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Biomedical subjects

H Miyahara

Publications and source records attributed to H Miyahara.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacodynamic analysis of steroid 5alpha-reductase inhibitory actions of Z-350 in rat prostate.

The pharmacodynamics of (S)-4-[3-[4-[1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy]benzoyl]indole-1-yl] butyric acid hydrochloride (Z-350), which has alpha(1)-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory effects, were investigated in rats. The disposition of Z-350 was a function of linear kinetics at doses from 1 to 30 mg/kg; the bioavailability was calculated to be 65.2%. The inhibition of 5alpha-reductase was dependent on the concentration of Z-350 in plasma and in the prostate. Analysis of the relationship between the concentration in the prostate and the inhibition seen after a single oral administration showed that the Hill constant was almost 1.0 and EC(50)(n(H)) was 47.4 ng/g of tissue; these parameters did not change after multiple administration. Z-350 inhibited 5alpha-reductase 1 h after oral administration at a dose of 3 mg/kg; maximum inhibition was observed after 2-4 h, and the inhibition (%) was maintained for 24 h after oral administration.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

LC determination of Z-338, novel gastroprokinetic agent in dog plasma by SCX solid phase extraction.

A simple high-performance liquid chromatographic assay with using UV detection (266 nm) was developed to determine a novel gastroprokinetic agent, Z-338 in dog plasma. The extraction procedure using solid-phase extraction with a Isolute SCX column produces extremely clean eluates and a high recovery. Intra- and inter-day variabilities were lower than 5%. The limit of quantitation of the method was 2.5 ng/ml. This assay was applied to the monitoring of Z-338 concentrations in dogs after oral administration. The method also appeared rapid, simple and suitable for therapeutic Z-338 monitoring.

Animals↗
PubMed2001

Precise emission probabilities of gamma-rays of 159Gd.

Measurement of emission probabilities for principal gamma-rays of 159Gd with 4pibeta(ppc)-gamma(HPGe) coincidence apparatus has given precise values as indicated by uncertainties of about 1%. Improved certainties are seen when comparing the present results with emission probabilities evaluated in Nuclear Data Sheets (Helmer, 1994, p. 72) for which the uncertainties are about 24%. The improvement resulted in precise decay scheme parameters of the nuclide.

Journal Article↗
PubMed2000

Transfection with mutant p53 gene inhibits heat-induced apoptosis in a head and neck cell line of human squamous cell carcinoma.

PURPOSE: To confirm that human cancer cells show p53-dependent heat sensitivity through an apoptosis-related mechanism, we examined the heat sensitivity and Bax-mediated apoptosis after heating in a human squamous cell carcinoma cell line, SAS, with identical genetic backgrounds except for the p53 status. MATERIALS AND METHODS: We performed colony formation assay, Western blotting and analyses of apoptosis, using the SAS cells transfected with pC53-248 vector with mutant p53 gene (SAS/Trp248 cells) or the cells transfected with pCMV-Neo-Bam vector (SAS/neo cells) as a control. RESULTS: SAS/Trp248 cells showed heat resistance due to the dominant negative nature of mp53, compared with SAS/neo cells. The incidence of DNA ladders and apoptotic bodies increased markedly after heating in SAS/neo cells, but increased very little in SAS/Trp248 cells. CONCLUSION: These results suggest that heat resistance brought by mp53-transfection is p53-dependent and closely correlates with the induction of apoptosis in human squamous cell carcinomas.

Apoptosis↗
PubMed2000

Precise measurements of the gamma-ray emission probabilities of 186Re and 188Re.

Gamma-ray emission probabilities of 186Re and 188Re are important in nuclear medicine, and have been precisely measured by 4pibeta-gamma coincidence using a live-timed two-dimensional data-acquisition system. The gamma-ray emission probabilities of the 137.2 keV for 186Re and 155.1 keV for 188Re were 0.09487+/-0.00029 and 0.15425+/-0.00072, respectively.

Gamma Rays↗
PubMed2000

Mannose binding lectin (MBL) gene mutation is not a risk factor for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Japanese.

