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Biomedical subjects

T Okada

Publications and source records attributed to T Okada.

At least 91 records · Page 5Linked to original sources
PubMed2001

Ideographic characters call for extra processing to correspond with phonemes.

Cortical areas used in the copying of Japanese ideographic characters and syllabic characters were studied using functional magnetic resonance imaging in healthy volunteers. Complexity of characters was controlled to illustrate differences resulting from character to sound conversion differences between the ideographic and syllabic characters. Statistical comparisons indicated extensive activation in the fusiform gyrus, posterior portions around the intraparietal sulcus and in the conjunction area of BA 6, 9 and 44 (which is assumed to be Exner's area) during the copying of ideographic characters. These findings suggested that indirectness between ideographic characters and their pronunciation demands extra processing such as semantic mediation and intensive grapheme processing in comparison with syllabic characters.

Adult↗
PubMed2001

Particle characterization and separation by a coupled acoustic-gravity field.

A coupled acoustic-gravity field is proposed as a novel external field for particle separation and characterization. When a standing plane ultrasound wave is generated, particles move to the node of the wave along the ultrasound force gradient. If the particles also undergo a sedimentation force, they aggregate at the equilibrium position, where these two forces are balanced. The equilibrium position, which is determined by the density and compressibility of a medium and particles, characterizes the particles. The local ultrasound energy, which is necessary for quantitative discussions, is evaluated by using a standard particle, the physical parameters of which are unambiguously determined; aluminum particles are used in the present study. The local ultrasound energy makes possible the determination of the compressibility of unknown materials. Nonporous particles of inorganic and polymeric materials, the particle sizes of which range from 3 to 100 microm, follow a derived model, suggesting that the local ultrasound energy and a derived model be valid. The proposed external field can be used for separation of particles having different acoustic natures.

Journal Article↗
PubMed2001

Chromatographic probing of electrostatic potential.

Electrostatic potential in the vicinity of the surface of a cation-exchange resin has been evaluated by modeling chromatographic retention. Binary mixtures of K+ and its crown ether complex in methanol are used as mobile phases, and two types of solutes, that is, cationic and crown ether probes, have been examined. The cationic probes show the sigmoidal retention changes with increasing concentration of a crown ether incorporated into the mobile phase, whereas crown ether probes give retention maximums. The model derived from the Poisson-Boltzmann theory well explains these specific changes in probe retention and gives the electrostatic potential at the closest approach of each probe molecule. The closest approaches for probe molecules correlate well with their molecular sizes. In addition, changes in retention of cationic probes also correlate well with the electrostatic potential changes at the closest approaches of probe molecules, indicating that simple sensing of the electrostatic potential is feasible using probe retention. The reduction of crown ether complexation occurs in the vicinity of the cation-exchange resin surface and causes the specific retention behaviors of crown ether probes in the mobile-phase systems composed of K+ and its complex with a modifier crown ether.

Journal Article↗
PubMed2001

Simultaneous control of electrostatic micellar partition and electroosmotic flow-rate by anion-dominated partition into zwitterionic micelles.

The zeta potentials of zwitterionic micelles and capillary walls have been evaluated with capillary electrophoresis. The zeta potential of the micelles is predominantly determined by the nature of anions, while cations of identical valence have marginal effects; the linear relation has been found between the induced zeta potential and the hydration energy of an anion. The zeta potential of the capillary wall is also varied with anionic natures, and there is a good correlation between micellar and capillary wall zeta potential. This strongly suggests that the zeta potential of capillary walls is determined by the partition of anions into the surfactant layer formed on the capillary wall. Thus, we can simultaneously control both the electroosmotic flow-rate and micellar surface potential (in turn electrostatic interaction between micelles and ionic solutes) by varying the type and concentration of electrolytes. This idea has been applied to the separation of aromatic cationic solutes.

Anions↗
PubMed2001

Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 2.

