Search PubMed⌕ Search

Biomedical subjects

N Mitsuhashi

Publications and source records attributed to N Mitsuhashi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Structure and expression pattern of a human MTG8/ETO family gene, MTGR1.

AML1-MTG8 fusion protein, which is produced from the rearranged gene formed between AML1 and MTG8 in myeloid leukemia with t(8;21) chromosomal translocation, plays an important role in the pathogenesis of leukemia. We previously showed that ectopically expressed AML1-MTG8 fusion protein is associated with an MTG8-like protein in the mouse myeloid precursor cell line L-G, and this association seemed to be required for AML1-MTG8 to stimulate proliferation. As a candidate cDNA for this MTG8-like protein, a 6.4 kb MTGR1 cDNA encoding human MTGR1b protein of 604 amino acids was isolated. Since this cDNA was shorter than the main mRNA (about 7.5 kb), the 5'-end of the MTGR1 cDNA was extended using Marathon Ready cDNA. When the newly obtained 5'-sequence was combined with the previous cDNA, the resultant MTGR1 cDNA (6995 bp), including exon 3 that the previous cDNA lacked, could encode MTGR1a protein of 575 amino acids. Transcripts of the MTGR1 gene were expressed ubiquitously in the human tissues and cell lines examined. PCR analyses of the cDNAs from human tissues showed the presence of various splicing variants with regard to the 5'-region including exons 1, 2 and 3. The MTGR1 gene consists of 14 exons and spans about 68 kb. The genomic structure of MTGR1 is highly similar to those of other MTG 8-family genes, MTG8 and MTG16. MTG16 was recently cloned from the translocation breakpoint of myeloid malignancies with t(16;21) chromosomal translocation.

Alternative Splicing↗
PubMed2000

Radiation therapy for elderly patient with squamous cell carcinoma of the uterine cervix.

OBJECTIVE: The purpose of this study was to profile cervical squamous cell carcinoma in elderly patients undergoing radiation therapy and to study the treatment outcome and side effects of therapy. MATERIALS AND METHODS: A retrospective analysis was carried out from the records of 380 patients with squamous cell carcinoma of the uterine cervix who had been given radiation therapy between 1970 and 1994. The patients were divided into three age groups: under 70 years (youngest group; n = 215), 70 to 79 years (intermediate group; n = 124), and 80 years or older (oldest group; n = 41). Radiation therapy was performed by a combination of external beam therapy and three brachytherapy fractions using low-dose-rate sources. RESULTS: The 5-year overall survival rates in the youngest, intermediate, and oldest groups were 58, 50, and 33%, respectively, while cause-specific survival rates were 68, 70, and 65%, respectively. For the patients with stage III, the 5-year overall survival rates in the youngest, intermediate, and oldest groups were 59, 48, and 36%, respectively, while cause-specific survival rates were 72, 70, and 70%, respectively. There was no statistical significance in the 5-year intrapelvic recurrence rates among the three groups. Grade 3 or 4 complications occurred in 6.5% of the youngest, 11.3% of the intermediate, and 7.3% of the oldest groups. CONCLUSION: Radiation therapy with external beam combined with three fractions of low-dose-rate brachytherapy proved both highly effective and safe for senior patients with cervical squamous cell carcinoma.

Adult↗
PubMed2000

Magnetic resonance images of primary malignant lymphoma of the uterine body: a case report.

Primary malignant lymphoma of the uterine body is extremely rare. There are few reports concerning magnetic resonance images (MR) of uterine body lymphoma although there are several reports concerning uterine cervical lymphoma. The MR images of a 66-year-old woman with primary malignant lymphoma of the uterine body showed that the myometrium was diffusely involved, exhibiting an almost homogeneous character, and the normal zonal anatomy of the uterine cervix was preserved, with the endometrium being partly recognized near the center of the tumor. We report suggestive findings on MR images of primary malignant lymphoma of the uterine body.

Aged↗
PubMed2000

Characterization of organelles in the vacuolar-sorting pathway by visualization with GFP in tobacco BY-2 cells.

