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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 127 records · Page 7Linked to original sources

Clinical application of three-dimensional ultrasound in fetal brain assessment.

AIM: To clarify the usefulness of three-dimensional (3D) ultrasound in the assessment of the fetal head and brain, according to 3D ultrasound surface reconstruction, multiplanar image analysis, three-dimensional angiography, and volume calculation. METHODS: We examined 326 normal fetuses between 10 and 40 weeks of gestation using 3D ultrasound (Voluson, 530D, Medison, Seoul, Korea), mainly with transvaginal 3D transducer. Fetal head structures, such as the skull, brain structure, and brain circulation, were presented by surface mode, multiplanar imaging mode, and three-dimensional Doppler mode. After automatic volume acquisition of the fetal head, image analyses were performed off-line, and 3D View software was used for volume imaging of the lateral ventricle and choroid plexus in randomly selected 30 normal fetuses. Seven fetuses with intracranial abnormalities were evaluated by 3D ultrasound functions. RESULTS: Surface mode of 3D ultrasound objectively depicted in vivo development of the cranial bones and formation of the cranial sutures and fontanelles in normal fetuses. Multiplanar image analysis of the brain structure presented a fetal brain in more cutting sections than conventional 2D ultrasound. Transvaginal 3D angiography was successful in 13% of normal fetuses and rotation of 3D circulatory image allowed the analysis of the intracranial vessels. Volume imaging showed the intracranial structures, such as the lateral ventricle and choroid plexus. Intracranial abnormalities were longitudinally evaluated by 3D ultrasound and objective images helped in reaching prenatal diagnoses. CONCLUSION: Advanced 3D ultrasonography and software for volume analysis can provide additional objective information about the fetal skull formation, brain structure, and brain circulation.

Angiography↗

UFT plus carboplatin for head and neck cancer.

Cisplatin plus fluorouracil (5-FU) is widely accepted as neoadjuvant and adjuvant chemotherapy in the treatment of head and neck squamous cell carcinoma; UFT is also an active agent against this disease. In the first retrospective study, we examined the efficacy of UFT as adjuvant chemotherapy in patients with maxillary cancer. The 5-year survival rate of those treated with UFT vs those not treated was 71.4% vs 23.8%, respectively. In the second study we developed the carboplatin plus UFT regimen--as a modification of cisplatin plus 5-FU--and studied its efficacy and toxicity in patients with advanced head and neck squamous cell carcinoma. These patients received UFT plus carboplatin. The objective response rate was 53.1%; grade > or = 3 leukopenia, anemia, and thrombocytopenia were rare. These findings suggest that UFT plus carboplatin in the outpatient setting is feasible for patients with head and neck squamous cell carcinoma.

Administration, Oral↗

Mild renal dysfunction is associated with insulin resistance in chronic glomerulonephritis.

BACKGROUND: Insulin resistance is associated with advanced and moderate chronic renal failure (CRF). However, insulin resistance in chronic glomerulonephritis (CGN) before onset of frank renal dysfunction is not fully evaluated. We attempted to investigate the association of insulin resistance with mild renal dysfunction and with abnormal calcium homeostasis. PATIENTS AND METHODS: Eighteen young, lean non-diabetic male patients with biopsy-proven CGN (age 30 +/- 7 years, body mass index 23.0 +/- 2.5 kg/m2) were enrolled. Insulin sensitivity was estimated by the glucose infusion rate (M value) during euglycemic hyperinsulinemic clamping for 60 to 120 min. Calcium-related parameters including intracellular calcium concentrations ([Ca2+]i) in platelets were also measured. Renal function was normal or slightly impaired (serum creatinine, 1.0 +/- 0.2 mg/dl; glomerular filtration rate (GFR), 68 to 131 ml/min/1.48 m2). We divided subjects into an insulin-sensitive (IS) group (M value > 7.3 mg/kg/min, the overall mean) and an insulin-resistant (IR) group (M value < 7.3 mg/kg/min). RESULTS: During a 75 g oral glucose tolerance test, the plasma glucose concentration at 120 min after glucose loading and the immunoreactive insulin concentration at 60 min were significantly higher in the IR group. GFR was notably lower in the IR group than in the IS group (p = 0.0003), and was significantly correlated with insulin sensitivity (p < 0.02, r = 0.58). The basal [Ca2+]i was significantly higher in the IR than in the IS group (39 +/- 9 vs. 30 +/- 9 nM, p < 0.05). CONCLUSION: Mild renal dysfunction and elevated basal [Ca2+]i are associated with insulin resistance in CGN.