Highly potent 1,3-beta-D-glucan synthase inhibitors, 7b, 10a, 10b and 12, have been identified by the chemical modification of the ornithine residue of a fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. These compounds showed stronger antifungal activity against systemic candidiasis as well as pulmonary aspergillosis in mice, and less hepatotoxicity as compared with 1.

Animals↗
PubMed2001

Promoter analysis for daily expression of Drosophila timeless gene.

Drosophila circadian clock gene timeless (tim) displays circadian oscillation in its mRNA level, and such oscillation is transcriptionally regulated. The promoter region up to -756 of tim is suggested to promote the circadian mRNA expression, however, the role of the sequence upstream of tim promoter region in the transcriptional regulation is still unrevealed. We novelly isolated and determined tim 5'-flanking sequence -2764 to -757, and found a putative cAMP-response element, six regions of the half site for PAR-basic leucine zipper transcription factors and six nonpalindromic E-boxes. Our in vivo reporter assay showed that 966 bp of tim promoter region, including a palindromic CACGTG E-box and a half site of PAR-basic leucine zipper transcription factors, was minimally required for its daily mRNA expression. While, the deletion of the 5'-flanking region -1970 to -967 caused a slight decrease in the reporter mRNA levels. These results indicate that the 5'-flanking sequence upstream of the promoter region have a role in the daily regulation of tim mRNA expression in Drosophila.

Animals↗
PubMed2001

Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response.

Eukaryotic cells control the levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element consisting of 19 nt (CCAATN(9)CCACG), the CCACG part of which is considered to provide specificity. We recently identified the basic leucine zipper (bZIP) protein ATF6 as a mammalian UPR-specific transcription factor; ATF6 is activated by ER stress-induced proteolysis and binds directly to CCACG. Here we report that eukaryotic cells express another bZIP protein closely related to ATF6 in both structure and function. This protein encoded by the G13 (cAMP response element binding protein-related protein) gene is constitutively synthesized as a type II transmembrane glycoprotein anchored in the ER membrane and processed into a soluble form upon ER stress as occurs with ATF6. The proteolytic processing of ATF6 and the G13 gene product is accompanied by their relocation from the ER to the nucleus; their basic regions seem to function as a nuclear localization signal. Overexpression of the soluble form of the G13 product constitutively activates the UPR, whereas overexpression of a mutant lacking the activation domain exhibits a strong dominant-negative effect. Furthermore, the soluble forms of ATF6 and the G13 gene product are unable to bind to several point mutants of the cis-acting ER stress response element in vitro that hardly respond to ER stress in vivo. We thus concluded that the two related bZIP proteins are crucial transcriptional regulators of the mammalian UPR, and propose calling the ATF6 gene product ATF6alpha and the G13 gene product ATF6beta.

Activating Transcription Factor 6↗
PubMed2001

Establishment and characterization of a human B cell line from the lung tissue of a patient with scleroderma; extraordinary high level of IL-6 secretion by stimulated fibroblasts.

Progressive systemic sclerosis is a connective tissue disease of unknown aetiology. This is the first study to demonstrate induction by a human B cell line of IL-6 secretion from fibroblasts. The cell line was established from lesional lung tissue of a patient with progressive systemic sclerosis. These cells, referred to as kon-1 cells, showed characteristics of pro-B cell by flow cytometry. Although kon-1 cells alone secreted a small amount of IL-6, a co-culture of kon-1 cells with normal lung fibroblasts significantly increased IL-6 levels. Whereas IL-6 mRNA was weakly expressed in kon-1 cells alone, it was clearly expressed in cells from the co-culture. Immunocytochemical identification of IL-6 showed localization in the cytoplasm of fibroblasts. IL-6 is a pleiotropic cytokine, essential for B cell differentiation, which has been shown to stimulate the production of collagen and glycosaminoglycan. Thus, abnormally augmented B cell proliferation and the inflammatory response stimulated by these cells may cause the fibrotic changes in patients with progressive systemic sclerosis.

