113 results on '"K. Tomiyoshi"'
Search Results
2. The photoperiodic response of lotus rhizome morphogenesis is determined quantitatively
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K. Tomiyoshi, Takahiro Matsuishi, K. Sakai, Yukio Ozaki, and J. Masuda
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photoperiodism ,Lotus ,Ornamental plant ,Botany ,Morphogenesis ,Horticulture ,Biology ,biology.organism_classification ,Rhizome - Published
- 2017
- Full Text
- View/download PDF
3. Development of an inspection probing system using laser monitoring for aging power plants
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A. Nishimura, K. Tomiyoshi, and F. Ito
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Distributed feedback laser ,Computer science ,business.industry ,Optical engineering ,Physics::Optics ,Condition monitoring ,Polarization-maintaining optical fiber ,Laser ,law.invention ,Optics ,law ,Fiber laser ,Fiber optic splitter ,business ,Optical attenuator - Abstract
An optical fiber coupling device for maintenance was developed. A function such as observation of target object by wide-angle image, and the technique such as the elemental analysis by spectroscope and laser were built in the very compact device. Therefore, this device would permit wide-angle image and laser processing at oppressive conditions. The target object was measured and observed by these functions. Finally, industry application of this device was discussed.
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- 2013
- Full Text
- View/download PDF
4. [Case of a giant pericardial cyst went under the thoracoscopic surgery using a double-balloon catheter]
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R, Ishibe, S, Shimokawa, K, Gejima, T, Nakazono, K, Tomiyoshi, H, Momi, and T, Miki
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Diagnostic Imaging ,Treatment Outcome ,Mediastinal Cyst ,Thoracoscopy ,Humans ,Female ,Middle Aged ,Catheterization - Abstract
A 45-year-old female was referred to our hospital due to right anterior chest pain. A chest X-ray and a computed tomographic examination showed a large cystic lesion in the right pleural cavity above the diaphragm. The internal surface of the cyst seemed to be smooth and the content was homogeneous suggesting clear liquid. Under the diagnosis of the benign pericardial cyst, a thoracoscopic surgery was performed using a double-balloon catheter. Aspiration of the cyst content by the double-balloon catheter minimized the spillage of the content into the thoracic cavity. Furthermore, the double-balloon catheter allowed the cyst wall to be more easily grasped and manipulated. We confirmed the usefulness of a double-balloon catheter for the thoracoscopic resection of giant cystic lesions.
- Published
- 2009
5. Tissue Lipid Quantification Using Narrow Bandwidth Magnetic Resonance Imaging with a Presaturation Pulse
- Author
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Tomio Inoue, H Ishizaka, Mitsuomi Matsumoto, and K Tomiyoshi
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Relaxometry ,Physics of magnetic resonance imaging ,Materials science ,Spectrometer ,Pulse (signal processing) ,Magnetic resonance microscopy ,Magnetic resonance spectroscopic imaging ,Magnetic resonance force microscopy ,General Medicine ,equipment and supplies ,Lipids ,Magnetic Resonance Imaging ,Models, Structural ,Nuclear magnetic resonance ,Spin echo ,Humans ,Radiology, Nuclear Medicine and imaging ,Artifacts - Abstract
RATIONALE AND OBJECTIVES: Chemical-shift artifact occurs within tissues when band-like presaturation pulses are applied perpendicular to the frequency-encoding axis in narrow band-width magnetic resonance imaging. This phenomenon was used to quantify the lipid fraction in phantoms used to simulate tissue. METHODS: Twenty phantoms with various lipid/water ratios were imaged on spin-echo sequence (repetition time/echo time, 2,000/20 msec) using a 1.5-T magnet. A narrow bandwidth that caused 6-mm chemical shift and a presaturation pulse 6-mm in width were used in the imagining. The lipid fraction values calculated from the resulting images were compared with values determined by a spectrometer. RESULTS: The image-derived values (LI) correlated strongly with the values determined by spectrometry (LS) (LI = 0.97 + 0.99 LS, r = .998). CONCLUSIONS: Chemical-shift artifact around the presaturation-applied areas should provide a simple and efficient method for the accurate quantification of tissue lipid fractions.
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- 1994
- Full Text
- View/download PDF
6. 18F alpha-methyl tyrosine PET studies in patients with brain tumors
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T, Inoue, T, Shibasaki, N, Oriuchi, K, Aoyagi, K, Tomiyoshi, S, Amano, M, Mikuni, I, Ida, J, Aoki, and K, Endo
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Adult ,Aged, 80 and over ,Male ,Fluorine Radioisotopes ,Adolescent ,Brain Neoplasms ,Brain ,Infant ,Middle Aged ,alpha-Methyltyrosine ,Fluorodeoxyglucose F18 ,Child, Preschool ,Humans ,Female ,Radiopharmaceuticals ,Child ,Aged ,Tomography, Emission-Computed - Abstract
We have developed 18F-labeled alpha-methyl tyrosine (FMT) for PET imaging. The aim of this study was to evaluate the clinical application potential of FMT for patients with brain tumors.Eleven healthy volunteers and 20 patients with brain tumors were injected with 185 MBq (5 mCi) FMT. In 3 healthy volunteers, whole-body imaging and urinary and plasma analysis were conducted for the assessment of the biodistribution of FMT. The normal range of cortical standardized uptake value (SUV) as a reference for comparing tumor SUV of FMT was estimated by using PET data obtained at 30 min postinjection in 8 healthy volunteers. Dynamic PET scans were conducted for 100 min in 4 healthy volunteers and for 30 min in 15 patients with brain tumors. The 10-min static images in another 4 volunteers and all patients were obtained at 30 min postinjection. In 13 patients, FMT uptake in the brain tumor was compared with 18F-fluorodeoxyglucose (FDG). Tumor-to-normal cortex count (T/N) ratio and tumor-to-white matter count (T/W) ratio and SUVs of brain tumors were determined on FMT and FDG PET images.Approximately 1480 MBq (40 mCi) FMT were produced in one radiosynthesis. Percentage injected dose (%ID) of FMT in the brain ranged from 2.8% to 4.9%, and approximately 50%ID of FMT was excreted in urine during 60 min postinjection, of which 86.6% was unmetabolized FMT. A faint physiological brain uptake with SUV of 1.61 +/- 0.32 (mean +/- SD, n = 8) was observed in healthy volunteers. Tumor SUV of FMT ranged from 1.2 to 8.2, with mean value of 2.83 +/- 1.57 (n = 23), which was significantly higher than that of the cortical area in healthy volunteers (P0.01). T/N and T/W ratios of FMT were significantly higher than those of FDG (2.53 +/- 1.31 versus 1.32 +/- 1.46, P0.001; 3.99 +/- 2.10 versus 1.39 +/- 0.65, P0.0001, respectively).FMT, like other radiolabeled amino acids, can provide high-contrast PET images of brain tumors.
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- 1999
7. 99mTc-labeled chimeric anti-NCA 95 antigranulocyte monoclonal antibody for bone marrow imaging
- Author
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M, Sarwar, T, Higuchi, K, Tomiyoshi, T, Inoue, N, Oriuchi, A, Kbalil, S, Alyafei, H, Sakahara, J K, Chung, and K, Endo
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Membrane Glycoproteins ,Time Factors ,Chimera ,Anemia, Aplastic ,Antibodies, Monoclonal ,Mice, Nude ,Technetium Tc 99m Medronate ,Iodine Radioisotopes ,Mice ,Antigens, Neoplasm ,Bone Marrow ,Isotope Labeling ,Animals ,Humans ,Tissue Distribution ,Radiopharmaceuticals ,Colorectal Neoplasms ,Radionuclide Imaging ,Cell Adhesion Molecules ,Granulocytes - Abstract
Chimeric mouse-human antigranulocyte monoclonal antibody (ch MAb) against non-specific cross-reacting antigen (NCA-95) was labeled with 99mTc (using a direct method) and 125I (using the chloramine T method), and its binding to human granulocytes and LS-180 colorectal carcinoma cells expressing carcinoembryonic antigen on their surfaces, cross-reactive with anti-NCA-95 chimeric monoclonal antibody, increased in proportion to the number of cells added and reached more than 80% and 90%, respectively. In biodistribution studies, 99mTc and 125I-labeled ch anti-NCA-95 MAb revealed high tumor uptake, and the tumor-to-blood ratio was 2.9 after 24 hours. The tumor-to-normal-organ ratio was also more than 3.0 in all organs except for the tumor-to-kidney ratio. Scintigrams of athymic nude mice confirmed the results of biodistribution studies that showed higher radioactivity in tumor and kidney of the mice administered with 99mTc-labeled ch MAb. A normal volunteer injected with 99mTc-labeled ch anti-NCA-95 antigranulocyte MAb showed clear bone marrow images, and a patient with aplastic anemia revealed irregular uptake in his lumbar spine, suggesting its utility for bone marrow scintigraphy and for the detection of hematological disorders, infections, and bone metastasis.
