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Biomedical subjects

Akira Sato

Publications and source records attributed to Akira Sato.

At least 55 records · Page 3Linked to original sources
PubMed2004

Structure refinements of Na0.8Ti1.2Ga4.8O10: X-ray diffraction analysis for the sodium ion distribution in a one-dimensional tunnel-like space.

The structure of Na0.8Ti1.2Ga4.8O10 was determined by means of single-crystal X-ray diffraction at 173 and 123 K and reinvestigated at 299 K. The host structure containing one-dimensional tunnels was retained over the temperatures examined, while significant changes were observed in the probability density distribution of Na+ ions in the tunnel. The refinement based on the local structure model with the deviated Na+ ion neighboring the vacancy gave a similar result to that from the conventional model, but with reduced standard uncertainties of the structural parameters for the Na+ ions. The potential barrier for the Na+ ion hopping between adjacent cavities was estimated to be ca 30-40 meV from the joint probability density function of deviated Na+ ions.

Journal Article↗
PubMed2004

SOUL in mouse eyes is a new hexameric heme-binding protein with characteristic optical absorption, resonance Raman spectral, and heme-binding properties.

SOUL is specifically expressed in the retina and pineal gland and displays more than 40% sequence homology with p22HBP, a heme protein ubiquitously expressed in numerous tissues. SOUL was purified as a dimer in the absence of heme from the Escherichia coli expression system but displayed a hexameric structure upon heme binding. Heme-bound SOUL displayed optical absorption and resonance Raman spectra typical of 6-coordinate low-spin heme protein, with one heme per monomeric unit for both the Fe(III) and Fe(II) complexes. Spectral data additionally suggest that one of the axial ligands of the Fe(III) heme complex is His. Mutation of His42 (the only His of SOUL) to Ala resulted in loss of heme binding, confirming that this residue is an axial ligand of SOUL. The K(d) value of heme for SOUL was estimated as 4.8 x 10(-9) M from the association and dissociation rate constants, suggesting high binding affinity. On the other hand, p22HBP was obtained as a monomer containing one heme per subunit, with a K(d) value of 2.1 x 10(-11) M. Spectra of heme-bound p22HBP were different from those of SOUL but similar to those of heme-bound bovine serum albumin in which heme bound to a hydrophobic cavity with no specific axial ligand coordination. Therefore, the heme-binding properties and coordination structure of SOUL are distinct from those of p22HBP, despite high sequence homology. The physiological role of the new heme-binding protein, SOUL, is further discussed in this report.

Amino Acid Sequence↗
PubMed2004

Sall1, a causative gene for Townes-Brocks syndrome, enhances the canonical Wnt signaling by localizing to heterochromatin.

The Spalt (sal) gene family plays an important role in regulating developmental processes of many organisms. Mutations of human SALL1 cause the autosomal dominant disorder, Townes-Brocks syndrome (TBS), and result in ear, limb, anal, renal, and heart anomalies. Targeted deletion of mouse Sall1 results in kidney agenesis or severe dysgenesis. Molecular mechanisms of Sall1, however, have remained largely unknown. Here we report that Sall1 synergistically activates canonical Wnt signaling. The transcriptional activity of Sall1 is related to its nuclear localization to punctate nuclear foci (pericentromeric heterochromatin), but not to its localization or association with beta-catenin, the nuclear component of Wnt signaling. In contrast, the RNA interference of Sall1 reduces reporter activities of canonical Wnt signaling. The N-terminal truncated Sall1, produced by mutations often found in TBS, disturbs localization of native Sall1 to heterochromatin, and also down-regulates the synergistic transcriptional enhancement for Wnt signal by native Sall1. Thus, we propose a new mechanism for Wnt signaling activation, that is the heterochromatin localization of Sall1.

Animals↗
PubMed2004

Activation of heme-regulated eukaryotic initiation factor 2alpha kinase by nitric oxide is induced by the formation of a five-coordinate NO-heme complex: optical absorption, electron spin resonance, and resonance raman spectral studies.

