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Biomedical subjects

Y Terada

Publications and source records attributed to Y Terada.

At least 91 records · Page 5Linked to original sources

Transmembrane helix 5 is critical for the high water permeability of aquaporin.

Aquaporin-2 (AQP2), a vasopressin-regulated water channel, plays a major role in urinary concentration. AQP2 and the major intrinsic protein (MIP) of lens fiber are highly homologous (58% amino acid identity) and share a topology of six transmembrane helices connected by five loops (loops A-E). Despite the similarities of these proteins, however, the water channel activity of AQP2 is much higher than that of MIP. To determine the site responsible for this gain of activity in AQP2, several parts of MIP were replaced with the corresponding parts of AQP2. When expressed in Xenopus oocytes, the osmotic water permeability (P(f)) of MIP and AQP2 was 48 and 245 x 10(-)(4) cm/s, respectively. Substitutions in loops B-D failed to increase P(f), whereas substitution of loop E significantly increased P(f) 1.5-fold. A similar increase in P(f) was observed with the substitution of the front half of loop E. P(f) measurements taken in a yeast vesicle expression system also confirmed that loop E had a complementary effect, whereas loops B-D did not. However, P(f) values of the loop E chimeras were only approximately 30% of that of AQP2. Simultaneous exchanges of loop E and a distal half of transmembrane helix 5 just proximal to loop E increased P(f) to the level of that of AQP2. Replacement of helix 5 alone stimulated P(f) 2.7-fold. Conversely, P(f) was decreased by 73% when helix 5 of AQP2 was replaced with that of MIP. Moreover, P(f) was stimulated 2.6- and 3.3-fold after helix 5 of AQP1 and AQP4 was spliced into MIP, respectively. Our findings suggested that the distal half of helix 5 is necessary for maximum water channel activity in AQP. We speculate that this portion contributes to the formation of the aqueous pore and the determination of the flux rate.

Animals↗

A specific inhibitor of factor Xa, DX-9065a, exerts effective protection against experimental tumor induced disseminated intravascular coagulation in rats.

(+)-2S-2-[4-[[(35S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-[7- amidino-2-napthyl]propanoic acid hydrochloride pentahydrate (DX-9065a) is an antithrombin III-independent, selective inhibitor of activated blood coagulation factor X (FXa). We investigated the protective effects of DX-9065a against tumor-bearing experimental disseminated intravascular coagulation (DIC) induced by the inoculation of AH-109A cells into rats. DX-9065a was subcutaneously administered at doses of 0.03 and 0.1 mg/kg/hour through an osmotic pump transplanted immediately after the inoculation of the tumor cells during the observation period. Platelet count decreased 12 days after the inoculation, concomitant with an increase in the thrombin-antithrombin III complex and fibrin and fibrinogen degradation products. Doses of 0.03 and 0.1 mg/kg/hour of DX-9065a significantly inhibited the decrease in plasma fibrinogen concentration and platelet count 13 days after the inoculation, respectively. These findings suggest that direct, selective inhibition of FXa by DX-9065a improves the hypercoagulable state induced by the progress of solid tumor.

Animals↗

Complete androgen insensitivity in a 47,XXY patient with uniparental disomy for the X chromosome.

We describe a unique patient with complete androgen insensitivity syndrome and a 47,XXY karyotype. Androgen receptor assay using cultured pubic skin fibroblasts showed no androgen-binding capacity. Sequence analysis of the androgen receptor gene demonstrated two nonsense mutations, one in exon D and one in exon E. Microsatellite marker analysis showed that the patient is homozygous for all five Xq loci examined. The results suggest that the long-arms of the two X chromosomes are identical, i.e., uniparental isodisomy at least for Xq, and carry the same mutations in the androgen receptor gene. This explains how complete androgen insensitivity syndrome occurred in this 47,XXY individual.