We have shown the localization and mobilization of modified green fluorescent proteins (GFPs) with various signals in different compartments in a vacuolar-sorting system of tobacco BY-2 cells. In contrast to the efficient secretion of GFP from the transformed cells expressing SP-GFP composed of a signal peptide and GFP, accumulation of GFP in the vacuoles was observed in the cells expressing SP-GFP fused with the C-terminal peptide of pumpkin 2S albumin. This indicated that this peptide is sufficient for vacuolar targeting. Interestingly, the fluorescence in the vacuoles disappeared sharply at 7 d after inoculation of the cells, but it appeared again after re-inoculation into a new culture medium. When SP-GFP was fused with the region, termed PV72C, including a transmembrane domain and a cytosolic tail of a vacuolar-sorting receptor PV72, GFP-PV72C was detected in the Golgi-complex-like small particles. Prolonged culture showed that GFP-PV72C that reached the prevacuolar compartments was cleaved off the PV72C region to produce GFP, that arrived at the vacuoles to be diffused. These findings suggested that the vacuolar-sorting receptor might be recycled between the Golgi complex and prevacuolar compartments.

Base Sequence↗
PubMed2000

New method to prevent bladder dysfunction after radical hysterectomy for uterine cervical cancer.

OBJECTIVE: The purpose was to improve the surgical procedures to prevent bladder dysfunction after radical hysterectomy. METHODS: Twelve patients with stage Ib cervical cancer underwent intraoperative electrical stimulation to identify the vesical branches of the pelvic nerves. Autonomic nerve localization in the vesicouterine ligament was examined in 10 patients immunohistochemically. According to the results of the above studies a new method to preserve the vesical branches was developed. Grades of postoperative bladder dysfunction were compared between new (n = 19) and conventional methods (n = 18). RESULTS: Electrical stimulation on the outer surface of the posterior sheath of the vesicouterine ligament caused the increase of intravesical pressure. S-100 protein localized also on this area. Postoperative compliance of the detrusor in cases with the new method demonstrated less decrement from preoperative values than in cases with the conventional method. The new method required significantly fewer days to achieve residual urine volumes less than 50 ml after surgery. CONCLUSIONS: The new method significantly reduces bladder dysfunction after radical hysterectomy.

Autonomic Pathways↗
PubMed2000

A prospective randomized study comparing endocrinological and clinical effects of two types of GnRH agonists in cases of uterine leiomyomas or endometriosis.

OBJECTIVE: In order to assess the endocrinological changes associated with 2 types of low-dose GnRH agonists depot as well as their clinical efficacy, we performed a randomized prospective comparison study of patients having uterine leiomyomas or endometriosis. METHODS: A prospective randomized study involving 67 patients with uterine leiomyomas or endometriosis was carried out. These patients were randomly administered either buserelin MP 1.8 mg (Group B, n = 34) or leuprolide 1.88 mg (Group L, n = 33). In each group we evaluated the symptoms of genital bleeding and hot flashes during GnRHa treatment, as well as the levels of serum LH, FSH, and estradiol 8 weeks after the start of treatment. In addition, the endometrial thickness was measured by transvaginal ultrasonography, and changes in the volume of the uterine leiomyoma or endometrial cyst at the end of treatment. The GnRHa depot was administered from 3 to 8 times, 28 days apart, in both groups. RESULTS: The incidence of menstruation-like genital bleeding 8 weeks after treatment was significantly (p < 0.01) higher in Group B. However this difference disappeared by 12 weeks after treatment. The climacteric symptom of hot flashes was found to be significantly (p < 0.01) more severe in Group L, and this tendency continued until 20 weeks after treatment. The 2 groups did not differ significantly with regard to the levels of the serum LH, FSH, and estradiol at 8 weeks after treatment or in the endometrial thickness at the end of the GnRHa treatment. In both groups, the volumes of the uterine leiomyomas were significantly (p < 0.01) lower after the treatment. In contrast, the volumes of the endometrial cysts did not decrease after administration of GnRHa in both groups. CONCLUSION: Leuprolide 1.88 induced pituitary down regulation more rapidly than buserelin MP. However the hypoestrogenic symptoms such as hot flashes were more severe in cases treated with leuprolide 1.88 than in those treated with buserelin MP. Our data confirm that the therapeutic efficacy of buserelin MP and leuprolide 1.88 are similar, with both being sufficient to treat uterine leiomyomas and endometriosis.

Adult↗
PubMed2000

[Clinical quality assurance at institutions according to a patterns of care study. Japanese PCS Working Group].