Heme-regulated eukaryotic initiation factor 2alpha kinase (HRI) regulates the synthesis of hemoglobin in reticulocytes in response to heme availability. HRI contains a tightly bound heme at the N-terminal domain. Earlier reports show that nitric oxide (NO) regulates HRI catalysis. However, the mechanism of this process remains unclear. In the present study, we utilize in vitro kinase assays, optical absorption, electron spin resonance (ESR), and resonance Raman spectra of purified full-length HRI for the first time to elucidate the regulation mechanism of NO. HRI was activated via heme upon NO binding, and the Fe(II)-HRI(NO) complex displayed 5-fold greater eukaryotic initiation factor 2alpha kinase activity than the Fe(III)-HRI complex. The Fe(III)-HRI complex exhibited a Soret peak at 418 nm and a rhombic ESR signal with g values of 2.49, 2.28, and 1.87, suggesting coordination with Cys as an axial ligand. Interestingly, optical absorption, ESR, and resonance Raman spectra of the Fe(II)-NO complex were characteristic of five-coordinate NO-heme. Spectral findings on the coordination structure of full-length HRI were distinct from those obtained for the isolated N-terminal heme-binding domain. Specifically, six-coordinate NO-Fe(II)-His was observed but not Cys-Fe(III) coordination. It is suggested that significant conformational change(s) in the protein induced by NO binding to the heme lead to HRI activation. We discuss the role of NO and heme in catalysis by HRI, focusing on heme-based sensor proteins.

Animals↗
PubMed2004

An omphalopagus parasitic twin after intracytoplasmic sperm injection.

OBJECTIVE: To describe a first case of parasitic twin achieved after intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: Perinatal center at a Japanese university hospital. PATIENT(S): A 30-year-old pregnant Japanese woman with a history of secondary infertility achieved after ICSI was diagnosed with an omphalopagus parasitic twin pregnancy by prenatal ultrasound at 28 weeks of gestation. INTERVENTION(S): A female infant was delivered by scheduled cesarean section at 30 weeks of gestation. The cesarean section was performed for dystocia. MAIN OUTCOME MEASURE(S): Brief review of parasitic twin and malformations in fetuses achieved after ICSI. RESULT(S): Resuscitation was not done because of the poor prognosis for both fetuses. Molecular analysis with informative genetic markers is consistent with monozygotic pregnancy. CONCLUSION(S): A careful ultrasound examination is indicated to detect additional anomalous findings in twin fetuses achieved after ICSI.

Abnormalities, Multiple↗
PubMed2004

Chromosomal analysis of mouse spermatozoa following physical and chemical treatments that are effective in inactivating HIV.

Human immunodeficiency virus (HIV) can be inactivated by heating at 56 degrees C for 30 min, treating with 50% ethanol at room temperature for 10 min, or treating with 2% sodium hypochlorite solution (NaClO) at room temperature for 60 min. Using a mouse model, we evaluated the risk of generating chromosome damage in spermatozoa following these treatments. The spermatozoa were all dead after the treatments. Although 41.3% of oocytes injected with ethanol-treated spermatozoa successfully activated, none of the oocytes injected with heated or NaClO-treated spermatozoa activated. When artificial stimulation with strontium was used, the fertilization of oocytes with heated or ethanol-treated spermatozoa was completely rescued. Sperm nuclei treated with NaClO neither decondensed nor developed to a male pronucleus. The incidences of structural chromosome aberrations in 1-cell zygotes derived from the heated spermatozoa (45.6%) and ethanol-treated spermatozoa (91.2%) were significantly higher than those in the matched controls (5.5% and 10.5%, respectively). Further study is needed to develop a methodology for the protection of spermatozoa against chromosome damage or the separation of damaged spermatozoa before intracytoplasmic sperm injection.

Animals↗
PubMed2004

The effect of magnesium sulfate on the behavioral activities of fetal goats.

OBJECTIVES: To investigate fetal heart rate accelerations, fetal breathing movements, and fetal electrocortical activities during administration of magnesium sulfate to fetal goats. METHODS: The fetal heart rate accelerations, fetal breathing movements, and fetal electrocortical activities during 6 hours of continuous magnesium sulfate infusion into the fetal jugular vein were examined in 8 chronically instrumented fetal goats at 124-131 days of gestation. Fetal breathing movements were defined as repetitive negative fluctuations of the fetal tracheal pressure. Fetal electrocortical activities were assessed by visual analysis of periods of high-voltage and low-voltage electrocortical activities. RESULTS: Continuous infusion of magnesium sulfate for 6 hours significantly increased the fetal plasma magnesium concentration from 2.8 +/- 1.2 to 8.3 +/- 2.6 mg/dL without significant changes in fetal arterial blood gases. The incidence of fetal heart rate accelerations during magnesium infusion was significantly decreased from that found during the control periods. After 2 hours of infusion, the incidence of fetal breathing movements significantly decreased from 33.9% +/- 20.5% to 1.2% +/- 1.4% and remained at this level during the remaining 4 hours of magnesium infusion. The percentage of time that the fetuses were found to have low-voltage electrocortical activities decreased from 51.6% +/- 9.0% to 40.4% +/- 8.2% after 2 hours of infusion but recovered to 49.9% +/- 12.0% by 6 hours of magnesium infusion. CONCLUSION: We concluded that fetal magnesium sulfate administration affected fetal heart rate accelerations and fetal breathing movements continuously but electrocortical activities only temporarily during 6 hours of observations.