Adult↗

Isolation and characterization of cyclic alpha-(1-->4)-glucans having degrees of polymerization 9-31 and their quantitative analysis by high-performance anion-exchange chromatography with pulsed amperometric detection.

Cyclic alpha-(1-->4)-glucans with degrees of polymerization (DPs) 9-31 were isolated from a mixture of cyclization products formed in the early stage of the action of cyclodextrin glucanotransferase (CGTase) on synthetic amylose, and characterized by matrix-assisted laser desorption ionization time-of-flight MS, 13C-NMR and HPLC of their partial acid hydrolyzates. High-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection for an accurate estimation of cyclic alpha-(1-->4)-glucans was developed using those isolate glucans as quantification standards, and by HPAEC, the time course of the cyclization reaction of CGTase from an alkalophilic Bacillus sp. A2-5a on synthetic amylose was determined.

Chromatography, High Pressure Liquid↗

Molecular phylogenetic studies on Theileria parasites based on small subunit ribosomal RNA gene sequences.

Classification of Theileria parasites of south-east Asian countries is still ambiguous due to the lack of basic studies, especially their molecular genetic information. In this study, we included 6 known species and 14 unclassified Theileria parasite isolates: Theileria annulata, Theileria parva, Theileria taurotragi, Theileria sergenti, Theileria buffeli, Theileria types Sable, Theileria types A, B, B1, B2, C, D, E, F, G, G1, Theileria type Medan (Indonesia), Theileria type Ipoh (Malaysia) and Theileria type Thong Song (Thailand). Small subunit ribosomal RNA (srRNA) nucleotide sequence data were collected by PCR, cloning and dideoxy sequencing. The srRNA nucleotide sequences were aligned and analyzed by distance methods, maximum parsimony algorithms and maximum likelihood methods to construct phylogenetic trees. Bootstrap analysis was used to test the strength of the different phylogenetic reconstructions. The data indicated that all of the tree-building methods gave very similar results. This study identified two groups of Theileria, the pathogenic and benign groups, which are strongly supported by bootstrap analysis. The analysis also indicated that three subgroups (A, B and C) were generated within the benign Theileria group whereas the classification of Theileria type D and Thong Song is questionable. However, more basic information such as life cycle differences, vectors, modes of transmission, virulent and genetic/sexual compatability is essential for clearer taxonomic definition of the benign Theileria parasites.

Animals↗

Sensitivity of foetal magnetocardiograms versus gestation week.

Foetal magnetocardiograms (FMCGs) were measured using a nine-channel SQUID system equipped with first-order gradiometers (60 mm baseline, 20 mm diameter). The system was installed in a magnetically shielded room in a hospital. The white noise level was less than 10 fT/square root of Hz, and FMCGs above 1 pT were detected. These results and the depth to the foetal heart were used to estimate the current dipole. The relationship between the current dipole (Q) and the gestation week (G) was calculated and the average performance was determined as Q = 18G - 295. By using the estimated foetal current dipole, the measurement limit (average value) between depth and gestation weeks was determined. When the depth from the pickup coil to the foetal heart is 50, 60, 70 and 80 mm, the first detectable gestation weeks of FMCGs above 1 pT measured by a first-order gradiometer with 60 mm baseline were determined at 21, 23, 26, and 30 weeks respectively, and the detectable gestation weeks in the case of a 30 mm baseline were determined at 22, 26, 30 and 36 weeks respectively.

Electrocardiography↗

Atrial fibrillation after coronary artery bypass grafting. An increase in high-frequency atrial activity in patients with right coronary artery revascularization.