The clinical quality assurance (QA) of an institution is important in any multiinstitutional prospective study. Patterns of Care Study (PCS) is a well-known study for QA activity in the United States. PCS is a nationwide retrospective study done by two-staged cluster sampling of institutions and patients and external audits. After data are accumulated, National averages on various survey items are calculated as a QA measure. In 1996, PCS was imported into the radiation oncology field in Japan with the support of the Ministry of Health and Welfare. Preliminary results showed significant differences in treatment process, structure, and preliminary outcome according to the stratification of institutions. These data can be useful in improving the structure and process at the institutional as well as the national level. PCS will also clarify the dissemination of positive clinical results into national practice.

Esophageal Neoplasms↗
PubMed1999

Potentially lethal damage repair and its inhibitory effect of caffeine in two yolk sac tumor cell lines with different radiosensitivities.

PURPOSE: In order to investigate the role of potentially lethal damage repair (PLDR) in cellular radiosensitivity, PLDR and its inhibitory effect by caffeine was examined. In addition, cell cycle distribution was also examined. MATERIALS AND METHODS: Two rat yolk sac tumor cell lines, NMT-1 and NMT-1R, with different radiosensitivities in vitro were used. The capacity for PLDR was examined using confluent-phase cells, and evaluated by calculating the recovery ratio. Inhibitory effect of caffeine on PLDR was examined with doses of 1, 5 and 10 mM. RESULTS: The capacity of PLDR in two cell lines reflected radiosensitivity. The recovery ratio after irradiation of 5 Gy was 2.8 in the radiosensitive NMT-1 and 5.2 in the radioresistant NMT-1R, and recovery reached its peak level at 6 h in both cell lines. The degree of inhibition of PLDR was weaker in NMT-1R than that in NMT-1 at the same dose level, and was correlated with reduction of G2-arrested cells by caffeine. CONCLUSIONS: The results of this study suggest that the capacity of PLDR may be one of the determinant factors for radiosensitivity in the two cell lines used, and the inhibitory effect of caffeine on PLDR was in part attributable to the modification of the cell cycle progression.

Animals↗
PubMed1999

Is radiosensitive cell line cross-sensitive to heat?: Effect of heat on two rat yolk sac tumor cell lines with different radiosensitivity.

The differences between two rat yolk sac tumor cell lines, which are of the same origin but differ in their response to irradiation, in thermal sensitivity and development of thermotolerance were investigated. A radiosensitive cell line NMT-1 is consistently less heat sensitive than the radioresistant cell line NMT-1R. The thermotolerances in NMT-1 and in NMT-1R preheated at 43 degrees C for 30 min, respectively, reached peaks at 6 h and at 12 h, but did not completely disappear at 48 h. Thermotolerance with a good correlation between both cell lines with HSP70 accumulation was observed in a different time course after a primary heating.

Animals↗
PubMed1999

Effect of metformin on advanced glycation endproduct formation and peripheral nerve function in streptozotocin-induced diabetic rats.

The effects of metformin treatment on advanced glycation endproduct formation and peripheral nerve function in streptozotocin-induced diabetic rats were examined. Streptozotocin-induced diabetic rats were treated with low dose metformin (50-65 mg kg(-1) daily) or high dose metformin (500-650 mg kg(-1) daily) for 10 weeks. While the metformin-untreated diabetic group showed a significant increase of advanced glycation endproducts (6.1-fold in the lens, 1.6-fold in the sciatic nerve, 2.3-fold in the renal cortex, and 1.9-fold in plasma; all P < 0.01) compared with the healthy control group, both metformin-treated groups had significantly less advanced glycation endproduct deposition. The % decrease in the diabetes-induced increase in advanced glycation endproduct formation by low and high dose metformin treatment was 25% and 72% in the lens (both P < 0.01), 31% and 42% in the sciatic nerve (both P < 0.05), and 16% and 33% in the renal cortex (P < 0.05 and P < 0.01), respectively. However, the plasma advanced glycation endproduct level showed no significant difference from that in the untreated diabetic group, in spite of slight decrease in plasma glucose and glycated hemoglobin levels in the metformin-treated groups. The diabetes-induced sciatic nerve conduction velocity deficits were improved by 46% and 42% by low and high dose metformin treatment, respectively (both P < 0.01). These data suggest that metformin may have a direct antiglycative action, which in turn contributes to amelioration of peripheral nerve function. Thus, metformin treatment may be effective in the prevention of diabetic complications through not only lowering plasma glucose, but also directly inhibiting advanced glycation endproduct formation.

Animals↗
PubMed1999

p53 mutation decreased radiosensitivity in rat yolk sac tumor cell lines.

