubMed1998

A carbon-centered radical as a reaction species in the DNA strand-breakage by D-glucosamine.

Electron spin resonance(ESR) studies using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and sodium 3,5-dibromo-4-nitrosobenzensulfonate (DBNBS) as a spin-trapping agent revealed the formation of both hydroxyl and carbon-centered radical-derived spin adducts in Cu2+-containing 50 mM Tris-HCl buffered solutions (pH 7.1) of D-glucosamine, D-mannosamine, and D-galactosamine, which were previously shown to have the ability to break the single-strand of plasmid pBR322 DNA in a nucleotide sequence-specific manner. HCl-free D-glucosamine has higher DNA breaking activity, and this activity is promoted more by the presence of Cu2+ than the original D-glucosamine hydrochloride, exhibits stronger radical signals in the ESR spectrum. It is suggested that D-glucosamine is unstable around neutral pH, being converted into certain intermediate(s) such as a dihydropyrazine compound, which generate(s) carbon-centered radicals, and that, besides the hydroxyl radical, the intermediate(s) is/are responsible for DNA strand breakage.

Benzenesulfonates↗

PubMed1998

Evaluation of the topical delivery of a prednisolone derivative based upon percutaneous penetration kinetic analysis.

Prednisolone (PN) and an esterified derivative (PND) were evaluated in pharmacological and pharmacokinetic studies. The pharmacological study was performed using a rat croton-oil induced ear edema model. The results for the topical effect in skin and the systemic effect through multiple topical applications showed that PN and PND were equally potent in suppressing edema, and that PN caused a reduction in thymus weight, whereas PND had little effect. The concentration of these steroids in hairless mouse skin was estimated from an in vitro percutaneous absorption study using the computer simulation program MULTI(FILT). PND was found to be poorly absorbed. In fact, the PND concentration in the viable skin remained low (0.79 microg/cm2), even after 7 d. However, the estimated concentration of PND in the viable skin appears to be in excess of the threshold for effective topical effect during the pharmacological evaluation. In contrast, in the case of PN, the estimated PN concentration increased gradually after application and reached a level of 10.22 microg/cm2 at day 7, suggesting that this increase in PN concentration in the viable skin could result in a systemic effect. The difference between PN and PND concentration in the skin during the time course could be due to the metabolism of PND to PN in the viable skin. Consequently, the difference between the pharmacological study is reflected from the results of the pharmacokinetics of PN and PND in the skin.

Administration, Topical↗

PubMed1998

[Preparation of optically active succinic acid derivatives. III. Regioselective condensation reactions of optically active 2-substituted succinic acids with diimidazolide].

We investigated the large scale synthesis of monocalcium bis [(2S)-2-benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl) propionate] dihydrate (KAD-1229), which has a potent hypoglycemic effect, in a single reaction vessel. (2S)-2-Benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl) propionic acid (7) was directly obtainable from (S)-2-benzylsuccinic acid (2) and cis-hexahydroisoindoline (4), without the isolation of intermediates by the method using thionyldiimidazole (9) and/or diimidazolide of the acid 2. Sequential reaction of imidazole with thionyl chloride, 2, and 4, followed by acid catalyzed hydrolysis gave amidecarboxylic acid 7 in 86% overall yield. The acid 7 was treated with 2 N NaOH, followed by the treatment with calcium chloride to give KAD-1229 in 91% yield.

Chemical Phenomena↗

PubMed1998

Vectorcardiographic evaluation of myocardial infarct size: departure parameters are superior to conventional spatial parameters.