The increase in atrial high-frequency activity has been reported as a marker of the risk of paroxysmal atrial fibrillation. The presence of proximal right coronary artery disease is a predictor of atrial fibrillation after bypass surgery, however, the potential mechanism remains controversial. In this study, high-frequency atrial activity to clarify the electrophysiologic background for the predisposition to have proximal right coronary artery disease leading to atrial fibrillation after coronary revascularization was investigated. Before and soon after coronary revascularization, frequency analyses were performed on the 100 ms segment at the end of signal-averaged P waves in 22 patients with right coronary artery disease as opposed to the 23 patients without disease. Under the spectrum curve, area ratio (AR50) and magnitude ratios (MR) were calculated as follows; AR50 = (area 20-50 Hz/0-20 Hz) x 100, and MR = (magnitude at 20, 30, 40 and 50 Hz, respectively/maximal magnitude) x 100. In patients with proximal right coronary artery disease, high-frequency atrial components increased significantly in the 20 to 50 Hz range after coronary revascularization, and the incidence of postoperative atrial fibrillation was higher than in those without disease. In patients without right coronary artery disease, the frequency distribution of P waves was unchanged. Postoperatively, the two groups showed the same atrial frequency distribution. This data suggests that the increase in high-frequency atrial activity after right coronary artery revascularization might be associated with the pathogenesis of postoperative atrial fibrillation.

Adult↗

Mitral regurgitation after pericardiectomy for constrictive pericarditis.

We report a case of constrictive pericarditis in which trace mitral valve regurgitation was detected preoperatively and temporarily worsened after a pericardiectomy was performed. The early postoperative data suggested that the increased mobility of the lateral wall, in conjunction with an increase in the left ventricular volume, might be one of the causes of the perioperative mitral valve dysfunction. The mitral valve function returned to the preoperative baseline thirteen months after the pericardiectomy.

Adult↗

Aortic dissection in an elderly patient with atrial septal defect.

We report a case of acute aortic dissection that occurred in the late course of surgically untreated atrial septal defect. A 60-year-old man with acute aortic dissection and atrial septal defect was operated on successfully, and we discuss the causal relationship between these two unusual conditions.

Aortic Dissection↗

Venous function and delayed leg swelling following saphenectomy in coronary artery bypass grafting.

Some patients are troubled by leg swelling following saphenectomy long after CABG. Postsaphenectomy venous function in the leg has not, however, been well clarified. To determine whether venous dysfunction caused postsaphenectomy swelling, we measured the maximum venous outflow and time constant (tau) in the leg by venous occlusion strain-gauge plethysmography in 45 patients; a venous Doppler test was also conducted in 33 of the 45 at a mean 57.6 +/- 21.3 months after CABG. The saphenous vein was harvested unilaterally from the lower leg or from both the thigh and lower leg in all patients. Edema was seen in 4 patients (8.9%) and 8 reported leg swelling after saphenous vein harvest (17.8%). Legs were classified into three groups: group 1 consisted of 12 with edema or reports of swelling ipsilateral to the saphenous vein harvest site, group 2 consisted of 33 ipsilateral to the saphenous vein harvest without edema, and group 3 consisted of the 45 nonoperated-on, contralateral legs of the same patients as controls. No significant differences were seen in maximum venous outflow, tau, or the incidence of deep vein reflux among groups. No significant relationship was found between venous function and leg swelling occurring delayed after saphenectomy.

Aged↗

Tolerability, pharmacokinetics, and pharmacodynamics of DX-9065a, a new synthetic potent anticoagulant and specific factor Xa inhibitor, in healthy male volunteers.

OBJECTIVE: The aim of this study was to assess the tolerability, pharmacokinetic and pharmacodynamic properties of DX-9065a, a novel low-molecule specific factor Xa inhibitor in healthy male volunteers. METHODS: DX-9065a was intravenously administered to healthy male Japanese volunteers at doses of 0.625 to 30 mg. The drug concentrations in plasma and urine were measured and pharmacokinetic parameters were calculated. Coagulation time and bleeding time were also measured. RESULTS: No serious adverse event was observed during or after administration of DX-9065a. The pharmacokinetics of DX-9065a in human subjects after intravenous dosing was linear. The simulated plasma concentrations of DX-9065 were well in accordance with the observed values. Though prolongation of coagulation times was dependent on plasma concentration of DX-9065, bleeding time did not increase even at the highest plasma concentration of 1640 ng/mL. CONCLUSIONS: DX-9065a had a good correlation between linear pharmacokinetics and pharmacodynamics after intravenous administration in humans.

