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Biomedical subjects

M Hiraoka

Publications and source records attributed to M Hiraoka.

At least 19 recordsLinked to original sources
PubMed2006

Health-related quality-of-life after external beam radiation therapy for localized prostate cancer: intensity-modulated radiation therapy versus conformal radiation therapy.

We compared health-related quality-of-life (HRQL) after intensity-modulated radiotherapy (IMRT) with statuses obtained after old and new protocols of three-dimensional conformal radiation therapy (3DCRT) for localized prostate cancer. We measured the general and disease specific HRQL using the MOS 36-Item Health Survey (SF-36), and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI), respectively. IMRT resulted in similar profiles of general and disease-specific HRQL to two other methods within the first year after treatment. Moreover, IMRT gave rise to comparable urinary, intestinal and sexual side effects despite the high dose of radiation applied.

Aged↗
PubMed2006

Stereotactic body radiation therapy (SBRT) for early-stage lung cancer.

Stereotactic body radiation therapy (SBRT) is a new treatment modality for early-stage non-small-cell lung cancer, and has been developed in the United States, the European Union, and Japan. We started a feasibility study of this therapy in July 1998, using a stereotactic body frame. The eligibility criteria for primary lung cancer were: 1) solitary tumor less than 4 cm (T1-3N0M); 2) inoperable, or the patient refused operation; 3) no necessity for oxygen support; 4) performance status equal to or less than 2; 5) the peripheral tumor which dose constraints of mediastinal organs are maintained. A total dose of 48 Gy was delivered in four fractions in 2 weeks in most patients. Lung toxicity was minimal. No grade II toxicities for spinal cord, bronchus, pulmonary artery, or esophagus were observed. The 3 years overall survival for 32 patients with stage IA, and 13 patients with stage IB were 83% and 72%, respectively. Only one local recurrence was observed in a follow-up of 6-71 months. We retrospectively analyzed 241 patients from 13 Japanese institutions. The local recurrence rate was 20% when the biological equivalent dose (BED) was less than 100 Gy, and 6.5% when the BED was over 100 Gy. Overall survival at 3 years was 42% when the BED was less than 100 Gy, and 46% when it was over l00 Gy. In tumors, which received a BED of more than 100 Gy, overall survival at 3 years was 91% for operable patients, and 50% for inoperable patients. Long-term results, in terms of local control, regional recurrence, survival, and complications, are not yet evaluated. However, this treatment modality is highly expected to be a standard treatment for inoperable patients, and it may be an alternative to lobectomy for operative patients. A prospective trial, which is now ongoing, will, answer these questions.

Adult↗
PubMed2005

Quantitative unspun-urine microscopy as a quick, reliable examination for bacteriuria.

The diagnosis and treatment of urinary infection are often delayed, causing renal damage, largely because of the unavailability of quick, accurate, diagnostic examinations. Three hundred and twenty-five urine samples from 130 patients were examined for significant bacteriuria using the standard culture method. The urine samples were also examined using the Gram-stain method and quantitative unspun-urine microscopy. When particles could not be distinguished definitely as bacilli by quantitative microscopy, the unspun urine was examined on a slide glass using oil-immersion microscopy at x 1000 magnification. Significant bacteriuria in 37 urine samples was detected by bacterial culture. Using quantitative microscopy, rods were found in 30, cocci in a chain in 3, and indefinite particles in 44 samples. In the 44 indefinite samples, oil-immersion microscopy was able to distinguish rods in one, cocci in a chain in one, cocci in a cluster in two, and negative in 40, which were confirmed by culture as rods, streptococci, staphylococci, and negative, respectively. The quantitative microscopy method was similarly reliable (94.6% sensitivity, 99.3% specificity) for diagnosis of significant bacteriuria when compared with the Gram-stain method (89.2% sensitivity, 98.6% specificity). Quantitative unspun-urine microscopy, confirmed by oil-immersion, is a quick, reliable method for diagnosis of significant bacteriuria, and is considered to be useful for early diagnosis of urinary infection.

