Biomedical subjects

M Miyauchi

Publications and source records attributed to M Miyauchi.

At least 37 records · Page 2Linked to original sources

PubMed2001

Analysis of a uranium solution for evaluating the total number of fissions in the JCO criticality accident in Tokai-mura.

The uranium solution in the precipitation tank in the JCO's uranium conversion facility was analyzed in order to evaluate the total number of fissions in the criticality accident. Two analytical groups at JAERI performed chemical analyses independently in order to check the validity of the results: the concentration of the fission products (95Zr, 99Mo, 103Ru, 131I, 140Ba, etc), uranium, boron and impurity elements in the solution. The analytical results obtained by the two groups were almost in agreement within the analytical error. The number of fissions per one gram of uranium in the accident was determined to be (1.5 +/- 0.1 ) x 10(14). Also, the total number of events was evaluated to be (2.5 +/- 0.1) x 10(18) fissions using the total amount of uranium (16.6 kg) fed into the precipitation tank at the accident.

Chemical Precipitation↗

PubMed2001

Spectral analysis of circadian rhythms in heart rate variability of dogs.

OBJECTIVE: To determine characteristics of power spectral analysis of heart rate variability (HRV) during a 24-hour period in dogs and to evaluate the effects of vagal and sympathetic tone on HRV ANIMALS: 16 healthy adult Beagles. PROCEDURE: Power spectral analysis of HRV was conducted, using 24-hour ambulatory ECG recordings. Circadian rhythms were evaluated in terms of absolute units of low-frequency (LF) and high-frequency (HF) powers, their ratio (LF:HF), and their adjusted (normalized) units (LF[norm] and HF[norm]). Three or 4 dogs were used for simultaneous measurement of heart rate and respiratory waveform as well as to evaluate treatment (propranolol, atropine, or both) administered to cause blockade of the autonomic nervous system. RESULTS: Values for LF and HF powers, LF:HF, LF(norm), and HF(norm) had obvious rhythmicity in clinically normal dogs. The HF power of HRV in dogs was extremely high, compared with that of other species, and HF peaks corresponded to peaks obtained from respiratory waveforms. Blockade of the autonomic nervous system documented that HRV in dogs was mostly attributable to vagal activity. CONCLUSION AND CLINICAL RELEVANCE: We determined characteristics of power spectral analysis of HRV in dogs, including circadian rhythm of the autonomic nervous system. Power spectral analysis of HRV may provide a useful noninvasive technique for assessing the effect of drugs on activity of the autonomic nervous system in dogs.

Animals↗

PubMed2001

Synthesis and antibacterial activity of novel 1beta-methyl carbapenems with cycloalkylamine moiety at the C-2 position.

Novel 1beta-methyl carbapenems with a cycloalkylamine moiety as a side chain were synthesized and their structure-activity relationships were studied. These carbapenems showed potent antibacterial activities against a wide range of Gram-positive and Gram-negative bacteria, and moderate urinary recovery when administered intraperitoneally in mice.

Anti-Bacterial Agents↗

PubMed2001

[Usefulness of ambulatory adjuvant chemotherapy with low-dose epirubicin in patients with axially-node positive breast cancer: Chiba Epirubicin Cooperative Study Group].

We evaluated the usefulness of adjuvant chemotherapy with low-dose epirubicin (EPI) as a key drug in patients with axially-node positive breast cancer. All the 24 patients who were entered in the study between January 1991 and December 1992 were shown histologically to have more than 4 axially-node involvement and underwent curable resection for the breast lesions. Twenty mg/m2 of EPI was administered intravenously every 4 weeks as ambulatory treatment for 1 year and 5-fluorouracil (5-FU) and tamoxifen (TAM) were concomitantly administered at a dose of 150 mg/day and 20-40 mg/day, respectively, daily for 2 years. The median follow-up period was 70 months with a 55.1% 5-year relapse-free survival and 67.4% 5-year survival rate. One patient developed Grade 3 nausea.vomiting, anorexia and general fatigue; however, the other toxicities were mild, such as Grade 1 leukopenia, liver dysfunction, nausea.vomiting, anorexia and general fatigue. This adjuvant therapy with low-dose EPI was safely administered to outpatients, and is considered to be useful for the treatment of axially-node positive breast cancer.

Adult↗

PubMed2001

Reporter gene transgenic mice as a tool for analyzing the molecular mechanisms underlying experimental carcinogenesis.