To determine whether the departure parameters derived from a "departure loop" of a vectorcardiogram are more accurate than conventional spatial parameters in evaluating myocardial infarct size, 74 patients with first-onset myocardial infarction (MI) were studied. The correlation between the departure parameters (amplitudes in scalar leads of the departure loop) and the percent defect volume of thallium myocardial scintigrams (%DV) was compared with that of the spatial parameters (magnitude, azimuth, and elevation of the original QRS loop). In anteroseptal MI, the amplitude of a 20-msec vector in the z-axis and the azimuth of a 30-msec vector (H30) were significantly correlated with %DV (r=0.783, p<0.001 and r=0.572, p<0.05). In anteroseptal MI with involvement of the lateral wall, the amplitude of a 30-msec vector in the x-axis and H30 showed significant correlation with %DV (r=0.802, p<0.001 and r=0.772, p<0.01). In inferior and inferoposterior MI, the amplitude of a 30-msec vector in the y-axis and the elevation of a 30-msec vector were significantly correlated with %DV (r=0.920, 0.891, p<0.001 and r=0.871, 0.678, p<0.01, respectively). In conclusion, the departure parameters are more accurate than the spatial parameters for evaluation of myocardial infarct size.

Aged↗

PubMed1998

The AMPA-receptor antagonist YM90K reduces AMPA receptor-mediated excitotoxicity in rat hippocampal cultures.

The effects of YM90K on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitotoxicity were investigated using kainate, AMPA and cyclothiazide in rat hippocampal cultures. YM90K had neuroprotective actions against both kainate toxicity and cyclothiazide-enhanced AMPA toxicity. YM90K induced a parallel and rightward shift of both kainate and AMPA dose-response curves. The application of YM90K even 3 hr after the start of kainate exposure significantly reduced kainate toxicity. These results indicate that YM90K protects neurons against AMPA receptor-mediated toxicity at an agonist site on the AMPA receptor and that YM90K protects against AMPA receptor-mediated toxicity even if applied after neurotoxic insult.

Animals↗

PubMed1998

Neuroprotective effect of YM-39558, orotic acid ethylester, in gerbil forebrain ischemia.

We studied the effects of orotic acid and YM-39558 (2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid ethyl ester), orotic acid ethylester, on delayed neuronal death of hippocampal CA1 neurons induced by transient forebrain ischemia. Our data indicated that YM-39558 had high permeability across the blood brain barrier and was hydrolyzed to orotic acid, the active substance, in the brain. The neuronal damage was reduced significantly in animals intraperitoneally treated with YM-39558 (100 mg/kg x 3) after ischemia, but not with orotic acid in the same way. The results also suggested that the maintenance of a few ten micromolar orotic acid in cerebrospinal fluid were needed for its neuroprotective effects.

Animals↗

PubMed1998

Itch-associated response and antinociception induced by intracisternal endomorphins in mice.

Endomorphin-1 and endomorphin-2 are newly identified endogenous peptides and have high affinity and selectivity for mu-opioid receptors. The present experiments were conducted to determine whether intracisternal injection of these peptides would produce an itch-associated response and antinociception and to compare their effects to that of morphine. Endomorphin-1 and endomorphin-2 (0.3-3 nmol/mouse) elicited facial scratching characterized by bell-shaped dose-response curves with a peak effect at endomorphin-1 at 0.3 nmol/mouse and endomorphin-2 at 1 nmol/mouse. Their peak effects were inhibited by subcutaneous pretreatment with naloxone (1 mg/kg). Morphine (0.3-30 nmol/mouse) produced facial scratching, and its dose-response curve was also bell-shaped. Scratching of the body trunk, head and ears were not elicited by these doses of endomorphins and morphine. Endomorphin-1 and -2 at doses of 0.3-3 nmol/mouse produced dose-dependent antinociception, as measured with the tail-pressure test. The potency and duration of actions of these peptides were comparable to those of morphine. The results suggest that endomorphin-1 and endomorphin-2 are involved in itch-signaling and pain-inhibiting functions of the brain.

Analgesics, Opioid↗

PubMed1998

Comparative study of [3H]ramosetron and [3H]granisetron binding in the cloned human 5-hydroxytryptamine3 receptors.

Characteristics of the binding of [3H]ramosetron to cloned human 5-hydroxytryptamine3 (5-HT3) receptors were investigated and directly compared to those of [3H]granisetron binding. Saturation studies revealed that [3H]ramosetron labeled more sites with high affinity (Kd=0.15+/-0.01 nM, Bmax =653 +/- 30 fmol/mg protein) than [3H]granisetron (Kd=1.17+/-0.25 nM, Bmax=427+/-43 fmol/mg protein). Kinetic studies revealed that dissociation of [3H]ramosetron was slower than that of [3H]granisetron. These results suggest that ramosetron is a highly potent 5-HT3-receptor antagonist.