Adolescent↗
PubMed2005

Elastic moduli of thyroid tissues under compression.

The aim of this study was to evaluate the elastic moduli of thyroid tissues under uniaxial compression and to establish the biomechanical fundamentals for accurate interpretation of thyroid elastograms. A total of 67 thyroid samples (24 samples of normal thyroid tissue, 2 samples of thyroid tissue with chronic thyroiditis, 12 samples of adenomatous goiter lesions and 7 samples of follicular adenoma, 19 samples of papillary adenocarcinoma (PAC) and 3 samples of follicular adenocarcinoma (FAC)) obtained from 36 patients who had received thyroid surgery were subjected to biomechanical testing within three hours after surgical resection at precompression strains of 5%, 10% and 20% and applied strains of 1%, 2%, 5% and 10% of sample height. As a result, the mean values of elastic moduli for benign thyroid lesions at all examined precompression levels were significantly higher than those for normal thyroid tissue measured at the same load (p<0.01). At low precompression (5%) and compression (1-2%) levels, benign thyroid nodule samples were 1.7 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 2.4 times. Stiffness of PAC samples was significantly higher than those for normal thyroid tissue and benign thyroid tumors measured at the same load (p<0.01). At low precompression (5%) and compression (1-2%) levels, PAC samples were 5.0 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 17.7 times. In contrast, samples of FAC were much softer than PAC (p<0.05) and were comparable in stiffness to normal thyroid tissues. The significant differences in the stiffness between normal thyroid tissue and thyroid tumors may provide useful information for accurate interpretation of thyroid elastograms.

Adult↗
PubMed2004

The usefulness of 2-nitroimidazole-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy.

We evaluated the usefulness of five new (10)B-compounds (TX-2016, TX-2017, TX-2018, TX-2041, and TX-2042) as (10)B-carriers in boron neutron capture therapy (BNCT). They are 2-nitroimidazole-sodium borocaptate-(10)B (BSH) conjugates, that is, hybrid compounds that have both hypoxic tumor cell sensitizing unit under gamma-ray irradiation, 2-nitroimidazoles, and thermal neutron-sensitizing unit, BSH. (10)B distribution analyses in tumors and blood indicated that TX-2041 has the most favorable characteristics for localizing a sufficient amount of (10)B into tumors and keeping the (10)B concentration high during neutron beam irradiation. In addition, TX-2041 showed a significantly higher radio-sensitization effect with reactor thermal neutron beams than BSH on both total (=proliferating (P) + quiescent (Q)) and hypoxia-rich Q cell populations in solid tumors. Further, TX-2041 clearly demonstrated a radio-sensitization effect with gamma-rays on both cell populations, which could never be achieved by BSH. (10)B-carriers with a hypoxic tumor cell-sensitizing effect on tumors with gamma-rays as well as the potential to selectively localize and keep (10)B in tumors, such as TX-2041, are promising for use in actual BNCT.

Animals↗
PubMed2004

Immuno-localization of COX-1 and COX-2 in the rat molar periodontal tissue after topical application of lipopolysaccharide.

Up-regulation of prostaglandin E2 (PGE2) production in the periodontal tissue is considered to be important for periodontal tissue destruction. The purpose of the study was to demonstrate the dynamic changes of immuno-localization of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in rat periodontal tissue after topical application of lipopolysaccharide (LPS: 5 mg/ml in physiological saline) from Escherichia coli into the rat molar gingival sulcus. In the normal periodontal tissue, small numbers of junctional epithelium (JE) cells and numerous osteocytes embedded in alveolar bone constitutively expressed COX-1. The COX-1 expression was not effected by LPS application. JE cells, especially in the coronal portion of JE also expressed COX-2. LPS application induced the JE cells with consequent transient expression of COX-2 with a peak at day 1. These findings suggest that JE cells may play a critical role in first defense line against LPS challenge and PGE2 from JE cells may be responsible for the initiation of periodontal inflammation. In the deep periodontal tissue, cementoblasts and osteoblasts showed constitutive expression of COX-2, which may be induced by continuous cyclic tension force due to occlusal pressure. LPS application caused a transient up-regulation of COX-2 expression in periodontal ligament fibroblasts, cementoblasts and osteoblasts. It is suggested that the inducible production of PGE2 via COX-2 by these cells may be associated with connective tissue destruction and alveolar bone resorption.