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- 1998
8. Comparative study of positron emission tomography and quantitative digital radiography (QDR) in detecting effects of aging and diet on bone metabolism of guinea pig
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K, Ahmed, T, Inoue, K, Tomiyoshi, M, Sarwar, N, Oriuchi, H, Mizunuma, and K, Endo
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Calcium, Dietary ,Radiographic Image Enhancement ,Aging ,Bone Diseases, Metabolic ,Fluorine Radioisotopes ,Bone Density ,Guinea Pigs ,Animals ,Female ,Bone and Bones ,Cholecalciferol ,Diet ,Tomography, Emission-Computed - Abstract
The purpose of this study was to compare positron emission tomography and quantitative digital radiography (QDR) in detecting the effects of aging and diet on bone metabolism. Bone imaging of guinea pigs was performed with fluorine-18 fluoride ions using a high-resolution animal PET system to analyze bone metabolism quantitatively in different age groups of guinea pigs, young (8 weeks), adult (36 weeks), and aged groups (96 weeks), and also in a dietary manipulation group (low calcium and low vitamin D3 diet for 1, 2, and 3 weeks). A three-compartment kinetic model was applied for the analysis of bone metabolism to evaluate the rate constant (K, K1-K4). There was a significant difference in K-constant between the young and other groups. The K-constant was higher (0.100+/-0.005 ml/min/ml) in the young group than in adults (0.028+/-0.001 ml/min/ml) (p0.001) and the aged group (0.047+/-0.020 ml/min/ml). This high value of the K-constant in the young group indicates high turnover in bone metabolism, but there was no significant difference between the adult and aged groups. Bone mineral density (BMD) was lower in the young group (0.15+/-0.026 g/cm2) than in the adult (0.230+/-0.021 g/cm2) (p0.001) and aged groups (0.26+/-0.03 g/cm2). There was no significant difference in BMD between the adult and aged groups. Although there was no difference in BMD between the control and dietary manipulation groups, PET study revealed a significant difference in K-constant between them (0.028+/-0.001 vs. 0.090+/-0.009 ml/min/ ml) (p0.001). The quantitative skeletal dynamic PET study with 18F fluoride ions was more sensitive and superior in the early detection of metabolic disorders in bone disease than QDR.
- Published
- 1998
9. In vivo comparison of PET and SPECT radiopharmaceuticals in detecting breast cancer
- Author
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S, Amano, T, Inoue, K, Tomiyoshi, T, Ando, and K, Endo
- Subjects
Tomography, Emission-Computed, Single-Photon ,Fluorine Radioisotopes ,Mice ,Mice, Inbred BALB C ,alpha-Methyltyrosine ,Animals ,Mice, Nude ,Breast Neoplasms ,Female ,Tissue Distribution ,Radiopharmaceuticals ,Neoplasm Transplantation ,Tomography, Emission-Computed - Abstract
Various radiopharmaceuticals for breast cancer detection have been used for scintimammography and PET. However, few comparative studies have described the uptake of radiopharmaceuticals as a method of detecting breast cancer. The aim of this study was to assess the radiopharmaceuticals for breast cancer imaging in experimental mice implanted with breast cancer cells.Six radiopharmaceuticals were studied: three for PET [18F-fluorodeoxyglucose (FDG), L-18F-alpha-methyltyrosine (FMT) and 11C-methionine (C-Met)] and three for scintimammography [99mTc-tetrofosmin (TF), 99mTc-sestamibi (MIBI) and 201Tl-chloride (Tl)]. Biodistributions of six different tracers in mice implanted with MCF-7 breast cancer cells were studied 1 and 3 hr after injection.Tumor uptake 1 hr after injection was FMT = C-MetFDG = TFMIBI = Tl. Thallium-201-chloride showed the highest tumor-to-blood ratio (T/B) among all radiopharmaceuticals because of its fast clearance from circulation. The T/B of the six radionuclides used in this study ranged from 1.26 for C-Met to 12.83 for Tl. Tumor-to-muscle ratio (T/M) revealed FMT = C-MetFDGMIBITF = Tl. The T/M ranged from 0.20 for TF to 2.29 for FMT. Tumor-to-lung ratio (T/L) varied from 0.45 for TF to 2.41 for FMT. FMT revealed the highest T/L of all six radiopharmaceuticals.Among radiopharmaceuticals for PET, FMT seemed to be suitable in detecting MCF-7 tumor; whereas for scintimammography, MIBI, TF and Tl appeared to have almost the same detectability of MCF-7 tumor. The results of this study strongly suggest that FMT may have a potential in breast cancer imaging.
- Published
- 1998
10. Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent
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T, Inoue, K, Tomiyoshi, T, Higuichi, K, Ahmed, M, Sarwar, K, Aoyagi, S, Amano, S, Alyafei, H, Zhang, and K, Endo
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Mice, Inbred BALB C ,Methyltyrosines ,Mice, Nude ,Biological Transport ,Neoplasms, Experimental ,Mice ,alpha-Methyltyrosine ,Fluorodeoxyglucose F18 ,Tumor Cells, Cultured ,Animals ,Humans ,Tyrosine ,Female ,Tissue Distribution ,Amino Acids ,Radionuclide Imaging ,Neoplasm Transplantation - Abstract
Iodine-123-alpha-methyl tyrosine has proven to be a promising SPECT agent for imaging amino acid uptake in tumors. We developed L-[3-(18)F]-alpha-methyl tyrosine (FMT) for PET studies. The aim of this study was to investigate its potential use as a tumor-detecting agent by using tumor-bearing mice.We investigated the biodistribution in normal BALB/C mice and BALB/cA nude mice bearing human rectal cancer cell line (LS180) until 120 min postinjection. FMT tumor uptake at 60 min postinjection in mice with LS180 rectal cancer, RPM11788 B-cell lymphoma and MCF7 mammary cell carcinoma was assessed, and the results were compared with 18F-fluoro-2-deoxy-D-glucose (FDG) tumor uptake. The effect of competitive inhibition of large neutral amino acid transport system using unlabeled L-alanine was also investigated.The amount of FMT in blood fell to 1.05%ID/20 g at 60 min postinjection, whereas that in the pancreas was 15.2%ID/20 g, resulting in a high pancreas-to-blood ratio of 14.5. In other organs, initial uptake peaked at 5 min postinjection and then declined with time. In LS180 tumor-bearing mice, peak FMT uptake in tumor was observed at 60 min postinjection. Tumor-to-blood and tumor-to-muscle ratios ranged from 1.60 to 2.94 and from 2.79 to 3.25 over the 120-min observation period. Tumor uptake of FMT was clearly reduced by inhibition of the amino acid transport system. In mice with LS180 and MCF7 tumors, FMT tumor uptake at 60 min postinjection was significantly higher than FDG tumor uptake, whereas in RPM11788 lymphoma, uptake of FDG was significantly higher than FMT tumor uptake. Tumor-to-blood ratios of FMT in mice with LS180, RPMI1788 and MCF7 tumor at 60 min postinjection were 1.82, 5.88 and 3.56, respectively.FMT, like other fluorinated amino acids, may become a promising tumor-detecting agent for PET, assuming that efficient methods of radiosynthesis are developed.
- Published
- 1998
11. Direct labeling of macroaggregated albumin with indium-111-chloride using acetate buffer
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N, Watanabe, Y, Shirakami, K, Tomiyoshi, N, Oriuchi, T, Hirano, T, Higuchi, T, Inoue, and K, Endo
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Mice, Inbred BALB C ,Sodium Acetate ,Indium Radioisotopes ,Buffers ,Indium ,Mice ,Isotope Labeling ,Ventilation-Perfusion Ratio ,Animals ,Humans ,Female ,Tissue Distribution ,Radionuclide Imaging ,Lung ,Serum Albumin - Abstract
Indium-111-labeled macroaggregated albumin (MAA) would be suitable for combined pulmonary perfusion and ventilation scan using a 99mTc ventilation agent.MAA suspended in 0.1 M sodium acetate buffer, pH 5.8, was incubated with 111In-chloride for 30 min at room temperature. An in vitro study of the obtained 111In-MAA was performed for labeling efficiency and stability in human normal serum. The 111In-MAA was intravenously injected into normal mice, and the biodistribution was studied at 15 and 180 min postinjection. A gamma camera image was obtained at 15 min after injection.MAA was directly and stably labeled with 111In-chloride, and the labeling efficiency of the preparation was more than 96%. More than 90% of the administered 111In-MAA was caught in the murine lung. The scintigraphy with 111In-MAA showed a clearly visualized murine lung.Indium-111-MAA can be conveniently prepared by direct labeling at room temperature. It provides an alternative perfusion tracer for combined perfusion-ventilation imaging.
- Published
- 1997
12. [The usefulness of 18F-FDG SPECT imaging in evaluating myocardial viability]
- Author
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H, Sato, T, Toyama, Y, Kaneko, R, Nagai, K, Tomiyoshi, T, Inoue, K, Endo, N, Ota, N, Kanazawa, and T, Suzuki
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Male ,Tissue Survival ,Tomography, Emission-Computed, Single-Photon ,Fluorine Radioisotopes ,Iodobenzenes ,Fatty Acids ,Myocardial Infarction ,Heart ,Deoxyglucose ,Middle Aged ,Iodine Radioisotopes ,Thallium Radioisotopes ,Fluorodeoxyglucose F18 ,Humans ,Female ,Aged - Abstract
We compared myocardial viability evaluated by 18F-deoxyglucose (FDG) SPECT in 14 old myocardial infarction patients with that evaluated by 201TI SPECT and 123I-beta-methyl-iodophenyl pentadecanoic acid SPECT as imaging of fatty acid metabolism. FDG-SPECT was performed after oral administration of glucose. From each SPECT image which was divided into 7 segments, the degree of accumulation of each radioisotope (RI) was visually classified into four grades of defect score (ranging from 0 as normal to 3 as severe defect). The % uptake in the same area was also quantitatively calculated.The degree of accumulation of myocardial Rl relative to regional wall motion. FDG is the most wide for a range of accumulation of Rl of infarct area. Also, at FDG, in the area of wall motion had done a disorder, the degree of accumulation was higher than other two methods. In the infarcted area, the degree of accumulation on FDG-SPECT in the area of decreased wall motion was greater than that on the other two procedures. These results suggest that FDG-SPECT is useful for evaluating myocardial viability.
