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Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 415 records · Page 23Linked to original sources

Synthesis of N2, N2, 7-trimethylguanosine cap derivatives.

Several derivatives of N2,N2-7-trimethylguanosine (m3(2,2,7G)-cap, which was found at the 5' ends of small nuclear RNAs, were synthesized by use of S-phenyl N2,N2,7-trimethylguanosine 5'-phosphorothioate (PhSpm3(2,2,7)G) as a key intermediate. This compound was activated by iodine in the presence of phosphoric acid and diphosphoric acid to give N2,N2,7-trimethylguanosine-5'-diphosphate (ppm3(2,2,7)G) and 5'-triphosphate (ppm3(2,2,7)G), respectively. Similar reactions of PhSpm3(2,2,7)G with ADP and GDP gave capped dinucleoside triphosphates, m3(2,2,7)G5'pppA and m3(2,2,7)G5'pppG, respectively.

Adenosine Diphosphate↗

Reinvestigation of deoxyribonucleoside phosphorothioites: synthesis and properties of deoxyribonucleoside-3' dimethyl phosphites.

Further investigation of the synthesis of deoxyribonucleoside-3' (t-butyl) O-(2-cyanoethyl) phosphorothioites as monomer building units for the phosphorothioite approach has led us to conclude that internucleotidic bond formation proceeded via bis(deoxyribonucleoside-3') (2-cyanoethyl) phosphite intermediates, which proved to be activated by iodine, rather than the mechanism previously reported. In connection with this study, deoxyribonucleoside-3' dimethyl phosphites were synthesized and detailed properties of them are also described.

Chemical Phenomena↗

Chemical synthesis of the 24 RNA fragments corresponding to hop stunt viroid.

A general and practical synthetic method of oligoribonucleotides (10-20 mers) by using the cyanoethyl phosphoramidite approach was described. In this experiment 9-phenylxanthen-9-yl (Pix) and 9-(4-methoxy)phenylxanthen-9-yl (Mox) groups were employed for the 5'-hydroxyls and tetrahydropyranyl (Thp) group was used for the 2'-hydroxyl protecting groups. In addition, suitable acyl groups were introduced for the protection of the lactam functions of guanine and uracil moieties.

Base Sequence↗

Pre-mRNA with a trimethylguanosine cap structure can be spliced efficiently in vitro.

A chemically synthesized 2,2,7-trimethylguanosine cap (TMG-cap) analogue was added to an in vitro pre-mRNA splicing system. A slight inhibition of the splicing was observed, but it was much less remarkable than that by a 7-methylguanosine cap analogue. This result does not favor a direct role of the TMG-cap structure of small nuclear RNAs in pre-mRNA splicing, and suggests that the TMG-cap does not effectively interact with the 7-methylguanosine cap binding factors. Using the SP6 in vitro transcription system and a TMG-cap analogue, we prepared a beta-globin transcript which has a TMG-cap at the 5' end. This TMG-capped transcript was spliced accurately and efficiently in vitro.

Binding, Competitive↗

Pre-activation strategy for oligodeoxyribonucleotide synthesis using triaryloxydichlorophosphoranes in the phosphotriester method.

Triaryloxydichlorophosphoranes were tested as condensing agents for oligodeoxyribonucleotide synthesis in the phosphotriester method. Tris(2,4,6-tribromophenoxy)dichlorophosphorane (BDCP) was found to be a relatively stable crystalline material which could be used as a chemical reagent. A notable feature of the BDCP-promoted condensation reaction was studied by 31P-NMR. A small amount of BDCP compared to the conventional condensing agent was effective for the generation of active nucleotide intermediates and BDCP itself was quantitatively converted into an inert material, tris(2,4,6-tribromophenyl)phosphate (2). Thus, BDCP enabled us to separate the activation step from the condensation process in the phosphotriester method. This preactivation method was applied to the solid-phase synthesis.

Indicators and Reagents↗

[Diagnosis and follow-up of ovarian cancer by a combination assay of serum sialyl SSEA-1 antigen and CA125 levels].

We used a combination assay of serum sialyl SSEA-1 antigen (SLX) and CA125 levels, and evaluated the clinical usefulness of this technique for a diagnosis of ovarian cancer and follow-up of the patient with ovarian cancer. In 28 patients with ovarian tumors, the sera of 8 (66.7%) of 12 with ovarian cancer and 5 (71.4%) of the 7 with endometriosis (endometrial cyst) were positive for both SLX and CA125, but serum SLX level was 50 U/ml or less in all these 5 SLX-and-CA125 positive patients with endometriosis. The sera of all 9 patients with benign ovarian tumor were negative for both tumor markers. No patient with endometriosis was negative for both markers. The diagnostic accuracy (true positive rate X true negative rate) of the combination assay for ovarian cancer was 50.3% when the cut-off value of the serum SLX was 38 U/ml but improved to 81.8% when the value was set at 50 U/ml. From the above observations, a combination assay of serum SLX and CA125 is promising method for the differential diagnosis of malignant and benign ovarian tumors. Our results also suggest that to improve the diagnostic accuracy, the cut-off value of the serum SLX level should be 50 U/ml for ovarian tumors alone. We found following-up two cases of ovarian cancer that the serum SLX level is not affected by the ascites and inflammation. We expect that this combination assay of serum SLX and serum CA125 will be beneficial for diagnosis and follow-up of ovarian cancer.

