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Biomedical subjects

T Ueda

Publications and source records attributed to T Ueda.

At least 253 records · Page 14Linked to original sources
PubMed1999

Effect of batroxobin on spontaneous echo contrast and hemorheology in left atrial appendage in atrial fibrillation assessed by transesophageal echocardiograpy.

Controversy exists regarding the effect of defibrination on spontaneous echo contrast and flow dynamics in left atrial appendage (LAA) in atrial fibrillation. We aimed to investigate the effect of batroxobin, which decreases plasma fibrinogen level, on the echo intensity of spontaneous echo contrast in LAA. In 36 patients with atrial fibrillation (duration 7 +/- 4 years), transesophageal echocardiography was performed at baseline and 24 hours after batroxobin administration (0.2 U/kg). At the orifice of the LAA, integrated backscatter of echo contrast and peak velocity of LAA emptying flow were measured. Plasma fibrinogen and whole blood viscosity were also measured. Fibrinogen and viscosity were significantly lower after batroxobin administration (96 +/-38 mg/dl and 4.35 +/- 0.56 cp) than those at baseline (320 +/- 61 mg/dl and 4.71 +/- 0.61 cp, both p <0.001). A significant positive correlation between changes in plasma fibrinogen and whole blood viscosity (r = 0.49, p = 0.002) was shown. The integrated backscatter significantly decreased from 14 +/- 3 to 12 +/- 3 decibels after batroxobin (p <0.001), and the changes in integrated backscatter and plasma fibrinogen was significantly correlated. Therefore, batroxobin administration improved blood rheology and decreased blood cell aggregation, which are effective in preventing left atrial thrombus formation.

Aged↗
PubMed1999

Chromosome rearrangement at 17q25 and xp11.2 in alveolar soft-part sarcoma: A case report and review of the literature.

BACKGROUND: Despite the characteristic histopathologic appearance of alveolar soft-part sarcoma (ASPS), its histogenesis remains unclear, and cytogenetic analysis of ASPS is limited to eight cases so far because of the extreme rarity of this disease. METHODS: The authors document a cytogenetic study of a primary case of ASPS in which a modern spectral karyotyping technique was used. RESULTS: A standard cytogenetic analysis of the primary tumor cells with G-banding revealed 46,XY, add(17)(q25) in 23 of 25 metaphases analyzed. This structural rearrangement of chromosome 17, involving band q25, was also present in 5 of 8 ASPS cases in the literature. Moreover, with the spectral karyotyping technique, the additional part of the long arm of chromosome 17 in the current case was found to originate from chromosome X, resulting in a final tumor karyotype of 46, XY, add(17)(q25).ish der(17)t(X;17) (p11.2;q25)(wcpX+). CONCLUSIONS: This case report documents a clonal chromosome abnormality of der(17)t(X;17)(p11.2;q25) in ASPS. The results of the current study indicate that further molecular analyses focused on 17q25 and Xp11.2 are of interest and could help to elucidate the pathogenesis of ASPS.

Child↗
PubMed1999

HLA antigens in patients with variant angina in Japan.

There have been few reports on examining the susceptibility of variant angina. Accordingly, the major histocompatibility complexes (HLA-A, -B, -C, -DR) of unrelated Japanese patients with variant angina were examined. There were no significant differences in the frequency of HLA-A,-B, -C, and -DR antigens between patients and controls (n = 100). Although endothelial dysfunction with pathological abnormalities is suggested to be one of the etiological factors in vasospasm, immunogenetic abnormalities linked to HLA system might not play a role in the pathogenesis of variant angina.

Adult↗
PubMed1999

An extra tRNAGly(U*CU) found in ascidian mitochondria responsible for decoding non-universal codons AGA/AGG as glycine.