Adult↗

[Teratogenicity study of 2,2,3,3,3-pentafluoro-1-propanol (5FP) in rats by oral administration].

Teratogenicity of 2,2,3,3,3-pentafluoro-1-propanol (5FP), an alternative cleaning agent for chlorofluorocarbon, was examined in rats. 5FP was diluted with sesame oil and given to pregnant rats (Crj: Wistar) by gavage once a day from day 7 to 17 of pregnancy at doses of 0, 250, 500 and 1000 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. In the pregnant rats, 5FP caused wheezing, salivation, ptosis, reduced body weight gain and reduced food consumption at 500 and 1000 mg/kg/day. In the fetuses, 5FP reduced body weight, increased the incidences of skeletal variations and retarded the ossification at 1000 mg/kg/day, but did not increase the incidences of malformations. It was concluded from these results that 5FP has no teratogenicity in rats when given by gavage. The no-observed-adverse-effect level was 500 mg/kg/day for rat fetuses, and 250 mg/kg/day for pregnant rats.

Abnormalities, Drug-Induced↗

[Teratogenicity study of morpholine salts of fatty acids (oleic acid, 50% water solution) in rats by oral administration].

Teratogenicity of morpholine salts of fatty acids was examined in Wistar rats (Crj: Wistar). Morpholine salts of fatty acids (oleic acid, 50% water solution) was given to pregnant rats by gavage once a day from day 6 through day 15 of pregnancy at doses of 0, 234, 468 and 936 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. Morpholine salts of fatty acids caused nasal discharge, dirty nose and salivation in pregnant rats at doses from 234 mg/kg/day. However, fetal effects, such as malformation and growth retardation, were not observed even at 936 mg/kg. It was concluded that morpholine salts of fatty acids has no teratogenicity in rats when given by oral administration. The no-observed-adverse-effect level was 936 mg/kg/day for rat fetuses and less than 234 mg/kg/day for pregnant rats.

Abnormalities, Drug-Induced↗

Production of soluble granulocyte colony-stimulating factor receptors from myelomonocytic cells.

It has been speculated that a soluble form of G-CSFR might be physiologically present in humans, since G-CSFR mRNA that lacks a transmembrane domain has been identified from a human myelomonocytic cell line. Here, we demonstrate human soluble G-CSFR (sG-CSFR) of two different molecular sizes (80 and 85 kDa) on an immunoblot analysis using Abs generated against the amino-terminal, extracellular domain of the full-length G-CSFR. Both isoforms of sG-CSFR were able to bind recombinant human G-CSF (rhG-CSF). RT-PCR analysis with primers targeted outside of the transmenbrane region revealed that membrane-anchored G-CSFR is expressed at all maturation stages of purified myeloid cells, including CD34+CD13+ cells (blasts), CD11b-CD15+ cells (promyelocytes or myelocytes), CD11b+CD15+ cells (metamyelocytes and mature neutrophils), and CD14+ cells (monocytes). On the other hand, sG-CSFR mRNA was detectable in CD11b-CD15+, CD11b+CD15+, and CD14+ cells, but not in the CD34+CD13+ blast population. The serum concentration of both isoforms of sG-CSFR appeared to be correlated with the numbers of neutrophils/monocytes before and after rhG-CSF treatment in normal individuals. Thus, two isoforms of sG-CSFR are physiologically secreted from relatively mature myeloid cells and might play an important role in myelopoiesis through their binding to serum G-CSF.

Amino Acid Sequence↗

Block by 5-hydroxytryptamine and apomorphine of recombinant human neuronal nicotinic receptors.

The effects of 5-hydroxytryptamine and apomorphine on human neuronal nicotinic acetylcholine receptor/channels were examined by expressing these channels in Xenopus oocytes. Functional channels were expressed by combining one type of alpha subunits (alpha3 or alpha4) and one type of beta subunits (beta2 or beta4). 5-Hydroxytryptamine (100 microM to 1 mM) and apomorphine (10 to 100 microM) inhibited an inward current activated by acetylcholine in the oocytes expressing the channels. The sensitivity to 5-hydroxytryptamine or apomorphine depended on subunit combinations. When concentration-response relationship was obtained for the acetylcholine-activated current, the maximal response was reduced by these compounds. The inhibition by these compounds exhibited voltage-dependence: the inhibition was augmented at negative potentials. The results suggest that 5-hydroxytryptamine and apomorphine noncompetitively inhibits human recombinant nicotinic acetylcholine receptor/channels, presumably by acting on channel pores.