PURPOSE: We reported that two established rat yolk sac tumor cell lines differ in their radiosensitivity by 1.7 fold, and the variation is most likely manifested by the differences seen in their apoptotic response. We investigated the relationship between radiosensitivity and p53 in these cell lines. METHODS AND MATERIALS: We assessed the status of p53 in cell lines by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequence analysis, and also analyzed protein expression of p53, p21, and bax as a function of time after irradiation to determine the signal transduction for p53 by immunoblotting. RESULTS: A band shift was observed only in exon 7 for the radioresistant NMT-1R cells and no band shift was detected for the radiosensitive NMT-1 cells. A band shift was confirmed also at the mRNA level. Exon 7 of p53 DNA showed a three base substitution of DNA at codon 267 to 268. Expression of p53, p21, and bax proteins in NMT-1R cells did not change after 10 Gy irradiation; however, in NMT-1 cells, the expression of these proteins was increased from 1-12 h after irradiation. CONCLUSION: A loss of p53 function by radiation-induced mutation of p53 decreased the radiosensitivity in these cell lines.

Animals↗
PubMed1999

Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer.

The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival.

Aged↗
PubMed1999

Asparaginyl endopeptidase (VmPE-1) and autocatalytic processing synergistically activate the vacuolar cysteine proteinase (SH-EP).

A vacuolar cysteine proteinase, designated SH-EP, is synthesized in cotyledons of germinated Vigna mungo seeds and is responsible for degradation of the seed proteins accumulated in protein bodies (protein storage vacuoles). SH-EP belongs to the papain proteinase family and has a large N-terminal prosegment consisting of 104 amino acid residues and a C-terminal prosegment of 10 amino acid residues. It has been suggested that an asparaginyl endopeptidase, V. mungo processing enzyme 1 (VmPE-1), is involved in the N-terminal post-translational processing of SH-EP. The recombinant proform of SH-EP (rSH-EP) was produced in Escherichia coli cells, purified to homogeneity and refolded by stepwise dialysis. 31P-NMR analysis of intact germinated cotyledons revealed that the vacuolar pH of cotyledonary cells changes from 6.04 to 5.47 during seed germination and early seedling growth. rSH-EP was converted in vitro to the mature form through autocatalytic processing at a pH mimicking the vacuolar pH at the mid and late stages of seed germination, but not at the pH of the early stage. VmPE-1 accelerated the rate of processing of rSH-EP in vitro at the pH equivalent to the vacuolar pH at the early and mid stages of germination. In addition, the cleavage sites of the in vitro processed intermediates and the mature form of SH-EP were identical to those of SH-EP purified from germinated cotyledons of V. mungo. We propose that the asparaginyl endopeptidase (VmPE-1)-mediated processing mainly functions in the activation of proSH-EP at the early stage of seed germination, and both VmPE-1-mediated and autocatalytic processings function synergistically in the activation of proSH-EP in cotyledons at the mid and late stages.

Amino Acid Sequence↗
PubMed1999

Interaction between low dose-rate irradiation, mild hyperthermia and low-dose caffeine in a human lung cancer cell line.

PURPOSE: To investigate cell killing by means of low dose-rate irradiation (LDRI) combined with concurrent mild hyperthermia and to determine the effect of low-dose caffeine on this combination treatment. MATERIALS AND METHODS: Human lung adenocarcinoma cells, LK87, were treated with LDRI (50 cGy/h) in combination with mild hyperthermia at 41 degrees C and low-dose caffeine (1 mM). Cell survival was estimated by clonogenic assay. Flow-cytometry was performed with PI staining using FACScan. Heat-shock protein (HSP72/73) was measured by the Western blotting method. All treatments were simultaneously performed for up to 48 h (24 Gy). RESULTS: LDRI cytotoxicities were enhanced by hyperthermia at 41 degrees C. D0 calculated from the dose-response curve for LDRI combined with 41 degrees C was 3.46 Gy whereas it was 6.55 Gy for LDRI alone. The survival curve for LDRI +41 degrees C demonstrated no chronic thermotolerance up to 48 h. For LDRI + simultaneous low-dose caffeine, cell killing was also enhanced, where D0 was 3.38 Gy at 37 degrees C. Radiosensitization caused by caffeine was enhanced by combination with simultaneous mild hyperthermia at 41 degrees C, where D0=1.78 Gy. Cell cycle analysis demonstrated remarkable G2 and mild G1 arrest for LDRI alone, but only G1 arrest was observed for LDRI combined with 41 degrees C and for LDRI combined with caffeine. Strong and early G1 arrest was observed in the treatment with LDRI + caffeine at 41 degrees C. The amount of HSP72/73 in the combination of LDRI with caffeine at 41 degrees C was less than that at 41 degrees C alone. CONCLUSION: LDRI cytotoxicity was enhanced by non-lethal hyperthermia. Low dose caffeine produced further cell killing in the combination of LDRI with mild hyperthermia.

