Biomedical subjects

T Yoshioka

Publications and source records attributed to T Yoshioka.

At least 91 records · Page 5Linked to original sources

PubMed2000

A Ca(2+) channel blocker-like effect of dehydrocurdione on rodent intestinal and vascular smooth muscle.

Effects of dehydrocurdione, a zedoary-derived sesquiterpene, on smooth muscle were investigated by recording the mechanical activity of intestines and aorta from guinea pigs and rats. Dehydrocurdione (0.1-3 mM) induced a sustained relaxation of rat duodenum and inhibited spontaneous motility. Dehydrocurdione (0.1-1 mM) inhibited the contractile response of guinea pig ileum induced by acetylcholine (0.01-10 microM), histamine (0.03-10 microM) and substance P (0.1-30 nM) in a non-competitive manner. Acetylcholine (0.5 microM) elicited a transient contraction followed by a sustained contraction of guinea pig ileum, and dehydrocurdione pretreatment inhibited the sustained component, which depends on Ca(2+) entry from the extracellular space. The high K(+)-induced contraction of rat aortic ring is reported to be blocked by Ca(2+) channel blockers, while the norepinephrine-induced contraction includes a Ca(2+) channel blocker-resistant component. Dehydrocurdione (1 mM) blocked the high K(+) (60 mM)-induced contraction of rat aortic ring by 81%, while it inhibited the norepinephrine (1 microM)-induced contraction by only 28%. Dehydrocurdione (1 mM) significantly reduced the high K(+)-stimulated increase in cytosolic Ca(2+) level of Fura-2-loaded mesenteric artery from rats. These results suggest that the inhibitory effects of dehydrocurdione on intestinal and vascular smooth muscle are mediated by blockade of Ca(2+) entry from the extracellular space.

Animals↗

PubMed2000

Expression of genes responsible for ethylene production and wilting are differently regulated in carnation (Dianthus caryophyllus L.) petals.

Carnation petals exhibit autocatalytic ethylene production and wilting during senescence. The autocatalytic ethylene production is caused by the expression of 1-aminocyclopropane-1-carboxylate (ACC) synthase and ACC oxidase genes, whereas the wilting of petals is related to the expression of the cysteine proteinase (CPase) gene. So far, it has been believed that the ethylene production and wilting are regulated in concert in senescing carnation petals, since the two events occurred closely in parallel with time. In the present study, we investigated the expression of these genes in petals of a transgenic carnation harboring a sense ACC oxidase transgene and in petals of carnation flowers treated with 1,1-dimethyl-4-(phenylsulfonyl)semicarbazide (DPSS). In petals of the transgenic carnation flowers, treatment with exogenous ethylene caused accumulation of the transcript for CPase and in-rolling (wilting), whereas it caused no or little accumulation of the transcripts for ACC oxidase and ACC synthase and negligible ethylene production. In petals of the flowers treated with DPSS, the transcripts for ACC synthase and ACC oxidase were accumulated, but no significant change in the level of the transcript for CPase was observed. These results suggest that the expression of ACC synthase and ACC oxidase genes, which leads to ethylene production, is differentially regulated from the expression of CPase, which leads to wilting, in carnation petals.

Journal Article↗

PubMed2000

Identification of a protein phosphorylated by cAMP-dependent protein kinase in drosophila brain.

In the present study, we examined the effects of reagents that elevate cAMP concentration on protein phosphorylation in Drosophila brain cells. Application of forskolin or dopamine to brain cells that were prelabeled with (32)Pi enhanced phosphorylation of a 25-kDa protein (p25a). To identify p25a, we isolated the protein, and partial amino acid sequences were analyzed. Database searches showed that p25a is a J-domain protein, dJDP that contains the J-domain found in the DnaJ (heat shock protein 40) family of molecular chaperones.

Animals↗

PubMed2000

Permeation of Liquids through Inorganic Nanofiltration Membranes.

Inorganic nanofiltration membranes were prepared using silica-zirconia composite sols by the sol-gel method and applied for the permeation experiments of nonaqueous solutions. Pure solvent permeabilities of methanol, ethanol, and 1-propanol were measured at temperatures from 25 to 60 degrees C. For membranes having pore sizes as large as 70 nm, the permeation mechanism of alcohols obeys the viscous flow mechanism irrespective of types of alcohols. On the other hand, the permeation mechanism through porous silica-zirconia membranes having pore diameters of 1 to 5 nm was found to be different from the viscous flow mechanism; small molecules showed larger permeabilities than large molecules. Activation energies of solvent permeability were found to be larger for large molecules and for membranes of smaller pore size. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor type-1 (PAI-1) gene expression in mesangial cells.

