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Biomedical subjects

T Okuda

Publications and source records attributed to T Okuda.

At least 91 records · Page 5Linked to original sources

Evaluation of dural sinus invasion and extension of extra-axial intracranial tumors. The advantages of a high-resolution postcontrast 3-D gradient-echo technique.

OBJECTIVE: To assess the usefulness of a postcontrast 3-D Fourier transform (3DFT) gradient-echo (GRE) technique in dural sinus invasion and extension of extraaxial intracranial tumors in comparison with a conventional spin-echo (SE) technique. MATERIAL AND METHODS: Fourteen consecutive patients with 15 extra-axial tumors in contiguity with the dural sinus, including 14 meningiomas and 1 adenoid cystic carcinoma, underwent postcontrast T1-weighted SE and GRE MR studies. Detectability of dural sinus invasion and extension was evaluated using two sequences by two neuroradiologists in a blinded manner and compared with surgical results. Quantitative analysis was also performed to calculate the contrast-to-noise ratio (CNR) between lesion and dural sinus on SE and GRE images. The data were analyzed statistically using a matched paired t-test. RESULTS: In the qualitative evaluation, the detectability of dural sinus invasion in 3DFT-GRE images was superior to that using SE images. The mean CNR for all lesions was 3.86 on SE images and 5.63 on 3DFT-GRE images (p = 0.03). CONCLUSION: For evaluation of dural sinus invasion and the extension of extra-axial tumors, postcontrast 3DFT-GRE MR images were superior to conventional SE images.

Adult↗

[A patient for craniotomy with ECG abnormality occurring on admission to the operating room].

We report a 72 year old male patient for craniotomy with ECG abnormality occurring on admission to the operating room. His preoperative ECG showed normal sinus rhythm without ST-T change and T wave abnormality. On admission to the operating room, negative T wave was noted on the ECG monitor. Therefore, we applied isosorbide dinitrate tape after the induction of anesthesia. When the dura mater was opened, subarachnoid hemorrhage was noticed. Intraoperative pathological examination revealed a glioblastoma multiforme. The tumor bled from inside and outside. The perioperative T wave abnormality was probably due to subarachnoid hemorrhage or bleeding from the tumor itself. The T wave abnormality disappeared on the 10th postoperative day.

Aged↗

Phase I trial of oral 2'-deoxy-2'-methylidenecytidine: on a daily x 14-day schedule.

2'-deoxy-2'-methylidenecytidine (DMDC) is a potent deoxycytidine analogue. Preclinical studies of DMDC demonstrated activity against a variety of murine and human tumors in cell cultures and murine models and indicate enhanced antitumor activity of DMDC when it was administered in a manner that provided prolonged systemic exposure. In view of this observation, this study was designed to determine the toxicities, maximum-tolerated dose, and pharmacokinetic profile of DMDC. DMDC was given p.o. under fasting conditions for 14 consecutive days every 4 weeks in patients with advanced solid tumors. The starting dose was 12 mg/m2/day. Pharmacokinetic studies were carried out on days 1 and 14 of the first cycle. Fourteen patients received 22 courses of DMDC. The dose-limiting toxicities were anorexia, leukopenia, thrombocytopenia, and anemia. General fatigue was the common nonhematological toxicity. The maximum-tolerated dose was 18 mg/m2/day, at which two of six patients developed grade 3 toxicities. This dose level could also be considered for Phase II testing with this schedule. At the 18-mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), the area under the plasma drug concentration-time curve (AUC(0-infinity)) on day 1 were 1.7496 h, 112.9 ng/ml, and 399.8 ng x h/ml, respectively. Forty to 50% of the administered dose was recovered in the urine, indicating a good bioavailability and resulting significant systemic exposure to the drug, which may enable chronic oral treatment.

Adenocarcinoma↗

[A case of drug allergy to hydroxyzine used for premedication].

A 37-year-old woman, scheduled for total knee replacement, complained of nausea and abdominal pain 30 min after pre-medication with intramuscular atropine and hydroxyzine. Hypoxemia and skin eruption all over her body was noticed in the operating room. Although hemodynamic changes were not observed, the operation was postponed. LST (lymphocyte stimulation test) showed the positive response with hydroxyzine but negative with atropine and antibiotics. This result suggests that hypersensitivity was caused by hydroxyzine in this patient.

Adult↗

Identification of new genes ndr2 and ndr3 which are related to Ndr1/RTP/Drg1 but show distinct tissue specificity and response to N-myc.

