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Biomedical subjects

Y Nishida

Publications and source records attributed to Y Nishida.

At least 73 records · Page 4Linked to original sources
PubMed2000

The impact of the CYP2D6 and CYP2C19 genotypes on venlafaxine pharmacokinetics in a Japanese population.

OBJECTIVE: The cytochrome P450 isozymes CYP2D6 and CYP2C19 exhibit genetic polymorphism in human, including a marked interethnic difference. As the functional status of the isozymes CYP2D6 and CYP2C19 have an impact on the pharmacokinetics of some antidepressants, we investigated whether the disposition of venlafaxine was affected by the CYP2D6 and CYP2C19 genotypes. METHODS: Twenty-eight adult Japanese men in good health participated in this study. Genomic DNA was isolated from peripheral lymphocytes, and the CYP2D6 genotype was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and XbaI-RFLP analysis. Subjects were categorized into the following four groups: group 1 CYP2D6*10/*10; group 2 CYP2D6*1/*10 and *2/*10; group 3 CYP2D6*1/*1, *1/*2 and *2/*2; and group 4 the other genotypes. Two defective CYP2C19 alleles (CYP2C19*2 and CYP2C19*3) were identified by means of PCR-RFLP analysis. Venlafaxine was administered orally following an overnight fast. Plasma concentrations of venlafaxine and O-desmethylvenlafaxine were monitored using high-performance liquid chromatography up to 24 h. RESULTS: The peak plasma concentration and values of area under the concentration-time curve up to 24 h for venlafaxine were 298% and 453% higher for group 1 than group 3, and 91% and 120% higher for group 2 than for group 3, respectively. The homozygote for two defective alleles of CYP2C19 showed a higher concentration of venlafaxine within group 1 and group 2. CONCLUSION: The CYP2D6*10 allele and two CYP2C19 defective alleles, common in an Asian population, are the most likely genetic factors to use in determining interindividual differences in the pharmacokinetics of venlafaxine, although the results with respect to CYP2C19 are preliminary because of the few subjects used.

Administration, Oral↗
PubMed2000

N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, markedly improves postischemic left ventricular dysfunction.

We examined whether pharmacological inhibition of glycogenolysis by N-methyl-1-deoxynojirimycin (MOR-14), a new compound which reduces the glycogenolytic rate by inhibiting the alpha-1,6-glucosidase activity of the glycogen-debranching enzyme, can protect the heart against postischemic left ventricular dysfunction. The hearts of male Sprague-Dawley rats were excised, and perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. The hearts were paced at 320 beats/min except during the ischemia. Left ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s), and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min including a 30-min preischemic period followed by a 30-min episode of global ischemia and 60 min reperfusion. with or without 0.5 or 2 mM of MOR-14 during the 30-min preischemic period or the first 30 min of reperfusion. In another series of experiments, the myocardial content of glycogen and lactate was measured during the 30-min episode of ischemia in groups treated with and without 2mM of MOR-14. Preischemic but not postischemic treatment with MOR-14 significantly improved LVDP and +/-dP/dt without altering coronary flow during reperfusion in a dose-dependent manner. MOR-14 significantly preserved the glycogen content and significantly attenuated the lactate accumulation during the 30-min episode of ischemia. Preischemic treatment with MOR-14 is protective against postischemic left ventricular dysfunction through the inhibition of glycogenolysis in the isolated rat heart.

1-Deoxynojirimycin↗
PubMed2000

MRI measurements of normal extraocular muscles and other orbital structures.