Angiotensin II (Ang II) up-regulates plasminogen-activator inhibitor type-1 (PAI-1) expression in mesangial cells to enhance extracellular matrix formation. The proximal promoter region (bp -87 to -45) of the human PAI-1 gene contains several potent binding sites for transcription factors [two phorbol-ester-response-element (TRE)-like sequences; D-box (-82 to -76) and P-box (-61 to 54), and one Sp1 binding site-like sequence, Sp1-box 1 (-72 to -67)]. We studied this region to determine the transcription factor(s) that mediates Ang-II-induced transcriptional activation of the PAI-1 gene. Various double-stranded decoy oligodeoxynucleotides (ODNs) corresponding to various sequences in the proximal promoter region were transfected to mesangial cells to examine the effects on Ang-II-induced PAI-1 mRNA expression. Transfection with the full-length decoy (bp -87 to -45, D-P-ODN) markedly attenuated Ang-II-induced PAI-1 mRNA expression by up to 70%. Transfection with D-ODN (-87 to -71) and P-ODN (-66 to -45), which correspond to each of the two TRE-like sequences, did not attenuate the expression. Gel-shift assays using nuclear extracts prepared from Ang-II-treated mesangial cells and D-P-ODN showed three specific complexes. The major complex was supershifted by anti-Sp1 antibody. The methylation-interference experiment demonstrated that human recombinant Sp1 bound to the so-called GT box (TGGGTGGGGCT, -78 to -69), which contains the Sp1-box 1. The complex that migrated with anti-Sp1 antibody was enhanced in the cells treated with Ang II. Further, D-Sp1-ODN (-85 to -63) containing the GT box attenuated up-regulation of PAI-1 mRNA expression induced by Ang II to a level (68+/-9% inhibition) comparable to D-P-ODN, whereas ODN with four mutations in the GT box had no effect. Our findings suggest that binding of Sp1 or an Sp1-like transcription factor to the GT box in the PAI-1 promoter up-regulates PAI-1 gene transcription in mesangial cells stimulated with Ang II. This transcription-factor binding site may be targeted to control Ang-II-dependent extracellular matrix formation by mesangial cells.

Angiotensin II↗

PubMed2000

Pre- and postsynaptic actions of serotonin on rat suprachiasmatic nucleus neurons.

Serotoninergic transmission is implicated in the photic and non-photic regulation of circadian rhythms. 5-HT (1-100 microM), carboxamidotryptamine (5-CT 0.1-10 microM) and (+)-8-hydroxy-dipropylaminotetraline (8-OH-DPAT, 1-30 microM) dose-dependently activated an outward current (5-100 pA) in 30% of neurons voltage-clamped at -60 mV in the suprachiasmatic nucleus (SCN) in vitro slice. EC(50) values were 7.0 microM for 5-HT and 0.2 microM for 5-CT. Serotonin-induced outward current was associated with an increase in input conductance, and the current was blocked by Ba(2+) (1 mM). The amplitude of the current was enhanced by depolarization, reduced by hyperpolarization, and reversed its polarity during a hyperpolarization beyond the potassium equilibrium potential. Mean amplitudes of the 5-HT outward current changed with time of the subjective circadian day. The value near CT2 (23.8 pA) was about 4 times greater than that around CT14 (6.7 pA). Cells that responded with an outward current showed four types of morphology: monopolar, simple bipolar, curly bipolar and radial shaped; they were localized in all parts of the SCN. The EPSC evoked by retino-hypothalamic-tract (RHT) stimulation was inhibited 26% but the inward current induced by exogenously applied glutamate or NMDA was not affected by serotonin agonists. Focal stimulation-induced and spontaneous IPSC but not the exogenous GABA-induced outward current were inhibited by 5-HT agonists in a subpopulation of cells. In conclusion, 5-HT regulates SCN neurons by both pre- and post-synaptic inhibitory mechanisms; the latter may play a key role in modulating SCN circadian rhythm by activation of 5-HT receptors and opening of a potassium channel.

Animals↗

PubMed2000

Involvement of glial fibrillary acidic protein (GFAP) expressed in astroglial cells in circadian rhythm under constant lighting conditions in mice.