Caffeine↗
PubMed1999

Stereotactic radiotherapy for locally recurrent nasopharyngeal carcinoma.

OBJECTIVE: To determine the efficacy of stereotactic radiotherapy (SRT) in the treatment of recurrent nasopharyngeal carcinoma. STUDY DESIGN: A retrospective review of the outcome of SRT for patients with recurrent nasopharyngeal carcinomas following definitive conventional radiation therapy. METHODS: Five patients were treated with daily static multiportal irradiation. Two Gy was administered with eight isocentric portals in a single plane 5 days a week, and the plane was changed for every 20 to 30 Gy. Of these patients, three had poorly differentiated squamous cell carcinoma. Tumor sizes ranged from 1 to 15 cm3, with a median size 3.2 cm3. Median follow-up time from SRT was 34 months (range, 4-61 mo). RESULTS: Four of five recurrent tumors responded well and achieved complete regression. Three patients have survived without evidence of local recurrence with a median follow-up time of 34 months. Marginal recurrence was observed at the posterosuperior wall in a patient with adenoid cystic carcinoma at 30 months after SRT. One patient who received SRT after the two complete courses of radiation therapy died 6 months after SRT as a result of rupture of a branch of the left carotid artery, but autopsy revealed no local residual tumor. CONCLUSIONS: Stereotactic radiotherapy with isocentric multiportals in one plane, which is changed at every 20 to 30 Gy, can provide local control with acceptable toxicity in patients with recurrent nasopharyngeal carcinoma, but increased clinical experience and longer follow-up will be necessary to evaluate the overall role of this technique in nasopharyngeal carcinoma.

Adult↗
PubMed1999

Immunoadsorption plasmapheresis as a treatment for pregnancy complicated by systemic lupus erythematosus with positive antiphospholipid antibodies.

PROBLEM: Our purpose was to study the effect of maternal immunoadsorption plasmapheresis (IA) on the outcome of pregnancies complicated by systemic lupus erythematosus (SLE) with positive antiphospholipid antibodies, which were known to have a strong correlation with abortion or stillbirth. METHOD OF STUDY: Eight pregnancies in 7 patients with SLE were treated according to our protocol. They were all positive for the lupus anticoagulant. The treatments provided in these cases were as follows: an oral low-dose steroid; oral low-dose aspirin; and IA. The outcomes of the pregnancies were then studied. RESULTS: Of eight pregnancies, seven resulted in preterm deliveries, and cesarean sections were performed at 26-36 weeks of gestation. In one case, intrauterine fetal death occurred at 24 weeks of gestation. The other seven pregnancies resulted in live births (survival rate of 87.5%). CONCLUSION: IA improves the outcome of pregnancy complicated by SLE with positive antiphospholipid antibodies, without increasing steroid dosage.

Adult↗
PubMed1999

Cancer in patients aged 90 years or older: radiation therapy.

PURPOSE: To investigate the clinical efficacy of radiation therapy for cancer in patients aged 90 years or older. MATERIALS AND METHODS: Cancer cases in 32 patients (11 men, 21 women) aged 90 years or older who underwent radiation therapy in 1970-1997 were retrospectively analyzed. The mean patient age was 92.2 years, with a range of 90-98 years. Head and neck cancer (n = 14 [44%]) and skin cancer (n = 6 [19%]) were the most common. RESULTS: Eleven (79%) of the 14 patients with head and neck cancer were treated with curative intent. Radiation response without any severe complication was observed in nine (90%) of the 10 patients with head and neck cancer treated with curative intent who finished treatment. The median survival time was 8 months (range, 3-55 months) in the 10 patients with head and neck cancer who completed treatment with curative intent. Complete response was achieved in all of the patients with skin cancer without any major sequelae. Complete response was also observed in all three of the patients with non-Hodgkin lymphoma, but two patients treated with adjuvant chemotherapy died of drug-induced pneumonitis. Palliation was achieved in all nine of the patients treated with palliative intent. CONCLUSION: Age of 90 years or older is not a limiting factor for radiation therapy.

Age Factors↗