Adult↗

Phylogenetic relationships of the benign Theileria species in cattle and Asian buffalo based on the major piroplasm surface protein (p33/34) gene sequences.

In order to examine the taxonomic relationship of Theileria sp. of Asian buffalo to the benign Theileria spp. of cattle, we sequenced and compared the major piroplasm protein (p33/34) genes of these parasites. The two consensus sequences determined for the buffalo parasite were of the same length (852 bp) and showed >80% identity with the sequences of the homologous genes (849 bp) in the cattle parasites. Alignment of the inferred aa sequences with those of Theileria sergenti and Theileria buffeli predicted that there is an insertion of a single residue at the N-terminus in the inferred polypeptide of the buffalo parasite. Phylogenetic analyses based on the aa sequences suggested that Theileria sp. of the Asian buffalo should be classified within the benign Theileria parasite group as a separate species from the cattle parasites. Based on this, we propose a rearrangement of the currently used classification for the benign Theileria species in cattle and Asian buffalo.

Amino Acid Sequence↗

Noninvasive visualization of multiple simultaneously activated regions on torso magnetocardiographic maps during ventricular depolarization.

The time course and instantaneous distribution of the electrophysiologic processes of the human heart were analyzed by using a multichannel superconducting quantum interference device (SQUID) system, enabling the tangential components of the cardiac magnetic fields to be measured. By visualizing the changing magnetic field pattern in a two-dimensional presentation of the anterior and posterior torso during depolarization, the existence of more than one simultaneously activated region and the effective intracardiac current distribution were estimated without using a mathematical algorithm. The mid-to-late QRS complex when the myocardium has widespread depolarizing regions was analyzed using this technique. Even in an early stage of the QRS, two discrete active regions were observed in the magnetic field maps, in all nine subjects (adults with normal hearts). Furthermore, differences in the current distribution between the front and back active region were observed.

Adult↗

Low-dose protamine based on heparin-protamine titration method reduces platelet dysfunction after cardiopulmonary bypass.

OBJECTIVE: The heparin-protamine titration method that uses the Hepcon hemostasis management system (Medtronic HemoTec Inc, Englewood, Colo) reduced blood loss in cardiac surgery in previous reports, but the mechanism is not fully understood. This study tests the hypothesis that reduced protamine administration preserves platelet function in human cardiac surgery. METHODS: Platelet count, alpha-granule secretion, and aggregation to thrombin before and after cardiopulmonary bypass in human beings were evaluated. In the control group (n = 14), a fixed dose of protamine (3 mg/kg) was administered. In the titration group (n = 20), protamine doses were based on the heparin concentration measured by the Hepcon system. RESULTS: Heparin concentrations before protamine administration were higher in the titration group (P =.0012), but protamine doses of patients in the titration group were markedly lower than those of the control group (P <.0001). During protamine infusion at a rate of 0.3 mg. kg(-1). min(-1), the percentage of granule membrane protein-140-positive platelets significantly increased in the control group compared with the titration group (18.8% +/- 8.6% vs 13.0% +/- 5.3%, P =.0188). After protamine administration, aggregation of washed platelets to thrombin recovered almost to the preoperative level in the titration group; however, it remained lower in the control group (20% +/- 20% vs 55% +/- 18%, P =.0009). CONCLUSION: Low-dose administration of protamine, based on a heparin-protamine titration method, restores not only the blood coagulation but also the platelet responses to thrombin and attenuates platelet alpha-granule secretion during heparin neutralization. Overdose of protamine activates platelets and may predispose patients to excessive bleeding after cardiac surgery.

Blood Loss, Surgical↗

Visualization of regional myocardial depolarization by tangential component mapping on magnetocardiogram in children.