Acetylcholine↗

Neighboring glycine residues are essential for P2X2 receptor/channel function.

The roles of a glycine-rich region in the cloned P2X2 receptor/channel were evaluated by site-directed mutagenesis. Responsiveness to ATP was lost when Gly247 was replaced by alanine. The sensitivity to ATP was reduced when Gly248 was replaced by alanine, and the responsiveness to ATP was lost when Gly248 was replaced by valine. The results suggest that the neighboring glycine residues are essential for P2X2 receptor/channel function.

Adenosine Triphosphate↗

Block and unblock by imipramine of cloned and mutated P2X2 receptor/channel expressed in Xenopus oocytes.

Effects of imipramine on the cloned P2X2 receptor/channel and its mutants expressed in Xenopus oocytes were examined. Imipramine (100 microM) partially blocked an ionic current mediated through the wild-type P2X2 receptor/channel. With a higher concentration (300 microM) of imipramine, the current block was attenuated, suggesting that the second, lower affinity, 'unblocking' binding-site for imipramine exists in addition to the 'blocking' binding-site. These profiles of the modulation by imipramine were influenced by the substitution of negatively charged or polarized amino acid residues near the outer mouth of the channel pore (Asp315, Thr330 and Asn333) with neutral amino acid residues (Val or Ile). With the neutralization of Asp315, the current 'block' by 100 microM imipramine was attenuated. With the neutralization of Thr330, the current 'block' by 100 microM imipramine was enhanced. With the neutralization of Asn333, the 'unblock' by 300 microM imipramine disappeared. The results suggest that imipramine modulates P2X2 receptor/channels by interacting these amino acid residues.

Animals↗

Effects of ascorbic acid on selenium teratogenicity in cultured rat embryos.

The effects of ascorbic acid, as an exogenous antioxidant, on selenium (Se) teratogenicity were examined using rat embryo culture. Rat embryos at day 9.5 of gestation were cultured for 48 h in the presence of sodium selenite at 10 and 20 microM or sodium selenate at 30 and 100 microM with or without the addition of 1 mM of L-ascorbic acid (AsA). Selenite or selenate alone increased the incidence of embryonic malformation. With AsA, the incidence of selenite-induced embryonic malformation was increased. On the contrary, the incidence of selenate-induced embryonic malformation was decreased with AsA. It was considered from these results that the redox states in the embryonic environment and of Se are critical in Se teratogenicity.

Animals↗

Purification and characterization of two amine N-sulfotransferases, AST-RB1 (ST3A1) and AST-RB2 (ST2A8), from liver cytosols of male rabbits.

Two sulfotransferases (STs), designated as AST-RB1 (ST3A1) and AST-RB2 (ST2A8), with high a amine N-sulfonating activity, were purified from male rabbit liver cytosols. AST-RB1 and AST-RB2 were purified to homogeneity by the anion-exchange, affinity, and hydroxyapatite chromatography. The N-terminus of both enzymes were blocked. The subunit molecular mass of both enzymes was estimated to be 34 kDa on SDS-PAGE. AST-RB1 efficiently catalyzed N-sulfonation of alicyclic, alkyl, and arylamines such as 4-phenyl-1,2,3, 6-tetrahydropyridine, 1-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-piperazine, desipramine, and aniline, whereas its catalytic activities toward 2-naphthol and dehydroepiandrosterone (DHEA) were very low. On the other hand, AST-RB2 efficiently catalyzed sulfonation of desipramine and DHEA, but had no activity toward 2-naphthol. Amino acid sequences of peptide fragments derived from the purified AST-RB1 showed no significant homology with previously reported STs, but those from the purified AST-RB2 shared a high similarity with those of the ST2 family. Both enzymes were expressed specifically in the liver. The present results strongly suggest that the purified AST-RB1 is a novel enzyme in terms of structure and catalytic properties showing high selectivity for amine substrates, and AST-RB2 is a quite unique from among ST2A enzymes of other species in its substrate specificity.

Amines↗

Developmental toxicity of indium in cultured rat embryos.