Mannose binding lectin (MBL) deficiency may be associated with increased susceptibility to infection and autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, we performed for the first systematic search for mutations in all the four exons of the MBL gene using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. Of 49 healthy Japanese individuals studied, only the previously reported mutation at the codon 54 (substitution from Gly to Asp; G54D) was identified. The allele frequencies of G54D in 105 healthy Japanese individuals, 95 SLE patients and 59 RA patients, were 0.233, 0.226 and 0.178, respectively, which were not significantly different. In addition, two polymorphisms at positions of -550 and -221 in the promoter region were not associated with SLE and RA. It is unlikely that MBL deficiency plays a major role in the pathogenesis of SLE and RA in Japanese.

Alleles↗
PubMed2000

Analysis of p53 tumour suppressor gene somatic mutations in rheumatoid arthritis synovium.

OBJECTIVE: In order to study the role of the p53 tumour suppressor gene in the proliferation of rheumatoid arthritis (RA) synovium, we analysed the mutation of p53 in the synovial fibroblast-like type B synoviocyte from RA patients. METHODS: Synovial fibroblast-like type B synoviocytes were prepared from the synovial tissues from nine Japanese patients with RA. The p53 cDNA region from exons 4-11 was screened for mutations by the streamlined mutation detection method in which polymerase chain reaction (PCR) products are post-labelled and are analysed by automated capillary electrophoresis using single-strand conformation polymorphism conditions, followed by direct sequencing of the subclones of the PCR products. RESULTS: p53 mutation with possible functional alteration was detected in four of the nine RA patients (44.4%). Of a total of 262 p53 cDNA subclones, 10 subclones were carrying 10 p53 mutations, eight of which were associated with amino acid alterations or protein truncation. Of the p53 functional mutations, a substitution of Gly at amino acid residue 245 to Asp (G245D) was identified in two patients in three subclones. G245D was the first mutation that was recurrently identified in different RA individuals. G245D is also one of the relatively common mutations in human cancers. CONCLUSIONS: In some patients with RA, dysfunction of p53 might play a role in the proliferation of the synovial tissue. G245D mutation might especially need further study as it is the first recurrently identified p53 mutation in RA and is also one of the frequently identified mutations in human cancers.

Arthritis, Rheumatoid↗
PubMed2000

Telemedicine for evaluation of brain function by a metacomputer.

A method of evaluating brain function using the metacomputer concept of the Globus system combined with a message-passing interface is described. The proposed method has the ability to exploit various geographically distributed resources and parallel computing linked to a high-technology medical instrumentation system, magnetoencephalography, to analyze the functional state of the brain. It is envisaged that the method will lead to the realization of an efficient telemedicine system for health care.

Brain↗
PubMed2000

CDDP induces p53-dependent apoptosis in tongue cancer cells.

We have investigated the CDDP sensitivities of two tongue cancer cell lines with differing p53 genetic status, one with wild-type p53 (SAS) and the other with mutant-type p53 (HSC-4). SAS was about 2 times more sensitive at the D10 dose and demonstrated increased p53 and Bax protein levels at 10 h after CDDP treatment on Western blot analysis. On the other hand, overexpression of p53 in HSC-4 was observed without CDDP treatment and no elevation of Bax could be detected. Apoptosis was observed after CDDP treatment in SAS but not in HSC-4 by Hoechst 33342-staining and electrophoresis methods. These findings indicate that p53 plays an important role in apoptosis as a positive regulator of Bax expression. It is suggested that p53 status may have predictive potential with regard to response to CDDP therapy.

Apoptosis↗
PubMed2000

Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy.