Amino acid assignments of metazoan mitochondrial codons AGA/AGG are known to vary among animal species; arginine in Cnidaria, serine in invertebrates and stop in vertebrates. We recently found that in the mitochondria of the ascidian Halocynthia roretzi these codons are exceptionally used for glycine, and postulated that they are probably decoded by a tRNA(UCU). In order to verify this notion unambig-uously, we determined the complete RNA sequence of the mitochondrial tRNA(UCU) presumed to decode codons AGA/AGG in the ascidian mitochondria, and found it to have an unidentified U derivative at the anticodon first position. We then identified the amino acids attached to the tRNA(U*CU), as well as to the conventional tRNAGly(UCC) with an unmodified U34, in vivo. The results clearly demonstrated that glycine was attached to both tRNAs. Since no other tRNA capable of decoding codons AGA/AGG has been found in the mitochondrial genome, it is most probable that this tRNA(U*CU) does actually translate codons AGA/AGG as glycine in vivo. Sequencing of tRNASer(GCU), which is thought to recognize only codons AGU/AGC, revealed that it has an unmodified guanosine at position 34, as is the case with vertebrate mitochondrial tRNASer(GCU) for codons AGA/AGG. It was thus concluded that in the ascidian, codons AGU/AGC are read as serine by tRNASer(GCU), whereas AGA/AGG are read as glycine by an extra tRNAGly(U*CU). The possible origin of this unorthodox genetic code is discussed.

Animals↗
PubMed1999

Evaluation of cell-killing effects of 1-beta-D-arabinofuranosylcytosine and daunorubicin by a new computer-controlled in vitro pharmacokinetic simulation system.

An in vitro pharmacokinetic simulation system that can simulate plasma pharmacokinetics was established to evaluate the cytotoxicity of two representative antileukemic agents, 1-beta-D-arabinofuranosylcytosine (ara-C) and daunorubicin. With this system, the survival rate of the cell line K562 treated with ara-C, relative to that of untreated control cells, was 7.1%, as determined by a clonogenic culture technique using a clinically intermediate dose of ara-C (1.0 g/m2; 2-h infusion). When the area under the serum concentration-time curve (AUC) was kept constant at infusion times of 2, 4, 8, and 16 h with a regular dose of ara-C (100-mg/m2 infusion), the relative cell survival rates were 75, 72, 34, and 14%, respectively. In contrast, with the use of a conventional culture system and a constant concentration-time product (C x T), no time-dependent inhibition effect by ara-C was observed, probably due to the ara-C inactivation in the cell-containing culture medium. For example, 93% of the ara-C in the cell-suspended medium in the conventional culture system was converted to its inactive form, 1-beta-D-arabinofuranosyluracil, within 16 h after addition of ara-C to the medium. For the simulations of the administration of 50 mg/m2 daunorubicin for 0.5-, 2-, 4-, and 8-h infusions, the relative survival rates [maximal concentrations (Cmaxs)] were 37.4% (0.24 microM), 49.7% (0.089 microM), 72.1% (0.055 microM), and 82.2% (0.032 microM), respectively. With the conventional culture system, the relative survival rates (Cmaxs) following daunorubicin treatment were 7.6% (0.48 microM), 18.6% (0.12 microM), 63.7% (0.06 microM), and 92.0% (0.03 microM) when the drug exposure times were 0.5, 2, 4, and 8 h, respectively, with a constant C x T. When the drug concentration for 90% cell killing by the conventional culture system was plotted against the exposure time on a logarithmic scale, the regression line for daunorubicin had a slope of -0.40, whereas the slope of cis-diamminedichloroplatinum (or cisplatin), a typical AUC-dependent drug, was -0.98. These results suggested that daunorubicin was Cmax dependent rather than AUC dependent. In the simulation system, this Cmax dependency was apparently reduced, probably because of the smaller difference of Cmaxs in the simulation system compared with the conventional system with the constant AUC. Thus, this simulation system can predict the effects of ara-C, daunorubicin, and other antineoplastic agents much more exactly than the conventional culture system in clinical use.

Antineoplastic Agents↗
PubMed1999

High-level expression of uniformly 15N-labeled hen lysozyme in Pichia pastoris and identification of the site in hen lysozyme where phosphate ion binds using NMR measurements.