Administration, Topical↗
PubMed2004

Effects of variation in superoxide dismutases (SOD) on oxidative stress and apoptosis in lens epithelium.

Among the critical antioxidant enzymes that protect the cells against oxidative stress are superoxide dismutases: CuZnSOD (Sod1) and MnSOD (Sod2). The latter is also implicated in apoptosis. To determine the importance of these enzymes in protection against reactive oxygen species (ROS) in the lens, we analysed DNA strand breaks in lens epithelium from transgenic and knockout (Sod1) mice following exposure to H2O2 in organ culture. Since Sod2 knockouts do not survive, comparison was made of lenses of partially-deficient (heterozygote) for Sod2 and the wild-type controls which have twice the enzyme level. Antioxidant potential of Sod2 was also studied in human lens epithelial cells (SRA01/04) in which the enzyme was up- and down-regulated by transfection with plasmids containing sense and antisense human cDNA for MnSOD. DNA strand breaks in the epithelium of Sod1 knockouts and Sod2 heterozygotes were much greater than in the corresponding wild-type or in transgenic mice over-expressing the enzymes when the lenses were exposed to H2O2. The functional role of Sod2 in apoptosis was examined in cultured human lens epithelial cells. Cells with higher enzyme levels were more resistant to the cytotoxic effects of H2O2, O2- and UV-B radiation. Furthermore, Sod2-deficient cells showed dramatic mitochondrial damage, cytochrome C leakage, caspase 3 activation and increased apoptotic cell death when they were challenged with O2-. Thus, mitochondrial enzyme (Sod2) deficiency plays an important role in the initiation of apoptosis in the lens epithelium.

Animals↗
PubMed2003

Inhibition of CD44v9 upregulates the invasion ability of oral squamous cell carcinoma cells.

The aim of the present study has been to determine the role of CD44v9 in the metastatic process of oral squamous cell carcinoma (OSCC). We have examined the expression intensity of CD44v9 in four OSCC cell lines, and using cell culture insert investigated the invasion ability of the cells expressing CD44v9 at higher levels (HSC-2, HSC-3), and the cells expressing this protein at lower levels (HSC-4, KB) with or without the treatment with an anti-CD44v9 antibody. In the highly expressing cells, the addition of anti-CD44v9 antibody enhanced their invasion ability, whereas it showed no effect on the invasion ability of the weakly expressing cells. These results suggest that the reduction of CD44v9 expression may weaken cell-to-cell adhesion in OSCC and make the tumor cells detach easily from their nests, resulting in the enhancement of their invasion ability. It may ultimately promote the establishment of a metastatic lesion.

Antigens, Neoplasm↗
PubMed2003

Association between interleukin-18 gene polymorphism 105A/C and asthma.