BACKGROUND: Studies of extraocular muscle (EOM) by magnetic resonance imaging (MRI) need to be extended to normal subjects of different ages to obtain data on the muscle thickness, cross-sectional area, and the volume of EOM and other orbital tissues. METHODS: Forty-two orbits of 21 normal subjects in three age groups with an age range of 19-70 years were examined with surface-coil MRI. The transverse and sagittal images were used to measure the thickness of the four rectus muscles during fixation in different gaze positions. The coronal images with eyes in the primary position were used to calculate the cross-sectional areas. The volumes of all six EOM, orbital fatty tissue, the optic nerve and the eyeball were measured in the coronal plane and in either the transverse or the sagittal plane. RESULTS: The horizontal muscles were thinner than vertical muscles. Muscle volume was larger in SR (superior rectus) than in IR (inferior rectus), larger in SO (superior oblique) than in IO (inferior oblique), and the same in LR (lateral rectus) as in MR (medial rectus). No significant differences were found in the values of the cross-sectional area in any image plane between the three age groups. There were no significant differences in muscle thickness and size and fatty tissue volume between age groups. The muscle thickness was linearly correlated to the angle of the eye deviation for all four rectus muscles, both in the "on" and "off" directions of the muscles. CONCLUSIONS: The study provides quantitative data, in normal subjects of different ages, on the thickness and size of EOM and the volume of other orbital tissues by MRI, to serve as a basis for further studies on the morphological changes of EOM in various orbital diseases.

Adult↗
PubMed2000

A child with adrenocortical adenoma accompanied by congenital hemihypertrophy: report of a case.

We report herein the findings of a 7-year-old male child with a ruptured adrenocortical adenoma and congenital hemihypertrophy which was incidentally detected after suffering a trauma. A review of 21 pediatric cases of adrenocortical neoplasms in the literature was made. The patient showed precocious puberty such as pubis and advanced bone age, but an endocrinological examination revealed no definite abnormalities. The right adrenal tumor with hematoma was resected after these evaluations. Adrenocortical adenoma is considered to occur more frequently in female children. However, the incidence of adrenocortical tumors accompanied by congenital hemihypertrophy does not differ between males and females. The outcomes were relatively good, although the observation periods were short in some patients. A large number of patients presented with a tumor and hemihypertrophy on the same side. This finding is of interest when considering the possible association between hemihypertrophy of the organs and tumor proliferation. However, their association in terms of development was unclear. It is necessary for patients with hemihypertrophy to have regular examinations for the possible development of malignant tumors, especially in the kidney, adrenal gland, and liver.

Adrenal Cortex Neoplasms↗
PubMed2000

Ethanol production by repeated batch culture using yeast cells immobilized within porous cellulose carriers.

Ethanol was efficiently produced for 20 d by repeated batch culture using yeast cells immobilized in porous cellulose carriers. The physical structure of the carrier beads, which had small pores distributed on the outer surface and relatively large pores distributed in the interior, was found to be effective for cell immobilization. The effects of chemical modifications to the basic cellulose carrier on cell immobilization and ethanol production were also examined in repeated batch cultures. The chemical modifications had little effect on either cell immobilization or ethanol production.

Journal Article↗
PubMed2000

A facile synthetic approach to L- and P-selectin blockers via copolymerization of vinyl monomers constructing the key carbohydrate modules of sialyl LewisX mimics.

A highly practical synthetic approach is described for artificial L- and P-selectin blockers. The synthesis involves radical bi- and terpolymerizations of p-(N-acrylamido)phenyl 3- or/and 6-sulfo-beta-D-galactoside with allyl alpha-L-fucoside in the presence of acrylamide. Each of the two glycosyl monomers constructs a key carbohydrate module responsible for selectins/sulfated sialyl LewisX (sLeX) bindings. Whereas an acrylamide copolymer carrying 3-sulfo-galactoside showed no activity for any selectins, the fucosylated terpolymer showed a potent activity to block both of P- and L-selectins/sLeX binding at a concentration of a few micrograms per milliliter. The enhanced activity is apparently ascribed to the cooperative binding effects of the fucoside and the 3-sulfo-galactoside residues.

Carbohydrate Sequence↗
PubMed2000

Expression and electrophysiological function of actin in chick cerebellar neurons.