Antigens, Tumor-Associated, Carbohydrate↗

Inhibitory effect of free fatty acids on plasma protein binding of disopyramide in haemodialysis patients.

The plasma (or serum) protein binding of disopyramide (DSP) in five haemodialysis patients was studied using an ultrafiltration technique. There was an increase in the free fraction of DSP in the plasma on dialysis days in comparison to the levels on interdialysis days, which was associated with an elevation of the free fatty acid levels in the plasma together with the increase of the free fraction of DSP. The inhibitory effect of free fatty acids on DSP binding in an in vitro study was enhanced in proportion to their concentrations, and was shown to be due to competition at one binding site by experiments with oleic acid as a representative displacer. Certain endogenous organic acids, such as indoxyl sulphate, 2-hydroxyhippuric acid and hippuric acid, which are characteristically elevated in chronic renal failure, scarcely affected the protein binding of DSP. The findings indicate that free DSP should be monitored in patients with elevated plasma free fatty acid levels, such as those on haemodialysis therapy.

Adult↗

Reperfusion through balloon catheter to minimize myocardial infarction during the interval between failed percutaneous transluminal coronary angioplasty and emergency coronary artery bypass grafting.

A 65-year-old man was admitted with chest pain. A diagnosis of spastic angina was made because of symptoms of recurrent anginal attacks associated with ST-segment elevations in the electrocardiogram. A selective coronary arteriogram revealed a 90% diameter narrowing of the proximal left anterior descending coronary artery (LAD). No angiographically visible collaterals from the right coronary artery to the LAD were observed. The ventriculogram showed normal contraction of the left ventricle with an ejection fraction of 65%. Percutaneous transluminal coronary angioplasty (PTCA) failed resulting in total occlusion of the stenosis. Repeat PTCA at a higher pressure and of longer duration failed to redilate the artery. Reperfusion with the blood from the femoral artery through the balloon catheter, which was used for the PTCA, was carried out until coronary artery bypass grafting (CABG). Blood flow rate of perfusion was approximately 25 ml/min. Reperfusion through the balloon catheter reduced chest pain and ST-segment elevations in the electrocardiogram. The patient tolerated the operative procedure well and his post-operative course was uncomplicated. The interval between the acute occlusion and revascularization by CABG was approximately 4 1/4 h. The ventriculogram taken 56 days after the CABG demonstrated normal contraction of the anterior wall of the left ventricle with an ejection fraction of 63%. Abnormal Q waves did not appear in precordial leads of the electrocardiogram after the surgery. The thallium scintigram showed no perfusion defects. In conclusion, this case suggested that autologous blood reperfusion through balloon catheter would be worth attempting in some cases for minimization of myocardial infarction during the interval between failed PTCA and emergency CABG.

Angioplasty, Balloon, Coronary↗

Umbilical artery velocity waveforms are not valid indices for assessing growth retardation in utero.

Blood flow velocity waveforms from the umbilical artery of 126 normal fetuses with no complications at 20-41 weeks and in 31 growth-retarded fetuses, were recorded using pulsed Doppler ultrasound. A total of 140 examinations were performed on normal fetuses and 49 on growth-retarded fetuses. The resistance index (RI) was used as an index of blood flow resistance. In 30 of the 31 growth-retarded fetuses (96.8%), the values of RI were within the mean +/- 2 S.D. of normal fetuses. Placental/fetal weight ratio (P/F ratio) was assessed. All values of P/F ratio of growth-retarded fetuses were within the mean +/- 2 S.D. of normal values. Small placentas expressed as a normal P/F ratio almost always associated with normal RI values. Therefore, measurement of RI on umbilical artery blood flow velocity waveform by Doppler ultrasound cannot serve as a valid diagnostic index to predict growth retardation of the fetus in utero.

Blood Flow Velocity↗

Ultrasonographic measurement of thoracic diameters of the early gestating fetus.

Eighty-two ultrasonographic examinations were performed on 60 of our pregnant patients with regular menstrual cycles and no complications. The pregnancies ranged from 7 to 13 weeks of gestation. Thoracic anteroposterior diameter (ETAPD), transverse diameter (ETTD), cross-sectional area (ETA) and crown-rump length (CRL) were measured on each ultrasonogram. A high correlation between CRL and gestational age was firstly confirmed in this study. ETAPD, ETTD and ETA correlated well with the gestational age and CRL, respectively. Correlations between ETAPD/CRL and ETTD/CRL ratios with the gestational age were negative. A positive correlation of ETA/CRL ratio with the gestational age was evident. Ultrasonographic measurement of the thoracic diameters of the fetus in utero should be a useful parameter to evaluate the gestational age and for early detection of growth retardation in utero.

