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Biomedical subjects

T Ito

Publications and source records attributed to T Ito.

At least 325 records · Page 18Linked to original sources
PubMed2000

Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers.

Fos family proteins form stable heterodimers with Jun family proteins, and each heterodimer shows distinctive transactivating potential for regulating cellular growth, differentiation, and development via AP-1 binding sites. However, the molecular mechanism underlying dimer specificity and the molecules that facilitate transactivation remain undefined. Here, we show that BAF60a, a subunit of the SWI.SNF chromatin remodeling complex, is a determinant of the transactivation potential of Fos/Jun dimers. BAF60a binds to a specific subset of Fos/Jun heterodimers using two different interfaces for c-Fos and c-Jun, respectively. Only when the functional SWI.SNF complex is present, can c-Fos/c-Jun (high affinity to BAF60a) but not Fra-2/JunD (no affinity to BAF60a) induce the endogenous AP-1-regulated genes such as collagenase and c-met. These results indicate that a specific subset of Fos/Jun dimers recruits SWI.SNF complex via BAF60a to initiate transcription.

Dimerization↗
PubMed2000

Time-course effects of a single administration of cocaine on receptor binding and subunit mRNAs of GABA(A) receptors.

We investigated the time-course effects of a single administration of cocaine (20 mg/kg) on GABA(A) receptor binding labeled by t-[(35)S]butylbicyclophophorothionate (TBPS) and on several types of GABA(A) receptor subunit mRNAs in the rat brain by in vitro quantitative receptor autoradiography and in situ hybridization. The levels of alpha 1, beta 2, and beta 3 subunit mRNAs in several brain regions such as the cortex, cerebellum, and striatum were significantly decreased within 1 h, while beta 3 subunit mRNA was increased in the dentate gyrus. All of these changes were transient, occurring within 1 h after the injection of cocaine. In the cortex and cerebellum, the reduction in alpha1 subunit mRNA was followed by a significant decrease in [(35)S]TBPS receptor binding, which occurred 4 h after cocaine injection. These findings suggest that acute cocaine administration discretely regulates GABA(A) receptor subunit mRNA levels in several brain regions through a change in transcription or turnover rates of subunit mRNAs, which may be closely related to cocaine-induced behavioral abnormalities.

Animals↗
PubMed2000

T(-786)--> C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis.

Recently, we discovered a T(-786)-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene that is associated with coronary spasm. The precise mechanism(s) of myocardial infarction (MI), especially without coronary organic stenosis, has not been elucidated, but it seems possible that coronary spasm plays a key role in the mechanism. In this study, we examined the frequency with which the T(-786)-->C mutation occurred in 359 patients with MI who were compared with 195 controls. In the MI group, the frequency of C/C, C/T, and T/T genotypes was 1%, 22%, and 77%, respectively. In the control group, the frequency of C/C, C/T, and T/T genotypes were 0%, 8%, and 92%, respectively. The frequency of the C allele was significantly higher in the MI group than in the control group (p < 0.001). In the MI group, 30 of 359 patients (8%) with MI had no stenosed vessels angiographically, 158 (44%) had 1 stenosed vessel, 80 (22%) had 2 stenosed vessels, and 91 (25%) exhibited 3 stenosed vessels. Total and low-density lipoprotein cholesterol levels and the incidence of diabetes mellitus increased as the number of stenosed vessels increased (p < 0.01, respectively). The frequency of the T(-786)-->C mutation was significantly higher in MI patients with no stenosed vessels (50%) than in those with stenosed vessels (p < 0.003). In conclusion, the T(-786)-->C mutation was strongly associated with MI, especially without coronary arterial stenosis, in Japanese patients. The association may be due to the impaired effects of nitric oxide in the cardiovascular system.

Adult↗
PubMed2000

Initial T-cell activation required for transplant vasculopathy in retransplanted rat cardiac allografts.