Animals↗

PubMed1998

HPLC method for evaluation of the free radical-scavenging activity of foods by using 1,1-diphenyl-2-picrylhydrazyl.

An HPLC method for evaluation of the free radical-scavenging activity of foods by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) is reported. The activity was evaluated by measuring the decrease of DPPH detected at 517 nm. By using this novel method, we determined the free radical-scavenging activity of several antioxidants: ascorbic acid, alpha-tocopherol, Trolox, and cysteine. The results gave good correlation between the radical-scavenging activity determined by HPLC and by conventional colorimetry. This methodology was applied to determine the free radical-scavenging activity of 8 beverages. The activity of coffee was the highest, followed by red wine, green tea, oolong tea, black tea, rosé wine, white wine, and orange juice. The results well agree with those of previous reports. This method is expected to be useful for a simple and rapid determination of free radical-scavenging activity in colored foods, because coloring substances in foods do not interfere with the measurement.

Antioxidants↗

PubMed1998

Purification and characterization of a novel cysteine synthase isozyme from spinach hydrated seeds.

A novel type of cysteine synthase (CSase, EC 4.2.99.8) isozyme, designated as CSase 1', was purified to homogeneity from hydrated spinach seeds. The enzyme had a molecular weight of 68,000 and consisted of two identical subunits of M(r), 34,000. The apparent K(m) for O-acetyl-L-serine was 8.33 mM and that for sulfide was 0.66 mM. The activity of CSase 1' was maintained when it was treated at 60 degrees C for 1 min. This novel enzyme was similar to CSases 1, 2, and 3 already purified from spinach leaves, in results of double immunodiffusion, molecular weight, subunit composition, K(m) values for O-acetyl-L-serine and sulfide, and heat stability. On the other hand, N-terminal amino acid sequence, effects of immunotitration, pH optimum, and effects of hydroxylamine on purified CSase 1' were different from those of the other CSases. Furthermore, it was found that CSases 2S and 3S isolated from hydrated spinach seeds were identical with the CSases 2 and 3 reported previously. It was also disclosed that CSases 1, 2, and 3 were localized in chloroplasts, cytosol, and mitochondria, respectively.

Amino Acid Sequence↗

PubMed1998

Complexes of serine acetyltransferase and isozymes of cysteine synthase in spinach leaves.

Polyclonal antibodies against cysteine synthase (CSase; EC 4.2.99.8) isozymes 1, 2, and 3 were used for the detection of complexes of these isozymes with serine acetyltransferase (SATase; EC 2.3.1.30). SATase was partially purified and found to complex with these isozymes by western blotting and immunotitration. When the complexes were treated with a high concentration of O-acetyl-L-serine, they did not dissociate. However, some complexes with CSase 1 or 3 dissociated when left for 24 h at 4 degrees C. Results of western blotting on SDS-PAGE showed that CSase 2 complexed with SATase. CSases 1, 2, and 3 all could complex with SATase, but the tightness of the bond differed.

Acetyltransferases↗

PubMed1998

Seroprevalence of infectious bursal disease virus in free-living wild birds in Japan.

Serum samples collected from 739 free-living wild birds of 44 species from Gifu, Mie and Hyogo Prefectures in Japan during the period 1989 to 1997 were tested for antibodies to infectious bursal disease virus (IBDV) serotypes 1 and 2 by a virus neutralization test. Serological evidence of infection with serotypes 1 and 2 was found in 15 (2%) of the sera of 6 species and 36 (4.9%) of the sera of 11 species, respectively. Antibodies to IBDV were detected from both sedentary and migratory species. These findings suggest that free-living wild birds have an important role in the natural history of IBDV. These findings raise the possibility that the IBDV prevalent in the breeding grounds of these birds in other countries could be imported by the migratory species. This is the first report of an extensive serological survey of IBDV in wild birds.

Animals↗