- Published
- 1997
13. [Tumor diagnosis using 18F-FDG SPECT]
- Author
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S, Sugiyama, Y, Suzuki, H, Matsuzaki, K, Tomiyoshi, and K, Endo
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Tomography, Emission-Computed, Single-Photon ,Fluorine Radioisotopes ,Fluorodeoxyglucose F18 ,Neoplasms ,Humans ,Gamma Cameras ,Deoxyglucose - Abstract
Fluorine-18-fluorodeoxyglucose (18F-FDG) single photon emission CT(SPECT) imaging was performed in four patients with malignant neoplasms. Acquisition of SPECT was started 40 minutes after intravenous administration of 370MBq of 18F-FDG using dual-headed gamma camera equipped with 511keV collimators. Whole body planar scintigraphy was also obtained after the SPECT study. Tumor uptake of 18F-FDG was detected in three of four patients on both SPECT and planar images, and a 2.5 x 1.5 cm lung tumor was clearly visualized on SPECT image. Excellent SPECT image of 18F-FDG using a conventional gamma camera system is promising for the wide use of this system in cancer diagnosis.
- Published
- 1996
14. [A basic and clinical evaluation of a new immunoradiometric assay kit for human serum tissue polypeptide antigen (TPA)]
- Author
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K, Shimojo, N, Watanabe, S, Sakai, M, Kobayashi, H, Ohtake, N, Hatori, K, Fukasawa, K, Tomiyoshi, T, Inoue, and K, Endo
- Subjects
Adult ,Aged, 80 and over ,Male ,Neoplasms ,Biomarkers, Tumor ,Antibodies, Monoclonal ,Humans ,Female ,Immunoradiometric Assay ,Reagent Kits, Diagnostic ,Tissue Polypeptide Antigen ,Middle Aged ,Aged - Abstract
A new immunoradiometric assay kit (IRMA) of human serum tissue polypeptide antigen (TPA) based on combination monoclonal antibodies was evaluated. Using a new TPA-IRMA, the procedure of TPA measurement was faster and the range of measurement was more wide than a conventional TPA-IRMA. 89% (76/85 cases) of patients with malignant tumor and 96.4% (27/28) of patients with metastatic malignant tumor were positively detected. This assay of new TPA-M kit is sensitive to the level of serum TPA which is corresponding to a therapy. It is concluded that a new TPA-IRMA is very useful in monitoring and assessing malignant tumors.
- Published
- 1996
15. Independent thallium-201 accumulation and fluorine-18-fluorodeoxyglucose metabolism in glioma
- Author
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N, Oriuchi, K, Tomiyoshi, T, Inoue, K, Ahmad, M, Sarwar, M, Tokunaga, H, Suzuki, N, Watanabe, T, Hirano, S, Horikoshi, T, Shibasaki, M, Tamura, and K, Endo
- Subjects
Male ,Tomography, Emission-Computed, Single-Photon ,Fluorine Radioisotopes ,Brain Neoplasms ,Glioma ,Deoxyglucose ,Middle Aged ,Thallium Radioisotopes ,Glucose ,Fluorodeoxyglucose F18 ,Case-Control Studies ,Humans ,Female ,Glioblastoma ,Tomography, Emission-Computed - Abstract
SPECT with 201TI is an effective procedure for evaluating the malignancy of glioma. Our goal was to investigate the diagnostic relevance of both 201TI SPECT and [18F]fluorodeoxyglucose (FDG) PET and the relation between 201TI uptake and glucose metabolism in glioma using comparative SPECT and PET studies.Thallium-201 SPECT and FDG dynamic PET studies were performed in 20 patients with untreated glioma (5 with glioblastoma, 5 with anaplastic glioma, 10 with low-grade glioma). Thallium-201 uptake in the tumor was estimated using the 201TI index, defined as the ratio of 201TI uptake in the tumor to that in the contralateral normal brain on SPECT images obtained 15 min after intravenous injection. We measured regional glucose metabolic parameters, including rate constants and regional cerebral metabolic rate of glucose utilization (rCMRgl), in the tumor. We then compared the regional 201TI index and glucose metabolic parameters with the histologic characteristics, malignancy and computed tomographic/ magnetic resonance imaging findings. In addition, we investigated the correlation between the 201TI index and glucose metabolic parameters.Thallium-201 SPECT showed abnormal 201TI uptake in all patients with glioblastoma and anaplastic glioma. Thallium-201 indices of glioblastoma (202.6 +/- 22.1%) and anaplastic glioma (176.6% +/- 26.6%) were significantly higher than that for low-grade glioma (106.7% +/- 13.8%). The rCMRgl value of glioblastoma (17.6 +/- 3.5 mumole/100 g/min) was also significantly higher than that for low-grade glioma (10.8 +/- 4.5 mumole/100 g/min), although rCMRgl showed a large variability in both high- and low-grade glioma. Rate constants of FDG kinetics had no correlation with histological grade of glioma. Some patients with high-grade glioma, however, showed false-negative results with FDG-PET because of high normal brain uptake of FDG. Conversely, most low-grade glioma could not be localized by 201TI SPECT. There was no correlation between the 201TI index and glucose metabolic parameters.Thallium-201 indices and rCMRgl values for glioblastoma were higher than those for low-grade glioma. Thallium-201 uptake in the tumor may be independent of increased glucose transport or metabolism. Thallium-201 SPECT and FDG-PET are complementary in the diagnosis of glioma, although 201TI SPECT is more significantly correlated with the malignancy of glioma.
- Published
- 1996
16. [Measurement of serum TSH receptor antibodies in thyroid patients using TRAb Dade kits]
- Author
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K, Ahmed, K, Tomiyoshi, K, Fukazawa, T, Inoue, M, Murakami, I, Kobayashi, and K, Endo
- Subjects
Radioligand Assay ,Evaluation Studies as Topic ,Humans ,Receptors, Thyrotropin ,Reagent Kits, Diagnostic ,Sensitivity and Specificity ,Graves Disease ,Autoantibodies - Abstract
TRAb Dade kit is a radioreceptor assay that detects autoantibodies in serum of patients with thyroid diseases which interfere with the binding of 125I labeled TSH to its receptor. In this paper we examined the basic and clinical usefulness of newly developed TRAb assay kits. The intra and inter assay coefficients of variation were 7.9% and 8.4%, respectively. There was no significant effect of temperature and incubation time on TRAb values. The influence of conjugated, unconjugated bilirubin, hemoglobin and turbidity was not so significant on TRAb values. TRAb values in serum of 68 untreated Graves' disease were above the normal range, but most (78%) treated Graves' patients who became euthyroid after receiving antithyroid drug, showed the normal range. In patients with chronic renal failure TRAb values were also within the normal range. A significant correlation (y = 1.0x-0.88, r = 0.95) was observed between this TRAb kit and TRAb Cosmic values in various thyroid conditions. This new assay for TRAb was simple, rapid and reproducible. The measurement of serum TRAb values was useful for the evaluation of physiological and pathological function and seemed to be helpful in the management of patients with thyroid disease.
- Published
- 1995
17. [Clinical evaluation of safety, pharmacokinetics and dosimetry of the somatostatin analog 111In-DTPA-D-Phe-octreotide--report of the phase 1 study]
- Author
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T, Inoue, H, Ootake, T, Hirano, K, Tomiyoshi, K, Endo, K, Tanaka, N, Shimizu, and T, Saito
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Adult ,Male ,Indium Radioisotopes ,Injections, Intravenous ,Humans ,Tissue Distribution ,Pentetic Acid ,Octreotide ,Radiometry ,Whole-Body Counting - Abstract
The safety, pharmacokinetics and dosimetry of the somatostatin analog 111In-DTPA-D-Phe-octreotide (111In-octreotide) were investigated in four young normal volunteers as phase 1 study in Japan. Neither adverse reactions nor significant changes of vital signs and clinical laboratory data were observed after intravenous injection of 111 MBq of 111In octreotide. The plasma clearance curve consisted of fast and slow exponential components with mean half life of 9.2 minutes and 2.2 hours, respectively. Seventy three percent of the injected dose were excreted in the urine by 24 hours after the injection of 111In-octreotide. With respect to the radiation dose to normal tissue, the most important organs were the urinary bladder, the kidney, the spleen and the liver. The effective dose equivalent was calculated as 3.26 +/- 0.43 mSv/37 MBq (mean +/- s.d.). This phase 1 study demonstrated the safety of scintigraphy with 111In-octreotide.