Embryonic and Fetal Development↗

Viremia and neutralizing antibody response in infants with exanthem subitum.

Mononuclear cell-associated viremia caused by human herpesvirus type 6 was detected in 39 (66%) of 59 blood samples from 38 children with exanthem subitum between day 0 and day 7 of the disease. The rate of virus isolation from mononuclear cells was 100% (26/26) on days 0 to 2 (just before appearance of skin rash), 82% (9/11) on day 3, 20% (2/10) on day 4, 7% (2/12) on days 5 to 7, and 0% (0/37) on day 8 and thereafter. The cell-free virus was detected in blood in 10 (21%) of 47 blood samples during the same period. The antibody activity to the virus, evaluated by a newly developed neutralization assay, was first detected on day 3 of the disease with a positive rate of 18% (2/11). It became 60% (6/10) on day 4, 75% (9/12) on days 5 to 7, and 100% on day 8 and thereafter. Thus the disappearance of the virus from blood was associated with the induction of specific immunity to the virus.

Adult↗

Sarcolemmal Ca2+ transport activities in cardiac hypertrophy caused by pressure overload.

To examine Ca2+ transport activities in sarcolemmal membrane in cardiac hypertrophy caused by pressure overload, rats were subjected to aortic banding for 28 days. Heart-to-body weight ratio was increased by 46% in aortic-banded animals in comparison with the sham-operated rats. Ouabain-sensitive Na+-K+-ATPase activity in sarcolemma (SL) from hypertrophied hearts was not different from that in the control preparation. The initial rate of Na+-dependent Ca2+ uptake in SL vesicles from the hypertrophied hearts was stimulated by 53% compared with the control vesicles. ATP-dependent Ca2+ uptake and Ca2+-stimulated adenosinetriphosphatase (ATPase) activities in SL from hypertrophied hearts were increased by 35%. The number of Ca2+ channels estimated by [5-methyl-3H]nitrendipine binding was decreased by 33% in SL from hypertrophied hearts. Total and individual phospholipid contents in the hypertrophied heart preparations were not different from those in the control, except that phosphatidylcholine and phosphatidylethanolamine contents were significantly increased. Sarcolemmal preparations from hypertrophied hearts from the 22-wk-old spontaneously hypertensive rats exhibited changes in Na+-Ca2+ exchange and Ca2+-pump activities (similar to those observed in banded hearts), whereas the Na+-K+-ATPase activity decreased, [3H]nitrendipine binding increased, and phospholipid contents were not different. Thus, although differences were defined between two types of hypertrophy, these results suggest alterations in the sarcolemmal Ca2+ transport activities that may serve as an adaptive mechanism for the removal of Ca2+ from the myocardial cells during the development of cardiac hypertrophy.

Animals↗

Ultrasonographic measurement of the fetal transverse cerebellum in utero.

Ultrasonographic examinations, done to measure the fetal transverse cerebellar diameter (FCD), were performed in 116 women with regular menstrual cycles, at 17-40 weeks of gestation. FCD correlated well with gestational age (r = 0.96, p less than 0.001). The 95% confidence interval of the linear regression was also given. FCD may be a more useful indicator of the accurate gestational age in case of dolichocephaly or brachycephaly, and facilitate antenatal detection of congenital disorders.

Cerebellar Diseases↗

Doppler color flow mapping of an invasive mole.

We report here Doppler color flow mapping carried out before and after chemotherapy for an invasive mole. This mapping revealed an abnormal color blood flow within the echo-free space in the uterine myometrium, and pulsed Doppler ultrasound showed a prominent arteriovenous shunt flow. Similar features were obtained by pelvic angiography (PAG). After 4 courses of chemotherapy, the area of abnormal colored flow was reduced and findings on the PAG were supportive. The patient is being closely followed, using Doppler color flow mapping.

Adult↗

Ultrasonographic identification and measurement of the normal ovary in postmenopausal Japanese women.

Real-time ultrasonic scanning examinations were performed on 31 postmenopausal Japanese women with no evidence of pathology. Both ovaries were visualized in 25 patients. Only the left ovary was imaged in 5 and only the right one in 1 patient. Ovarian sectional area (OSA) was 1.45 +/- 0.61 cm2 in the left-sided ovary and 1.36 +/- 0.64 cm2 in the right-sided ovary, with no statistically significant difference. In all 56 ovaries, the OSA was 1.41 +/- 0.63 cm2. These normal values in postmenopausal women provide a useful indicator for detection of postmenopausal palpable ovary syndrome.

Aged↗