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Biomedical subjects

H Murata

Publications and source records attributed to H Murata.

At least 91 records · Page 5Linked to original sources

[Evaluation of clinical utility of 123I-MIBG scintigraphy in localization of tumors of sympathetic and adrenomedullary origin--a report of multicenter phase III clinical trials].

Phase III clinical study was performed to evaluate clinical utility of 123I-MIBG in the localization of tumors in 48 patients with tumors of sympathetic and adrenomedullary origin, diagnosed or strongly suspected. Sixteen patients had pheochromocytoma, 23 had neuroblastoma, 7 had medullary carcinoma of the thyroid, and 2 had Sipple syndrome. In 3 out of 48 patients, 123I-MIBG scintigraphy was performed twice. The clinical utility of 123I-MIBG was evaluated in 50 cases. Out of 140 lesions, 123I-MIBG scintigraphy demonstrated 51 true positive, 79 true negative, 1 false positive, and 2 false negative. Seven lesions were not evaluable. Sensitivity was 96.2%, Specificity was 98.8%, and Accuracy was 97.7%. An acquisition between 4 hrs and a day after injection was adequate for tumor detection. Neither adverse reactions nor abnormal laboratory findings were noted in relation to 123I-MIBG injections. Our study indicates that 123I-MIBG is a safe and useful radiotracer for visualization and localization of tumors of sympathetic and adrenomedullary origin.

3-Iodobenzylguanidine↗

New functional polar maps for estimating regional cardiac function using ECG-gated technetium-99m-tetrofosmin SPECT.

OBJECTIVE: The purpose of this work was to develop functional parameters to analyze regional cardiac function using ECG-gated 99mTc-tetrofosmin SPECT. Our goal was to develop a methodology that used slice thickness correction, the generation of a time-activity curve and a polar map. METHODS: Fourteen normal patients without evidence of coronary artery disease were studied. One hour after intravenous injection of 740-1110 MBq (20-30 mCi) 99mTc-tetrofosmin, ECG-gated SPECT data were acquired by dividing a cardiac cycle into 12 frames. The SPECT data were reconstructed from 11 of 12 frames into 3 views. The reconstruction of these images was repeated after performing slice thickness correction. Excluding the effect of different apex-to-base lengths at any frame during a cardiac cycle, 10 short-axis images with the same slice thickness were obtained. Each short-axis image was divided by 40 radii into 40 segments. The time-activity curve was generated from the total counts included in each segment plus both neighboring segments. Subsequently the curve fitting was performed using the second Fourier function. RESULTS: From fitted curves and their differentials, we calculated end-systolic count, end-diastolic count, percent count increase, uptake, peak contraction rate, peak distention rate and contraction time. CONCLUSION: The functional polar maps visually demonstrated regional myocardial function. This method is expected to be helpful for assessing regional cardiac function using 99mTc-tetrofosmin.

Adult↗

Saccharomyces cerevisiae cultured under aerobic and anaerobic conditions: air-level oxygen stress and protection against stress.

Cells of Saccharomyces cerevisiae were grown aerobically and anaerobically, and levels of the protective compounds, cysteine and glutathione, and activities of defensive enzymes, catalase and superoxide dismutase, against an oxygen stress were determined and compared in both cells. Aerobiosis increased both the compounds and enzyme activities. The elevated synthesis of glutathione could be associated with the increased levels of cysteine which in its turn was found to be controlled by the oxygen-dependent activation of cystathionine beta-synthase.

Aerobiosis↗

Microchimerism in Japanese women patients with systemic sclerosis.

To examine whether microchimerism occurs in Japanese women patients with systemic sclerosis, we analysed the Y-chromosome in DNA by PCR. There was no significant difference between patients and healthy people, suggesting that microchimerism may not be the sole pathogenesis in Japanese women with systemic sclerosis.

Chimera↗

Prognostic value of DNA ploidy response to chemotherapy in human osteosarcomas.

We analyzed the DNA ploidy alterations after preoperative chemotherapy in 30 patients with non-metastatic osteosarcomas of the extremities. All of the patients received intensive chemotherapy with doxorubicin, cisplatin and methotrexate as well as wide tumor resection. DNA ploidy was determined by DNA cytofluorometry using isolated and smeared cells from biopsied and resected tumors after preoperative chemotherapy. The results showed that 12 diploid and nine non-diploid osteosarcomas did not change their ploidy pattern, but nine non-diploid tumors changed to a diploid pattern with the disappearance of the aneuploid cells. The nine patients with altered ploidy tumors had a better histologic response to chemotherapy and a better prognosis than the patients with non-altered tumors especially diploid tumors (P = 0.0138). Therefore, we conclude that a decrease in aneuploid cells after chemotherapy is closely correlated with a good prognosis in half of the cases of aneuploid osteosarcoma. These results also suggest that aneuploid cells are more chemosensitive than diploid cells in human osteosarcomas.