To clarify the role of glial fibrillary acidic protein (GFAP)-expressed glial cells in the circadian clock, we examined GFAP expression in the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) under various lighting conditions in mice. We demonstrated that GFAP expression did not show daily change in the SCN under a light-dark cycle; however, long-term housing under constant lighting conditions led to dramatic changes in GFAP expression, i.e., a decrease in the SCN and an increase in the IGL. Furthermore, mice that had a targeted deletion in the GFAP gene (GFAP mutant mice) showed longer and more arrhythmic circadian activity rhythms in constant lighting conditions than wild-type mice, while GFAP mutant mice exhibited stable circadian rhythms both in a light-dark cycle and constant darkness, and showed normal entrainment to environmental light stimuli. These results suggest that the GFAP-expressed astroglial cells in the SCN and the IGL may have some role in circadian oscillation under constant lighting conditions.

Animals↗

PubMed2000

PLC beta 4-independent Ca2+ rise via muscarinic receptors in the mouse suprachiasmatic nucleus.

Cholinergic regulation of the suprachiasmatic nucleus (SCN) has been extensively studied although the intracellular signaling mechanisms are not well understood. We examined immunostaining for phospholipase C-beta (PLC-beta) families that couple to muscarinic acetylcholine receptors (mAChR) and demonstrated the expression of PLC-beta 1 and beta 4 in the mouse SCN. Ca2+ imaging analysis indicated that the MI-mAChR antagonist, pirenzepine blocked carbachol-induced Ca2+ elevation in the SCN and the response was equivalent between the wild type and the PLC-beta 4-knockout mice. In addition, the knockout mice displayed locomotor and temperature rhythms coupling to 24 h light/dark cycles. Therefore, it was proposed that PLC-beta 1 but not PLC-beta 4 was involved in the mAChR-mediated Ca2+ signaling in the SCN.

Animals↗

PubMed2000

Rat receptor-activity-modifying proteins (RAMPs) for adrenomedullin/CGRP receptor: cloning and upregulation in obstructive nephropathy.

Adrenomedullin (AM) is a potent vasorelaxing peptide originally isolated pheochromocytoma. Recently, a family of receptor-activity-modifying proteins (RAMPs 1-3) were identified in humans. Associated with the calcitonin receptor-like receptor (CRLR), RAMP2 or RAMP3 may function as the AM receptor. Here we cloned rat RAMP family, analyzed their distribution in rat tissues, and examined regulation of their expression in the kidney using an obstructive nephropathy model. Northern blot analyses revealed that the RAMP family genes are expressed in various tissues with different tissue specificity; RAMP1 is abundantly expressed in the brain, fat, thymus, and spleen, RAMP2 in the lung, spleen, fat, and aorta, while RAMP3 is most abundant in the kidney and lung. After ureteral obstruction, RAMP1, RAMP2, and CRLR gene expressions in the obstructed kidney were markedly upregulated, whereas RAMP3 expression was unchanged. Thus, RAMPs are regulated differently in obstructive nephropathy, suggesting their distinct roles in renal pathophysiology.

Amino Acid Sequence↗

PubMed2000

beta-blocker therapy in patients after aortic valve replacement for aortic regurgitation.

BACKGROUND: beta-blocker therapy for dilated or ischemic cardiomyopathy is now an accepted and effective treatment. However, little is known about its efficacy in patients with postoperative impaired left ventricular function. This retrospective study was designed to assess the effects of beta-blocker therapy in patients after aortic valve replacement (AVR) for aortic regurgitation (AR). METHODS: A total of 59 patients who underwent AVR for chronic AR were assigned to four groups. Twelve patients were treated with both ACE inhibitors and beta-blockers, 12 patients with only ACE inhibitors, eight patients with only beta-blockers, and 27 patients without beta-blockers or ACE inhibitors. A postoperative echocardiographic study was performed one year after surgery. RESULTS: The heart rate was significantly reduced in patients with beta-blockers despite the use of ACE inhibitors after surgery. Postoperative left ventricular volume was more significantly decreased in beta patients than in non-beta patients despite the use of ACE inhibitors. There were also significant reductions in left ventricular mass index in ACE+beta patients compared to ACE+non-beta patients. However, there were no significant differences in NYHA functional class and survival rate between beta patients and non-beta patients. CONCLUSIONS: beta-blocker therapy may improve cardiac performance by reducing cardiac volume and mass in patients with impaired LV function after AVR for AR.

Adrenergic beta-Antagonists↗

PubMed2000

Mutant mice lacking ryanodine receptor type 3 exhibit deficits of contextual fear conditioning and activation of calcium/calmodulin-dependent protein kinase II in the hippocampus.