Carcinogenic compounds are classified into 2 categories, genotoxic and non-genotoxic, which are basically judged from in vitro genotoxicity data. However, it is well documented that genotoxicants do not necessarily exert in vivo carcinogenicity in rodents, partly because of a discrepancy between in vitro and in vivo mutagenicities. Recently, transgenic animal models with reporter genes such as lacI, lacZ and gpt have been developed as a tool for assessing in vivo mutagenicity as well as carcinogenicity. In this article, data using lacI transgenic mice and gpt delta mice are presented and their application is discussed. In lacI transgenic mice, dimethylnitrosamine (DMN) treatment significantly increased lacI mutant frequency (MF) in the liver, kidenys and lungs, but not in other non-target organs. Repeated dose ip administration of DMN was more effective than single dose treatment in the induction of lacI MF. The spectrum of mutant plaques induced by DMN was characterized by deletions as well as GC to AT base transitions. The remaining mice receiving DMN proved to have liver adenomas at a high frequency after 78 weeks. Meanwhile, dietary 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) significantly increased lacI and gpt MFs in the liver and colon. The characteristic spectrum of mutant plaques induced by MeIQx was a GC to TA base transversion in both the lacI and gpt mutations. Our results thus strongly suggest that these reporter gene transgenic animal models could offer a useful tool for analyzing molecular mechanisms underlying experimental carcinogenesis and for assessing the carcinogenic risk of environmental chemicals.

Animals↗

PubMed2000

Psychophysiological correlates of social skills deficits in persons with schizophrenia.

Social skill deficits in schizophrenia profoundly affect patients' life-long outcome, although the profile of the underlying cognitive dysfunction still remains a matter of debate. In the present study, we investigated the relationship between social skills and event-related potentials (ERPs) in an auditory selective attention task, in addition to the neurocognitive indices obtained from the degraded-stimulus continuous performance test (CPT) and clinical indices, such as Brief Psychiatric Rating Scale (BRPS) and global assessment of function (GAF) scores. Social skills were assessed using a Japanese version of the structured role play test. Fourteen persons with schizophrenia participated in the study. Non-verbal skills showed a positive correlation with GAF, the performance level, N1 and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Verbal communication skills showed a positive correlation with GAF, the performance level and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Processing skills showed a positive correlation with the performance level and N1 amplitude in the ERP task and a negative correlation with reaction time in the CPT. These findings suggested that the social skill deficits of persons with schizophrenia were related to the vigilance level and controlled stimulus detection processing.

Adult↗

PubMed2000

Modifying effects of 4-phenylbutyl isothiocyanate on N-nitrosobis(2-oxopropyl)amine-induced tumorigenesis in hamsters.

The modifying effects of dietary 4-phenylbutyl isothiocyanate (PBITC), given during the initiation stage of carcinogenesis, were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). A total of 120 female 5-week-old hamsters were divided into six groups. Animals in groups 1-3, each consisting of 30 hamsters, were given BOP by two subcutaneous injections, 1 week apart, at a dose of 20 mg/kg body weight, plus 0, 10 or 100 micromol/animal of PBITC in corn oil by gavage 2 h prior to each carcinogen treatment. Ten animals in group 4 served as a vehicle control, and animals in groups 5 and 6, each consisting of ten hamsters, were given 10 and 100 micromol of PBITC alone in corn oil. Sacrifice was 52 weeks after the first BOP injection. The PBITC treatments significantly (P<0.05) inhibited the development of pancreatic ductal dysplasias and adenocarcinomas. Also, lung tumors (adenomas and adenocarcinomas) were significantly (P<0.05) reduced in a dose-dependent manner. In contrast, both hepatocellular and cholangiocellular tumors (adenomas and carcinomas) tended to be or were significantly increased by PBITC. These results, taken together with our previous findings, indicate that the natural isothiocyanate, phenethyl isothiocyanate (PEITC), has a more potent chemopreventive action against BOP-induced tumorigenesis than synthetic isothiocyanates with longer alkyl chains, such as 3-phenylpropyl isothiocyanate (PPITC) and PBITC. Thus, their lipophilicity does not necessarily reflect the chemopreventive potential because the strength of lipophilicity is PEITC<PPITC<PBITC.

Adenocarcinoma↗

PubMed2000

Effects of octreotide, a somatostatin analogue, on initiation of pancreatic carcinogenesis in hamsters with N-nitrosobis(2-oxopropyl)amine.