Adolescent↗

Relationship between chromosomal aberrations by fluorescence in situ hybridization and DNA ploidy by cytofluorometry in osteosarcoma.

An analysis of the chromosomal aberrations and DNA ploidy in the interphase nuclei of seven human osteosacomas was preformed by double-target fluorescence in situ hybridization (FISH) and DNA cytofluorometry. The FISH study of the numerical aberrations in chromosomes 1 and 17 or the structural aberrations in chromosome arm 1p or 17p was carried out by using four locus specific DNA markers, with one pair consisting of 1q12 and 1p36 and the other pair consisting of the 17 cemtromere and 17p13.3. There was no significant differences in the percentage of deletions in chromosome 1 and 17 between osteosarcomas and normal tissues. However, all seven tumors studied had extra copies. Cells with more than three probe signals were regarded as having chromosome polysomy. The percentage of polysomy of chromosome 1 was 20.0-64.0%, and chromosome 17 was 28.0-60.0%. The DNA ploidy patterns of hyperdiploid cells showing a greater DNA content than diploid cells were obtained by DNA cytoflurometry. Five of the seven tumors were non-diploid, and the remaining two were diploid. The percentage of polysomy was correlated with the percentage of hyperdiploid cells in each tumor. Thus, these findings indicated that the DNA ploidy changes were closely correlated with aberrations in the chromosome copy number in osteosarcomas.

Adolescent↗

Response of DNA ploidy to chemotherapy in primary and metastatic lesions in human osteosarcomas.

Primary and pulmonary metastatic and pulmonary metastatic tumors (two synchronous and seven metachronous metastases) in nine patients with osteosarcomas were studied by DNA cytofluorometry. All patients were treated with both pre and postoperative chemotherapy. The results showed that all five diploid osteosarcomas and three of the four aneuploid tumors did not markedly change their ploidy pattern after preoperative chemotherapy, and had almost the same ploidy patterns as the pulmonary metastatic lesions. Those eight tumors showed poor histologic response and chemoresistance by the doxorubicin binding assay. Only one aneuploid osteosarcoma showing good histologic response and chemosensitivity changed its ploidy pattern to diploid, with the disappearance of aneuploid tumor cells and its synchronous pulmonary metastatic tumor also showed conversion to a diploid pattern with massive tumor necrosis. It is evident that those tumors showing no change in their ploidy pattern after chemotherapy were resistant to the chemotherapy. Therefore, we conclude that regardless of whether the pulmonary metastatic tumors were synchronous or metachronous, they showed the same change in their ploidy pattern as well as their chemosensitivity as the primary human osteosarcoma from which they were derived.

Adolescent↗

Relationship between P-glycoprotein positivity, doxorubicin binding ability and histologic response to chemotherapy in osteosarcomas.

We previously reported that the doxorubicin binding ability detected by the doxorubicin (adriamycin) binding assay was closely correlated with the chemosensitivity of human osteosarcomas. In this study, we undertook to clarify the relationship between P-glycoprotein positivity (%PPG) and doxorubicin binding ability (%DB) in human osteosarcomas in order to determine which is a more sensitive index of histologic response to chemotherapy. Ten primary osteosarcomas were analyzed by the doxorubicin binding assay and by immunofluorescence to detect cellular P-glycoprotein positivity. Three good responders to chemotherapy containing doxorubicin showed a %DB greater than 90% (average: 96.43%), whereas the seven poor responders had values less than 80% (average: 35.31%). The difference between the two groups was statistically significant (P = 0.0167). However, the average %PPG of the three good responders was 6.73%, whereas the %PPG of the seven poor responders was 14.27%. There was no significant difference in %PPG between the two groups (P = 0.3051). No negative correlation between the %DB and the %PPG of all osteosarcomas (r = 0.536, P = 0.1104) was found, although there was a trend that those tumors with a high %PPG showed a low %DB. These results suggest that osteosarcomas showing a low %DB and %PPG with poor response to chemotherapy, may have multidrug resistance mechanisms other than P-glycoprotein. Therefore, we conclude that doxorubicin binding ability, which reflects all of the doxorubicin-resistant mechanisms, was more sensitive than P-glycoprotein positivity in predicting the chemosensitivity of human osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prognostic significance of DNA ploidy pattern in osteosarcomas in association with chemotherapy.