- Published
- 1995
18. Visualization of dopamine nerve terminals in monkey by positron emission tomography using 4-[18F]fluoro-L-m-tyrosine
- Author
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N, Hayase, K, Tomiyoshi, K, Watanabe, S, Horikoshi, M, Hirato, T, Shibasaki, and C, Ohye
- Subjects
Nerve Endings ,Fluorine Radioisotopes ,Dopamine ,Animals ,Macaca ,Tyrosine ,Tomography, Emission-Computed - Abstract
4-[18F]Fluoro-L-m-tyrosine (FMT) is an L-Dopa analog that essentially follows the L-Dopa metabolic pathway, but without 3-O-methylation or extensive peripheral metabolism. As such, FMT may serve as a useful probe of striatal dopaminergic function with positron emission tomography (PET). FMT was synthesized, as previously described by Perlmutter et al. [Appl Radiat Isot 1990;41:801-807]. Scanning was undertaken with the SHR2000 positron tomograph (image spatial resolution, 3.5 x 4.5 x 6.5 mm). Two Macaca monkeys were anesthetized with ketamine (10 mg/kg) and pentobarbital (20 mg/kg). FMT was administered intravenously (5-6 mCi; specific activity 1-2 Ci/mmol) following carbidopa pretreatment (5 mg/kg i.v., 60 min before FMT administration). Dynamic image acquisition was done for 2 h immediately after tracer injection. This emission acquisition involved twelve 2-min frames followed by nine 4-min frames, and six 10-min images. Arterial blood samples were collected according to a schedule for assay of plasma [18F] radioactivity. Specific uptake of FMT in aromatic L-amino-acid-decarboxylase-rich areas of the monkey striatum was observed with PET imaging. The striatum-to-cerebellum ratio of the accumulation increased over time to 3.0 at 2 h. These results show the promise of FMT as a PET tracer in evaluating the CNS dopaminergic system.
- Published
- 1994
19. Clinical evaluation of thallium-201 SPECT in supratentorial gliomas: relationship to histologic grade, prognosis and proliferative activities
- Author
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N, Oriuchi, M, Tamura, T, Shibazaki, C, Ohye, N, Watanabe, M, Tateno, K, Tomiyoshi, T, Hirano, T, Inoue, and K, Endo
- Subjects
Adult ,Male ,Tomography, Emission-Computed, Single-Photon ,Supratentorial Neoplasms ,Glioma ,Middle Aged ,Prognosis ,Survival Rate ,Thallium Radioisotopes ,Bromodeoxyuridine ,Humans ,Female ,Child ,Cell Division ,Aged - Abstract
We performed 201Tl SPECT and cell kinetic studies on 28 presurgical patients with supratentorial gliomas by administering bromodeoxyuridine (BUdR). All patients had surgery and had follow-up for more than 25 mo. In patients with grade IV glioma (198.1% +/- 32.8%, n = 10), the 201Tl index, expressed as the count rate of the tumor site to the count rate over the contralateral normal region, was significantly higher than that in patients with grade III glioma (140.5% +/- 15.1%, n = 4, p0.01) or low-grade glioma (104.1% +/- 22.6%, n = 14, p0.001). A significant correlation was observed between the 201Tl index and BUdR-positive cells in excised tumor specimens (r = 0.67, p0.001). The 201Tl index of the 12 patients who died was higher than those who survived (173.2% versus 122.4%, p0.01). These results show the clinical utility of 201Tl brain SPECT in imaging supratentorial glioma and that the 201Tl index is representative of proliferative activity of the tumor.
- Published
- 1993
20. [Basic study of CA125 measurement using a newly developed 'SD-8729' IRMA kit]
- Author
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A, Yamaguchi, M, Kobayashi, T, Imai, H, Otake, K, Matsubara, N, Hatori, K, Tomiyoshi, T, Inoue, and K, Endo
- Subjects
Ovarian Neoplasms ,Evaluation Studies as Topic ,Biomarkers, Tumor ,Antibodies, Monoclonal ,Humans ,Antigens, Tumor-Associated, Carbohydrate ,Female ,Immunoradiometric Assay ,Reagent Kits, Diagnostic - Abstract
"SD-8729" is a one-step IRMA kit employing OC125 antibody as 125I-labeled tracer and M-11 antibody as an immunoadsorbent. Higher bound-radioactivity to beads was observed with shorter incubation time than that of a currently used CA125 IRMA kit which employed OC125 antibody both as 125I-labeled ligand and immunoadsorbent attached to beads. Almost identical CA125 values were obtained by using two kits. The antigenic nature recognized by the M-11 antibody seems substantially different from those of 130-22 or 145-9 antibodies recognizing CA130 antigen.
- Published
- 1993
21. [Basic and clinical studies of serum CA195 antigen assay with 'BL-CA195' kit]
- Author
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M, Kobayashi, A, Yamaguchi, T, Imai, H, Otake, H, Igarashi, N, Hatori, K, Tomiyoshi, T, Inoue, K, Endo, and H, Sakahara
- Subjects
Adult ,Male ,Evaluation Studies as Topic ,Neoplasms ,Biomarkers, Tumor ,Antibodies, Monoclonal ,Humans ,Antigens, Tumor-Associated, Carbohydrate ,Female ,Immunoradiometric Assay ,Reagent Kits, Diagnostic ,Middle Aged - Abstract
We performed basic and clinical studies of IRMA "BL-CA195" kit in which monoclonal antibody CC3C195 was used as 125I-labeled tracer and solid phase antibody. The reproducibility of the assay results and dilution curves were satisfactory. There was a close correlation between serum CA195 and CA19-9 values, and many patients with pancreatic and colorectal cancer had elevated serum CA195 concentrations. Unlabeled CC3C195 antibody dose-dependently and completely inhibited the binding of 125I-labeled anti-CA19-9 antibody to its corresponding antigen. These findings suggest that CA195 and CA19-9 share common antigenic determinants.
- Published
- 1993
22. MR quantification of bone marrow cellularity: use of chemical-shift misregistration artifact
- Author
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Hiroshi Ishizaka, K Tomiyoshi, and Mitsuomi Matsumoto
- Subjects
Adult ,Models, Anatomic ,Artifact (error) ,Lumbar Vertebrae ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Bone Marrow Cells ,General Medicine ,Magnetic Resonance Imaging ,Thoracic Vertebrae ,Bone marrow cellularity ,medicine.anatomical_structure ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Bone marrow ,business ,Nuclear medicine ,Artifacts - Published
- 1993
23. Technetium-99m-labeled anti-fibrin monoclonal antibody accumulation in an inflammatory focus
- Author
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T, Hirano, K, Tomiyoshi, N, Watanabe, M, Tateno, N, Oriuch, T, Inoue, and K, Endo
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Adult ,Inflammation ,Male ,Fibrin ,Antibodies, Monoclonal ,Humans ,Insect Bites and Stings ,Technetium ,Radionuclide Imaging - Published
- 1992
24. [Pulmonary alveolar proteinosis with reverse ventilation/perfusion mismatch; a case report]
- Author
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N, Watanabe, T, Inoue, N, Oriuchi, M, Tateno, T, Hirano, K, Tomiyoshi, K, Endo, Y, Sasaki, M, Inagaki, and H, Michimata
- Subjects
Male ,Tomography, Emission-Computed, Single-Photon ,Ventilation-Perfusion Ratio ,Humans ,Middle Aged ,Pulmonary Alveolar Proteinosis ,Lung - Abstract
Generally, non-ventilated segments are not perfused on lung scans (V/Q match). Now we report a very rare case with pulmonary alveolar proteinosis whose scintigraphy shows the decreased ventilation, but well perfused (reverse V/Q mismatch).
- Published
- 1991
25. [Effect of the magnetic field to the uniformity of a gamma camera]
- Author
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H, Igarashi, M, Kubozuka, M, Suzuki, A, Shiraishi, N, Hatori, K, Tomiyoshi, T, Inoue, K, Hirano, T, Matsumoto, and Y, Sasaki
- Subjects
Electromagnetic Fields ,Gamma Cameras - Published
- 1991
26. [Fundamental studies for the detection of P-32 in DNA probe using gamma camera]
- Author
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H, Igarashi, M, Kubota, A, Shiraishi, T, Imai, N, Hatori, T, Inoue, K, Tomiyoshi, N, Oriuchi, M, Tateno, and H, Koide
- Subjects
Autoradiography ,Gamma Cameras ,RNA Probes ,DNA Probes ,Phosphorus Radioisotopes - Published
- 1991
27. [Distribution of N-isopropyl-p-[I-123]iodoamphetamine among the peripheral blood components: an in vitro study]
- Author
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S, Kumazaki, N, Oriuchi, K, Tomiyoshi, T, Inoue, and Y, Sasaki
- Subjects
Iodine Radioisotopes ,Plasma ,Blood Cells ,Amphetamines ,Humans ,Technetium Tc 99m Pentetate ,Organotechnetium Compounds ,In Vitro Techniques ,Pentetic Acid ,Iofetamine - Abstract
With the purpose to clarify dynamics of N-isopropyl-p-[I-123]iodoamphetamine (I-123 IMP) in the blood stream its binding to the peripheral blood components was determined by in vitro experiment. I-123 IMP was added to the peripheral venous blood obtained from healthy volunteers to be incubated for different length of time (0-30 min) at 37 degrees C. The blood was then separated into blood cells and plasma. From the latter platelet rich plasma were separated. Radioactivity in each blood component was counted in a well type scintillation counter respectively. To evaluate the affinity of I-123 IMP to red blood cell the component containing blood cells were washed repeatedly with salines. It was found that the fraction of radioactivity in the blood cell component was 68.0 +/- 6.3% (m +/- 1 S.D.), which was higher than that in the plasma (32.0% +/- 6.3%). The radioactivity in the platelet-rich plasma was only 1.7 +/- 1.1% of the total I-123 IMP activity. This percentage did not change by the incubation time. When Tc-99m DTPA was incubated with blood, radioactivity in the blood cell component was only 22.5%, which is further lowered by 32 +/- 2.1% after each washing to reach 6.8% after three times washing. In contrast the radioactivity of I-123 IMP in blood cell component remained as high as 31.1% after eight times washing. Almost constant fraction (8.20 +/- 0.57%) of radioactivity was freed into supernate by each washing. These findings suggest that a certain specific binding mechanism is involved in the binding of I-123 IMP to red blood cells.