BACKGROUND: A precise understanding of immunological mechanisms is needed to prevent transplant vasculopathy. METHODS: The developing process of transplant vasculopathy was investigated by retransplanting rat cardiac allografts and measuring the expressions of 21 different genes inside the retransplanted allografts under nonimmunosuppressive conditions. RESULTS: Significant transplant vasculopathy developed if WKY hearts were grafted to LEW and retransplanted to WKY 5 days after the initial grafting, but it did not in allografts retransplanted 3 days after the initial grafting. The disease did not progress in retransplanted isografts or if nude rats were used as the initial recipients. However, the development of transplant vasculopathy was not affected by changing the second recipients to the F1 progeny of donor x recipient or to nude animals. Among the expressions of 21 different genes observed in allografts at 1, 14, 30, or 60 days after retransplantation, those of T-cell activation-related genes, such as interferon-y and Fas ligand, showed the earliest and the most dramatic difference between 3- and 5-day-retransplanted allografts whereas macrophage/monocyte activation-related genes showed little difference. Furthermore, reverse transcription-polymerase chain reaction analyses of allografts retransplanted to nude animal indicated that T cells of the initial recipient origin survive and remain activated even 60 days after retransplantation. CONCLUSIONS: The T-cell response occurring between 3 and 5 days after grafting was identified as the critical parameter to the disease progression. Once alloreactive T cells enter a graft, they may be able to survive a long period and promote chronic rejection.

Animals↗
PubMed2000

Pushing the limits of lithography

The phenomenal rate of increase in the integration density of silicon chips has been sustained in large part by advances in optical lithography--the process that patterns and guides the fabrication of the component semiconductor devices and circuitry. Although the introduction of shorter-wavelength light sources and resolution-enhancement techniques should help maintain the current rate of device miniaturization for several more years, a point will be reached where optical lithography can no longer attain the required feature sizes. Several alternative lithographic techniques under development have the capability to overcome these resolution limits but, at present, no obvious successor to optical lithography has emerged.

Journal Article↗
PubMed2000

p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone.

We have used a purified recombinant chromatin assembly system, including ACF (Acf-1 + ISWI) and NAP-1, to examine the role of histone acetylation in ATP-dependent chromatin remodeling. The binding of a transcriptional activator (Gal4-VP16) to chromatin assembled using this recombinant assembly system dramatically enhances the acetylation of nucleosomal core histones by the histone acetyltransferase p300. This effect requires both the presence of Gal4-binding sites in the template and the VP16-activation domain. Order-of-addition experiments indicate that prior activator-meditated, ATP-dependent chromatin remodeling by ACF is required for the acetylation of nucleosomal histones by p300. Thus, chromatin remodeling, which requires a transcriptional activator, ACF and ATP, is an early step in the transcriptional process that regulates subsequent core histone acetylation. Glycerol gradient sedimentation and immunoprecipitation assays demonstrate that the acetylation of histones by p300 facilitates the transfer of H2A-H2B from nucleosomes to NAP-1. The results from these biochemical experiments suggest that (1) transcriptional activators (e.g., Gal4-VP16) and chromatin remodeling complexes (e.g., ACF) induce chromatin remodeling in the absence of histone acetylation; (2) transcriptional activators recruit histone acetyltransferases (e.g., p300) to promoters after chromatin remodeling has occurred; and (3) histone acetylation is important for a step subsequent to chromatin remodeling and results in the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone such as NAP-1. Our results indicate a precise role for histone acetylation, namely to alter the structure of nucleosomes (e.g., facilitate the loss of H2A-H2B dimers) that have been remodeled previously by the action of ATP-dependent chromatin remodeling complexes. Thus, transcription from chromatin templates is ordered and sequential, with precise timing and roles for ATP-dependent chromatin remodeling, subsequent histone acetylation, and alterations in nucleosome structure.

Acetylation↗
PubMed2000

Holes in a Quantum Spin Liquid.