In this study, we analysed the DNA ploidy of osteosarcomas at biopsy and attempted to clarify the relationship between DNA ploidy pattern and prognosis. Thirty patients with non-metastatic osteosarcoma of an extremity were studied. All underwent intensive chemotherapy with doxorubicin, cisplatin and methotrexate, in addition to wide tumor resection. DNA ploidy was detected by DNA cytofluorometry, using isolated and smeared cells of biopsied tumor tissue. Twelve tumors showed a diploid ploidy pattern and 18 showed a non-diploid pattern such as aneuploidy (15 tumors) and euploid-polyploidy (3 tumors). The event-free survival rate at 9 years was 63.5% in non-diploid osteosarcoma patients and 13.3% in diploid osteosarcoma patients. There was a statistically significant difference between the two groups (P = 0.0278). These results lead us to conclude that a non-diploid osteosarcoma may be more sensitive to chemotherapy than a diploid tumor.

Adolescent↗

Cytofluorometric DNA ploidy analysis in giant cell tumor of bone: histologic and prognostic value.

DNA ploidy analysis by DNA cytofluorometry was performed on 41 tumors obtained from 37 patients with primary giant cell tumor of bone (GCT). Histologically, 26 of the tumors from primary or recurrent lesions were evaluated as grade I, and 13 tumors as grade II. Among the 33 primary GCT patients, 4 patients had local recurrence or pulmonary metastasis. The DNA ploidy pattern and the percentage of hyperdiploid cells showing a greater DNA content than diploid cells, were obtained from DNA cytofluorometry. All of the 33 primary tumors were diploid. Of 6 recurrent tumors, 4 were diploid and 2 were euploid-polyploid. One of the two pulmonary metastatic tumors was diploid, but another that demonstrated a malignant transformation to malignant fibrous histiocytoma was aneuploid. The percentage of hyperdiploid cells was significantly different between primary and recurrent tumors (P = 0.0188) and between grade I and grade II tumors (P = 0.0052), while there was no difference between primary tumors in the cases that recurred or metastasized and those that did not. Thus, these data indicate that cell proliferative activity is closely correlated with biological aggressiveness and histological grading, although DNA ploidy is not useful for predicting prognosis.

Adolescent↗

Clinical outcome of total scapulectomy in 10 patients with primary malignant bone and soft-tissue tumors.

BACKGROUND AND OBJECTIVES: Limb reconstruction after total scapulectomy for malignant bone and soft-tissue tumors around the scapula is difficult. This study was undertaken to clarify the clinical results of total scapulectomy in patients with malignant bone and soft-tissue tumors around the shoulder girdle in our institute between 1984 and 1998. METHODS: Ten patients undergoing total scapulectomy had an age range of 12-82 years (average = 56 years). There were 5 cases of bone tumor and 5 cases of soft-tissue tumor. The follow-up period ranged from 8 months to 13 years 5 months. RESULTS: Seven patients are currently alive; the remaining 3 patients died of other diseases. One case of local recurrence was detected. The 2-year survival rate of all cases was 78.8%, and the 5-year survival rate was 52.5%. The average function evaluated by Enneking's criteria was 64.6%. Although the range of motion in the shoulder joint was seriously limited in all patients, the elbow and hand functions were almost normal. Recently, we have used a bone-anchoring system to suture between the clavicle and muscles, including the biceps, triceps, and deltoid muscles. CONCLUSIONS: Patients who undergo total scapulectomy may achieve much better upper limb function than those who undergo forequarter amputation (interscapulothoracic amputation).

Adolescent↗

Effect of edetate calcium disodium on yttrium-90 activity in bone of mice.

The kinetics of Yttrium-90 (Y-90) in bone of mice was investigated in combination with edetate calcium disodium (CaNa2EDTA). One group of mice were intraperitoneally administered 37.5 mg/kg CaNa2EDTA or 0.9% NaCl as a control at 1, 22, 34, 46, 58, 70, 82, 94, 154 and 166 h after injection of Y-90 acetate (post-administration), and the biodistribution was studied at 3, 24, 72, 120 and 168 h postinjection of Y-90 acetate. No difference between the post-CaNa2EDTA-treated mice and the control was demonstrated in the radioactivity in the bone. A decrease in radioactivity in the liver and kidneys was accelerated, and the radioactivity was lower than the control at 120 h postinjection. The other group of mice were also given the same dose of chelator at 12 h and 1 h preinjection of Y-90 acetate and at 1, 22, 34, 46, 58, 70, 82, 94, 154 and 166 h after injection of Y-90 acetate (pre- and post-administration), the radioactivity in bone at 3 h postinjection was significantly lower than in the control (24.4 +/- 3.92% ID/g vs. 31.7 +/- 2.26% ID/g, p < 0.05), but the decrease was not sequential. A significant reduction in radioactivity in the blood, kidneys and liver was demonstrated at 3 h, 72 h and 72 h postinjection. In conclusion, the CaNa2EDTA with the administration schedule employed here cannot chelate the Y-90 from bone but the free Y-90 before deposition into bone.