The non-enzymatic deamidation of Asn to Asp is known to occur in proteins and peptides and is accelerated by phosphate buffer [Tyler-Cross, R. and Schirch, V. (1991) J. Biol. Chem. 25, 22549-22556]. We attempted to identify the site in lysozyme where a phosphate ion binds by means of 1H-15N HSQC measurements of 15N-labeled lysozyme, which was successfully obtained using Pichia pastoris. As a result, we found that the phosphate ion was preferentially bound to Asn-103 in hen lysozyme. The method presented here may be useful for identifying the binding site of a protein with low molecular weight substances.

Animals↗
PubMed1999

The presence of pseudouridine in the anticodon alters the genetic code: a possible mechanism for assignment of the AAA lysine codon as asparagine in echinoderm mitochondria.

It has been inferred from DNA sequence analyses that in echinoderm mitochondria not only the usual asparagine codons AAU and AAC, but also the usual lysine codon AAA, are translated as asparagine by a single mitochondrial (mt) tRNAAsn with the anticodon GUU. Nucleotide sequencing of starfish mt tRNAAsn revealed that the anticodon is GPsiU, U35 at the anticodon second position being modified to pseudouridine (Psi). In contrast, mt tRNALys, corresponding to another lysine codon, AAG, has the anticodon CUU. mt tRNAs possessing anti-codons closely related to that of tRNAAsn, but responsible for decoding only two codons each-tRNAHis, tRNAAsp and tRNATyr-were found to possess unmodified U35 in all cases, suggesting the importance of Psi35 for decoding the three codons. Therefore, the decoding capabilities of two synthetic Escherichia coli tRNAAla variants with the anticodon GPsiU or GUU were examined using an E.coli in vitro translation system. Both tRNAs could translate not only AAC and AAU with similar efficiency, but also AAA with an efficiency that was approximately 2-fold higher in the case of tRNAAlaGPsiU than tRNAAlaGUU. These findings imply that Psi35 of echinoderm mt tRNAAsn actually serves to decode the unusual asparagine codon AAA, resulting in the alteration of the genetic code in echinoderm mitochondria.

Amino Acid Substitution↗
PubMed1999

A cytotoxic ribonuclease targeting specific transfer RNA anticodons.

The carboxyl-terminal domain of colicin E5 was shown to inhibit protein synthesis of Escherichia coli. Its target, as revealed through in vivo and in vitro experiments, was not ribosomes as in the case of E3, but the transfer RNAs (tRNAs) for Tyr, His, Asn, and Asp, which contain a modified base, queuine, at the wobble position of each anticodon. The E5 carboxyl-terminal domain hydrolyzed these tRNAs just on the 3' side of this nucleotide. Tight correlation was observed between the toxicity of E5 and the cleavage of intracellular tRNAs of this group, implying that these tRNAs are the primary targets of colicin E5.

Anticodon↗
PubMed1999

Analysis of the relationship between enzyme activity and its internal motion using nuclear magnetic resonance: 15N relaxation studies of wild-type and mutant lysozyme.

A mutant lysozyme where R14 and H15 are deleted together has higher activity and a similar binding ability to an inhibitor, trimer of N-acetylglucosamine ((NAG)3), compared with wild-type lysozyme. Since this has been attributed to intrinsic protein dynamic properties, we investigated the relationship between the activity and the internal motions of proteins. Backbone dynamics of the free and the complex forms with the (NAG)3 have been studied by measurement of the 15N T1 and T2 relaxation rates and NOE determinations at 600 MHz. Analysis of the data using the model-free formalism showed that the generalized order parameters (S2) were almost the same in wild-type and mutant lysozyme in unbound state, indicating that the mutation had little effect on the global internal motions. On the other hand, in the presence of (NAG)3, although some signals located around the active site were broadened or decreased in intensity because of strong perturbation by (NAG)3, there were several residues that showed increased or decreased backbone S2 in the complexed lysozymes. A comparison of the internal motions of the wild-type and mutant complexes showed a number of distinct dynamic differences between them. In particular, many residues located at or near active-site regions (turn 1, strand 2, turn 2 and long loop), displayed greater backbone dynamics reflecting the order parameter in mutant complex relative to mutant free. Furthermore, the Rex values at the loop C-D region, which was considered to be important for enzymatic activity, significantly increased. From these results, it was suggested that variations in the dynamics of these regions may play an important role in the enzyme activity.

