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Biomedical subjects

N Mitsuhashi

Publications and source records attributed to N Mitsuhashi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Unresponsiveness to glibenclamide during chronic treatment induced by reduction of ATP-sensitive K+ channel activity.

The insulin response to the sulfonylurea glibenclamide was markedly impaired in pancreatic beta-cell line MIN6 cells with chronic glibenclamide treatment (MIN6-Glib). The intracellular calcium concentration increased only slightly in response to glibenclamide in MIN6-Glib. While the properties of the voltage-dependent calcium channels were not altered, the conductance of the K(ATP) channels, the primary target of glibenclamide, was significantly reduced in MIN6-Glib. The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits. MIN6 cells have both high- and low-affinity binding sites for glibenclamide. The binding affinities at these two sites were unchanged, but the maximum binding capacities at both sites were similarly increased by chronic glibenclamide treatment. Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib. In addition, electron microscopic examination revealed a majority of the SUR1 to be present in a cluster near the plasma membrane in control MIN6, while it tends to be distributed in the cytoplasm in MIN6-Glib. These data suggest that chronic glibenclamide treatment causes the defect in acute glibenclamide-induced insulin secretion by reducing the number of functional K(ATP) channels on the plasma membrane of the beta-cells.

ATP-Binding Cassette Transporters↗
PubMed1999

Apoptosis and appearance of Trp53-positive micronuclei in murine tumors with different radioresponses in vivo.

The purpose of this paper is to determine the relationship between the response to radiation and the appearance of apoptosis and micronuclei with Trp53 protein in murine tumors after irradiation. Two murine tumors, EL4, which was derived from a mouse lymphoma, and FM3A, which was derived from a mouse mammary carcinoma, were locally irradiated with 15 Gy and sections were stained with H&E and an anti-Trp53 antibody. The response to radiation was greater in EL4 tumors than in FM3A tumors. The frequency of apoptotic cells in EL4 tumors was 6.1 +/- 1.2% at time zero, reached a peak of 36.3 +/- 3. 8% at 6 h, and then decreased with time through 72 h to 2.5 +/- 1.5% after 15 Gy irradiation. In FM3A tumors, no apoptotic cells were detected at 0, 1, 3, 6 or 24 h after exposure. At 48 and 72 h, the frequency was only 3.0 +/- 0.6% and 1.3 +/- 0.3%. Apoptotic cells increased significantly at 3, 6 and 24 h after irradiation in EL4 tumors (P < 0.008) and at 48 and 72 h in FM3A tumors (P < 0.006). The frequency of Trp53-positive cells was 17.9 +/- 2.2 and 15.2 +/- 2.3% at time zero in EL4 and FM3A tumors, respectively, increased to 74.5 +/- 4.5% in EL4 cells (P = 0.001), and increased to 33.9 +/- 1. 1% in FM3A cells (P = 0.005) 1 h after irradiation. Trp53-positive micronuclei appeared in cells in both tumors from 24 to 72 h after irradiation. The frequency of Trp53-positive micronuclei was 3.8 +/- 0.5 and 13.5 +/- 1.3% at 24 h in EL4 and FM3A tumors, respectively, and gradually decreased by 72 h. After exposure to 15 Gy, Trp53-positive micronuclei increased significantly in FM3A tumors compared to EL4 tumors at both 24 and 48 h (P < 0.02). The frequency of these micronuclei increased with increasing dose in FM3A tumors, and the difference between these percentages after 3 Gy and after 5, 10 and 15 Gy was significant (P < 0.02). Many apoptotic cells were observed in the radiosensitive EL4 tumor after irradiation. Death by apoptosis may be related to an early response to radiation in these tumors. The appearance of micronuclei may be an important mechanism of cell death in FM3A tumors in which no apoptosis was induced.

Animals↗
PubMed1999

Giant cell tumor of the thoracic spine simulating mediastinal neoplasm.