- Published
- 1990
28. In Memoriam Professor Edward Robert Hitchcock
- Author
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D.B. Jacques, Michael Dogali, Antonio V. Delgado-Escueta, Sang Sup Chung, A. Beriç, R. Quiñones-Molina, E. Waidhauser, Barbara E. Swartz, Gonzalo Flores, Takamitsu Yamamoto, B.A. Meyerson, Raul Marino, C. Dills, S.G. Diamond, C. González, J. Piedra, J. Guridi, D. Albe-Fessard, M. Dogali, David H. Kidd, Ettore Lettich, Bodo Lippitz, Z.H.T. Kiss, U. Steude, Jeffrey Lewine, D.R. Samelson, Lawrence Goldbe, J. Leiphart, J. Gonçalves, D. Hoffmann, O. Torres, Mario Meglio, O.V. Kopyov, J.A. Barcia, J.L. Barcia-Salorio, N. Hayase, Jean Siegfried, Thomas T. Lee, R. Pantieri, E.H. Kolodny, Jin Woo Chang, P. Mertens, B. Linderoth, J. Mukawa, J. Guillen, M. Sindou, K. Mori, R.W. Rand, G. Carbone, D. Servello, I. Onzaín, N. Tomiyama, Maria Herrero, Matthew A. Howard, C.M. Markham, Christopher C. Gallen, George A. Ojemann, Y. Terada, Lauri V. Laitinen, S. Takikawa, M. Leon, Fiacro Jiménez, Brian B. Gallagher, D. Sterio, Abdelhamid Benazzouz, F. Mauguière, David Eidelberg, J. Teijeiro, A. Laurent, J.L. Llácer, K. Tomiyoshi, Antonio A.F. De Salles, R.Q. Quiñones-Molina, J. Conçalves, A. Alaminos, K. Watanabe, P. Mazzone, Michael S. Lee, R. Pisani, A. L. Benabid, B. Snow, Javier Muñoz, Joon Hyong Cho, I. Dones, Blaine S. Nashold, L. Alvarez, Ana Luisa Velasco, Rubin Mezrich, R. Luquin, Don W. King, R.M. Lehman, Joseph R. Smith, J.O. Dostrovsky, L. Pentimalli, G. Turano, K. Cuétara, Francisco Velasco, Chihiro Ohye, E. Fazzini, Steven Piantodosi, R. Macías, W.H. Sweet, F. Morales, O. Devinsky, W. Soler, Rodolfo Ondarza, M.J. Sánchez-Ledesma, Anthony M. Murro, P. Herregodts, Ch. Ohye, A. Arrigo, Pierre Pollak, Marcos Velasco, N. Pizio, I. Ortega, Manuel Velasco-Suárez, H. Molina, J. Perret, I. Silva, C. Ohye, Beatrice Cioni, G. Garcia-March, Jacob Sage, Jose A. Obeso, Richard B. North, Daniel J. Luciano, Eduardo Garcia-Flores, A. Torres, S. Vergari, B. Ren, Jorge Aceves, M. Gentil, A. Takahashi, G. Marano, Massimiliano Visocchi, Edward Hitchcock, D.M. Gao, C. Gross, M. Hirato, J. Broseta, Ronald R. Tasker, K. Yamashiro, Eun Ik-Son, Takashi Tsubokawa, T. Shibasaki, G. Broggi, Yong Gou Park, S. Horikoshi, A. Tancredi, Barry J. Schwartz, Orrin Devinsky, Richard Levy, A. Ishida, Yoichi Katayama, Flavio Nobili, William W. Orrison, M. Rojas, Kenneth Perrine, and Julian Hitchcock
- Subjects
Cognitive science ,business.industry ,Nectar ,Art history ,Medicine ,Surgery ,Neurology (clinical) ,business - Published
- 1994
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29. The usefulness of 18F-FDG SPECT imaging in evaluating myocarial viability
- Author
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N Ota, T Inoue, Keigo Endo, Tadashi Suzuki, T Toyama, K Tomiyoshi, Hideki Sato, Kanazawa N, Kaneko Y, and Ryozo Nagai
- Subjects
business.industry ,Spect imaging ,Medicine ,Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine ,Nuclear medicine ,business - Published
- 1997
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30. Prof. E. Hitchcock
- Author
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Eduardo Garcia-Flores, C. González, W. Soler, Abdelhamid Benazzouz, J.L. Llácer, Don W. King, Ettore Lettich, Bodo Lippitz, Z.H.T. Kiss, U. Steude, Jeffrey Lewine, D. Hoffmann, Lawrence Goldbe, J. Leiphart, B. Linderoth, Anthony M. Murro, Mario Meglio, Ronald R. Tasker, J. Piedra, J. Guridi, A. Beriç, F. Morales, J. Mukawa, G. Carbone, Manuel Velasco-Suárez, H. Molina, A. Laurent, E.H. Kolodny, J. Perret, William W. Orrison, R.Q. Quiñones-Molina, M. Hirato, J. Conçalves, S. Horikoshi, A. Torres, Jacob Sage, David Eidelberg, J. Teijeiro, George A. Ojemann, Richard B. North, Jorge Aceves, M. Gentil, I. Dones, Matthew A. Howard, G. Marano, R. Pisani, Eun Ik-Son, M. Rojas, Michael Dogali, Yong Gou Park, Steven Piantodosi, Edward Hitchcock, D.R. Samelson, A. Takahashi, N. Hayase, J. Broseta, Massimiliano Visocchi, K. Mori, R. Quiñones-Molina, G. Turano, Julian Hitchcock, D.M. Gao, I. Onzaín, E. Waidhauser, Lauri V. Laitinen, K. Cuétara, L. Pentimalli, R. Pantieri, C. Gross, C. Ohye, G. Garcia-March, N. Tomiyama, J. Guillen, Fiacro Jiménez, Ch. Ohye, B. Ren, R. Macías, M.J. Sánchez-Ledesma, Chihiro Ohye, Maria Herrero, O. Devinsky, C.M. Markham, B.A. Meyerson, I. Ortega, G. Broggi, I. Silva, Daniel Luciano, P. Herregodts, A. Arrigo, K. Tomiyoshi, Raul Marino, A. L. Benabid, Brian B. Gallagher, N. Pizio, M. Sindou, A. Tancredi, Christopher C. Gallen, Joon Hyong Cho, Beatrice Cioni, D. Servello, F. Mauguière, P. Mazzone, Yoichi Katayama, Y. Terada, Rubin Mezrich, Kenneth Perrine, Flavio Nobili, R.W. Rand, Joseph R. Smith, S. Vergari, Richard Levy, Ana Luisa Velasco, A. Ishida, Jean Siegfried, K. Watanabe, D.B. Jacques, E. Fazzini, L. Alvarez, B. Snow, Barry J. Schwartz, David H. Kidd, C. Dills, S.G. Diamond, Orrin Devinsky, Antonio V. Delgado-Escueta, Sang Sup Chung, K. Yamashiro, Francisco Velasco, Takashi Tsubokawa, T. Shibasaki, M. Leon, Marcos Velasco, Antonio A.F. De Salles, D. Sterio, Gonzalo Flores, Barbara E. Swartz, Takamitsu Yamamoto, A. Alaminos, M. Dogali, Javier Muñoz, O.V. Kopyov, R. Luquin, J.L. Barcia-Salorio, O. Torres, Jin Woo Chang, P. Mertens, Michael S. Lee, R.M. Lehman, Blaine S. Nashold, S. Takikawa, J.O. Dostrovsky, D. Albe-Fessard, Thomas T. Lee, J. Gonçalves, J.A. Barcia, W.H. Sweet, Rodolfo Ondarza, Pierre Pollak, and Jose A. Obeso
- Subjects
Surgery ,Neurology (clinical) - Published
- 1994
- Full Text
- View/download PDF
31. On the mechanism of the thermal F + C2H4 reaction. the molecular elimination of HF from chemically activated C2 H4F radicals
- Author
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John W. Root, Chester A. Mathis, Xue Zhi-len, Mark B. Knickelbein, and K. Tomiyoshi
- Subjects
Reaction behavior ,Recoil ,Computational chemistry ,Chemistry ,Radical ,Thermal ,Physics::Atomic and Molecular Clusters ,General Physics and Astronomy ,Physics::Atomic Physics ,Physics::Chemical Physics ,Physical and Theoretical Chemistry ,Nuclear Experiment ,Mechanism (sociology) - Abstract
The moderated nuclear recoil technique has been used to investigate the gas-phase unimolecular reaction behavior of activated C2H418F radicals produced by addition of thermal 18F atoms to C2H4. At low pressures, these radicals decompose both by H-atom loss and by molecular H18F elimination.