Among several monoclonal antibodies obtained by immunizing Balb/c mice with cerebellar synaptic membrane fractions from E20 chick embryos, the antibody, named M35, suppressed Ca-spikes in immature cultured chick cerebellar neurons. M35 immunoprecipitated 43 kDa protein from a 125I-labeled embryonic crude cerebellar membrane fraction. Immunohistochemically, the M35 antigen was expressed most intensively in Purkinje cells, but its expression was limited to highly motile structures at developmental neuronal remodeling. Electrophysiologically, M35 facilitated current responses to AMPA and inhibited the responses to GABA in cultured cerebellar Purkinje neurons. The several peptides derived from the affinity-purified 43 kDa protein were found to have homologous amino acid sequences to non-muscle actins. These results suggest that the antigen recognized by M35 may play an essential role probably as membrane ion channels modulating synaptic functions in not only the development and growth but also the neuronal activity of chick cerebellar Purkinje cells.

Actins↗
PubMed2000

T-0162, a novel free radical scavenger, reduces myocardial infarct size in rabbits.

1. We investigated the effects of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl)urea hydrochloride (T-0162), a novel low-molecular weight free radical scavenger, on the generation of superoxide anions and hydroxyl radicals in vitro and in vivo and on myocardial infarct (MI) size in an in vivo model of MI in rabbits. 2. It was found that T-0162 scavenged both superoxide anions and hydroxyl radicals in a concentration-dependent manner in vitro. 3. In an in vivo rabbit model with 30 min coronary occlusion and 30min reperfusion, T-0162 scavenged hydroxyl radicals generated in the myocardium during reperfusion. 4. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion. The pretreatment group (n = 10) was infused with T-0162 dissolved in 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion at a rate of 400 microg/kg per min. The post-treatment group (n = 10) was injected with an i.v. bolus of 10 mg/kg T-0162 and was then infused with 400 microg/kg per min T-0162 for 190 min from 10 min before reperfusion to 180 min after reperfusion. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of area at risk (AAR). 5. There was no significant difference in haemodynamic parameters among the three groups throughout the experimental period. The per cent infarct size of the AAR in the T-0162 groups (24.8+/-4.3 and 30.5+/-3.9% for pre- and posttreatment groups, respectively) was significantly reduced compared with control (44.7+/-4.1%; P<0.05). There was no significant difference in the AAR among the three groups. 6. In conclusion, T-0162 reduces MI size through the inhibition of reperfusion injury.

Animals↗
PubMed2000

A Drosophila Winged-helix nude (Whn)-like transcription factor with essential functions throughout development.

A Drosophila gene, Dwhn (Drosophila whn-like), encoding a putative transcriptional regulator with a DNA binding domain similar to that of mouse Winged-helix nude (Whn) was cloned. Analyses of the phenotypes produced by a hypomorphic mutation and transgene expression suggested a role in cell fate decision during the differentiation of the compound eye, wing veins and bristles. During embryonic development, Dwhn expression started ubiquitously followed by more restricted expression in striking contrast to the expression patterns of other Drosophila forkhead (fkh) family genes whose local expression correlate well to their roles as local homeotic genes. This broad expression may correspond to the multiple defects in embryos homozygous for strong alleles, such as defects in the formation of central and peripheral nervous systems, germ band retraction, head involution, and dorsal closure. The DNA binding specificity of Dwhn differed from that of Whn despite the strong sequence conservation in the DNA binding domain. Dwhn is the first invertebrate Whn-like transcriptional regulator, and should provide insights into the basic functions and evolution of the whn family genes.

Amino Acid Sequence↗
PubMed2000

Osteogenic protein-1 promotes the synthesis and retention of extracellular matrix within bovine articular cartilage and chondrocyte cultures.