A case of giant cell tumor of the thoracic spine simulating mediastinal neoplasm was identified on plain films, CT scans, MR images, and with scintigraphy. CT showed a hypervascular soft-tissue mass with shell-like calcification in the right upper mediastinum. MR imaging showed a collapse of the T1 vertebral body and a mass extending to the mediastinum. The mass had a low signal on T1-weighted MR images and a predominantly high signal on T2-weighted images with heterogeneity. Technetium-99m methylene diphosphonate bone scintigraphy showed intense uptake in both the T1 and marginal parts of the mediastinal mass. There was no accumulation of gallium-67 citrate, but 18-fluorine fluorodeoxyglucose positron emission tomography showed marked uptake. The variation in these imaging findings played an important role in the differential diagnosis of this uncommon mediastinal mass.

Adult↗
PubMed1998

Early radiation effects in highly apoptotic murine lymphoma xenografts monitored by 31P magnetic resonance spectroscopy.

PURPOSE: Phosphorus-31 magnetic resonance spectra (31P-MRS) were obtained from highly apoptotic murine lymphoma xenografts before and up to 24 hr following graded doses of radiation ranging from 2 to 30 Gy. Radiation-induced apoptosis was also estimated up to 24 hr by scoring apoptotic cells in tumor tissue. METHODS AND MATERIALS: Highly apoptotic murine lymphoma cells, EL4, were subcutaneously transplanted into C57/BL mice. At 7 days after transplantation, radiation was given to the tumor with a single dose at 3, 10, and 30 Gy. The beta-ATP/Pi, PME/Pi, and beta-ATP/PME values were calculated from the peak area of each spectrum. Radiation-induced apoptosis was scored with counting apoptotic cells on hematoxylin and eosin stained specimens (% apoptosis). RESULTS: The values of % apoptosis 4, 8, and 24 hr after radiation were 21.8, 19.6, and 4.6% at 3 Gy, 35.1, 25.6, and 14.8% at 10 Gy, 38.4, 38.0, and 30.6% at 30 Gy, respectively (cf. 4.4% in control). There was no correlation between early change in beta-ATP/Pi and % apoptosis at 4 hr after radiation when most of the apoptosis occurred. An early decrease in PME/Pi was observed at 4 hr after radiation dose at 30 Gy. For each dose, the values of beta-ATP/Pi 24 hr after radiation were inversely related to radiation dose. CONCLUSION: The increase in beta-ATP/Pi observed by 31P-MRS was linked to the degree of histological recovery from radiation-induced apoptosis.

Adenosine Triphosphate↗
PubMed1998

Effect of radiation on the expression of E-cadherin and alpha-catenin and invasive capacity in human lung cancer cell line in vitro.

PURPOSE: To investigate the effect of radiation on E-cadherin and alpha-catenin expression in a human lung cancer cell line, and also evaluate invasive capacity in the membrane invasion culture system using the Boyden Chamber. MATERIALS AND METHODS: The immunoblot and immunofluorescence analyses were performed using the human lung cancer cell line A549 to examine altered expression of E-cadherin and alpha-catenin after irradiation. We also compared invasive capacity of untreated cells with that of irradiated cells. RESULTS: Immunoblot analysis revealed that the expression of E-cadherin increased after irradiation. In a time-course analysis, the expression was increased 6 h after irradiation with 10 Gy and reached its peak level at 24 h, being 2.3 times the control value, whereas expression at 1 and 3 h after irradiation was almost equivalent to that of the control. A slight increase in expression was observed after irradiation of 2 Gy and the expression reached peak levels after 5 Gy. After fractionated irradiation, the increase in expression of both E-cadherin and alpha-catenin was observed, and the alteration of alpha-catenin was more prominent than that after a single irradiation of the same total dose. In the immunofluorescence study for E-cadherin antibody analyzed by confocal laser scanning microscopy, increased intensity in irradiated cells produced as a nondisrupted and continuous line at cell-cell contact sites. In an invasive assay, the number of migrated cells in irradiated cells after a dose of 5 and 10 Gy was reduced significantly compared to untreated cells. CONCLUSION: The results indicate that irradiation of A549 increased the expression of E-cadherin, possibly preserving their functional property.