Acetylglucosamine↗
PubMed1999

Quantitative analysis of myocardial response to dobutamine by measurement of left ventricular wall motion using omnidirectional M-mode echocardiography.

Although dobutamine stress echocardiography is important for assessing cardiac ischemia and viability, analysis of wall motion is qualitatively performed. We quantitatively evaluated left ventricular wall motion using a newly developed omnidirectional M-mode echocardiography that can depict the M-mode at the site of region of interest on the 2-dimensional image in real time, and established its usefulness for analyzing the myocardial response to dobutamine infusion. Dobutamine stress echocardiography with omnidirectional M-mode was performed in 57 patients with coronary lesions. In 38 of these patients, exercise stress single-photon emission computed tomographic thallium scintigraphy (Tl-201 SPECT) was performed. Endocardial excursion of 103 regions was measured from omnidirectional M-mode at baseline, low-dose (6 microg/kg/min), and at peak dose (30 microg/kg/min) dobutamine. A decrease and increase in wall excursion was scored (from -3 to 3) for a changes of every 2 mm, and a quantitative wall motion score (QWMS) was calculated as a summation of the scores from baseline to low dose and from low to peak doses. Quantitative coronary stenosis score (QCSS) was calculated as a summation of stenotic and collateral scores. The stenosis scores were graded as: 1 = 0% to 50%, 2 = 50% to 75%, 3 = 75% to 90%, 4 = 90% to 95%, 5 = 95% to 100%; collateral scores were graded as: -1 = poor collateral, -2 = good collateral. Based on the QWMS at each dose of dobutamine, the serial changes in wall motion were divided into 4 groups: augmented, biphasic, no change, and worsening. The QCSS was clearly different among these groups. QWMS was significantly correlated with QCSS (r = 0.657, p <0.001). The incidence of redistribution in Tl-201 SPECT was high in the region with low score of QWMS. In conclusion, omnidirectional M-mode is useful for quantitatively determining the grade of cardiac ischemia by assessing the serial change of ventricular wall motion during dobutamine infusion.

Adrenergic beta-Agonists↗
PubMed1999

In vitro binding study of adaptor protein complex (AP-1) to lysosomal targeting motif (LI-motif).

Lysosomal membrane glycoproteins carry targeting information in cytoplasmic regions. Two distinct targeting motifs in these regions, GY (glycine-tyrosine) and LI (leucine-isoleucine), have been identified and characterized. Accumulating evidence suggests that the adaptor complexes (AP-1, AP-2, and AP-3) recognize this information in cytoplasmic tails of transmembrane proteins. Here we report two different in vitro analyses (affinity beads and surface plasmon resonance) which revealed specific interaction between the cytoplasmic tail of LGP85 and AP-1 but not so with AP-2. We also noted requirement of the LI motif of the LGP85 tail in binding to the AP-1 complex. Our data and others which indicated the binding of AP-3 to the LIMP II (synonym of LGP85) tail suggest that the cytoplasmic tail of LGP85 interacts with AP-1 at the trans-Golgi network (TGN) and AP-3 at late endosomes, respectively. We propose that this sequential interaction between the lysosomal targeting signal and distinct APs along its transport pathway is responsible for the critical sorting of lysosomal membrane proteins and/or the potential proofreading system of mistargeted molecules.

Adaptor Protein Complex alpha Subunits↗
PubMed1999

CDK4 gene amplification in osteosarcoma: reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons.