Curative radiotherapy is the first choice of therapy for T1 and T2 stage laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation. Patients with recurrent tumors who undergo salvage surgery require prolonged nasal feeding. Therefore, clinical interest has been focused on elucidating a predictive factor indicating which tumors are likely to be radiosensitive before radiotherapy. We analyzed the relations between radiosensitivity and clinicopathological factors (gender, tumor location, histological factors, and clinical tumor-node-metastasis stage), expression of apoptosis-related proteins (p53, bax, bcl-2), apoptotic index using the terminal deoxynucleotidyltransferase-mediated nick end labeling method, expression of cell proliferation-related proteins (Ki-67-labeling index and epidermal growth factor receptor overexpression) and microvessel density (MVD, vessels/field = 0.391 mm2) in biopsy specimens from 31 LSCC patients given radiotherapy (total radiotherapy dose of 52-70 Gy over 4-6.5 weeks). Univariate analysis revealed that tumors with a high MVD (> or =35 vessels/field) showed better radiosensitivity than those with a low MVD (<35 vessels/field, P = 0.008) and that a high Ki-67-labeling index (> or =40%) was weakly associated with radiosensitivity (P = 0.056). Multivariate analysis and Kaplan-Meier analysis showed that MVD alone had significant predictive power for radiosensitivity in T1 and T2 stage LSCCs after radiotherapy (P = 0.012, 0.0003, respectively). No significant association between clinicopathological factors, or of overexpression of p53, bax, bcl-2, epidermal growth factor receptor, or apoptotic index, with radiosensitivity was found. These results indicate that MVD is a potentially useful clinical factor predicting radiosensitivity for patients with early stage LSCCs before treatment.

Aged↗
PubMed1998

Different ras gene mutational frequencies in thyroid papillary carcinomas in Japan and Thailand.

The incidence and pattern of ras oncogene mutations in human malignancies demonstrate geographic and racial differences. For example, specificity of alterations is found in cholangiocellular carcinomas in Thai patients with a different etiology from those in Japanese patients. In the present study, a comparison of ras gene mutations in thyroid papillary carcinomas from Japanese and Thai patients was performed using single-strand conformation polymorphism and direct sequencing analyses. The incidence of ras mutation differed markedly in Japanese (two of 24 carcinomas, 8.3%) and Thai (five of 10 carcinomas, 50%) patients. In addition, all but one ras mutation occurred at codon 12 of the K-ras gene in the Thai cases. These results suggest that thyroid cancers in Thailand may be due to specific genetic and/or environmental factors.

Adult↗
PubMed1998

WinArrhythmia: a Windows based application for studying cardiac arrhythmias.

We have developed Windows-based software for ECG training as a tool in teaching physiology. A standard user interface allows the user to choose which arrhythmia to review. The arrhythmia is drawn in real time with sound beeps synchronized to R waves. The system also presents a brief summary or multiple choice question corresponding to the arrhythmia. A ladder diagram shows how simulate the conduction system, which consisted of 4 modules characterized by 4 parameters: automaticity, refractory period, antegrade- and retrograde-conduction time. This system has proved both useful and effective for training medical students in ECG interpretation of arrhythmias.

Arrhythmias, Cardiac↗
PubMed1998

Amplification of int-2 and bcl-1 genes in squamous cell carcinoma of the larynx.

We studied int-2 and bcl-1 gene amplification in 21 operated patients with cancer of the larynx. In 9 cases, the int-2 gene was amplified (42.9%) and in 4 cases. the bcl-1 gene was amplified (25.0%). Co-amplification of int-2 and bcl-1 was observed in three cases (18.8%), all of which were glottic carcinomas. Other amplified cases were supraglottic carcinomas. Tumor specimens with int-2 amplification were associated with a significantly worse prognosis. We suggest that int-2 amplification is one of the prognostic factors in laryngectomized patients with cancer of the larynx.

Adult↗
PubMed1998

Hemodynamics of a simulation of the vertebrobasilar system using silicone tube.

We investigated the hemodynamics of the vertebrobasilar system (VBS) using a simulation model tube made of silicone which had different diameters between the bilateral vertebral artery (VA) ducts (stenotic and normal VA ducts). Using the ultrasonic Doppler method. the laterality index (L.I.) of the flow velocity in the VA duct was 32.88%. The flow volume of the anterior inferior cerebellar artery duct and the posterior inferior cerebellar artery duct also had significant laterality. By investigating the effects of the rotatory pulse rate and fluid viscosity, a maximal decrease to below 40-50% of the flow volume of the branches, and to below 71.93% in the mean flow velocity of the basilar artery (BA) duct (BA duct) were observed. and the maximum L.I. increased to 43.15%. When the unilateral stenotic VA duct was occluded by clamping (clamping occlusion), the flow volume profiles of the branches were the same as without clamping occlusion. The L.I. showed no significant changes and the maximal decrease in the mean flow velocity of the BA duct was 68.61%. Using the laser Doppler method, the flow velocity distribution of the BA duct was shifted towards the side of the stenotic VA duct. These results suggest that the rheological dynamics in the main vessels can certainly reflect the posterior circulatory dynamics, and that modulating factors also aggravate the hemodynamics of the VBS with this disorder.