Cadherins↗
PubMed1998

Change in E-cadherin expression after X-ray irradiation of a human cancer cell line in vitro and in vivo.

PURPOSE: To investigate changes in E-cadherin expression after X-ray irradiation of a human cancer cell line in vitro and in vivo. METHODS AND MATERIALS: E-cadherin expression on a human squamous cell carcinoma of the thyroid gland (T-SCC cell), which was established in our laboratory, at 24 h after graded single doses of irradiation and at 7 successive times after 10-Gy irradiation were investigated in vitro by immunoblot analysis with the monoclonal antibody to human E-cadherin. The changes in E-cadherin expression caused by irradiation of T-SCC tumors that were transplanted into athymic nude mice were also determined in vivo by immunohistochemical staining and immunoblot analysis in a similar fashion to that in vitro. RESULTS: In vitro studies revealed that E-cadherin expression had increased significantly on T-SCC cells at 24 h after irradiation with doses of 2 to 10 Gy and that, in a time-course analysis, the expression had increased significantly at 3 to 72 h after irradiation compared with an unirradiated control cell, although it was not observed at 1 h after irradiation. In in vivo studies, a significant increase in E-cadherin expression was observed at 24 h after irradiation with 5 and 10 Gy by immunohistochemical staining and time-course studies demonstrated that E-cadherin increased temporarily at 12 to 24 h after 10-Gy irradiation; however, immunoblot analysis did not show alteration of E-cadherin expression by irradiation. CONCLUSION: X-ray irradiation upregulated E-cadherin expression on T-SCC cells in vitro and in vivo.

Animals↗
PubMed1998

Radiotherapeutic Management of Brain Metastases from Breast Cancer.

We have reviewed the medical records of 28 breast cancer patients with brainmetastases who were treated with radiotherapy at our clinic from 1980 through 1994(4 patients, postoperatively; 24 patients, radiotherapy alone). Radiotherapy was delivered as whole brain irradiation using lateral opposed 10 MV X-rays. Tenpatients received an additional boost to a reduced field. One patient was treated with localized stereotactic irradiation alone. The radiation dose for tumorsranged from 32 Gy to 60 Gy(mean, 49 Gy)in 2 or 3 Gy daily fractionated doses. The brain was the first site of metastatic involvement in only two patients. In the 26 evaluable patients, neurologic functional improvement was achieved in 24 patients(92%)with complete response(CR)in 12 patients(46%)and partial response(PR)in 12 patients(46%). The survival rates from the initial treatment were 39% at 5 years and 16% at 10 years(median survival time, 50 months), and those after treatment of brain metastases were 29% at one year and 18% at 2 years(median survival time, 6 months). Performance status tended to be associated with survival(p=0.10), and the presence of liver metastasis was the most important risk factor concerning survival(p=0.056). Two patients suffered severe chronic complications.One patient developed severe dementia after whole brain irradiation with a total dose of 45 Gy in 3 Gy daily fractionated dose, and another patient developed widespread brain necrosis after combined radiotherapy with intrathecal local infusion of methotrexate. Radiotherapeutic management is useful for breast cancer patients with brain metastasis, and long-term survival may also be possible even if patients have preexisting extracranial metastases, except for hepatic involvement. Radiation-related complications should therefore be avoided in these patients.

Journal Article↗
PubMed1998

Malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy.