Animals↗

Stabilizing record bases for edentulous obturator prostheses with silicone resilient relining material.

Stable record bases are critical for recording accurate maxillomandibular relations and in the evaluation of the esthetics and phonetics of wax trial prostheses. However, the record base for a maxillary obturator is often compromised because of a surgical defect and/or because the weight of the record base creates instability. This article describes a simple procedure for retaining and stabilizing a record base for an edentulous obturator prosthesis using silicone resilient relining materials.

Denture Liners↗

Labeling of phosphorothioate antisense oligonucleotides with yttrium-90.

Novel yttrium-90 (90Y)-labeled phosphorothioate antisense oligonucleotides were designed as a potential targeted radionuclide therapeutic agent for malignant tumors. A 15-mer phosphorothioate antisense oligonucleotide, which was complementary to the translation start region of the N-myc oncogene mRNA, was conjugated with isothiocyanobenzyl ethylenediamine tetraacetic acid (SCN-Bn-EDTA), via a C-5-substituted deoxyuridine that had replaced a thymine in the oligonucleotide, and was then labeled with 90Y-acetate. Following purification, the radiochemical purity of the 90-Y-Bn-EDTA-phosphorothioate antisense oligonucleotides was estimated by 2.0% agarose gel electrophoresis, and the specific hybridization of 90Y-Bn-EDTA-phosphorothioate antisense oligonucleotide to a phosphorodiester sense oligonucleotide was investigated by 20% polyacrylamide gel electrophoresis in a cell-free system. Radiochemical purity was 98.7 +/- 0.4% at 72 h after labeling and 90.3 +/- 0.9% after 72-h incubation with human normal serum. The 90Y-Bn-EDTA-phosphorothioate antisense oligonucleotide hybridized specifically to a complementary phosphorodiester sense oligonucleotide. In conclusion, phosphorothioate antisense oligonucleotides can be labeled stably with 90Y using SCN-Bn-EDTA without loss of hybridization properties.

Blood Physiological Phenomena↗

Localization of indium-111 in human malignant tumor xenografts and control by chelators.

The kinetics of soluble indium-111 ((111)In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of (111)In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. (111)In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of (111)In-chloride. Secondly, the effect of edetate calcium disodium (CaNa2EDTA) on radioactivity in (111)In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa2EDTA significantly reduced (111)In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa2EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with (111)In-chloride was investigated. In one group of mice CaNa2EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of (111)In-chloride (postadministration), the localization of (111)In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa2EDTA administered intraperitoneally at 12 and 1 h before injection of (111)In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa3DTPA had a more powerful effect than CaNa2EDTA. In conclusion, (111)In-activity in tumors consists of intracellular and extracellular components, and the extracellular (111)In may be cleared by chelators. Pre- and postadministration of CaNa3DTPA could remove (111)In-nonspecific localization in tumors when (111)In is released from the radiolabeled agents.

Animals↗

Yttrium-90-labeled human macroaggregated albumin for internal radiotherapy: combined use with DTPA.

The aim of this study was to investigate the possibility of yttrium-90-labeled human macroaggregated albumin (90Y-MAA) as an internal radiotherapeutic agent for whole-lung irradiation in combination with diethylenetriamine pentaacetic acid (DTPA). The influence of trisodium calcium DTPA (CaNa3DTPA) on the radioactivity of 90Y-MAA in serum was investigated in vitro. The effect of CaNa3DTPA on the biodistribution of radioactivity in normal mice intraveneously injected with 90Y-MAA was examined. CaNa3DTPA could deprive in vitro radioactivity of 90Y-MAA in 48-h incubation. Most of the radioactivity (>90% injected dose per lung) was observed at murine lung after injection of 90Y-MAA. Pulmonary radioactivity was cleared within 72 h postinjection, whereas the radioactivities in the bone, liver, kidneys, and spleen increased with a peak at 48 h. CaNa3DTPA-treatment reduced the in vivo radioactivities in bone, liver, and kidneys without influence on the radioactivity of lung. In conclusion, combined use of CaNa3DTPA enables 90Y-MAA to be used as a radiopharmaceutical for internal irradiation against whole lung.

Albumins↗