The modifying effects of octreotide acetate, a somatostatin (SMS) analogue shown to inhibit secretion of digestive enzymes, bicarbonate and pancreatic juice, on the initiation phase of pancreatic carcinogenesis were investigated in hamsters simultaneously treated with N-nitrosobis(2-oxopropyl)amine (BOP). Groups 1-3, each consisting of 20 animals, were given BOP subcutaneously once a week three times at a dose of 10 mg/kg body weight during administration of octreotide acetate for 28 days via osmotic pumps implanted subcutaneously at doses of 6 microg/day (group 1), 3 microg/day (group 2) or 0 microg/day (saline) (group 3). Group 4-6 animals (each group ten animals) were similarly administered octreotide acetate for the same period with five subcutaneous injections of saline. At the termination of experimental week 40, the incidences and multiplicities of pancreatic ductal adenocarcinomas and dysplastic lesions did not significantly differ among groups 1-3. No neoplastic lesions were found in groups 4-6. Subcutaneous administration of octreotide acetate resulted in obviously increased plasma octreotide levels. Our results thus suggest that this SMS analogue may not modulate the initiation of BOP-induced pancreatic carcinogenesis, regardless of its pharmacological action.

Adenocarcinoma↗

PubMed2000

Transduction of the human deoxycytidine kinase gene in rodent tumor cells induces in vivo growth retardation in syngeneic hosts.

Deoxycytidine kinase (dCK) mediates the phosphorylation of nucleoside analogues that can be used as anti-cancer agents. We examined whether susceptibility of mouse colon carcinoma (Colon 26) and rat gliosarcoma (9L) cells to 1-beta-D-arabiofuranosylcytonsine (AraC), a chemotherapeutic agent, can be increased after the tumor cells were transduced with the human dCK gene. Expression of the dCK gene in both cell lines conferred increased sensitivity in vitro to AraC. Although their proliferation rates in vitro remained the same as those of parental cells, tumor growth of the transduced cells in syngeneic host animals was unexpectedly retarded compared with that of respective parental cells. In contrast, the growth of the transduced cells was not different from that of parental cells, when they were inoculated in T cell-defective nude mice. A histological examination revealed infiltration of eosinophils into the dCK gene-transduced but not into parental Colon 26 tumor. These data suggest that a therapeutic gene, when expressed in xenogenic animals, can be a tumor antigen which is recognized by a host defense system.

Animals↗

PubMed2000

Concurrent administration of fish meal and sodium nitrite does not promote renal carcinogenesis in rats after initiation with N-ethyl-N-hydroxyethylnitrosamine.

The modifying effects of concurrent administration of fish meal and sodium nitrite on the development of renal tumors after initiation with N-ethyl-N-hydroxyethylnitrosamine (EHEN) were investigated. A total of 120 male 6-week-old Wistar rats were divided into six groups. Groups 1-3 (30 animals each) were given 1000 ppm EHEN in their drinking water for 3 weeks as an initiation treatment for renal cancer induction and thereafter fed respective diets containing 64, 32, and 8% (original concentration in the basal diet) fish meal, and simultaneously given 0.12% sodium nitrite in the drinking water for 33 weeks. Groups 4-6 (ten animals each) were similarly treated without the prior application of EHEN. At the end of the 37th experimental week, all surviving animals were autopsied and examined histopathologically for the existence of renal proliferative lesions. The incidences of dysplastic lesions, adenomas or adenocarcinomas of the kidney were not significantly different among groups 1-3. No renal proliferative lesions were found in groups 4-6. Chronic nephropathy was slightly but significantly enhanced in the 64 and 32% fish meal-treated groups as compared with group 3. Our results suggest that concurrent administration of fish meal and sodium nitrite does not affect the post-initiation phase of EHEN-induced renal carcinogenesis in the rat.

Adenocarcinoma↗

PubMed2000

Organ-dependent modifying effects of oltipraz on N-nitrosobis(2-oxopropyl)amine (BOP)-initiation of tumorigenesis in hamsters.