BACKGROUND: IL-18 has been shown to exert anti-allergic or allergy-promoting activities, but the existence of genetic polymorphisms in the coding regions of IL-18 gene has not been demonstrated. OBJECTIVE: The aim of this study was to investigate whether polymorphism is present in the coding regions of the IL-18 gene and, if so, to further analyse the association between polymorphism and asthma in a case-control study. METHODS: We screened the coding regions of the IL-18 gene for polymorphisms by using PCRsingle-stranded conformation polymorphism and direct sequencing of PCR products, followed by analysis of the association between polymorphism and asthma. RESULTS: We identified one polymorphism (105A/C) in the coding regions. The frequency of the 105A allele was significantly higher in asthmatic patients than in controls (P<0.01; odds ratio (OR)=1.83 (1.37-2.26)). Significant linkage disequilibrium was observed between the 105A/C and -137G/C polymorphisms in the 5' flanking region of the IL-18 gene (D=0.58, P<0.0001). However, in asthmatic patients the 105A allele was not associated with either total serum IgE or IL-18 levels. CONCLUSION: The 105A/C polymorphism of the IL-18 gene may be associated with the pathogenesis of asthma.

Adolescent↗
PubMed2002

Dechlorination and destruction of PCDD, PCDF and PCB on selected fly ash from municipal waste incineration.

The potential of fly ash to dechlorinate and destroy PCDD, PCDF and PCB was tested under oxygen deficient conditions in the laboratory. Specifically, two types of fly ash were compared, originating either from a fluidized bed incinerator using Ca(OH)2 spray (FA1), or a stoker incinerator without Ca(OH)2 impact (FA2). Results from the present study indicate that on FA2 type fly ash, the degradation processes of OCDD, OCDF and D10CB occurred primarily via dechlorination/hydrogenation up to temperature settings of 340 degrees C. In contrast, FAI type fly ash was found to effect both dechlorination and destruction of these compounds already at temperature settings of 260 degrees C. The dechlorination velocity of PCDD and PCDF did not differ significantly. However, the first dechlorination step of OCDF in the 1,9-position occurred faster compared to the first dechlorination step of OCDD. The isomer pattern resulting from the dechlorination processes was quite similar on both FAI and FA2, indicating that differences in alkalinity or elemental composition of the two types of fly ashes do not have a significant influence on the position of dechlorination. PCDD and PCDF dechlorination of the 2,3,7,8-positions was not favoured over dechlorination of the 1,4.6,9-positions on either type of fly ash. In contrast, dechlorination of PCB occurred predominantly on the toxicological relevant 3- and 4-positions. The dechlorination/destruction processes were completed on both types of fly ash at 380 degrees C within one hour, which correlates well with results obtained from actual plant operation practices.

Air Pollution↗
PubMed2002

Effects of selected metal oxides on the dechlorination and destruction of PCDD and PCDF.

OCDD and OCDF spiked silica/graphite based model fly ash containing various copper compounds and metal oxides were thermally treated under oxygen deficient conditions. All copper compounds tested showed a considerable dechlorination/hydrogenation reaction at 260 degrees C. After 30 min at 340 degrees C, less than 1% of the spiked OCDD and OCDF was recovered as T4CDD/F to OCDD/F. Other compounds tested demonstrated a lower rate of dechlorination compared to the copper compounds. However, all other metal oxides showed a small dechlorination effect at 260 degrees C, which was considerably increased at 340 degrees C. The model fly.ash containing the different copper compounds or metal oxides showed comparable PCDD and PCDF isomer patterns after thermal treatment. However, small differences were observed among the different tested compounds. The PCDD and PCDF isomer patterns on the model fly ashes were similar to patterns found during dechlorination experiments on fly ashes from waste incineration processes. Model fly ash containing Ca(OH)2 exhibited the highest destruction potential, but a low dechlorination potential. In contrast, model fly ash containing any of the remaining compounds tested, was found to predominantly dechlorinate the spiked OCDD and OCDF.

Benzofurans↗
PubMed2002

Characterization of Ca(2+) signaling pathways in human mesenchymal stem cells.