Ndr1 was isolated as a gene upregulated in N-myc mutant mouse embryos and is repressed by N-myc and c-myc. Consistent with Myc regulation, the same gene was also isolated as one sensitive to transformation (Drg1), and in addition as one induced under a few stress conditions (RTP). Two new genes, Ndr2 and Ndr3, were identified which encode proteins highly related to Ndr1/RTP/Drg1 and constitute the Ndr gene family. Ndr2 and Ndr3 are under spatio-temporal regulations distinct from Ndr1, and are not activated in N-myc mutants. When whole embryo RNA was analyzed, Ndr3 expression was already high at 9.5 days postcoitus (dpc), while expression of Ndr2 and Ndr1 became significant after 12.5 dpc and 13. 5 dpc, respectively. At 14.5 dpc, expression of these genes partially overlaps, but many tissues are unique to one of them. For instance, Ndr1 is strongly expressed in the liver and gut epithelium, Ndr2 in the ventricular zone throughout the CNS, and Ndr3 in the spinal cord and the thymus rudiment. Genes of the Ndr family probably have tissue-dependent allotments of the possibly related functions.

Adaptor Proteins, Signal Transducing↗

Molecular cloning of macrophin, a human homologue of Drosophila kakapo with a close structural similarity to plectin and dystrophin.

We have determined the complete cDNA coding sequence of a novel cytoskeletal protein by the degenerative primer-mediated PCR strategy. This novel gene, named as macrophin (microfilament and actin filament cross-linker protein related to plectin and dystrophin, Accession No. AB029290), appears to be a human homologue of a Drosophila gene, kakapo, and shows close similarity to plectin and dystrophin on the search of BLAST homology-computed database. Comparison of the deduced protein sequences for macrophin and kakapo revealed that they were 66% similar, and both of them have an NH2-terminal actin-binding domain, a central rod region composed of spectrin-like repeats, and COOH-terminal Gas2-related region. The predicted sequences for macrophin are 5430 amino acids in length with a calculated molecular mass of 620 kDa, which is one of the largest size idenfied in human cytoskeletal proteins. High expression of macrophin was observed in brain, heart, lung, placenta, liver, kidney, and pancreas. In pancreas, we found that macrophin was specifically expressed in acinar cells than islet cells by in situ hybridization. By using radiation hybrid panel, we have mapped the macrophin gene to the chromosome 1p31-32.

Amino Acid Sequence↗

Anti-tumor promoting activity of polyphenols from Cowania mexicana and Coleogyne ramosissima.

Chemical investigation on polyphenol-rich fractions of Cowania mexicana and Coleogyne ramosissima (Rosaceae) which showed significant inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), has led to the characterization of 10 compounds including C-glucosidic ellagitannin monomers and dimers from the former plant, and 17 polyphenols including flavonoid glycosides from the latter. The effects of individual components and their analogues with related structures on the TPA-induced EBV-EA activation were then evaluated. Among the compounds isolated from C. mexicana, two C-glucosidic ellagitannins, alienanin B and stenophyllanin A and a nitrile glucoside (lithospermoside), and among the constituents from C. ramosissima, two flavonoid glycosides, isorhamnetin 3-0-beta-D-glucoside and narcissin were revealed to possess strong inhibitory effects on EVB-EA activation, the potencies of which were either comparable to or stronger than that of a green tea polyphenol, (-)-epigallocatechin gallate. These polyphenols except for nitrile glucoside, which was not tested owing to an insufficient amount, were also found to exhibit anti-tumor promoting activity in two-stage mouse skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) and TPA.

9,10-Dimethyl-1,2-benzanthracene↗

Complete two-dimensional separation for analysis of acidic compounds in plasma using column-switching reversed-phase liquid chromatography.

A complete two-dimensional separation technique for the determination of acidic compounds in plasma was developed by using column-switching reversed-phase liquid chromatography. This technique was based on solute peak enrichment at the top of the second column during heart-cutting and an ion-pair chromatographic separation in the second column using tetrabutylammonium ion, where different separation modes in the first and second columns and solute peak enrichment at the top of the second column during heart-cutting were achieved coincidentally. Retention behaviors of two solutes, zidovudine-beta-D-glucuronide (AZT-beta-D-Gluc) and probenecid, in the first and second column and solute peak enrichment at the top of the second column were investigated for establishment of the system. Different retention behaviors of the solutes in the first and second column, which were evaluated by changes in capacity factor versus acetonitrile concentration in the mobile phases, and peak enrichment could be accomplished by using ion-pair chromatography in the second column. System suitability was confirmed by assessing the number of theoretical plates (N) of the second column for the solutes after heart-cutting. The N values in the second column after column switching were almost same as those in the case that the solutes were directly injected onto the second column. These results indicate that complete two-dimensional separation should be achieved by using this system. Furthermore, this technique was applied to method development for the determination of AZT-beta-D-Gluc and probenecid in rat plasma. The peaks of each analyte in the plasma extract obtained by deproteinization were well separated from those of endogenous substances, and easy determination of the analytes could be accomplished at the ng/ml level only by changing the acetonitrile concentration in the mobile phases.