- Published
- 1983
- Full Text
- View/download PDF
32. Electronic structures and NMR of some hydroxycarbonium ions
- Author
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T. Yoshida, K. Ohkubo, and K. Tomiyoshi
- Subjects
Coupling constant ,Fermi contact interaction ,Proton ,Chemistry ,Chemical shift ,Organic Chemistry ,Analytical Chemistry ,Ion ,Inorganic Chemistry ,Paramagnetism ,Physical chemistry ,Diamagnetism ,Molecule ,Atomic physics ,Spectroscopy - Abstract
The proton and isotropic ( 13 C) magnetic resonances of some hydroxycarbonium ions (HCHOH + , CH 3 CHOH + (CH 3 ) 2 COH + HCO 2 H 2 + , CH 3 CO 2 H 2 + , and CH 3 OH 2 + ) are discussed in relation to their electronic structures computed by means of the INDO—SCF method. The proton and carbon-13 chemical shifts, which depend directly on the local diamagnetic and paramagnetic contributions respectively, are reasonably explained by the electronic structures of the hydroxycarbonium ions relative to those of the corresponding parent molecules. The Fermi contact interaction term is found to be well reflected in the hydrogen-hydrogen and carbon-hydrogen coupling constants, and the differences in the coupling constants between rotational isomers of the ions are discussed from the viewpoint of their electronic properties.
- Published
- 1977
- Full Text
- View/download PDF
33. Reactions of recoil halogen atoms in liquid aqueous solutions of 5-bromouridine. Interaction and association of solutes and population distribution of associated species
- Author
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L. R. Opelanio-Buencamino, K. Tomiyoshi, and E. P. Rack
- Subjects
education.field_of_study ,Aqueous solution ,Chemistry ,Population ,Inorganic chemistry ,General Engineering ,Photochemistry ,chemistry.chemical_compound ,Recoil ,Ionization ,Halogen ,5-Bromouridine ,Physical and Theoretical Chemistry ,education - Published
- 1985
- Full Text
- View/download PDF
34. Electronic structures and configurational transformations of some protonated compounds
- Author
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M. Okada, T. Yoshida, K. Ohkubo, and K. Tomiyoshi
- Subjects
Inorganic Chemistry ,Crystallography ,Chemistry ,Organic Chemistry ,Protonation ,Bending ,Rotation (mathematics) ,Spectroscopy ,Analytical Chemistry - Abstract
The equilibrium geometries of HCHOH+, CH3CHOH+, (CH3)2COH+, HCO2H+2, and CH3CO2H+2 were determined by means of the semiempirical INDO—SCF method. The total-energy difference between the protonated isomers was found to be reasonable as compared with that obtained from the NMR observations. The computed barriers of the transformation between the isomers via the pure or distorted rotation or the bending motion were in good agreement with the experimental results.
- Published
- 1976
- Full Text
- View/download PDF
35. Optimization Processes of Clinical Chelation-Based Radiopharmaceuticals for Pathway-Directed Targeted Radionuclide Therapy in Oncology.
- Author
-
Tomiyoshi K, Wilson LJ, Mourtada F, Mourtada JS, Namiki Y, Kamata W, Yang DJ, and Inoue T
- Abstract
Targeted radionuclide therapy (TRT) for internal pathway-directed treatment is a game changer for precision medicine. TRT improves tumor control while minimizing damage to healthy tissue and extends the survival for patients with cancer. The application of theranostic-paired TRT along with cellular phenotype and genotype correlative analysis has the potential for malignant disease management. Chelation chemistry is essential for the development of theranostic-paired radiopharmaceuticals for TRT. Among image-guided TRT,
68 Ga and99m Tc are the current standards for diagnostic radionuclides, while177 Lu and225 Ac have shown great promise for β- and α-TRT, respectively. Their long half-lives, potent radiobiology, favorable decay schemes, and ability to form stable chelation conjugates make them ideal for both manufacturing and clinical use. The current challenges include optimizing radionuclide production processes, coordinating chelation chemistry stability of theranostic-paired isotopes to reduce free daughters [this pertains to225 Ac daughters221 Fr and213 Bi]-induced tissue toxicity, and improving the modeling of micro dosimetry to refine dose-response evaluation. The empirical approach to TRT delivery is based on standard radionuclide administered activity levels, although clinical trials have revealed inconsistent outcomes and normal-tissue toxicities despite equivalent administered activities. This review presents the latest optimization methods for chelation-based theranostic radiopharmaceuticals, advancements in micro-dosimetry, and SPECT/CT technologies for quantifying whole-body uptake and monitoring therapeutic response as well as cytogenetic correlative analyses.- Published
- 2024
- Full Text
- View/download PDF
36. Fibulin-4 as a potential extracellular vesicle marker of fibrosis in patients with cirrhosis.
- Author
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Kumagai M, Tsuchiya A, Yang Y, Takeda N, Natsui K, Natusi Y, Tomiyoshi K, Yamazaki F, Koseki Y, Shinchi H, Imawaka N, Ukekawa R, Nishibu T, Abe H, Sasaki T, Ueda K, and Terai S
- Subjects
- Humans, Male, Female, Middle Aged, Extracellular Matrix Proteins metabolism, Extracellular Matrix Proteins blood, Proteomics methods, Aged, Adult, Liver Cirrhosis metabolism, Liver Cirrhosis pathology, Biomarkers blood, Biomarkers metabolism, Extracellular Vesicles metabolism
- Abstract
Chronic liver injury leads to decreased liver function and increased fibrosis. Fibrosis is not only associated with the development of portal hypertension and carcinogenesis, but with the occurrence of events and a poor prognosis, highlighting the importance of non-invasive fibrosis assessment in patients. In the present study, we searched for markers related to liver fibrosis via proteomic analysis of small extracellular vesicles (sEVs). In the discovery cohort, proteomic analysis was carried out in the sEVs extracted from the sera of 5 patients with decompensated cirrhosis, 5 patients with compensated cirrhosis, and 5 controls without liver disease. Interestingly, in this cohort, fibulin-4 was significantly associated with cirrhosis while in the validation cohort [formed by 191 patients: 7 patients without disease, 16 patients without liver disease (other diseases), 38 patients with chronic liver disease (CLD), 75 patients with cirrhosis of Child-Pugh class A (36 without hepatocellular carcinoma [HCC], 29 with HCC), and 65 patients with cirrhosis of Child-Pugh class B-C (39 without HCC, 26 with HCC)], fibulin-4/CD9 levels increased with cirrhosis progression. Furthermore, the fibulin-4/CD9 ratio was significantly higher in patients with varices. Immunostaining also revealed strong fibulin-4 expression in cholangiocytes within the fibrous areas and mesothelial cells in liver tissue blood vessels. Taken together, our results suggest that fibulin-4, essential for lysyl oxidase activation, might be a new liver fibrosis marker found in the sEVs of patients with cirrhosis., (© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2024
- Full Text
- View/download PDF
37. Accurate gamma-ray dose measurement up to 10 MeV by glass dosimeter with a sensitivity control filter for BNCT.
- Author
-
Kamisaki F, Inoue T, Tomiyoshi K, Matsuki M, Aoki K, Kusaka S, Tamaki S, Sato F, and Murata I
- Abstract
Glass dosimeters are very useful and convenient detection elements in radiation dosimetry. In this study, this glass dosimeter was applied to a BNCT treatment field. Boron Neutron Capture Therapy (BNCT) is a next-generation radiation therapy that can selectively kill only cancer cells. In the BNCT treatment field, both neutrons and secondary gamma-rays are generated. In other words, it is a mixed radiation field of neutrons and gamma-rays. We thus proposed a novel method to measure only gamma-ray dose in the mixed field using two RPLGD (Radiophoto-luminescence Glass Dosimeter) and two sensitivity control filters in order to control the dose response of the filtered RPLGD to be proportional to the air kerma coefficients, even if the gamma-ray energy spectrum is unknown. As the filter material iron was selected, and it was finally confirmed that reproduction of the air kerma coefficients was excellent within an error of 5.3% in the entire energy range up to 10 MeV. In order to validate this method, irradiation experiments were carried out using standard gamma-ray sources. As the result, the measured doses were in acceptably good agreement with the theoretical calculation results by PHITS. In the irradiation experiment with a volume source in a nuclear fuel storage room, the measured dose rates showed larger compared with survey meter values. In conclusion, the results of the standard sources showed the feasibility of this method, however for the volume source the dependence of the gamma-ray incident angle on the dosimeter was found to be not neglected. In the next step, it will be necessary to design a thinner filter in order to suppress the effect of the incident angle., Competing Interests: Declaration of competing interest We have no conflict of interest for the contents in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
38. Actinium-225 Targeted Agents: Where Are We Now?
- Author
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Mourtada F, Tomiyoshi K, Sims-Mourtada J, Mukai-Sasaki Y, Yagihashi T, Namiki Y, Murai T, Yang DJ, and Inoue T
- Subjects
- Humans, Radiopharmaceuticals therapeutic use, Actinium therapeutic use, Brachytherapy methods, Neoplasms radiotherapy
- Abstract
α-particle targeted radionuclide therapy has shown promise for optimal cancer management, an exciting new era for brachytherapy. Alpha-emitting nuclides can have significant advantages over gamma- and beta-emitters due to their high linear energy transfer (LET). While their limited path length results in more specific tumor 0kill with less damage to surrounding normal tissues, their high LET can produce substantially more lethal double strand DNA breaks per radiation track than beta particles. Over the last decade, the physical and chemical attributes of Actinium-225 (
225 Ac) including its half-life, decay schemes, path length, and straightforward chelation ability has peaked interest for brachytherapy agent development. However, this has been met with challenges including source availability, accurate modeling for standardized dosimetry for brachytherapy treatment planning, and laboratory space allocation in the hospital setting for on-demand radiopharmaceuticals production. Current evidence suggests that a simple empirical approach based on225 Ac administered radioactivity may lead to inconsistent outcomes and toxicity. In this review article, we highlight the recent advances in225 Ac source production, dosimetry modeling, and current clinical studies., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
39. Analysis of distribution, collection, and confirmation of capacity dependency of small extracellular vesicles toward a therapy for liver cirrhosis.