Magnetic neutron scattering provides evidence for nucleation of antiferromagnetic droplets around impurities in a doped nickel oxide-based quantum magnet. The undoped parent compound contains a spin liquid with a cooperative singlet ground state and a gap in the magnetic excitation spectrum. Calcium doping creates excitations below the gap with an incommensurate structure factor. We show that weakly interacting antiferromagnetic droplets with a central phase shift of pi and a size controlled by the correlation length of the quantum liquid can account for the data. The experiment provides a quantitative impression of the magnetic polarization cloud associated with holes in a doped transition metal oxide.

Journal Article↗
PubMed2000

Importance of donor-derived lymphocytes in the protection of pancreaticoduodenal or islet grafts from recurrent autoimmunity: a role for RT6+NKR-P1+ T cells.

BACKGROUND: A rat pancreas transplantation model with insulin-dependent diabetes mellitus (IDDM) recurrence was established using a Wistar-Furth (WF; RT1u, RT6.2) rat as a donor and diabetes-prone (DP; RT1u, rt6.1 gene carrier) BioBreeding rat as a recipient. Interestingly, NKR-P1+TCRalphabeta+ (NKT) cells have recently been reported to have immunoregulatory functions in preventing autoimmune diabetes. The purpose of this study was to specifically examine the contribution of NKT cells in the prevention of IDDM recurrence. METHODS: Graft survivals with or without anti-intercellular adhesion molecule-1/leukocyte function-associated antigen-1 monoclonal antibodies were examined comparing pancreaticoduodenal (PD) transplantation with islet transplantation or pancreas-alone transplantation excluding duodenum and peripancreatic lymph nodes, in an IDDM recurrent model. The cells of the spleen were analyzed by flow cytometry (including intracellular interleukin (IL)-4 analysis), and serum cytokine levels (IL-4 and interferon-gamma) were determined by enzyme-linked immunosorbent assays (ELISA). RESULTS: Only those DP recipients transplanted with PD grafts with monoclonal antibody treatment were free from IDDM. Flow cytometric analyses of spleen cells showed that NKT cells in them, compared with those in the recurrent DP recipients (mean <7%), increased significantly (13.7+/-3.1% in the total splenic T cells), most of which (85.9+/-4.3%) were derived from the donor (RT6.2+). The absolute number of RT6+NKT cells significantly increased in the nonrecurrent DP recipients, whereas that of RT6-NKT cells was similar with those of the other recurrent DP recipients. These RT6+NKT cells were predominantly CD4+ and showed significantly more expressions of intracellular IL-4 than the other T cells. By ELISA, serum interferon-gamma was not detectable (< 13 pg/ml) in any of the rats. However, IL-4 was detected at 111.6+/-47.8 pg/ml only in the nonrecurrent DP recipients. CONCLUSIONS: Unlike islet or pancreas-alone transplants, NKT cells, especially RT6+NKT cells derived from PD grafts, may have an important immunoregulatory function of preventing IDDM recurrence, involving a Th2 deviation.

ADP Ribose Transferases↗
PubMed2000

Cyanide-bridge Fe-Fe and Fe-Co molecular squares: structures and electrochemistry of