5-(2-Pyrazinyl)-4-methyl-1,2-dithiole-thione (oltipraz), a substituted 1,2-dithiole-3-thione, is known to inhibit tumorigenesis induced by variety of carcinogens in several animal model systems. In the present experiment, the modifying effects of dietary oltipraz, given during N-nitrosobis(2-oxopropyl)amine (BOP) initiation of carcinogenesis, were investigated in Syrian hamsters. A total of 120 six-week-old females were divided into six groups. Groups 1-3 (30 animals each) were thrice given subcutaneous injections of BOP (10 mg/kg, body weight) at 1 week intervals and fed diets supplemented with 400 or 200 ppm of oltipraz or basal diet alone, starting 1 week prior and finishing 1 week after the carcinogen exposure. Groups 4-6 (10 animals each) were similarly treated without application of BOP. At the end of the 52nd experimental week, all surviving animals were autopsied and examined histopathologically for proliferative lesions of the major target organs for BOP tumorigenicity, including pancreas, liver, kidney, and lung. The incidences and multiplicity of adenocarcinomas of the pancreas were higher in groups 1 and 2 than in group 3 although without statistical significance. The incidence of pancreatic duct dysplasias was significantly (P<0.05) increased in group 2 (62.0%) but not in group 1 (50.0%) as compared with group 3 (46.6%). While the incidences of alveolar adenomas and carcinomas were significantly (P<0.05) decreased by the high dose, the multiplicities of hepatocellular adenomas, cholagiocellular carcinomas and gall bladder adenomas were elevated in the BOP/oltipraz groups (P<0.05). The results of the present study suggest that oltipraz exerts organ-dependent modifying effects on BOP-induced carcinogenesis in hamsters when given in the initiation stage.

Animals↗

PubMed2000

Inhibition by methionine of pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl) amine.

The modifying effects of dietary L-methionine in the post-initiation phase of pancreatic carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Groups consisting of 20 and 30 animals, respectively, were given BOP subcutaneously, once a week five times at a dose of 10 mg/kg body wt. and then continuously fed diet supplemented with 2% (group 1) or 0% (group 2) methionine (weeks 5-32). After five subcutaneous injections of saline, group 3 animals were similarly fed diet supplemented with 2% methionine for the same period. The incidence of pancreatic ductal adenocarcinomas was significantly lower in group 1 (36.8%, P<0.05) than in group 2 (71.4%). Multiplicity of adenocarcinomas was also significantly lowered (0.52 and 1.28/hamster, P<0.05). Similarly, total numbers of combined adenocarcinomas and dysplastic lesions were significantly decreased in group 1 (2.05, P<0.05) as compared with group 2 (3.67). Methionine enhanced atrophic change of pancreatic acinar cells in hamsters given BOP, indicating that the inhibitory effects on the post-initiation stage of BOP-induced pancreatic carcinogenesis in hamsters could be generally linked to suppression of growth.

Adipose Tissue↗

PubMed2000

Reduced expression of p27(Kip1) correlates with an early stage of cancer invasion in oral squamous cell carcinoma.

Down-regulation of p27(Kip1) has been reported to correlate with poor survival of various carcinoma patients including oral squamous cell carcinomas (OSCCs). It is still unclear, however, at what stage of oral carcinogenesis the down-regulation of this protein occurs. In this study, therefore, we evaluated immunoexpression of p27(Kip1) protein in 17 cases of oral epithelial dysplasia and succeeding invasive OSCC in the same patient. We reported here that 88% cases showed high p27(Kip1) expression in dysplastic lesions, whereas 82% cases of succeeding invasive OSCC exhibited reduced expression. The reduction of p27(Kip1) expression was also observed in 16 of 19 (84%) early invasive lesions and well correlated with Ki-67 expression which is good indicator of cell proliferation. We also investigated immunoexpression of p53 protein of which abnormality has been known to occur during the early stage of OSCC development. Overexpression of p53 protein was demonstrated in 29% of dysplastic lesions, 42% of early invasive and 71% of invasive OSCCs. These findings suggest that abnormalities of both p53 and p27(Kip1) are involved in the carcinogenesis of OSCC, but they seem to play their role at different stages of oral cancer development, respectively. Reduced expression of p27(Kip1) may concern the cancer invasion directly or indirectly as well as abnormal proliferation.

Carcinoma, Squamous Cell↗

PubMed2000

Homonojirimycin analogues and their glucosides from Lobelia sessilifolia and Adenophora spp. (Campanulaceae).