OBJECTIVE: We have used recombinant osteogenic protein-1 to investigate our hypothesis that proper repair and maintenance of cartilage requires not only enhanced biosynthesis and replenishment of the extracellular matrix but also the enhancement of components necessary for matrix retention. DESIGN: The effects of osteogenic protein-1 were examined on bovine articular cartilage slices as well as isolated chondrocytes grown in alginate beads. Cartilage slices were examined for accumulation of proteoglycan by incorporation of 35S-sulfate and staining using Safranin O or, a biotinylated probe specific for hyaluronan. Bovine chondrocytes were characterized by use of a particle exclusion assay, in-situ hybridization, quantitative-competitive RT-PCR and a hyaluronan-binding assay. RESULTS: Osteogenic protein-1 treatment substantially enhanced the accumulation of hyaluronan and proteoglycan within cartilage tissue slices. As with the tissue, osteogenic protein-1 enhanced the size of cell-associated matrices assembled and retained by chondrocytes in vitro. This enhanced matrix assembly was paralleled by an increased expression of mRNA for aggrecan, hyaluronan synthase-2 and CD44. Of the two hyaluronan synthase genes expressed by chondrocytes, only hyaluronan synthase-2 was upregulated by osteogenic protein-1. Coupled with the increase in the CD44 mRNA was an increase in functional hyaluronan binding activity present at the chondrocyte cell surface. CONCLUSIONS: These results demonstrate that osteogenic protein-1 stimulates not only the synthesis of the major cartilage extracellular matrix component aggrecan, but also two associated molecules necessary for the retention of aggrecan, namely hyaluronan and CD44.

Aggrecans↗
PubMed2000

Platelet-activating factor induces an imbalance between matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 expression in human uterine cervical fibroblasts.

Platelet-activating factor (PAF) is involved in such reproductive processes as parturition. We investigated the effect of PAF on the expression of matrix metalloproteinase-1 (MMP-1) and that of tissue inhibitor of metalloproteinases-1 (TIMP-1) in human uterine cervical fibroblasts. Uterine cervical tissue was obtained from patients who underwent cesarean section at term. Collagenase-dispersed fibroblasts were cultured and used in the experiments. PAF receptor was identified in the uterine cervical fibroblasts by use of reverse transcription-polymerase chain reaction and Southern blot analysis. Northern blot analysis showed that PAF increased the expression of MMP-1 mRNA in a time-dependent manner, whereas expression of TIMP-1 mRNA was not affected by PAF. Concentration of MMP-1 protein in the PAF-treated culture media significantly exceeded that in control cultures. The PAF-induced production of MMP-1 protein was abolished by treatment with WEB 2170, a specific PAF receptor antagonist. Results suggest that PAF may accelerate collagenolysis in the human uterine cervix by inducing an imbalance in the activity between MMP-1 and TIMP-1, thus contributing to the cervical ripening during parturition.

Adult↗
PubMed2000

Elucidation of vascular structure of molar villi in complete hydatidiform mole by CD-34 antibody.

Vasculature was examined immunohistochemically in the villous stroma in 22 cases of complete hydatidiform mole (CHM). Only antibody CD-34 was able to detect the vasculature. Serial thin and thick sections and squashed preparations of molar villi were stained by CD-34, and sequential photographs of the vasculature were taken and projected on paper, and the vasculature was described and reconstructed. In the stroma of almost all molar villi examined, vessels were found, but their density and structure varied greatly in each molar villus even in the same CHM, and the vessels were irregular in diameter. In fully distended molar villi the vessels often became narrow, continuing like a broken line but eventually vanishing. Generally the density of the vessels was inversely proportional to the grade of the swelling of villi. The vessels sometimes passed through two adjacent molar vesicles. No significant differences in vasculature were found in molar villi at different gestational ages.

Adult↗
PubMed2000

Observation of spatial asymmetry of THz oscillating electron plasma wave in a laser wakefield

The asymmetric spatial distribution of electron density perturbation is observed by using a frequency-domain interferometry technique. The wake amplitude of the outside bump is enhanced by the elliptical distribution of the pump laser pulse. This asymmetry can be explained with a two-dimensional analytical model expanded from cylindrically symmetric linear theory.