Cyanide-bridged iron-iron and iron--cobalt molecular squares of [Fe(II/4)(mu-CN)4(bpy)8[(PF6)4 x 4H2O (1), [Fe(II/2)Co(II/2)(mu-CN)4(bpy)8](PF6)4 x 3CHCl3 x 2CH3CN (2), and [Fe(II/2)Co(III/2)(mu-CN)4(bpy)8](PF6)6 x 2CHCl3 x 4CH3NO2 (3) (bpy =2,2'-bipyridine) were prepared. X-ray structure analyses for 1-3 were performed and their electrochemistry was studied. In 1-3, four metal ions are bridged by cyanide groups to form tetranuclear macrocycles ("molecular squares"). Each metal ion in the square is six-coordinate: four of the coordination sites are occupied by the nitrogen atoms of two of bpy ligands and the remaining cis coordination sites are occupied by cyanide-carbon or cyanide-nitrogen atoms. In 1, Fe-C (cyanide) (1.899(4)-1.927(4)A) and Fe-N(cyanide) (1.929(4)-1.950(4)A) distances are typical of low-spin Fe2+ ions. In 2, Fe-C(cyanide) and Co(2+)-N(cyanide) bond lengths are in the range 1.919(5)-1.963(5)A and 1.850(5)-2.017(5) A, respectively: in contrast, shorter bond lengths are observed for the metal to cyanide-carbon and cyanide-nitrogen (1.878(7)- 1.893(7) A) in 3. As a result, the molecular squares in 1. 2, and 3 have sides of 4.947(1)4.986(1) A, 5.001(1)-5.053(1) A, and 4.910(1)-4.918(1) A, respectively. Magnetic susceptibility measurements revealed that the Fe2+ and Co3- ions in 1 and 3 are diamagnetic, while the high-spin Co2+ ions in 2 are weakly coupled through the low-spin Fe2 ions. Cyclic voltammograms of the squares are presented, and the electrochemically generated mixed-valent species [Fe(II/2)Fe(III/2)(mu-CN)4(bpy)8]6+ was discussed in terms of the intervalence transfer band.

Journal Article↗
PubMed2000

Chronic peripheral administration of the angiotensin II AT(1) receptor antagonist candesartan blocks brain AT(1) receptors.

Brain Angiotensin II, through stimulation of brain AT(1) receptors, regulates pituitary hormones and autonomic activity. We have administered the insurmountable AT(1) antagonist Candesartan, s.c. via osmotic minipumps for 14 days, to determine whether peripheral chronic AT(1) blockade affects AT(1) receptor binding and mRNA in the brain. Peripherally administered Candesartan (0.1, 0.5 or 1.0 mg/kg per day) inhibits AT(1) binding in adrenal gland zona glomerulosa and kidney glomeruli. In addition, Candesartan dose-dependently decreases AT(1) binding in brain areas outside (subfornical organ and area postrema) and inside (paraventricular nucleus of the hypothalamus and nucleus of the solitary tract) the blood-brain barrier. Conversely, peripheral treatment with Candesartan does not affect AT(1A) receptor mRNA, the predominant receptor subtype expressed in these areas, or Angiotensin II binding to AT(2) receptors in the locus coeruleus or inferior olive. Our results demonstrate that chronic peripheral treatment with selective, potent AT(1) antagonists not only inhibits peripheral but also brain AT(1) receptors. These central effects may play a role in the antihypertensive effects of the AT(1) antagonist Candesartan.

Angiotensin Receptor Antagonists↗
PubMed2000

GI domain-mediated association of the eukaryotic initiation factor 2alpha kinase GCN2 with its activator GCN1 is required for general amino acid control in budding yeast.

In response to the starvation of a single amino acid, the budding yeast Saccharomyces cerevisiae activates numerous genes involved in various amino acid biosynthetic pathways, all of which are under the control of transcription factor GCN4. This general amino acid control response is based on de-repressed translation of GCN4 mRNA, which is induced by the activation of the eIF2alpha kinase, GCN2. Although it is known that in vivo activation of GCN2 requires GCN1, the mode of GCN1 action remains to be elucidated at the molecular level. Here, we show that GCN2 interacts with GCN1 via the GI domain, a novel protein-binding module that occurs at the N terminus; mutations to conserved residues of this domain abolish its binding to GCN1. Furthermore, the yeast cells with GCN2 defective in interaction with GCN1 fail to display general control response. A similar phenotype is observed in cells overexpressing the GI domain of GCN2 or its target region on GCN1. Thus, GI domain-mediated association of GCN2 to GCN1 is required for general amino acid control. This finding provides the first insight into the molecular mechanism for the activation of GCN2 by GCN1.

Amino Acid Sequence↗
PubMed2000

Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16(INK4a) and Cdk2/cyclin E complex activation.