A case of malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy is reported. A thoracotomy was performed on a 57-year-old male and a mass was found to invade the trachea, main bronchus, and left atrium. The tumor was unresectable. Subsequently, cisplatin was administered, but the tumor grew in size and radiation therapy was recommended. The tumor responded well to thoracic irradiation (56 Gy) and disappeared. Three months later, lymph nodes metastases were noted in the retrocrural and upper abdominal paraaortic regions, but these were controlled again with palliative irradiation. Without further treatment, he survived free of disease for over 5 years. Specimens obtained during the thoracotomy showed that the tumor consisted mainly of small round cells with a rosette formation. Immunohistochemically the tumor was positive to NSE and slightly positive to keratin, but negative to LCA, L26, UCLH-1, EMA, Leu7, and chromogranin, suggesting a malignant tumor derived from neuroendocrine tissue.

Diagnosis, Differential↗
PubMed1998

Cytotoxic effect of paclitaxel (taxol) either alone or in combination with irradiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro.

PURPOSE: To investigate the differences between two rat yolk sac tumour cell lines with different radiosensitivities in paclitaxel sensitivity and in the sensitizing effects of paclitaxel in combination with irradiation. MATERIALS AND METHODS: NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. RESULTS: Clonogenic assay demonstrated almost the same paclitaxel sensitivity with Do of 5.15 nM in NMT-1 and 5.02 nM in NMT-1R. Many apoptotic cells and DNA ladder formations were observed at 24 h after exposure to paclitaxel in both cell lines. The incidence of DNA fragmentation after 24 h exposure to 20 nM paclitaxel was 12.4 +/- 3.3% for NMT-1, and 13.0 +/- 1.9% for NMT-1R. Paclitaxel showed a supra-additive effect in combination with irradiation in both cell lines at 12 h after paclitaxel treatment only when the accumulation of cells in the G2/M phase reached its peak. CONCLUSIONS: Paclitaxel had the same cytotoxic effect in two cell lines with different radiosensitivity due to the induction of apoptosis. A supra-additive effect to radiation was observed with 12 h pretreatment in both cell lines. Paclitaxel may be effective for tumours with a component of different radiosensitivity in combination with irradiation.

Animals↗
PubMed1998

Nasopharyngeal cancer with neck recurrence at 8 years and a lung metastasis at 15 years after the first definitive radiotherapy: a case report.

We report a patient with nasopharyngeal cancer with long-term follow-up of more than 16 years after the first course of radiotherapy in 1981. He developed a lung metastasis in 1996 after having a second course of radiotherapy for neck recurrence in 1989. The patient was a 42-year-old man with a nasopharyngeal tumor and a fixed upper neck metastasis (T1N1M0), which was treated with definitive radiotherapy. He manifested regional recurrence, at the margin of the radiation portal, with an 8 year disease-free interval, which was treated successfully by definitive re-irradiation. He developed a solitary lung metastasis, which was treated by video-assisted thoracoscopic lung resection, 7 years disease-free after the second course of radiotherapy. For 20 months after the removal of the lung metastasis he has been generally well without any signs of recurrence of sequelae. This case indicates the efficacy of definitive re-irradiation for regional recurrence and the necessity for long-term observation after radiation therapy for nasopharyngeal cancer.

Adult↗
PubMed1998

Adenophostin, a potent agonist of the inositol 1,4,5-trisphosphate receptor, is useful for fertilization of mouse oocytes injected with round spermatids leading to normal offspring.