Acids↗

Usefulness of diffusion-weighted MRI with echo-planar technique in the evaluation of cellularity in gliomas.

The purpose of this study was to evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) with echo-planar imaging (EPI) technique in depicting the tumor cellularity and grading of gliomas. Twenty consecutive patients (13 men and 7 women, ranging in age from 13 to 69 years) with histologically proven gliomas were examined using a 1.5 T superconducting imager. Tumor cellularity, analyzed with National Institutes of Health Image 1.60 software on a Macintosh computer, was compared with the minimum apparent diffusion coefficient (ADC) and the signal intensity on the T2-weighted images. The relationship of the minimum ADC to the tumor grade was also evaluated. Tumor cellularity correlated well with the minimum ADC value of the gliomas (P = 0.007), but not with the signal intensity on the T2-weighted images. The minimum ADC of the high-grade gliomas was significantly higher than that of the low-grade gliomas. Diffusion-weighted MRI with EPI is a useful technique for assessing the tumor cellularity and grading of gliomas. This information is not obtained with conventional MRI and is useful for the diagnosis and characterization of gliomas.

Adolescent↗

3D TOF turbo MR angiography for intracranial arteries: phantom and clinical studies.

This work investigated whether turbo magnetic resonance angiography (MRA) can replace conventional MRA in screening examination of intracranial arteries. A phantom was used to evaluate the effect of the zero-filling interpolation (ZFI) technique on spatial resolution and partial volume effect. Thirty-one consecutive patients underwent both turbo MRA with a slice thickness of 0.7 mm (data were measured as 1.33 mm sections) and conventional MRA with 1.0 mm sections. In the phantom studies, ZFI did not improve the spatial resolution, but the partial volume effect was somewhat reduced. In the clinical evaluation, turbo MRA showed better signal-to-noise and contrast-to-noise ratios of the intracranial major vessels than conventional MRA. The lesions included cerebral aneurysms less than 3 mm in diameter, occlusive vascular disease, arteriovenous malformations, and arteriovenous fistulas. These were all depicted on both turbo MRA and conventional MRA. Turbo MRA is a useful screening procedure because of its capability of delineating lesions in approximately half the usual imaging time. J. Magn. Reson. Imaging 1999;10:939-944.

Adult↗

Dendritic cells/chimerism/alleviation of chronic allograft rejection.

Chronic rejection (CR) is the major obstacle of long-term successful organ transplantation. Using a recently developed rat model of CR, we found that heart allografts susceptible to development of CR showed an early (< 10 days) dramatic disappearance of donor MHC class II+ cells, including ED2+ tissue macrophages, and an influx of recipient ED1+ macrophages intermixed with small numbers of recipient ED2+ and OX62+ cells. In contrast, donor MHC class II+ cells persisted in allografts resistant to CR with a small influx of recipient macrophages. MHC class II+ cells function as potent modulators of the immune system and may mediate both stimulatory and tolerogenic immune reactions after transplantation. Persistence of donor MHC class II+ antigen-presenting cells (APC) in CR-free graft acceptance suggests that transplantation tolerance is an active immune response requiring antigen presentation to the recipient immune system in the proper context by dendritic cells and other APC.

Animals↗

A novel in-frame deletion mutation in a case of lactate dehydrogenase (LD) H subunit deficiency showing an atypical LD isoenzyme pattern in serum and erythrocytes.

OBJECTIVE: We report a case showing an atypical lactate dehydrogenase (LD) isoenzyme pattern involving deficiency only of LD-1 and LD-2 in serum and erythrocytes. LD activity in serum from this patient was extremely low, similar to complete LD-H deficiency, and also that in erythrocytes was low. DESIGN: The DNA fragment containing exon 1 through 7 of the LD-H gene were amplified by PCR and directly sequenced. Total RNA was prepared from venous blood and the proportion of LD-H cDNA to total LD cDNA was semiquantified. RESULTS: Genetic analysis by DNA sequencing detected a three base deletion (AAT) at codon 220 of exon 5, which caused a deletion of one asparagine. The present case did not show reduced LD-H expression at the mRNA level in whole blood. Residue 220 is involved in turning beta-J to alpha1-G and is not buried in the interior of the protein. The novel homozygous in-frame deletion mutation at codon 220 may cause a three-dimensional change of the subunit-binding domain.

Adult↗