Survivin is observed uniquely in tumor cells and developmental cells, which undergo either inappropriate or programmed cell growth. In the current study, we investigated the influence of Survivin on cell cycle. Overexpression of Survivin resulted in accelerated S phase shift, resistance to G1 arrest, and activated Cdk2/Cyclin E complex leading Rb phosphorylation. In addition, nuclear translocation of Survivin followed by an interaction with Cdk4 was detected. Interestingly, Survivin nuclear translocation coincided with S phase shift, and prevention of nuclear transport suppressed Survivin nuclear translocation and S phase shift. Further, we also observed that Survivin competitively interacted with the Cdk4/p16(INK4a) complex in a cell free system and in vivo. These results suggest that Survivin initiates the cell cycle entry as a result of nuclear translocation followed by an interaction with Cdk4.

Amino Acid Sequence↗
PubMed2000

Expression of facilitative glucose transporter 1 mRNA in colon cancer was not regulated by k-ras.

The expression of facilitative glucose transporter isoforms in colon adenocarcinoma and the possible role of k-ras in inducing GLUT (glucose transporter) mRNA were studied. RT-PCR demonstrated GLUT2 and GLUT3 expression in 100% of the ten normal colon mucosa samples but detected no GLUT1 mRNA. By contrast, GLUT1 mRNA was detected in all 20 (100%) colon cancer samples examined. GLUT4 mRNA was not detected in either normal mucosa or colon cancer tissues. Semiquantitative PCR demonstrated equal amounts of GLUT2 and GLUT3 mRNA in both normal mucosa and colon cancer samples. A point mutation in codon 12 of k-ras was detected in only six of the 20 (30%) colon cancer samples. Thus, a major difference between normal colon epithelia and colon cancer was the acquisition of GLUT1 expression, which was unlikely to have been induced by a point mutation in codon 12 of k-ras.

Adenocarcinoma↗
PubMed2000

Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth.

We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting MKN45 cells with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector alone. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase. This was accompanied by overexpression of p21 protein. Tumorigenicity in the nude mice injected with antisense GLUT1 expressing cells was significantly slower than in those with wild-type MKN45 cells. These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and that expression of antisense GLUT1 mRNA via gene therapy can be used as a tool in the treatment of cancer.

Adenocarcinoma↗
PubMed2000

Time to recover from atrial hormonal, mechanical, and electrical dysfunction after successful electrical cardioversion of persistent atrial fibrillation.

Although transient atrial dysfunction has been reported after electrical cardioversion of atrial fibrillation (AF), the difference in the time to recover from the atrial hormonal, mechanical, and electrical dysfunction has not been described. Thus, we evaluated the time course of recovery from atrial hormonal, mechanical, and electrical dysfunction after cardioversion in patients with nonvalvular AF. We attempted electrical cardioversion in 87 consecutive patients with nonvalvular AF that had persisted for > or =6 months, and in 24 patients (28%) with maintained sinus rhythm for > or =6 months. To evaluate atrial hormonal, mechanical, and electrical dysfunction in these 24 patients, we measured plasma concentration of atrial natriuretic peptide, the atrial peak velocity in transmitral flow, and the ratio of peak systolic-to-diastolic pulmonary venous flow (S/D ratio) using echocardiography, and the duration and the root mean voltage for the terminal 20 ms (LP20) of the filtered P wave using P-wave signal-averaged electrocardiography. Atrial natriuretic peptide rapidly returned to baseline within 1 day after cardioversion, and maintained these levels for 6 months. Atrial peak velocity in transmitral flow and S/D ratio were significantly increased at 2 weeks, and continued to increase until 1 month, and then reached a plateau. The duration and LP20 began to recover only 6 months after cardioversion. One to 3 years after conversion, the duration and LP20 had nearly reached a plateau, but the latter value remained below normal. In patients with nonvalvular AF of prolonged duration, recovery from atrial electrical dysfunction after sinus conversion took much longer than that from either atrial hormonal or mechanical dysfunction.

Aged↗