Precursor male gametes such as round spermatids and secondary spermatocytes are known to possess the potential to achieve fertilization and embryonic development when injected into mature oocytes, but in previous studies, injected mouse spermatids did not activate the oocytes. In this study, we confirmed that this was the case because spermatids by themselves could not induce an increase in intracellular Ca2+ concentration ([Ca2+]i) of oocytes, the pivotal signal in oocyte activation. Repetitive rises in [Ca2+]i (Ca2+ oscillations), lasting for at least 3 h as observed at fertilization, were produced by a single injection of adenophostin B isolated from fungal products, a novel nonmetabolizable agonist of the inositol 1,4,5-trisphosphate receptor (InsP3r), which mediates Ca2+ release from the endoplasmic reticulum. Ca2+ oscillations were blocked by an antibody against the type 1 InsP3r. About 95% of oocytes were activated by adenophostin (0.3-0.4 microM in the oocyte). Simultaneous injection of a round spermatid and adenophostin resulted in 55% fertilization success in association with male and female pronucleus formation and development to two-cell embryos. Furthermore, 25% of two-cell embryos that were transplanted to foster mothers developed to normal offspring. All infants grew into adults that reproduced healthy second generations. Adenophostin will be useful for parthenogenetic oocyte activation in the biotechnology of animal reproduction. Injection combined with precursor spermatozoa may be applicable to assisted conception therapy for patients with defective spermatogenesis.

Adenosine↗
PubMed1998

Placental metastasis from maternal primitive neuroectodermal tumor.

The occurrence of placental metastasis from maternal primitive neuroectodermal tumor (PNET) is extremely rare. A 33-year-old woman at 33 weeks' gestation was admitted to the hospital. She died of the disease on hospital day 28 because the unresectable tumor was located over a wide area of the retroperitoneum. A neonate was delivered by a caesarean section without evidence of disease and has survived to 1 year of age. Pathologically, the tumor consisted of monotonous small round cells with a high nuclear cytoplasmic ratio, including several pseudorosettes and Homer-Wright-type rosettes. On immunohistochemical examination, the tumor cells were positively stained for neuron-specific enolase. Microscopically, the placenta showed intervillous metastasis from the maternal PNET. This case may be the first one of placental metastasis from PNET ever reported in the literature.

Adult↗
PubMed1998

Transrectal ultrasonography in evaluation of chronic rectal complications after radiation therapy for carcinoma of the uterine cervix.

RATIONALE AND OBJECTIVES: The authors studied the ability of transrectal ultrasonography (TRUS) to assess chronic rectal complications after radiation therapy for carcinoma of the uterine cervix. METHODS: One hundred twenty-five TRUSs were performed for 67 consecutive patients with carcinoma of the uterine cervix. Transrectal ultrasonography images of the rectal anterior wall and perirectal connective tissue adjacent to the uterine cervix were recorded with real-time scanner with 7.5 MHz transducer. The severity of TRUS abnormalities was graded on a scale developed by the authors. The relationships of the TRUS grade with the clinical grade of chronic rectal complications and with rectal radiation doses were analyzed retrospectively. RESULTS: Thickening of the perirectal connective tissue associated with obscuration of the submucosal echogenic layer in rectal anterior wall was observed between 6 months to 2 years after radiation therapy in all 19 patients who developed chronic rectal complications. The TRUS grade correlated with the clinical grade of chronic rectal complications, but did not correlate with rectal radiation doses. CONCLUSIONS: Transrectal ultrasonography can monitor the chronic rectal complications after radiation therapy for the patients with carcinoma of the uterine cervix.

Adult↗
PubMed1998

The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1.

The AML1-CBFbeta transcription factor complex is essential for the definitive hematopoiesis of all lineages and is the most frequent target of chromosomal rearrangements in human leukemia. In the t(8;21) translocation associated with acute myeloid leukemia (AML), the AML1(CBFA2/PEBP2alphaB) gene is juxtaposed to the MTG8(ETO/CDR) gene. We show here that the resultant AML1-MTG8 gene product specifically and strongly interacts with an 85-kDa phosphoprotein. Molecular cloning of cDNA indicated that the AML1-MTG8-binding protein (MTGR1) is highly related to MTG8 and similar to Drosophila Nervy. Comparison of amino acid sequences among MTGR1, MTG8, and Nervy revealed four evolutionarily conserved regions (NHR1 to NHR4). Ectopic expression of AML1-MTG8 in L-G murine myeloid progenitor cells inhibits differentiation to mature neutrophils and induces cell proliferation in response to granulocyte colony-stimulating factor (G-CSF). Analysis with C-terminal deletion mutants of AML1-MTG8 indicated that the region of 51 residues (488 to 538), which contains NHR2, is essential for the induction of G-CSF-dependent cell proliferation. Immunoprecipitation analysis indicates that this region is required for AML1-MTG8 to form a stable complex with MTGR1. Overexpression of MTGR1 stimulates AML1-MTG8 to induce G-CSF-dependent proliferation of L-G cells and to interfere with AML1-dependent transcription. These results suggest that AML1-MTG8 could function as a complex with MTGR1 and that the complex might be important in promoting leukemogenesis.