B-Lymphocytes↗
PubMed2001

Transitions of macroscopic structures and self-induced chaos observed in plasmas by a dc hollow cathode discharge having features of nonlinear open systems.

A novel experimental investigation is presented on the connection between discontinuous transitions of macroscopic structures of plasma and self-induced chaotic oscillations characterized by the positive Lyapunov exponents lambda(L) through the period-doubling route in a dc hollow cathode discharge, which has features of nonlinear open systems. We have clarified experimentally that there appear different discharge modes accompanying the discontinuous transitions, and detailed qualitative explanations are presented about the mechanism of those transitions. It is shown that fundamental frequencies of the self-induced periodic oscillations with nonpositive lambda(L) change with the changes of discharge current, and the amplitude of chaotic oscillations with the positive lambda(L) jumps up almost one order higher than that of nonchaotic ones with the nonpositive lambda(L). The self-induced chaotic oscillations with the positive lambda(L) have been observed near two edges of discontinuous transitions of plasma structures, suggesting that the chaotic mode is associated with the discontinuous transition of macroscopic structures in some nonlinear open systems.

Journal Article↗
PubMed2001

Structural characteristics of the N-glycans of two isoforms of prostate-specific antigens purified from human seminal fluid.

Prostate-specific antigen (PSA) is a glycosylated chymotrypsin-like serine protease and is found mainly in prostatic tissue and seminal fluid. We purified two forms of PSA (PSA-A and PSA-B) from human seminal fluid with pI values of approx. 7.2 and approx. 6.9, respectively. To characterize the N-glycans of the two isoforms, the sugar chains were liberated by hydrazinolysis followed by N-acetylation, and derivatized with 2-aminobenzamide. Both PSA-A and PSA-B contained mono- and disialylated sugar chains, although PSA-B had a much higher content of the latter. After removal of sialic acid residues by sialidase digestion, mono- and biantennary N-glycans and three outer chain moieties (Galbeta1-4GlcNAcbeta1-, GlcNAcbeta1-, GalNAcbeta1-4GlcNAcbeta1-) were found in both samples. However, the ratios of each N-glycan were different. These results indicate that PSA-A and PSA-B differ not only in their sialic acid contents, but also in their outer chain features.

Carbohydrate Sequence↗
PubMed2001

The transient receptor potential protein homologue TRP6 is the essential component of vascular alpha(1)-adrenoceptor-activated Ca(2+)-permeable cation channel.

The Drosophila transient receptor potential protein (TRP) and its mammalian homologues are thought to be Ca(2+)-permeable cation channels activated by G protein (G(q/11))-coupled receptors and are regarded as an interesting molecular model for the Ca(2+) entry mechanisms associated with stimulated phosphoinositide turnover and store depletion. However, there is little unequivocal evidence linking mammalian TRPs with particular native functions. In this study, we have found that heterologous expression of murine TRP6 in HEK293 cells reproduces almost exactly the essential biophysical and pharmacological properties of alpha(1)-adrenoceptor-activated nonselective cation channels (alpha(1)-AR-NSCC) previously identified in rabbit portal vein smooth muscle. Such properties include activation by diacylglycerol; S-shaped current-voltage relationship; high divalent cation permeability; unitary conductance of 25 to 30 pS and augmentation by flufenamate and Ca(2+); and blockade by Cd(2+), La(3+), Gd(3+), SK&F96365, and amiloride. Reverse transcriptase-polymerase chain reaction and confocal laser scanning microscopy using TRP6-specific primers and antisera revealed that the level of TRP6 mRNA expression was remarkably high in both murine and rabbit portal vein smooth muscles as compared with other TRP subtypes, and the immunoreactivity to TRP6 protein was localized near the sarcolemmal region of single rabbit portal vein myocytes. Furthermore, treatment of primary cultured portal vein myocytes with TRP6 antisense oligonucleotides resulted in marked inhibition of TRP6 protein immunoreactivity as well as selective suppression of alpha(1)-adrenoceptor-activated, store depletion-independent cation current and Ba(2+) influx. These results strongly indicate that TRP6 is the essential component of the alpha(1)-AR-NSCC, which may serve as a store depletion-independent Ca(2+) entry pathway during increased sympathetic activity.