Human mesenchymal stem cells (HMSC) have the potential to differentiate into many cell types. The physiological properties of HMSCs including their Ca(2+) signaling pathways, however, are not well understood. We investigated Ca(2+) influx and release functions in HMSCs. In Ca(2+) imaging experiments, spontaneous Ca(2+) oscillations were observed in 36 of 50 HMSCs. The Ca(2+) oscillations were completely blocked by the application of 10 micro M cyclopiazonic acid (CPA) or 1 micro M thapsigargin (TG). A brief application of 1 micro M acetylcholine (ACh) induced a transient increase of [Ca(2+)](i) but the application of caffeine (10 mM) did not induce any Ca(2+) transient. When the stores were depleted with Ca(2+)-ATPase blockers (CPA or TG) or muscarinic agonists (ACh), store-operated Ca(2+) (SOC) entry was observed. Using the patch-clamp technique, store-operated Ca(2+) currents (I(SOC)) could be recorded in cells treated with ACh or CPA, but voltage-operated Ca(2+) currents (VOCCs) were not elicited in most of the cells (17/20), but in 15% of cells examined, small dihydropyridine (DHP)-sensitive Ca(2+) currents were recorded. Using RT-PCR, mRNAs were detected for inositol 1,4,5-trisphosphate receptor (InsP(3)R) type I, II, and III and DHP receptors alpha1A and alpha1H were detected, but mRNA was not detected for ryanodine receptor (RyR) or N-type Ca(2+) channels. These results suggest that in undifferentiated HMSCs, Ca(2+) release is mediated by InsP(3)Rs and Ca(2+) entry through plasma membrane is mainly mediated by the SOCs channels with a little contribution of VOCCs.

Calcium↗
PubMed2002

Establishment of human cementifying fibroma cell lines by transfection with temperature-sensitive simian virus-40 T-antigen gene and hTERT gene.

Human cementifying fibroma (HCF) is a benign fibro-osseous neoplasm of periodontal ligament (PDL) origin containing varying amounts of mineralized material resembling cementum. In the present study, we established cell lines from HCF, which were detected in the mandible of a 54-year-old Japanese man. To obtain immortalized cell clones, we undertook transfection with temperature-sensitive simian virus-40 (SV40) T-antigen and hTERT into HCF cells. Cells transfected with SV40 T-antigen entered "crisis" state between passages 22 and 35, but activation of telomerase by transfection with hTERT in the SV40-transformed HCF cells resulted in bypass of the crisis and maintenance over passage 200. HCF cell lines decreased the expression of SV40 T-antigen and the activity of cell proliferation at a nonpermissive temperature (39 degrees C) in comparison with that at a permissive temperature (33 degrees C). High activities of alkaline phosphatase and mineralization and the expression of type I collagen, osteocalcin, osteopontin, and bone sialoprotein by reverse transcription-polymerase chain reaction (RT-PCR) were observed in HCF cells at 39 degrees C. Overall, these findings suggest that: (i) HCF cell lines may represent a novel in vitro human cell model for the study of the regulatory mechanism of differentiation and proliferation of the human PDL; and (ii) transfection of plasmids encoding the temperature-sensitive SV40 T-antigen gene and hTERT gene may be useful for obtaining immortalized cell lines from benign human tumor and, probably, nonneoplastic human tissues.

Alkaline Phosphatase↗
PubMed2002

Sensor system using polarization analysis method to monitor oil-on-water in water purification plants and rivers.

Some 80% of accidental pollution in river water is caused by oil spills. Oil spills can cause serious damage such as suspension of water intake at water purification plants and major harm to ecosystems in the lower reaches of rivers. This is because oil-on-water tends to spread easily, quickly exacerbating the damage. To address this problem, an automated, continuous sensor system with high sensitivity can be used for early detection of spill accidents. We have developed a sensor system for detecting oil-on-water based on a polarization analysis method. Its advantages include: a) no direct contact with sample water; b) minimal maintenance; c) largely unaffected by foreign matter and waves on the water surface; and d) much higher sensitivity than simple visual observation. This paper describes the measurement principle and configuration of the sensor system, and discusses the results of sensitivity tests and tests on the influence of water turbidity, foreign matter and waves. We will also consider some of the limitations of the new system.