Animals↗
PubMed2004

Expression of iNOS mRNA and inhibitory effect of NO on uterine contractile activity in rats are determined by local rather than systemic factors of pregnancy.

Our purpose was to investigate whether the local or systemic factors of pregnancy are associated with inducible nitric oxide synthase (iNOS) mRNA expression and to determine the inhibitory effects of pharmacological agents that increase cGMP levels in rat myometrium. iNOS mRNA expression was determined in uterine tissues from nonpregnant rats and on day 17 of gestation in the pregnant and non-pregnant uterine horns by RT-PCR. In addition, uterine rings from the pregnant and non-pregnant uterine horns were placed in Krebs-Henseleit solution for isometric recordings of spontaneous contractions. Concentration-inhibition relationships to diethylamine/nitric oxide complex, 8-bromo-cGMP, and the selective phosphodiesterase V inhibitor were obtained. Compared to nonpregnant rats, expression of iNOS mRNA in myometrium increased during pregnancy, which was maximal on day 17, followed by a decrease on day 21 of gestation. Expression of iNOS mRNA at day 17 of gestation was greater in pregnant uterine horns than in nonpregnant ones. Maximal inhibition of phosphodiesterase V and increasing cGMP induced similar inhibition of spontaneous contractions in nonpregnant and pregnant uterine horns, while NO induced less inhibition in the former. The results suggest that the local pregnancy factor is needed for signal transduction from NO to soluble guanylate cyclase at a time when maximal expression of iNOS mRNA is evident.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2004

Effects of nitric oxide and prostacyclin on hemodynamic response by big endothelin-1 in near term fetal sheep.

AIMS: To measure plasma concentrations of endothelin (ET)-1, NO metabolites (nitrate/nitrite; NOx) and 6-keto PGF1 alpha (PGF1 alpha) in maternal and fetal sheep blood, and to evaluate the effects of big ET-1 on hemodynamic response, blood gases and NO and 6-keto PGF1 alpha production in near term fetal sheep. METHODS: Hemodynamic parameters were measured during infusion of big ET-1 into the carotid vein in chronically catheterized fetal sheep on day 125 of gestation. Fetal arterial blood samples were obtained for ET-1, PGF1 alpha) and nitrate/nitrite (NOx) measurements. RESULTS: ET-1, NOx and PGF1 alpha plasma concentrations were all significantly higher in fetal compared with the maternal plasma. Big ET-1 significantly decreased fetal systolic and diastolic blood pressure and significantly increased fetal heart rate. Big ET-1 stimulated plasma PGF1 alpha), but not NOx , concentration. CONCLUSIONS: Circulatory regulating factors in the fetus were up-regulated. The effects of ET-1 on fetal hemodynamic response may be mediated via prostacyclin, but not via the NO pathway.

Animals↗
PubMed2004

Fertilization failure from a sperm chromatin defect in couples with unexplained infertility.

OBJECTIVE: To investigate the relationship between unexplained infertility and fertilization failure from nucleoprotein defects in ejaculated human sperm and to study the usefulness of sperm chromatin assays, using AO fluorescence dye, to evaluate patients with unexplained infertility before treatment. STUDY DESIGN: From January 1999 to January 2000, 513 infertile couples had the clinical causes of their infertility assessed. During the next investigative period (February 2000-February 2001), 137 cases of unexplained infertility (n = 80) were chosen for this study, as were cases of tubal factor infertility (n = 57) as controls. The status of nuclear chromatin in ejaculated sperm was examined using acridine orange staining, followed by a conventional in vitro fertilization procedure. RESULTS: The number of patients with immature ejaculated sperm was 16 of 30 (53.3%) unexplained infertility cases involving fertilization failure, 8 of 50 (16.0%) unexplained infertility cases without fertilization failure and 5 of 57 (8.8%) tubal factor infertility cases. A significant difference was observed between unexplained infertility cases with fertilization failure and the other groups (P < .0001). CONCLUSION: These results suggest that the nuclear immaturity of ejaculated human sperm may be 1 of the primary factors underlying unexplained infertility.

Acridine Orange↗
PubMed2003

An unnatural hydrophobic base, 4-propynylpyrrole-2-carbaldehyde, as an efficient pairing partner of 9-methylimidazo[(4,5)-b]pyridine.

