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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 19 recordsLinked to original sources
PubMed2000

Zic2 regulates the kinetics of neurulation.

Mutation in human ZIC2, a zinc finger protein homologous to Drosophila odd-paired, causes holoprosencephaly (HPE), which is a common, severe malformation of the brain in humans. However, the pathogenesis is largely unknown. Here we show that reduced expression (knockdown) of mouse Zic2 causes neurulation delay, resulting in HPE and spina bifida. Differentiation of the most dorsal neural plate, which gives rise to both roof plate and neural crest cells, also was delayed as indicated by the expression lag of a roof plate marker, Wnt3a. In addition the development of neural crest derivatives such as dorsal root ganglion was impaired. These results suggest that the Zic2 expression level is crucial for the timing of neurulation. Because the Zic2 knockdown mouse is the first mutant with HPE and spina bifida to survive to the perinatal period, the mouse will promote analyses of not only the neurulation but also the pathogenesis of human HPE.

Animals↗
PubMed2000

Key amino acids of vasopressin V1a receptor responsible for the species difference in the affinity of OPC-21268.

A non-peptide, vasopressin V1a receptor-selective antagonist, OPC-21268, exhibited a markedly higher affinity for the rat V1a receptor (Ki = 380 nM) than for the human V1a receptor (Ki = 140 microM). To delineate the region responsible for the high affinity binding of OPC-21268 for the rat V1a receptor, we have constructed a series of chimeric human and rat V1a receptors, and examined the chimeric and point-mutated receptors by competitive radioligand binding analysis. The results showed that the transmembrane domain (TMD) VI-VII of the vasopressin V1a receptor, in particular the amino acid residue Ala-342 in TMD VII, is the major component conferring the rat-selective binding of OPC-21268 to the V1a receptor.

Amino Acid Sequence↗
PubMed2000

Sex differentiation and mRNA expression of P450c17, P450arom and AMH in gonads of the chicken.

The present study was conducted to reveal effects of in ovo injection of nonsteroidal aromatase inhibitor (Fadrozole) or estradiol at day 3 of incubation on mRNA levels of P45017alphahydroxylase (P450c17), P450 aromatase (P450arom) and anti-Müllerian hormone (AMH) in the chicken gonads. The mRNA levels in the gonads at days 4-8 of incubation were assessed by in situ hybridization analysis using digoxigenin labeling method. The in situ hybridization data were analyzed by relative expression of specific hybridizable signals of each mRNA corrected by the non-specific background by employing an image analyzer. P450c17 mRNA expression increased rapidly at day 6 of incubation in the male but decreased thereafter. In contrast to the transient expression in the male, the expression was gradually increased in the female. P450arom mRNA was not expressed in the male but was detectable in the female as early as day 6 and increased subsequently with days of incubation. AMH mRNA was expressed as early as day 5 of incubation followed by a sharp increase on day 6, which was maintained in the male thereafter. In contrast, the female showed very little expression. The injection of Fadrozole caused no effect on P450c17 mRNA expression, while it suppressed P450arom mRNA expression but increased AMH mRNA expression in the female. In contrast, the injection of estradiol induced P450arom mRNA expression significantly but suppressed AMH mRNA expression in the male. These results indicate that expression of P450arom and AMH is sexually dimorphic and is reciprocally regulated during early ontogenic life in chicken gonads.

Animals↗
PubMed2000

Nationwide epidemiological survey of chronic pancreatitis in Japan.

The aim of this study was to estimate the number of patients treated for chronic pancreatitis in 1994 in Japan and to explore the clinico-epidemiological features of chronic pancreatitis. Two surveys were conducted. Stratified random sampling was used to select departments in which patients with chronic pancreatitis were treated, and two different questionnaires were administered to obtain relevant information. From the first survey, the total number of patients treated for chronic pancreatitis in Japan in the year 1994 was estimated as 32,000 (95% confidence interval, 25,000-39,000). Clinico-epidemiological features, based on the 2,523 patients reported from the second survey, were subsequently clarified. The sex ratio (male/female) of the patients was 3.5. Alcoholic pancreatitis was the most common type in males (68.5%), and idiopathic pancreatitis in females (69.6%). Compared with the findings in the last survey in 1985, the proportion of patients with alcoholic pancreatitis has decreased slightly, from 58.7% to 55.5%, while that of idiopathic chronic pancreatitis has increased in both males and females. Patients diagnosed by advanced techniques such as computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) accounted for 68.1% of the total. The number of patients with chronic pancreatitis treated in 1994 in Japan, was estimated as 32,000, with an overall prevalence rate of 45.4 per 100,000 population in males and 12.4 per 100,000 population in females.

Adolescent↗
PubMed2000

Proliferative involvement of ENX-1, a putative human polycomb group gene, in haematopoietic cells.