Arteries↗
PubMed1998

Influence of hyperlipidemia and smoking on age-related changes in caloric response and pure-tone hearing.

To examine the influence of hyperlipidemia and smoking on age-related changes in caloric response and pure-tone hearing, a caloric test and pure-tone audiometry were performed in 14 healthy volunteers and in 78 tinnitus patients without subjective hearing loss. The patients were from 24 to 84 years of age, and were divided into 4 groups: the no-risk group (N group), the smoking alone group (S group), the hyperlipidemia alone group (L group), and the smoking plus hyperlipidemia group (S-L group). Slow phase eye velocity of the caloric nystagmus (SPEV) and average hearing level at high frequencies were compared between the N groups and the other groups. There was a significant difference in SPEV only between the N and S-L groups, but not in the hearing level. This suggests that age-related changes in the caloric response be promoted by atherosclerosis, unlike presbycusis.

Adult↗
PubMed1998

Radiation-induced cancers of the head and neck region.

A total of 65 patients with radiation-induced cancers of the head and neck region were treated and evaluated. The primary disease for which the radiotherapy had been applied was benign disease in 48 patients (including tuberculous lymphadenitis in 39 patients), and malignant tumors in 17 patients (including 9 laryngeal cancers and 5 thyroid cancers). The radiation-induced cancers included 35 cases of hypopharyngeal cancer, 15 of thyroid cancer, and 13 of cervical esophageal cancer. The mean duration from radiotherapy until the diagnosis of cancer was 12.8 years in the patients with malignant primary tumor and 32.9 years in those with benign primary diseases. Most of the patients underwent surgery for their cancer. The clinical course was poor and the outcome extremely poor, especially in those patients with field carcinogenesis. It is emphasized that excessively high dosage and wide radiation field should be avoided, and that radiotherapy for young patients with malignancies requires extremely careful management.

Female↗
PubMed1998

[Flow cytometric analysis of proliferative activity of pleomorphic adenoma of salivary gland].

Pleomorphic adenoma (PA) of the salivary gland has diverse biological behavior in spite of its being a benign tumor. So the nuclear DNA content of 36 PAs was measured by flow cytometry to determine the relationship between proliferative activity and histopathological variable. DNA histograms were evaluated according to the rate of S and G2+ M phase cells (S + G2M%). We assumed that the DNA histogram measured algebraically, S + G2 M% < or = 0%, is the near diploid pattern and calculated its ratio to the near diploid pattern. A statistically significant difference between PA and normal salivary gland was found by the ratio to the near diploid pattern (P < 0.05), which confirmed the usefulness of the ratio to the near diploid pattern for measuring low proliferative activity. The tumors were divided into 3 groups: epitheloid type, intermediate type and myxochondroid type. In the 3 groups no differences were found by S + G2M% and the ratio to the near diploid pattern. The areas of the tumor were divided into 5 groups according to the ratio in the epitheloid region and the myxochondroid region. In the 5 groups, the area which consists partly of epitheloid components and mostly of myxochondroid components had the lowest ratio to the near diploid pattern and the highest S + G2M%, and the area which consists of only myxochondroid components had the highest ratio to the near diploid pattern and the lowest S + G2M%. Between only these two areas a statistically significant difference was found by the ratio to the near diploid pattern (P < 0.05). We considered that the area which consists partly of epitheloid components, and mostly of myxochondroid components has the highest proliferative activity in PA. Neither aneuploid or polyploid cells were found in any tumor, but the S + G2M% is more than 20% in 4 tumors. None of these high S + G2M% tumors except one recurrent tumor had clinical and histopathological features. A differences between PAs of the parotid glands and PAs of the submandibular glands was not found in S + G2M%.

Adenoma, Pleomorphic↗