Journal Article↗
PubMed2000

Oral sensory papillae, chemo- and mechano-receptors, in the snake, Elaphe quadrivirgata. A light and electron microscopic study.

The oral sensory papillae of the snake (Elaphe quadrivirgata), comprising a compound sensory system located along the tooth rows, were studied by light microscopy, immunohistochemistry for neuron specific enolase and S 100 protein, and scanning and transmission electron microscopy. Each sensory papilla exhibited a single taste bud and free nerve endings in the epithelium, and Meissner-like corpuscles, branched coiled terminals, and lamellated corpuscles in the connective tissue. The taste buds consisted of four types of cells; the type III cells, exclusively synapsing onto intragemmal nerves, were identified as gustatory in function. The gustatory cells included dense-cored and clear vesicles in the cytoplasm. These vesicles were accumulated both in the presynaptic and infranuclear regions, suggesting dual functions: the synaptocrine and paracrine/endocrine release of signal substances. The free nerve endings constantly contained mitochondria and frequent clear vesicles. The Meissner-like corpuscles were located in the uppermost zone of the connective tissue. These corpuscles consisted of nerve fibers and lamellar cells. The nerve fibers, rich in mitochondria, were folded and layered on each other. The branched coiled terminals were localized in the connective tissue along the side wall of the papillae. Nerve fibers, free from a Schwann-cell covering, swelled up to make terminals which accumulated mitochondria and glycogen particles. The lamellated corpuscles were associated with the nerve-fiber bundles in the connective tissue. Consisting of a central nerve axon and lamellar cells encircling it, these corpuscles resembled mammalian Vater-Pacini corpuscles, except that they lacked a capsule. These findings demonstrated that the snake sensory papilla represents one of the most specialized, compound sensory systems among vertebrates, which may play an important role in receiving chemical and mechanical information on prey.

Animals↗
PubMed2000

[Quantitation of human immunodeficiency virus type 1 RNA by ultrasensitive method in the analysis of samples with low viral load].

With the introduction of combination therapy to the patients with Human Immunodeficiency Virus Type 1(HIV-1) infection, HIV-1 RNA levels in plasma have been reduced, frequently to less than limit of quantitation(400 copies/ml). To achieve enhanced sensitivity, a modified specimen preparation procedure that allows the quantitation of plasma HIV-1 RNA levels as low as 50 copies/ml was developed. Of 67 samples with less than 400 copies/ml of HIV-1 RNA by standard method, 39(58.2%) were not detected by the "ultrasensitive" method. Among 5 samples obtained from patients who were treated with 2 nucleoside reverse transcriptase inhibitors, 4 samples still had detectable copies of HIV-1 RNA. Those suggest that the ultrasensitive assay for HIV-1 RNA has advantage for clinical practice.

HIV Infections↗
PubMed2000

[A clinical study on active vitamin D pulse therapy in hemodialysis patients with secondary hyperparathyroidism].

The oral active vitamin D pulse therapy was performed for 20 chronic hemodialysis patients with secondary hyperparathyroidism (2 degrees HPT). Before pulse therapy, all patients showed high-turnover bone diseases, elevated serum alkaline phosphatase (Alp) and elevated serum parathyroid hormone (PTH). They had at least one parathyroid gland detected by ultrasonography. In one patient, serum PTH level did not decrease during three months. In five patients, hypercalcemia was observed so that the pulse therapy was with drawn. Another patient was resistant to the second pulse therapy for recurrence of 2 degrees HPT. Total parathyroidectomy and autotransplantation was performed in these seven patients. The size of parathyroid gland in patients undergoing surgical treatment was significantly larger than those estimated by ultrasonography in patients successfully treated with pulse therapy (p < 0.005). In all patients with surgical treatment, the conventional oral active vitamin D therapy was performed with caution to hypercalcemia preoperatively. The preoperative Alp levels decreased compared with those of at the beginning of the pulse therapy. Postoperatively, the total amount of intravenous administered calcium decreased, and serum calcium levels were easily controlled.

Administration, Oral↗