Homeobox genes have important roles in haematopoiesis and are regulated in an activated state by the trithorax group (trxG) of genes. In a repressed state, they are regulated by the Polycomb group (PcG) of genes. ENX-1, a putative human PcG gene product, interacts with the proto-oncogene product Vav. We report an investigation of the role of ENX-1 in human haematopoiesis. CD34+ cells mobilized to peripheral blood strongly expressed ENX-1. When stimulated to proliferate, both T and B lymphocytes rapidly up-regulated ENX-1. ENX-1 was expressed in all cell lines of the various lineages examined. When HL-60 cells were differentiated to mature granulocytes with all-trans retinoic acid, ENX-1 was down-regulated. Moreover, ENX-1 antisense oligodeoxynucleotide suppressed DNA synthesis in HL-60 cells. Our data indicate that ENX-1 is involved in the proliferation of both normal and malignant haematopoietic cells.

Antineoplastic Agents↗
PubMed2000

Fat intake and breast cancer risk in an area where fat intake is low: a case-control study in Indonesia.

BACKGROUND: Associations of fat and other macronutrients with breast cancer risk are not clear in areas where fat intake is low. METHODS: We conducted a hospital-based case-control study from 1992 to 1995 in Jakarta, Indonesia. RESULTS: The study, based on 226 cases and 452 age and socioeconomic status matched controls, provided the following findings. (a) In the pre-marriage period, the greater the fat or protein consumption, the larger the risk, whereas decreasing risk with increasing carbohydrate intake was detected. The odds ratio (OR) for the highest quartile of intake relative to the lowest was 8.47 (95% CI: 4.03-17.8) for fat, 2.19 (95% CI: 1.30-3.69) for protein, and 0.16 (95% CI: 0.08-0.31) for carbohydrate. A positive association with fat and a negative one with carbohydrate were also observed for the post-marriage period, but of weaker magnitude compared to the pre-marriage period. (b) The effects of macronutrient intakes were stronger among premenopausal than among postmenopausal women. (c) Most of the associations of protein and carbohydrate were insignificant after adjustment for fat intake. CONCLUSIONS: These findings suggest that fat intake might be an important determinant of breast cancer among populations with a low fat diet in Indonesia.

Adult↗
PubMed2000

Mapping of four simple sequence repeat (SSR) markers on rat chromosome 4.

We previously reported that several markers on rat chromosome (Chr) 4 cosegregated with the occurrence of cerebral stroke and brain edema in stroke-prone spontaneously hypertensive rats (SHRSP). To obtain insights into the positional candidate genes for stroke susceptibility in this region, we mapped four genes, Taurine transporter (Tau), tumor necrosis factor receptor (Tnfr), GABA transporter (Gat1) and glucose transporter-3 (Glut3) genes, using newly developed simple sequence repeat (SSR) markers on rat Chr 4. We isolated the SSRs for the genes either by screening a rat genomic library or by searching the GenBank database. By linkage analysis using two sets of backcrosses, Gat1 and Tnfr were mapped in the region associated with stroke, while Taut was located distant from the region. The Glut3 locus was also assigned to rat Chr 4 using a rat x mouse hybrid clone panel. These results indicated that the Tnfr, Gat1 and Glut3 genes were good positional candidates for the stroke susceptibility in SHRSP, suggesting that further evaluation of these genes by functional studies could prove useful.

Animals↗
PubMed2000

Prevalence of idiopathic hypoparathyroidism and pseudohypoparathyroidism in Japan.

A nationwide epidemiologic survey of idiopathic hypoparathyroidism and pseudohypoparathyroidism was conducted in 1998 to clarify the prevalence of the two disorders in Japan. From a total of 14,100 departments of pediatrics, internal medicine, neurology, and endocrinology in whole Japan, 2952 (20.9%) study departments were selected at random. Of these departments receiving the first questionnaire, 1855 (62.8%) responded. From these departments 390 patients with idiopathic hypoparathyroidism and 203 with pseudohypoparathyroidism who visited the hospitals in 1997 were reported. The total numbers of patients were estimated to be 900 (690-1100) for idiopathic hypoparathyroidism and 430 (330-520) for pseudohypoparathyroidism (95% confidence intervals in parentheses). Using these data, the period prevalence of the diseases were 7.2 (5.5-8.8) per million population in idiopathic hypoparathyroidism, and 3.4 (2.6-4.2) in pseudohypoparathyroidism (95% confidence intervals in parentheses).

Adolescent↗
PubMed2000

Sleep patterns and total mortality: a 12-year follow-up study in Japan.

A population-based cohort study was conducted to assess the relationship between total mortality and self-reported sleep patterns as regards not only to sleep duration but also subjective sleep quality. A total of 5,322 inhabitants in Gifu Prefecture, Japan, completed a self-administered questionnaire on health status and lifestyles including habitual sleep patterns, and were followed-up for an average of 11.9 years. Relative risks were computed by using Cox proportional hazards models. Both longer and shorter sleep, compared to 7-8 hour-sleep, was related to significantly increased risk of total mortality in males (relative risk [RR] for > or = 10 hours = 1.94, and RR for < 7 hour = 1.90), but not in females. Females complaining of poor awakening state experienced a higher mortality risk compared to those who woke up normally (RR: 1.97). Males who usually fell asleep easily showed a marginally lower mortality risk compared to those who fell asleep normally (RR: 0.70). Female users of sleeping pills were at an elevated risk (RR: 1.89). These findings were almost unchanged after adjustment for sleep duration and other confounders. Poor self-reported quality of sleep seemed to be associated with an increased risk of mortality independently of sleep duration.

Adult↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