- Author
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Takeda N, Tsuchiya A, Mito M, Natsui K, Natusi Y, Koseki Y, Tomiyoshi K, Yamazaki F, Yoshida Y, Abe H, Sano M, Kido T, Yoshioka Y, Kikuta J, Itoh T, Nishimura K, Ishii M, Ochiya T, Miyajima A, and Terai S
- Abstract
Background: The progression of liver fibrosis leads to portal hypertension and liver dysfunction. However, no antifibrotic agents have been approved for cirrhosis to date, making them an unmet medical need. Small extracellular vesicles (sEVs) of mesenchymal stem cells (MSCs) are among these candidate agents. In this study, we investigated the effects of sEVs of MSCs, analyzed their distribution in the liver post-administration, whether their effect was dose-dependent, and whether it was possible to collect a large number of sEVs., Methods: sEVs expressing tdTomato were generated, and their uptake into constituent liver cells was observed in vitro, as well as their sites of uptake and cells in the liver using a mouse model of liver cirrhosis. The efficiency of sEV collection using tangential flow filtration (TFF) and changes in the therapeutic effects of sEVs in a volume-dependent manner were examined., Results: The sEVs of MSCs accumulated mostly in macrophages in damaged areas of the liver. In addition, the therapeutic effect of sEVs was not necessarily dose-dependent, and it reached a plateau when the dosage exceeded a certain level. Furthermore, although ultracentrifugation was commonly used to collect sEVs for research purposes, we verified that TFF could be used for efficient sEV collection and that their effectiveness is not reduced., Conclusion: In this study, we identified some unknown aspects regarding the dynamics, collection, and capacity dependence of sEVs. Our results provide important fundamentals for the development of therapies using sEVs and hold potential implications for the therapeutic applications of sEV-based therapies for liver cirrhosis., (© 2023. Japanese Society of Inflammation and Regeneration.)
- Published
- 2023
- Full Text
- View/download PDF
40. Response control of RPLGD for gamma-ray dose measurement using lead filters for BNCT.
- Author
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Tochitani K, Tomiyoshi K, Inoue T, Kamisaki F, Matsuki M, Hiramatsu K, Aoki K, Kusaka S, Tamaki S, Sato F, and Murata I
- Abstract
Boron Neutron Capture Therapy (BNCT) is a cell-selective radiotherapy using a neutron capture reaction of
10 B. In recent years, Accelerator Based Neutron Sources (ABNS) are under development instead of nuclear reactors for the next-generation neutron irradiation system for BNCT. However, ABNS as well as nuclear reactor usually generates unavoidable secondary gamma-rays by neutron-nuclear reactions such as capture reaction. In this research, we aimed to develop a separate measurement method of only gamma-rays in a mixed field of neutrons and gamma-rays using a fluorescent glass dosimeter (RPLGD), because most dosimeters have sensitivity to both radiation types. For this purpose, we proposed a lead filter method using two RPLGDs and lead filters. However, this method has a problem that the sensitivity to low energy gamma-rays (∼100 keV) is very small. In order to improve the sensitivity to low energy gamma-rays, we devised a method using a specially shaped lead filter. From theoretical calculations, we have shown that it was possible to estimate the air dose rate of the field where the gamma-ray energy spectrum shape was known for energies up to 10 MeV. In addition, we produced the specially shaped lead filter and experimentally confirmed the validity of the lead filter method using several gamma-ray standard sources and by measurements in a nuclear fuel storage room., Competing Interests: Declaration of competing interest We have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
41. Escherichia coli-derived outer-membrane vesicles induce immune activation and progression of cirrhosis in mice and humans.
- Author
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Natsui K, Tsuchiya A, Imamiya R, Osada-Oka M, Ishii Y, Koseki Y, Takeda N, Tomiyoshi K, Yamazaki F, Yoshida Y, Ohashi R, Ling Y, Ueda K, Moritoki N, Sato K, Nakajima T, Hasegawa Y, Okuda S, Shibata S, and Terai S
- Subjects
- Humans, Mice, Animals, Liver Cirrhosis, Inflammation, Escherichia coli, Ascites
- Abstract
Background and Aims: Decompensated cirrhosis with fibrosis progression causes portal hypertension followed by an oedematous intestinal tract. These conditions weaken the barrier function against bacteria in the intestinal tract, a condition called leaky gut, resulting in invasion by bacteria and bacterial components. Here, we investigated the role of outer-membrane vesicles (OMVs) of Escherichia coli, which is the representative pathogenic gut-derived bacteria in patients with cirrhosis in the pathogenesis of cirrhosis., Methods: We investigated the involvement of OMVs in humans using human serum and ascites samples and also investigated the involvement of OMVs from E. coli in mice using mouse liver-derived cells and a mouse cirrhosis model., Results: In vitro, OMVs induced inflammatory responses to macrophages and neutrophils, including the upregulation of C-type lectin domain family 4 member E (Clec4e), and induced the suppression of albumin production in hepatocytes but had a relatively little direct effect on hepatic stellate cells. In a mouse cirrhosis model, administration of OMVs led to increased liver inflammation, especially affecting the activation of macrophages, worsening fibrosis and decreasing albumin production. Albumin administration weakened these inflammatory changes. In addition, multiple antibodies against bacterial components were increased with a progressing Child-Pugh grade, and OMVs were detected in ascites of patients with decompensated cirrhosis., Conclusions: In conclusion, OMVs induce inflammation, fibrosis and suppression of albumin production, affecting the pathogenesis of cirrhosis. We believe that our study paves the way for the future prevention and treatment of cirrhosis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
42. Synthesized HMGB1 peptide prevents the progression of inflammation, steatosis, fibrosis, and tumor occurrence in a non-alcoholic steatohepatitis mouse model.
- Author
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Ishii Y, Tsuchiya A, Natsui K, Koseki Y, Takeda N, Tomiyoshi K, Yamazaki F, Yoshida Y, Shimbo T, Tamai K, and Terai S
- Abstract
Aim: Non-alcoholic steatohepatitis (NASH) with fibrosis eventually leads to cirrhosis and hepatocellular carcinoma. Thus, the development of therapies other than dietary restriction and exercise, particularly those that suppress steatosis and fibrosis of the liver and have a long-term beneficial effect, is necessary. We aimed to evaluate the therapeutic effects of the HMGB1 peptide synthesized from box A using the melanocortin-4 receptor-deficient (Mc4r-KO) NASH model mouse., Methods: We performed short- and long-term administration of this peptide and evaluated the effects on steatosis, fibrosis, and carcinogenesis using Mc4r-KO mice. We also analyzed the direct effect of this peptide on macrophages and hepatic stellate cells in vitro and performed lipidomics and metabolomics techniques to evaluate the effect., Results: Although this peptide did not show direct effects on macrophages and hepatic stellate cells in vitro, in the short-term administration model, we could confirm the reduction of liver damage, steatosis, and fibrosis progression. The results of lipidomics and metabolomics suggested that the peptide might ameliorate NASH by promoting lipolysis via the activation of fatty acid β-oxidation and improving insulin resistance. In the long-term administration model, this peptide prevented progression to cirrhosis but retained the steatosis state, that is, the peptide prevents the progression to "burnt-out NASH." This peptide inhibited carcinogenesis by about one-third., Conclusion: This HMGB1 peptide can reduce liver damage, improve fibrosis and steatosis, and inhibit carcinogenesis, suggesting that the peptide would be a new treatment candidate for NASH and can contribute to the long-term prognosis for patients with NASH., (© 2022 Japan Society of Hepatology.)
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- 2022
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43. Small extracellular vesicles and liver diseases: From diagnosis to therapy.
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Tsuchiya A, Natsui K, Ishii Y, Koseki Y, Takeda N, Tomiyoshi K, Yamazaki F, Yoshida Y, and Terai S
- Abstract
Extracellular vesicles (EVs), especially small EVs (sEVs) derived from liver cells, have been the focus of much attention in the normal physiology and pathogenesis of various diseases affecting the liver. sEVs are approximately 100 nm in size, enclosed within lipid bilayers, and are very stable. The lipids, proteins, and nucleic acids, including miRNAs, contained within these vesicles are known to play important roles in intercellular communication. This mini-review summarizes the application of sEVs. First, liver diseases and the related diagnostic markers are described, and the current active status of miRNA research in diagnosis of hepatocellular carcinoma (HCC) is reported. Second, the biodistribution and pharmacokinetics of sEVs are described, and the liver is highlighted as the organ with the highest accumulation of sEVs. Third, the relationship between sEVs and the pathogenesis of liver disorders is described with emphesis on the current active status of miRNA research in HCC recurrence and survival. Finally, the possibility of future therapy using sEVs from mesenchymal stem (stromal) cells for cirrhosis and other diseases is described., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2022
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44. Rare Genotype of His/His in NUDT15 Codon 139 and Thiopurine-associated Adverse Events in a Case of Ulcerative Colitis.