To develop unnatural base pairs that function in replication, we designed 4-propynylpyrrole-2-carbaldehyde (designated as Pa') and synthesized the nucleoside derivatives of Pa'. The base pairing of Pa' with the partner, 9-methylimidazo[(4,5)-b]pyridine (Q), was compared to that of pyrrole-2-carbaldehyde (Pa), which was previously developed as a specific pairing partner of Q. The thermal stability of a DNA duplex containing the Q-Pa' pair and the incorporation efficiency of the Pa' substrate (dPa'TP) into DNA opposite Q by the Klenow fragment of Escherichia coli DNA polymerase I were improved, in comparison with those of the Q-Pa pair. These improvements result from the increased hydrophobicity and stacking stability of Pa' by the introduction of the propynyl group to Pa, providing valuable information for the further development of unnatural base pairs toward the expansion of the genetic alphabet.

Base Pairing↗
PubMed2003

Association of the polymorphisms in the 5'-untranslated region of PTEN gene with type 2 diabetes in a Japanese population.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is known to act as a lipid phosphatase hydrolyzing phosphatidylinositol (PI)(3,4,5)P(3) to PI(4,5)P(2). Since the PI3-kinase product, PI(3,4,5)P(3), is an important second messenger leading to the metabolic action of insulin, PTEN functions as a potent negative regulator of insulin signaling and its gene is one of the possible candidates involved in susceptibility to the development of type 2 (non-insulin-dependent) diabetes. In the present study, we investigated the polymorphisms of the PTEN gene in Japanese patients with type 2 diabetes and non-diabetic control subjects. We identified three mutations of the gene in the type 2 diabetes patients. Among these mutations, the frequency of the substitution of C with G at position -9 (-9C-->G) (SNP1), located in the untranslated region of exon 1, was significantly higher in type 2 diabetic patients than in control subjects. In addition, transfection of the PTEN gene with SNP1 resulted in a significantly higher expression level of PTEN protein compared with that of the wild-type PTEN gene in Cos1 and Rat1 cells. Furthermore, insulin-induced phosphorylation of Akt in HIRc cells was decreased more greatly by transfection of SNP1 PTEN gene than that of wild-type PTEN gene. These findings suggest that the change of C to G at position -9 of the PTEN gene is associated with the insulin resistance of type 2 diabetes due possibly to a potentiated hydrolysis of the PI3-kinase product.

5' Untranslated Regions↗
PubMed2003

CO binding study of mouse heme-regulated eIF-2alpha kinase: kinetics and resonance Raman spectra.

Heme-regulated eukaryotic initiation factor (eIF)-2alpha kinase (HRI) regulates the synthesis of globin chains in reticulocytes with heme availability. In the present study, CO binding kinetics to the 6-coordinated Fe(II) heme of the amino-terminal domain of mouse HRI and resonance Raman spectra of the Fe(II)-CO complex are examined to probe the character of the heme environment. The CO association rate constant, k(on)', and CO dissociation rate constant, k(off), were 0.0029 microM(-1)s(-1) and 0.003 s(-1), respectively. These values are very slow compared with those of mouse neuroglobin and sperm whale myoglobin, while the k(off) value of HRI was close to those of the 6-coordinated hemoglobins from Chlamydomonas and barley (0.0022 and 0.0011 s(-1)). The dissociation rate constant of an endogenous ligand, which occurs prior to CO association, was 18.3 s(-1), which was lower than those (197 and 47 s(-1)) of the same 6-coordinated hemoglobins. Resonance Raman spectra suggest that the Fe-C-O adopts an almost linear and upright structure and that the bound CO interacts only weakly with nearby amino acid residues.

Animals↗
PubMed2003

An unnatural hydrophobic base pair with shape complementarity between pyrrole-2-carbaldehyde and 9-methylimidazo[(4,5)-b]pyridine.

An unnatural hydrophobic base, pyrrole-2-carbaldehyde (denoted as Pa), was developed as a specific pairing partner of 9-methylimidazo[(4,5)-b]pyridine (Q). The Q base is known to pair with 2,4-difluorotoluene (F) as an isostere of the A-T pair, and F also pairs with A efficiently in replication. In contrast, the Q-Pa pair showed specific selectivity in replication, and the five-membered-ring base Pa paired efficiently with Q but paired poorly with A. In addition, the interaction of Pa with DNA polymerases was superior, in comparison to that of F. The aldehyde group of Pa was recognized well by the Klenow fragment of Escherichia coli DNA polymerase I and the reverse transcriptase of Avian myeloblastosis virus. The structural features of the Q-Pa pair in a DNA duplex were analyzed by NMR, showing the shape complementarity of the Pa fitting with Q. The structurally unique base Pa provides valuable information for the development of unnatural base pairs toward the expansion of the genetic alphabet.

Base Pairing↗