Environmental Monitoring↗
PubMed2001

Recombinant annexin II modulates impaired fibrinolytic activity in vitro and in rat carotid artery.

Fibrinolytic activity has been reported to be decreased in atherosclerosis. Recently, annexin II was identified as a coreceptor on endothelial cells for plasminogen and tissue plasminogen activator. In this study, we examined whether recombinant annexin II (rAN II) protein can modulate fibrinolytic activity on vascular endothelium in vitro and in vivo. The effect of rAN II on human umbilical vein endothelial cells (HUVECs) was measured. Addition of a fluorescent plasmin substrate revealed that HUVECs treated with rAN II exhibited significantly more plasmin generation than those treated with BSA. Moreover, rAN II treatment of HUVECs restored plasmin generation impaired by plasminogen activator inhibitor-1 or homocysteine pretreatment. In a rat carotid artery thrombus model, the patency of thrombosed carotid arteries was significantly enhanced by rAN II injection, in contrast to BSA injection, without systemic blood coagulation dysregulation. We found that rAN II enhanced plasmin generation on vascular endothelium in vitro and reduced thrombus formation in vivo, and concluded that enhancement of endothelial fibrinolytic activity by annexin II could modulate the hypercoagulable state of atherosclerosis. Further study of rAN II in vitro and in vivo may lead to the establishment of novel therapeutic approaches to thrombogenic vascular disease.

Animals↗
PubMed2001

Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells.

Yeast Rad52 DNA-repair mutants exhibit pronounced radiation sensitivity and a defect in homologous re combination (HR), whereas vertebrate cells lacking Rad52 exhibit a nearly normal phenotype. Bio chemical studies show that both yeast Rad52 and Rad55-57 (Rad51 paralogs) stimulate DNA-strand exchange mediated by Rad51. These findings raise the possibility that Rad51 paralogs may compensate for lack of Rad52 in vertebrate cells, explaining the absence of prominent phenotypes for Rad52-deficient cells. To test this hypothesis, using chicken DT40 cells, we generated conditional mutants deficient in both RAD52 and XRCC3, which is one of the five vertebrate RAD51 paralogs. Surprisingly, the rad52 xrcc3 double-mutant cells were non-viable and exhibited extensive chromosomal breaks, whereas rad52 and xrcc3 single mutants grew well. Our data reveal an overlapping (but non-reciprocal) role for Rad52 and XRCC3 in repairing DNA double-strand breaks. The present study shows that Rad52 can play an important role in HR repair by partially substituting for a Rad51 paralog.

Animals↗
PubMed2001

Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma in the extremities.

PURPOSE: To evaluate the outcome and adverse effects in patients with osteosarcoma treated with very high-dose definitive intraoperative radiotherapy (IORT), with the intention of saving the affected limb. METHODS AND MATERIALS: Thirty-nine patients with osteosarcoma in their extremities were treated with definitive IORT. The irradiation field included the tumor plus an adequate wide margin and excluded the major vessels and nerves. Forty-five to 80 Gy of electrons or X-rays were delivered. The median follow-up of the surviving patients was 124 months. RESULTS: The cause-specific and relapse-free 5-year survival rate was 50% and 43%, respectively. Distant metastasis developed in 23 patients; 19 died and 4 were alive for >10 years. Nine local recurrences were found 4-29 months after IORT in the affected limb. No radiation-induced skin reaction or nerve palsy was observed in the patients treated with X-rays. Experiments using phantoms also confirmed that the scatter dose was below the toxic level in the IORT setting with X-rays. CONCLUSIONS: Very high-dose definitive IORT combined with preventive nailing and chemotherapy appeared to be a promising quality-of-life-oriented alternative to treating patients with osteosarcomas in the extremities, although the problem of recurrences from the surrounding unirradiated soft tissue remains to be solved.

Adolescent↗