- Author
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Tomiyoshi K, Sato H, Tominaga K, Kawata Y, Okamoto D, Kakuta Y, Yokoyama J, and Terai S
- Subjects
- Alopecia chemically induced, Asian People genetics, Azathioprine pharmacokinetics, Azathioprine therapeutic use, Codon, Genetic Predisposition to Disease, Genotype, Humans, Leukopenia chemically induced, Risk Factors, Azathioprine adverse effects, Colitis, Ulcerative drug therapy, Pyrophosphatases genetics
- Abstract
Thiopurine drugs are commonly used to treat immunologic diseases. However, the narrow therapeutic safety margin demands evidence-based precision medicine approaches. NUDT15 variants are associated with thiopurine-induced adverse events, particularly in Asians. We herein report a rare genotype of His/His in NUDT15 codon 139 in a case of ulcerative colitis and review the relevant literature. The patient experienced severe thiopurine-associated adverse events, including leukopenia and alopecia. There is no literature on the His/His genotype in NUDT15 codon 139, and our case suggests cautious use or the contraindication of thiopurines for patients with this genotype.
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- 2020
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45. Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases.
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Tsuchiya A, Takeuchi S, Iwasawa T, Kumagai M, Sato T, Motegi S, Ishii Y, Koseki Y, Tomiyoshi K, Natsui K, Takeda N, Yoshida Y, Yamazaki F, Kojima Y, Watanabe Y, Kimura N, Tominaga K, Kamimura H, Takamura M, and Terai S
- Abstract
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)
- Published
- 2020
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46. Hemorrhagic Gastric Metastasis from Hepatocellular Carcinoma Successfully Treated Using Coil Embolization of the Left Gastric Artery.
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Imai M, Ishikawa T, Okoshi M, Tomiyoshi K, Kojima Y, Horigome R, Nozawa Y, Sano T, Iwanaga A, Honma T, Nemoto T, Takeda K, Nishikura K, Ishihara N, and Yoshida T
- Subjects
- Chemoembolization, Therapeutic methods, Humans, Liver Neoplasms physiopathology, Male, Middle Aged, Stomach Neoplasms physiopathology, Treatment Outcome, Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular surgery, Gastric Artery surgery, Gastrointestinal Hemorrhage etiology, Gastrointestinal Hemorrhage surgery, Liver Neoplasms surgery, Neoplasm Metastasis therapy, Stomach Neoplasms surgery
- Abstract
A 62-year-old man initially underwent transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). One year after the initial treatment, he developed anemia. Upper gastrointestinal endoscopy revealed irregularly elevated tumors in the lower anterior gastric body, which were diagnosed to be metastasis from HCC. Left gastric artery coil embolization was performed to prevent sustained bleeding, and his anemia partially improved. In addition to direct invasion, hematogenous metastasis to the stomach from HCC is possible and therefore should be considered during treatment. Transcatheter arterial embolization for gastric metastasis is an effective treatment method which achieves a good degree of hemostasis in patients without any surgical indications.
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- 2019
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47. Efficacy and safety of repeated use of lusutrombopag prior to radiofrequency ablation in patients with recurrent hepatocellular carcinoma and thrombocytopenia.
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Ishikawa T, Okoshi M, Tomiyoshi K, Kojima Y, Horigome R, Imai M, Nozawa Y, Iwanaga A, Sano T, Honma T, and Yoshida T
- Abstract
Aims: Thrombocytopenia is often associated with chronic liver disease. Lusutrombopag is a small molecule thrombopoietin receptor agonist designed to temporarily increase the platelet count in patients with chronic liver disease for whom elective invasive procedures are planned. In the present study, the efficacy and safety of repeated use of lusutrombopag prior to radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma were examined., Methods: Eight patients with hepatocellular carcinoma who had a platelet count <50 000/μL prior to both initial and repeat RFA at the time of recurrence received lusutrombopag (3 mg/day) orally for 7 days between March 2016 and August 2018. The following were compared: the effect of lusutrombopag to increase the platelet count as determined by the platelet count after the initial and repeated use of lusutrombopag, the rate of avoiding platelet transfusion, and the presence of any complications., Results: The platelet count increased to 103 100 ± 22 800/μL 14 days after the first treatment and to 110 700 ± 17 800/μL 14 days after the repeated use. None of the patients required platelet transfusion. None of the patients developed clinical symptoms such as thrombosis, fever, rash, portal vein thrombosis, bleeding, or any other serious adverse events., Conclusions: Repeated use of lusutrombopag increased the platelet count. It did not cause any serious adverse events and led to avoidance of platelet transfusion. Radiofrequency ablation was carried out safely in all patients. Future studies with more cases of repeated use are needed to examine the long-term efficacy and safety of lusutrombopag., (© 2019 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society of Hepatology.)
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- 2019
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48. Cone beam versus conventional computed tomography angiography volume measurement in partial splenic embolization.
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Ishikawa T, Imai M, Okoshi M, Tomiyoshi K, Kojima Y, Horigome R, Nozawa Y, Sano T, Iwanaga A, Honma T, and Yoshida T
- Subjects
- Aged, Angiography, Digital Subtraction, Cohort Studies, Female, Humans, Liver Diseases etiology, Male, Middle Aged, Computed Tomography Angiography, Cone-Beam Computed Tomography, Embolization, Therapeutic, Liver Diseases diagnostic imaging, Liver Diseases therapy, Splenic Artery
- Abstract
When performing partial splenic arterial embolization (PSE), it can be difficult to determine the embolization ratio based on 2-dimensional digital subtraction angiography (DSA) image diagnosis alone. Therefore, at our department, we conduct computed tomography (CT) imaging intraoperatively and postoperatively to determine whether the planned embolization has been achieved. In recent years, developments in interventional radiology devices have enabled diagnostic imaging using cone beam CT. Here, we investigated whether the embolization ratio could be predicted from volume measurement with cone beam CT in PSE.We investigated correlations between volume measurement with conventional CT angiography (CTA) and volume measurement with cone beam CTA in 11 cases that underwent PSE with cone beam CT guidance (Allura Clarity FD20; Phillips, Amsterdam, The Netherlands) between December 2013 and May 2018.The mean subject age was 65.0 ± 5.8 years (6 men, 5 women). The subjects had underlying liver disorders of hepatitis C virus infection (4 cases), nonalcoholic steatohepatitis (4 cases), and alcohol-related disease (3 cases). A positive correlation was noted between conventional CTA and cone beam CTA, with infarction rates of 61.28 ± 9.31% and 64.04 ± 9.24%, respectively. The correlation coefficient between the 2 variables was .772.Because blood washout occurs rapidly in the spleen, contrast medium had to be continuously injected during imaging to enable dual-phase imaging with cone beam CT. However, we successfully performed imaging up to the second phase and volume measurement for the embolization ratio by inserting a catheter into the splenic artery and confirming the cone beam CT arrival time from the DSA images. The results were almost identical to those obtained from volume measurement with conventional CT based on CTA imaging. Thus, our results suggest that the splenic embolization ratio measurement obtained via cone beam CTA can be used to assess PSE treatment endpoints.
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- 2019
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49. Evaluation of affinity of newly developed radiolabeled compound EISB on normal mice and amyloid deposition mice and its SPECT/CT imaging with 125 I-EISB.
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Tokunaga Y, Suzuki R, Kashiwa K, and Tomiyoshi K
- Subjects
- Animals, Drug Evaluation, Preclinical, Mice, Radiopharmaceuticals pharmacokinetics, Radiopharmaceuticals pharmacology, Amyloid metabolism, Amyloidosis diagnostic imaging, Amyloidosis metabolism, Iodine Radioisotopes pharmacokinetics, Iodine Radioisotopes pharmacology, Single Photon Emission Computed Tomography Computed Tomography
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- 2019
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50. End Joining-Mediated Gene Expression in Mammalian Cells Using PCR-Amplified DNA Constructs that Contain Terminator in Front of Promoter.
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Nakamura M, Suzuki A, Akada J, Tomiyoshi K, Hoshida H, and Akada R
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- DNA Fragmentation, DNA Primers, HEK293 Cells, HeLa Cells, Hepatitis B Surface Antigens chemistry, Humans, Nuclear Localization Signals, Oligopeptides, Polymerase Chain Reaction, Sequence Analysis, DNA, Sequence Deletion, Transfection, Gene Expression Regulation, Nucleic Acid Amplification Techniques, Peroxisomes chemistry, Promoter Regions, Genetic, Terminator Regions, Genetic
- Abstract
Mammalian gene expression constructs are generally prepared in a plasmid vector, in which a promoter and terminator are located upstream and downstream of a protein-coding sequence, respectively. In this study, we found that front terminator constructs-DNA constructs containing a terminator upstream of a promoter rather than downstream of a coding region-could sufficiently express proteins as a result of end joining of the introduced DNA fragment. By taking advantage of front terminator constructs, FLAG substitutions, and deletions were generated using mutagenesis primers to identify amino acids specifically recognized by commercial FLAG antibodies. A minimal epitope sequence for polyclonal FLAG antibody recognition was also identified. In addition, we analyzed the sequence of a C-terminal Ser-Lys-Leu peroxisome localization signal, and identified the key residues necessary for peroxisome targeting. Moreover, front terminator constructs of hepatitis B surface antigen were used for deletion analysis, leading to the identification of regions required for the particle formation. Collectively, these results indicate that front terminator constructs allow for easy manipulations of C-terminal protein-coding sequences, and suggest that direct gene expression with PCR-amplified DNA is useful for high-throughput protein analysis in mammalian cells.
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- 2015
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