BACKGROUND: Tangential components to the body surface on magnetocardiography theoretically reflect regional myocardial current sources just below the gradiometer. The usefulness of tangential component mapping on magnetocardiography in determination of regional myocardial abnormalities has not been investigated in children. METHODS: Twenty-six children with ventricular hypertrophy, including a child with a left ventricular diverticulum (aged 7 to 15), and age matched 22 healthy children (aged 7 to 15) were studied. Tangential components on magnetocardiography were measured using a newly-developed super-conducting quantum interference device system housed in a magnetically shielded room. Isomagnetic maps and current vector maps were constructed from the data obtained. RESULTS: The peak magnetic fields and current dipoles were demonstrated to be located at the interventricular septum initially, and then were shifted to the anterior and inferior walls of the left ventricle and to the right ventricular outflow tract, successively. In patients with right ventricular hypertrophy whose systolic right ventricular pressure was over 60 mmHg, the peak magnetic fields were located in the right half with rightward directed current vectors throughout ventricular depolarization. In patients with left ventricular hypertrophy, the maximal magnetic fields during depolarization were shifted to the hypertrophic site, showing significantly stronger forces than those in healthy children (35.5+/-11.7 pT vs 26.5+/-11.9 pT, p < 0.01). In a patient with left ventricular diverticulum, two discrete depolarizing current dipoles were visualized. The mean time required in measuring MCGs among all subjects was 10 minutes. CONCLUSION: The time course as well as the location of the regional electrical activities of the myocardium in children can be visualized, in a short time, as a two-dimensional projection to the frontal plane by tangential component mapping on magnetocardiography.

Adolescent↗

Induction of the p16INK4a senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis.

Synovial tissue affected by rheumatoid arthritis is characterized by proliferation, which leads to irreversible cartilage and bone destruction. Current and experimental treatments have been aimed mainly at correcting the underlying immune abnormalities, but these treatments often prove ineffective in preventing the invasive destruction. We studied the expression of cyclin-dependent kinase inhibitors in rheumatoid synovial cells as a means of suppressing synovial cell proliferation. Synovial cells derived from hypertrophic synovial tissue readily expressed p16INK4a when they were growth-inhibited. This was not seen in other fibroblasts, including those derived from normal and osteoarthritis-affected synovial tissues. In vivo adenoviral gene therapy with the p16INK4a gene efficiently inhibited the pathology in an animal model of rheumatoid arthritis. Thus, the induction of p16INK4a may provide a new approach to the effective treatment of rheumatoid arthritis.

Adenoviridae↗

The effect of an oral prosthesis on the quality of life for head and neck cancer patients.

The quality of life (QOL) in patients with cancer in the head and neck regions has become an increasingly important factor in medical treatment. We examined the effect of a prosthesis on the QOL based on the patients' own subjective evaluations. Sixty-eight head and neck cancer patients who had been treated in the Department of Prosthetic Dentistry of the Faculty of Dentistry, Kyushu University, were compared with 35 denture wearers as a control. General denture satisfaction in the control group showed a statistical correlation with eating (P<0.01, t-test; rho = 0.72, Spearman rank correlation), aesthetic satisfaction (P<0.01, rho = 0.57) and pain (P<0.01, rho = 0.51). On the other hand, for cancer patients, general denture satisfaction showed a statistical correlation with not only eating (P<0.01, rho = 0.34), aesthetic satisfaction (P<0.01, rho = 0.33) and pain (P<0.01, rho = 0.41) but also health (P<0.01, rho = 0.33) and mental well-being (P<0.01, rho = 0.41). A statistical correlation between the Denture score and the QOL score was thus observed in cancer patients (P<0.0001, rho = 0.56), while the correlation for the control group was not statistically significant. This study showed that oral prostheses for head and neck cancer patients are important factors not only for eating but also for the overall patient QOL.

Adaptation, Psychological↗