As it is known that ryanodine receptor type 3 is expressed in the hippocampus, we examined the contribution of this receptor to contextual fear conditioning behavior and to the activation of Ca(2+)/calmodulin-dependent protein kinase II using mice lacking the receptor. Ryanodine receptor type 3-deficient mice exhibited impairments of performance in the contextual fear conditioning test, passive avoidance test, and Y-maze learning test. Both the activities of Ca(2+)/calmodulin-dependent protein kinase IIbeta and Ca(2+)/calmodulin-dependent protein kinase IIalpha were significantly increased in the experimental group compared to the control group in the hippocampus, but not in the cingulate cortex on the testing day 24 h after contextual fear training. However, the activities of Ca(2+)/calmodulin-dependent protein kinase IIbeta and alpha were almost the same in the experimental and control groups in the hippocampus on the training day. Ryanodine receptor type 3-deficient mice did not show the increment of Ca(2+)/calmodulin-dependent protein kinase IIbeta and alpha activities in the hippocampus on the testing day. In addition, these mutant mice showed the reduction of fear response in the elevated plus-maze test. The present results suggest that calcium-induced calcium release through the activation of ryanodine receptor type 3 in the hippocampus is important to the expression of the performance of contextual learning through the elevation of Ca(2+)/calmodulin-dependent protein kinase IIbeta and alpha activities.

Animals↗

PubMed2000

Acetyl-seryl-aspartyl-lysyl-proline is a novel natural cell cycle regulator of renal cells.

A natural tetrapeptide, acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological negative regulator of hematopoiesis. The precursor of AcSDKP, thymocin beta 4, is expressed in many tissues including kidney. The present study examined the antiproliferative effect of AcSDKP in two renal cell lines, namely, renal interstitial fibloblasts cell line (NRK 49F) and renal proximal tubular epitherial cells (LLC-PK1). An addition of AcSDKP for 48 hours in theses cells resulted in a concentration-dependent attenuation in the proliferation rate (significant difference to non-treated cells was observed at 10(-9) to 10(-5) M AcSDKP) determined by a colorimetry of alamer blue oxidation. The cell cycle analysis of NRK 49F cells treated with AcSDKP showed that AcSDKP significantly reduced the ratio of S-phase to G2/M-phases. Thus, physiological concentrations of AcSDKP is capable of altering cell cycle to inhibit the proliferation of renal cells.

Animals↗

PubMed2000

Human cerebellar activity reflecting an acquired internal model of a new tool.

Theories of motor control postulate that the brain uses internal models of the body to control movements accurately. Internal models are neural representations of how, for instance, the arm would respond to a neural command, given its current position and velocity. Previous studies have shown that the cerebellar cortex can acquire internal models through motor learning. Because the human cerebellum is involved in higher cognitive function as well as in motor control, we propose a coherent computational theory in which the phylogenetically newer part of the cerebellum similarly acquires internal models of objects in the external world. While human subjects learned to use a new tool (a computer mouse with a novel rotational transformation), cerebellar activity was measured by functional magnetic resonance imaging. As predicted by our theory, two types of activity were observed. One was spread over wide areas of the cerebellum and was precisely proportional to the error signal that guides the acquisition of internal models during learning. The other was confined to the area near the posterior superior fissure and remained even after learning, when the error levels had been equalized, thus probably reflecting an acquired internal model of the new tool.

Adult↗

PubMed2000

Down-regulation of antigen-specific antibody production by TCR antagonist peptides in vivo.

The efficacy of TCR antagonist peptides in inhibition of antigen-specific antibody production and T cell responses in vivo was evaluated. Among amino acid-substituted analogs of a peptide corresponding to residues 119 - 133 of bovine beta-lactoglobulin (p119 - 133), pR124Q and pD129S, prepared by substitution of Gln and Ser for Arg(124) and Asp(129), respectively, have been shown to display TCR antagonist activity for three out of four distinct p119 - 133-specific T cell clones and for polyclonal T cells derived from p119 - 133-immunized C57BL / 6 mice. Both pD129S and pR124Q inhibited in vivo priming and subsequent activation of T cells by p119 - 133 when co-injected with p119 - 133 into mice, as shown by the decreased proliferation of T cells in response to p119-133 in vitro. pD129S significantly inhibited production of anti-p119 - 113 antibodies of IgG1, IgG2b and IgE isotype in vivo when co-injected into mice together with p119 - 133 at the time of the first immunization. However, pR124Q was totally ineffective in inhibition of the antibody responses. Anti-p119 - 133 antibodies from p119 - 133-immunized mice could bind to pR124Q but not to pD129S, suggesting that the difference in cross-reactivity is responsible for the different effect of these two peptides on specific antibody production. Our findings demonstrate that a single TCR antagonist peptide can inhibit antigen-specific polyclonal antibody production when this antagonist peptide does not cross-react with the antibody elicited in response to an antigenic peptide.