Adrenergic alpha-Agonists↗
PubMed2001

The maternal transcript for truncated voltage-dependent Ca2+ channels in the ascidian embryo: a potential suppressive role in Ca2+ channel expression.

Ca2+ entry during electrical activity plays several critical roles in development. However, the mechanisms that regulate Ca2+ influx during early embryogenesis remain unknown. In ascidians, a primitive chordate, development is rapid and blastomeres of the muscle and neuronal lineages are easily identified, providing a simple model for studying the expression of voltage-dependent Ca2) channels (VDCCs) in cell differentiation. Here we isolate an ascidian cDNA, TuCa1, a homologue of the alpha(1)-subunit of L-type class Ca2+ channels. We unexpectedly found another form of Ca2+ channel cDNA (3-domain-type) potentially encoding a truncated type which lacked the first domain and a part of the second domain. An analysis of genomic sequence suggested that 3-domain-type RNA and the full-length type have alternative transcriptional start sites. The temporal pattern of the amount of 3-domain-type RNA was the reverse of that of the full-length type; the 3-domain type was provided maternally and persisted during early embryogenesis, whereas the full-length type was expressed zygotically in neuronal and muscular lineage cells. Switching of the two forms occurred at a critical stage when VDCC currents appeared in neuronal or muscular blastomeres. To examine the functional roles of the 3-domain type, it was coexpressed with the full-length type in Xenopus oocyte. The 3-domain type did not produce a functional VDCC current, whereas it had a remarkable inhibitory effect on the functional expression of the full-length form. In addition, overexpression of the 3-domain type under the control of the muscle-specific actin promoter in ascidian muscle blastomeres led to a significant decrease in endogenous VDCC currents. These findings raise the possibility that the 3-domain type has some regulatory role in tuning current amplitudes of VDCCs during early development.

Amino Acid Sequence↗
PubMed2001

Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 1.

Highly potent 1,3-beta-D-glucan synthase inhibitors 10, 11 and 13 have been identified by the chemical modification of the fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. D-Ornithine derivative (10) showed improved antifungal activity in the systemic candidiasis model in mice and reduced hepatotoxicity in vitro, as compared with 1.

Animals↗
PubMed2001

Sex- and age-related response to aromatase deficiency in bone.

Deficiency of sex steroids causes osteoporosis, but the relationship between estrogen and androgen is not clear because androgen is converted into estrogen by aromatase. In this study, we characterized bone metabolism in the aromatase-deficient (ArKO) mouse. At 9 weeks old, a marked loss of cancellous bone due to increased bone resorption was observed not only in female ArKO mice but also in males. The degree of bone loss in ArKO males was similar to that in females, and treatment with 17beta-estradiol completely restored the bone mass in both sexes. At 32 weeks old, female ArKO mice showed severe loss of cancellous and cortical bone. Male ArKO mice of this age also showed reduced bone mass, but the degree of bone loss in females was more marked than that in males. Here, we report sex- and age-related responses to aromatase deficiency in bone.

Age Factors↗
PubMed2001

Solution structure and dynamic character of the histidine-containing phosphotransfer domain of anaerobic sensor kinase ArcB from Escherichia coli.