2,6-Dideoxy-7-O-(beta-D-glucopyranosyl) 2,6-imino-D-glycero-L-gulo- heptitol (7-O-beta-D-glucopyranosyl-alpha-homonojirimycin, 1) was isolated from the 50% methanol extract of the whole plant of Lobelia sessilifolia (Campanulaceae), which was found to potently inhibit rice alpha-glucosidase. Adenophorae radix, roots of Adenophora spp. (Campanulaceae), yielded new homonojirimycin derivatives, adenophorine (2), 1-deoxyadenophorine (3), 5-deoxyadenophorine (4), 1-C-(5-amino-5-deoxy-beta-D-galactopyranosyl)butane (beta-1-C-butyl-deoxygalactonojirimycin, 5), and the 1-O-beta-D-glucosides of 2 (6) and 4 (7), in addition to the recently discovered alpha-1-C-ethylfagomine (8) and the known 1-deoxymannojirimycin (9) and 2R,5R-bis(hydroxymethyl)-3R,4R- dihydroxypyrrolidine (DMDP, 10). Compound 4 is a potent inhibitor of coffee bean alpha-galactosidase (IC50 = 6.4 microM) and a reasonably good inhibitor of bovine liver beta-galactosidase (IC50 = 34 microM). Compound 5 is a very specific and potent inhibitor of coffee bean alpha-galactosidase (IC50 = 0.71 microM). The glucosides 1 and 7 were potent inhibitors of various alpha-glucosidases, with IC50 values ranging from 1 to 0.1 microM. Furthermore, 1 potently inhibited porcine kidney trehalase (IC50 = 0.013 microM) but failed to inhibit alpha-galactosidase, whereas 7 was a potent inhibitor of alpha-galactosidase (IC50 = 1.7 microM) without trehalase inhibitory activity.

1-Deoxynojirimycin↗

PubMed2000

Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer.

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.

Axilla↗

PubMed2000

Investigation of menstruation recovery after LH-RH agonist therapy for premenopausal patients with breast cancer.

BACKGROUND: Recently Luteinizing hormone-releasing hormone (LH-RH) agonist has been used for premenopausal patients with breast cancer as endocrine therapy. However, there is no consensus regarding recovery of menstruation after long-term treatment with LH-RH agonist. We investigated recovery of menstruation after this treatment. METHODS: We investigated 28 premenopausal patients with breast cancer who underwent operation at Chiba Cancer Center Hospital in 1995 or 1996. The patients were treated with LH-RH agonist (goserelin) for 24 months as an adjuvant therapy, and were observed for more than 6 months after the last goserelin depot. Ages ranged 31-55 years old from at the time of last treatment. We defined recovery of menstruation as regular menstruation occurring more than three times. RESULTS: There were 22 patients in the recovery group (range: 31-53 years, mean 45.1 years). There were 6 patients in the non-recovery group (range: 50-55 years, mean 52.2 years). The overall recovery rate was 78.6%. Recovery rate was 81.8% for the patients under 50 years, and 66.7% for over 51 years. We separated all patients into groups by age at 5 years intervals, and investigated the distribution of the recovery time. In the recovery group (22 patients), there were 15 patients (68.2%) who confirmed recovery of menstruation within 6 months. CONCLUSION: Our investigation suggested that the recovery of menstruation after this therapy would occur in those less than 50 years old, within 6 months from the last treatment.

Adult↗

PubMed2000

Immunoexpression of transforming growth factor beta in desmoplastic ameloblastoma.

Desmoplastic ameloblastoma (DA) is an unusual subtype of ameloblastoma histologically characterized by the pronounced collagenized stroma. In the present study, the immunolocalization of transforming growth factor beta (TGF-beta), one of the most potent local factors for modulating extracellular matrix formation, was observed in DA in order to study its participation in the stromal desmoplasia. Seven cases of DA, including a "hybrid" lesion, were studied together with ten cases of ordinary follicular and plexiform ameloblastomas as the control. In contrast to ordinary ameloblastomas, marked immunoexpression was observed in all DAs but one. In the "hybrid" lesion, TGF-beta was not expressed in the area of follicular ameloblastoma but in that of DA. These results show that TGF-beta produced by tumor cells of DA plays a part in the desmoplastic matrix formation.

Adolescent↗

PubMed2000

Polyhydroxylated pyrrolidine and piperidine alkaloids from Adenophora triphylla var. japonica (Campanulaceae).

Adenophora triphylla var. japonica (Campanulaceae) yielded two new alkaloids, the 6-C-butyl derivative of 2R,5R-bis(hydroxymethyl)-3R,4R-dihydroxypyrrolidine (DMDP) and alpha-1-C-ethyl-fagomine, together with the known alkaloids 1,4-dideoxy-1,4-imino-D-arabinitol, 1-deoxynojirimycin, and 1-deoxymannojirimycin. 6-C-Butyl-DMDP showed inhibitory activity toward almond beta-glucosidase (IC50 = 68 microM), whereas alpha-1-C-ethyl-fagomine inhibited bovine liver beta-galactosidase (IC50 = 29 microM).

Alkaloids↗