Developmental toxicity of indium was examined using rat embryo culture with reference to toxicokinetics. Rat embryos at day 9.5 of pregnancy were cultured for 48 h under various exposure conditions to indium trichloride. Indium was embryotoxic to cultured rat embryos at concentrations ranging from 25 to 50 microM for 24 h exposure according to the embryonic age, and the exposure concentration was more critical than the exposure time. The embryotoxic concentrations were comparable to the serum concentration at a developmentally toxic dose by intravenous administration in an in vivo experiment. It was considered from these results that the developmental toxicity of indium is a direct effect on the embryo or yolk sac and that weak developmental toxicity of indium by oral administration was due to low exposure concentrations in the embryo.

Animals↗

Effects of glutathione depletion on selenite- and selenate-induced embryotoxicity in cultured rat embryos.

Effects of depletion of reduced glutathione (GSH) on selenium (Se) embryotoxicity in cultured rat embryos were examined. Rat embryos at day 9.5 of gestation were cultured for 48 h in the presence of Se as either sodium selenite at 10 and 20 microM or sodium selenate at 30 and 100 microM. Embryonic GSH was depleted by the addition of 0.1 mM of L-buthionine-[S,R]-sulfoximine (BSO) without embryotoxicity, i.e., significant growth retardation and malformation of the embryos. Selenite at 10 microM or selenate at 100 microM significantly increased the incidence of malformation of the embryos. The incidence of selenite-induced malformation of the embryos at 20 microM was significantly decreased with BSO. On the contrary, the incidence of selenate-induced malformation at 30 microM was significantly increased with BSO. It was noted that the major malformed regions of the embryos by the embryotoxic concentration of BSO alone were the same to those affected by selenite or selenate. It was considered from these results that embryonic GSH was involved in the embryotoxicity of selenite and selenate. The embryotoxicity of selenate may not be mediated through the reduction to selenite. It was suggested that the formation of selenodiglutathione and the oxidative stress were involved in the embryotoxicity of selenite and selenate, respectively.

Animals↗

Ophthalmic artery velocimetry in normotensive and preeclamptic women with or without photophobia.

OBJECTIVE: To compare ophthalmic arterial velocimetry in normotensive and preeclamptic gravidas with and without photophobia. METHODS: Ophthalmic arteries were studied by color-flow Doppler ultrasonography in 118 normotensive pregnant women, 20 gravidas with preeclampsia and no visual symptoms, and 11 with preeclampsia, photophobia, and retinal edema. RESULTS: The ophthalmic arterial pulsatility index (PI) correlated negatively with gestational age (y = -0.01x + 1.84, r = -0.41, P<.01). Pulsatility index in preeclamptics with photophobia (0.71+/-0.17) was lowest among the three groups (P<.01) and was highest in normotensive pregnant women (1.41+/-0.21, P<.01). Mean velocity in normotensive pregnant women (0.19+/-0.05 m/second) was highest among the groups (P<.01) and was not significantly different in preeclamptic women with no visual symptoms (0.27+/-0.03 m/second) and with photophobia (0.30+/-0.02 m/second). CONCLUSION: Preeclamptic women, especially those with photophobia, have orbital vascular vasodilation or hyperperfusion, or both.

Adult↗

Effects of perospirone, a novel 5-HT2 and D2 receptor antagonist, on Fos protein expression in the rat forebrain.

The effects of perospirone, a novel 5-HT2 and D2 receptor antagonist, on Fos protein expression in the nucleus accumbens (NA) and dorsolateral striatum (DLSt) were compared with those of typical (i.e., haloperidol and fluphenazine) and atypical (i.e., clozapine and risperidone) antipsychotics using immunohistochemical techniques in rats. Perospirone and other antipsychotics tested at doses that exerted D2 blocking actions increased Fos-like immunoreactivity both in the NA and DLSt. However, the levels of Fos expression in the DLSt induced by perospirone and clozapine were less than those induced by haloperidol and fluphenazine. When compared the differences in numbers of Fos-positive neurons between in the NA and DLSt, perospirone, clozapine, and risperidone preferentially increased Fos expression in the NA. These findings suggest that perospirone has a preferential action on the mesolimbic (vs. nigrostriatal) dopaminergic system in inducing Fos protein in the rat brain, which may be related to its atypical antipsychotic properties.

Animals↗