An Escherichia coli sensor kinase, ArcB, transfers a phosphoryl group to a partner response regulator in response to anaerobic conditions. Multidimensional NMR techniques were applied to determine the solution structure of the histidine-containing phosphotransfer signaling domain of ArcB (HPt(ArcB)), which has a phosphorylation site, His717. The backbone dynamics were also investigated by analyses of the (15)N relaxation data and amide hydrogen exchange rates. Furthermore, the protonation states of the histidine imidazole rings were characterized by means of (1)H and (15)N chemical shifts at various pHs. The determined solution structure of HPt(ArcB) contains five helices and forms a four-helix bundle motif like other HPt domains. The obtained order parameters, S (2), [(1)H]-(15)N heteronuclear NOE values, and chemical exchange parameters, R(ex), showed that the alpha-helical regions of HPt(ArcB) are rigid on both picosecond to nanosecond and microsecond to millisecond time scales. On the other hand, helix D, which contains His717, exhibited low protection factors of less than 4000, indicating the presence of fluctuations on a slower time scale in helix D. These results suggest that HPt(ArcB) may undergo a small conformational change in helix D upon phosphorylation. It was also shown that the imidazole ring of His717 has a pK(a) value of 6.76, which is similar to that of a solvent-exposed histidine imidazole ring, and that a pair of deprotonated neutral tautomers are rapidly exchanged with each other. This is consistent with the solution structure of HPt(ArcB), in which the imidazole ring of His717 is exposed to the solvent.

Amides↗
PubMed2001

Evaluation of female intrapelvic tumors by clinical proton MR spectroscopy.

We measured metabolites in large tumors of the female pelvis (23 cases total: 6 malignant cases, 17 benign cases) using single-voxel proton magnetic resonance (MR) spectroscopy and evaluated the clinical significance of this method in the differential diagnosis of female pelvic tumors. The characteristically obtained signal was lactate, which was detected not only in all the malignant tumors but also in some of the benign tumors. However, the lactate signals of the malignant tumors tended to form higher peaks than those of benign tumors, which was a finding consistent with the result of the earlier in vitro study reported in ovarian tumors. The signal of choline-containing compounds (Cho) was found only in solid tumors, and the signal intensity varied among different histological types of tumors, possibly reflecting metabolic activity of the cell membrane. We considered that proton MR spectroscopy (MRS) of intrapelvic tumors would be useful for the diagnosis of the nature of female intrapelvic tumors. J. Magn. Reson. Imaging 2001;13:912-917.

Adult↗
PubMed2001

Prostaglandins and nitric oxide mediate superoxide-induced myocardial contractile dysfunction in isolated rat hearts.

Oxygen-derived free radicals have been implicated in the pathogenesis of myocardial injury. We therefore investigated the pathophysiology of myocardial injury induced in isolated rat hearts by perfusion with superoxide radical generated by reacting 2.5 mmol/l purine, 0.03 U/ml xanthine oxidase and 300 U/ml catalase. Perfusion with superoxide significantly (P<0.05) increased left ventricular end-diastolic pressure within 15 to 20 min. During the same time period, heart rate and left-ventricular developed pressure significantly declined to 44.6+/-8.2% and 31.0+/-4.9% of control, respectively. Superoxide perfusion also significantly increased production of prostaglandins, nitric oxide (detected as nitrites) and peroxynitrite (detected immunohistochemically as nitrotyrosine). N(G)-nitro-l-arginine (100 micromol/l), a nitric oxide synthase inhibitor, attenuated superoxide-induced generation of peroxynitrite, increased synthesis of prostacyclin, and partially blocked myocardial dysfunction, as did 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (30 micromol/l), a selective inhibitor of soluble guanylate cyclase, and ONO-3708 (10 micromol/l), a selective thromboxane A(2)receptor antagonist. In contrast, nitroglycerin (4 micromol/l) and sodium nitroprusside (1 micromol/l) each exacerbated the superoxide-induced myocardial dysfunction. These results suggest that nitric oxide and related reactive species contribute to myocardial injury induced by superoxide. Moreover, they suggest that oxidative stress can be delayed or inhibited by reducing levels of nitric oxide, by inhibiting soluble guanylate cyclase, and by blocking thromboxane/prostaglandin receptors.

1-Methyl-3-isobutylxanthine↗