The INK4A gene, localized to human chromosome 9p21, encodes p16INK4A, a tumor suppressor that functions at least in part through the inhibition of CDK4, a cyclin-dependent kinase encoded by a gene at 12q13. To examine INK4A gene alterations in uncultured samples of osteosarcoma and the relationship between INK4A and CDK4 alterations, we analyzed the INK4A and CDK4 genes in 87 specimens from 79 patients. INK4A deletion and CDK4 gene amplification were determined by quantitative Southern blot analysis. INK4A exon 2 was screened for mutation by polymerase chain reaction and single-strand conformational polymorphism analysis. Methylation at the CpG island in INK4A, associated with loss of p16INK4A expression, was assessed by Southern blot analysis using methylation-sensitive restriction enzymes. INK4A deletion (4/55) or rearrangement (1/55) was found in 5 of 55 cases. No INK4A exon 2 point mutations and methylation were detected. CDK4 gene amplification was found in 6 of 67 samples, but not in tumors with INK4A alteration. Amplification analysis of other genes at 12q13 (GLI, CHOP, HMGI-C and MDM2) in these 6 cases supports the view that CDK4 and MDM2 are independent targets for amplification, with variable amplification of the intervening region containing HMGI-C. Of 46 patients studied for both INK4A alterations and CDK4 amplification, the tumors in 22% contained one or the other. The prevalence of these alterations, in conjunction with the reported inactivation of RB in up to 80% of cases, suggests that genetic lesions deregulating the G1 to S cell cycle checkpoint may be an almost constant feature in the pathogenesis of osteosarcoma.

Adolescent↗
PubMed1999

Surface characterization and on-line activity measurements of microorganisms by capillary zone electrophoresis.

Capillary zone electrophoresis (CZE) was applied to the electrophoretic characterization for microorganisms. The electrophoretic peaks detected using light scattering phenomena were characteristic of the microorganisms used. The electrophoretic mobility (mu) evaluated by CZE was in good agreement with that obtained by classical electrophoresis of microorganisms. The migration time was reproducible and depended on the ionic strength (I). Analysis of the mu vs. I relationship provided information regarding the charge density and the hardness of the microbial cell surface. The redox enzymatic activity of microorganisms was also evaluated by CZE using a running buffer containing a corresponding substrate and an appropriate exogenous electron acceptor. A decrease in the concentration of the electron acceptor due to microbial activity can be simultaneously monitored during the electrophoretic process without significant modification of the CZE instrument. Effects of some chemical treatments of microbial cells were also studied using this technique.

Bacteria↗
PubMed1999

Clinical application of perfusion and diffusion MR imaging in acute ischemic stroke.

With the advances in new neuroimaging modalities, the role of imaging of acute ischemic stroke has broadened and progressed from making diagnoses to providing valuable information for patient management. The goal of thrombolytic therapy for acute ischemic stroke should be to salvage the ischemic tissue reversibility that can respond to recanalization and avoid reperfusion of the dead (nonviable) tissue. It is essential to have rapid diagnostic modalities that can distinguish viable ischemic tissue from irreversibly damaged tissue, because there is a risk of reperfusion injury such as hemorrhagic complications with early intervention. Although diffusion magnetic resonance (MR) imaging has been reported to have a high sensitivity and specificity for acute ischemia in acute stroke patients without early reperfusion therapy, the capability to differentiate reversible from irreversible ischemia by diffusion MR imaging has not been established. Perfusion MR imaging techniques provide direct information on parenchymal perfusion status (adequacy of the collateral circulation) and may have the potential for providing important information about tissue viability and/or reversibility for selecting appropriate patients for thrombolytic therapy.

Animals↗
PubMed1999

Evaluation of coronary artery bypass grafts using helical scan computed tomography.

The patency of coronary artery bypass grafts was evaluated by helical computed tomographic (CT) scan. One hundred forty patients who received an enhanced chest CT scan and a coronary angiography after bypass surgery were studied before discharge at the Fukui Cardiovascular Center. Among them was a total of 398 grafts and 436 anastomoses. For the evaluation of 248 vein grafts, the CT scan showed a 99.5% correct positive ratio and an overall accuracy of 96.4%. In 122 internal thoracic arteries tested, an overall accuracy of 64.7% was obtained. In gastroepiploic artery tests the overall accuracy was 33.3% and in radial artery tests it was 45.5%. Thirty-seven venous sequential anastomoses in 34 grafts and 1 internal thoracic artery sequential anastomosis were also evaluated. In the venous sequential anastomosis, the CT scan showed a 73.0% of accuracy overall. This study showed that the helical CT scan was useful to evaluate graft patency following bypass surgery.

Adolescent↗