Amino Acid Sequence↗
PubMed1997

Outcome of radiation therapy for patients with Kasabach-Merritt syndrome.

PURPOSE: The efficacy of radiation therapy for Kasabach-Merritt syndrome, which is characterized by a huge hemangioma with consumption coagulopathy, remains controversial. In this study, we retrospectively investigated the treatment outcome of radiation therapy for seven neonates with Kasabach-Merritt syndrome. METHODS AND MATERIALS: During the past 25 years we have seen seven children with Kasabach-Merritt syndrome who were treated with radiation therapy. Their ages ranged from 1 day to 5 months, with a median age of 1 month. The hemangioma was located in the extremities in four of seven children. Tumor sizes ranged from 70 cm to more than 150 cm in greatest diameter. Initial platelet counts were all less than 40,000/mm3 except for one patient. In principle, the total dose applied to the hemangioma was 8-10 Gy, with a daily dose of 1 Gy five times a week. RESULTS: Four of seven hemangiomas responded dramatically, with a concomitant rise of the platelet count to radiation therapy. Although the remaining three hemangiomas, all of which were ill circumscribed by widespread overlying shiny, dusky purple skin, became less tense during radiation therapy. Disseminated intravascular coagulopathy was not improved, but they have responded favorably to two or three courses of radiation therapy with an extended radiation field by 1.5 years of age. As a result, all seven patients are now surviving with no evidence of hemangioma or hematological abnormalities. Shortening of the extremity was observed in three patients who received multiple courses of radiation therapy. CONCLUSIONS: Radiation therapy appears to be one of the effective treatment options for Kasabach-Merritt syndrome despite the risk of growth delay and malignancy.

Disseminated Intravascular Coagulation↗
PubMed1997

Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features.

The contiguous 874.423 base pair sequence corresponding to the 50.0-68.8 min region on the genetic map of the Escherichia coli K-12 (W3110) was constructed by the determination of DNA sequences in the 50.0-57.9 min region (360 kb) and two large (100 kb in all) and five short gaps in the 57.9-68.8 min region whose sequences had been registered in the DNA databases. We analyzed its sequence features and found that this region contained at least 894 potential open reading frames (ORFs), of which 346 (38.7%) were previously reported, 158 (17.7%) were homologous to other known genes, 232 (26.0%) were identical or similar to hypothetical genes registered in databases, and the remaining 158 (17.7%) showed no significant similarity to any other genes. A homology search of the ORFs also identified several new gene clusters. Those include two clusters of fimbrial genes, a gene cluster of three genes encoding homologues of the human long chain fatty acid degradation enzyme complex in the mitochondrial membrane, a cluster of at least nine genes involved in the utilization of ethanolamine, a cluster of the secondary set of 11 hyc genes participating in the formate hydrogenlyase reaction and a cluster of five genes coding for the homologues of degradation enzymes for aromatic hydrocarbons in Pseudomonas putida. We also noted a variety of novel genes, including two ORFs, which were homologous to the putative genes encoding xanthine dehydrogenase in the fly and a protein responsible for axonal guidance and outgrowth of the rat, mouse and nematode. An isoleucine tRNA gene, designated ileY, was also newly identified at 60.0 min.

Base Sequence↗