Animals↗

PubMed2000

Differential effects on T cell and NK cell development by tissue-specific expression of H-2D(d) transgene.

The effect of tissue-specific expression of the MHC class I molecule H-2D(d) on T cell and NK cell specificity was studied in transgenic mice expressing the H-2D(d) gene under the control of the mouse metallothionein-I promoter. MTD mice expressed high amounts of H-2D(d) in the liver, intestine and testis, but only minute amounts in the thymus, spleen and kidney. Zinc administration resulted in a 1.5- and 8.5-fold increase in H-2D(d) expression in the liver and the intestine, respectively, but did not affect expression in the other organs tested. T cell tolerance developed towards H-2D(d) in MTD mice, even in the absence of zinc. In contrast, NK cell-mediated natural resistance against lymphoma grafts was not seen in MTD mice, despite zinc administration. NK cells in MTD mice also failed to develop self tolerance to H-2D(d). The lack of functional effects did not result from inability of NK cells in MTD mice to interact with H-2D(d), as down-regulation of Ly49A receptor expression was observed on liver NK cells in MTD mice. Our data reveal a difference between T cells and NK cells in their requirements for MHC class I molecules in specificity development.

Animals↗

PubMed2000

Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis.

OX40 ligand (OX40L) and OX40 (CD134) are a pair of cell surface molecules belonging to the TNF/TNF receptor family. Interaction of OX40L with its receptor OX40 is thought to be important in T cell activation through T cell/antigen-presenting cell interaction. However, involvement of these molecules in the pathogenesis of rheumatoid arthritis (RA) remains unclear. To explore the contribution of OX40/OX40L interaction to the pathogenesis of RA in vivo, we evaluated the effect of a neutralizing anti-OX40L monoclonal antibody (mAb) on the development of collagen-induced arthritis (CIA) in DBA/1 mice as an animal model for RA. Administration of anti-OX40L mAb into type II collagen (CII) -immunized DBA/1 mice dramatically ameliorated the disease severity. In vivo treatment with anti-OX40L mAb did not inhibit the expansion of CII-reactive T cells, but suppressed IFN-gamma and anti-CII IgG2a production. Therefore, OX40/OX40L interaction appears to play a critical role in the development of CIA by enhancing Th1-type autoimmune response. In addition, T lymphocytes in synovial fluid and synovial tissue from RA patients expressed OX40, while OX40L was expressed on sublining cells in synovial tissue. These results indicate that OX40/OX40L interaction may play a critical role in the development of RA.

Animals↗

PubMed2000

HGF/SF-induced spreading of MDCK cells correlates with disappearance of barmotin/7H6, a tight junction-associated protein, from the cell membrane.

Changes in expression of the two tight junction-associated proteins, barmotin/7H6 and ZO-1, as well as the adherence junction-associated protein, E-cadherin, were followed during hepatocyte growth factor/scatter factor (HGF/SC)-induced migration process of MDCK cells. Modulation of the HGF/SF-induced migration process by staurosporine, an inhibitor of protein kinase C (PKC), was also examined. Cell migration induced by HGF/SF consisted of two distinct phases, initial cell spreading between 2 and 9 h after the start of treatment, and the scattering phase which started approximately 12 h after treatment. Both ZO-1 and E-cadherin were expressed at the cell-cell border of adherent cells in the scattering phase, whereas barmotin/7H6, a barrier function-related tight junction protein, was not seen during the early spreading phase. Confluent cultures of MDCK cells, which did not spread after HGF/SF treatment, were positive for barmotin/7H6 expression at cell-cell borders. Blocking PKC activation during HGF/SF treatment with staurosporine inhibited cell spreading, and the cells retained barmotin/7H6 expression until at 6 h after HGF/SF treatment. The results indicate that disappearance of the tight junction protein, barmotin/7H6, is closely associated with cell spreading, with both barmotin/7H6 expression and cell spreading seemingly being regulated by PKC-mediated signaling.

Animals↗

PubMed2000

Coronary surgery through partial sternotomy in a patient with tracheostoma.

We report successful coronary artery bypass grafting through a lower partial sternotomy for a patient with a tracheostoma. He required a tracheotomy for serious laryngeal edema which developed during anesthetic induction prior to elective conventional coronary surgery. A safe alternative approach, comprising a lower midline skin incision with a lower partial sternotomy distant from the stoma, facilitated coronary artery bypass grafting to the left and right coronary arteries after four weeks.

Coronary Artery Bypass↗