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Biomedical subjects

Masao Suzuki

Publications and source records attributed to Masao Suzuki.

At least 19 recordsLinked to original sources

Mutation induction in cultured human cells after low-dose and low-dose-rate gamma-ray irradiation: detection by LOH analysis.

To study the genetic effects of low-doses and low-dose-rate ionizing radiation (IR), human lymphoblastoid TK6 cells were exposed to 30 mGy of gamma-rays at a dose-rate of 1.2 mGy/hr. The frequency of early mutations (EMs) in the thymidine kinase (TK) gene locus was determined to be 1.7 x 10(-6), or 1.9-fold higher than the level seen in unirradated controls. These mutations were analyzed with a loss of heterozygosity (LOH) detection system, a methodology which has been shown to be sensitive to the effects of radiation. Among the 15 EMs observed after IR exposure, 8 were small interstitial-deletion events restricted to the TK gene locus. However, this specific type of event was not found in unirradiated controls. Although these results were observed under the limited conditions, they strongly suggest that the LOH detection system can be used for estimating the genetic effects of a low-dose IR exposure delivered at a low-dose-rate.

Cell Line↗

Gene expression profile changes correlating with radioresistance in human cell lines.

PURPOSE: To identify gene expression profiles specific to radioresistance of human cells. METHODS AND MATERIALS: Global gene expression profiles of a total of 15 tumor and normal fibroblast cell lines were analyzed using DNA microarrays and statistical clustering methods. Initially, six of the cell lines were categorized into radioresistant (RG) or nonradioresistant (NRG) groups according to the radiation dose required to reduce their survival to 10% (D10). Genes for which expression was specific to each group at 1 or 3 h after irradiation were identified using statistical procedures including analysis of variance and a two-dimensional hierarchical clustering method. The remaining nine cell lines were subjected to the k-nearest neighbor pattern classification. RESULTS: The nine test cell lines were successfully classified by their D10 value using 46 and 44 genes for which transcription levels had significantly changed at 1 and 3 h after irradiation, respectively. Of these genes, 25 showed altered expression at both time points in the NRG or RG, but independently were unable to classify the test cell lines. CONCLUSIONS: Radioresistant cell lines analyzed in this study showed certain radiation-induced changes in gene expression profiles that are different from the profile changes of the more-sensitive cell lines.

Cell Line, Tumor↗

Radiation protection by deferiprone in animal models.

The effectiveness of deferiprone (L1) in removing depleted uranium (DU) and protecting animals from radiation exposure was examined. Rats that had received 2 mg/kg DU via intramuscular injection were orally administered 100, 200 or 400 mg/kg L1 for 3 days. In all of the groups, significant increases in urinary DU excretion and decreases in DU concentration in the injected muscle were observed, indicating that L1 combined with DU and DU was excreted in the urine. No significant increase in the amount of DU in the excreta or decrease in DU concentration in organs other than the muscles was found. As a preliminary test, the effectiveness of L1 in reducing radiation damage was examined in mice injected with 400 mg/kg L1 and rats administered orally with 200 and 400 mg/kg L1 before and just after x-ray exposure. The results were inconclusive.

Administration, Oral↗

The PCC assay can be used to predict radiosensitivity in biopsy cultures irradiated with different types of radiation.

The aim of this study was to identify potential biomarkers for radiosensitivity using the relationship between cell killing and the yield of excess chromatin fragments detected with the premature chromosome condensation (PCC) technique. This method was applied to primary cultured cells obtained from biopsies from patients. Six primary culture biopsies were obtained from 6 patients with carcinoma of the cervix before starting radiotherapy. The cultures were irradiated with two different LET carbon-ion beams (LET = 13 keV/microm, 77.1+/-2.8 keV/microm) and 200 kV X-rays. The carbon-ion beams were produced by Heavy Ion Medical Accelerator in Chiba (HIMAC). PCC was performed using the polyethylene glycol-mediated cell fusion technique. The yield of excess chromatin fragments were measured by counting the number of unrejoined chromatin fragments detected with the PCC technique after a 24-h post-irradiation incubation period. Obtained results indicated that cultures which were more sensitive to killing were also more susceptible to the induction of excess chromatin fragments. Furthermore there was a good correlation between cell killing and excess chromatin fragments among the 6 cell cultures examined. There is also evidence that the induction of excess chromatin fragments increased with increasing LET as well as cell-killing effect in the same cell culture. The data reported here support the idea that the yield of excess chromatin fragments detected with the PCC technique might be useful for predicting the radiosensitivity of cells contained in tumor tissue, and to predict responses to different radiation types.

Biomarkers↗

Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions.

We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/microm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to (137)Cs gamma-rays. The mutation frequency increased up to 105 keV/microm and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/mum showed all or partial deletions of exons, while among gamma-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not.

Cell Line↗

Immortalization of human small airway epithelial cells by ectopic expression of telomerase.

Two immortalized human airway epithelial cell lines were established by the ectopic expression of human telomerase reverse transcriptase (hTERT). These cell lines have been continuously cultured for >200 population doublings (PDs). They are characterized by an overexpression of hTERT mRNA, elongated telomere length and higher telomerase activity. Early passage of these cells (<20 PDs) expressed the p16 protein at a level comparable to their parental cells. In later passages (>150 PDs), p16 protein was decreased but recovered to the early passage level upon treatment with a methylation inhibitor, 5-Aza-CdR. Chromosome analysis showed a near-diploid karyotype albeit with a gain or loss of certain chromosomes and a few stable translocations in both cell lines. No p53 gene alterations were found in these cell lines. They remained anchorage dependent in growth and were non-tumorigenic in nude mice. These two cell lines are the first reported immortalized human airway epithelial cell lines by hTERT expression without incorporation of virus or other genes, which may serve as a useful model system for studies on bronchial carcinogenesis.

Animals↗

LET and ion species dependence for cell killing in normal human skin fibroblasts.

We studied the LET and ion species dependence of the RBE for cell killing to clarify the differences in the biological effects caused by the differences in the track structure that result from the different energy depositions for different ions. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon, neon, silicon and iron ions that were generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS) in Japan. Cell killing was measured as reproductive cell death using a colony formation assay. The RBE-LET curves were different for carbon ions and for the other ions. The curve for carbon ions increased steeply up to around 98 keV/microm. The RBE of carbon ions at 98 keV/microm was 4.07. In contrast, the curves for neon, silicon and iron ions had maximum peaks around 180 keV/microm, and the RBEs at the peak position ranged from 3.03 to 3.39. When the RBEs were plotted as a function of Z*2/beta2 (where Z* is the effective charge and beta is the relative velocity of the ion) instead of LET, the discrepancies between the RBE-LET curves for the different ion beams were reduced, but branching of the RBE-Z*2/beta2 curves still remained. When the inactivation cross section was plotted as a function of either LET or Z*2/beta2, it increased with increasing LET. However, the inactivation cross section was always smaller than the geometrical cross section. These results suggest that the differences in the energy deposition track structures of the different ion sources have an effect on cell killing.

Cell Survival↗

Tobacco and alcohol tax relationships with suicide in Switzerland.

Previous research has shown an empirical link between tobacco and alcohol use and suicide. If tobacco and alcohol use contribute to suicidal behaviors, then policies designed to reduce the tobacco and alcohol consumption may succeed in reducing suicides as well. To test this hypothesis, correlations for suicide rates with alcohol consumption, taxes on alcohol and tobacco in Switzerland were examined using sets of time-series data from Switzerland in 1965-1994. The tax on tobacco correlated significantly negatively with male standardized suicide rate. The tax on alcohol also correlated significantly with male standardized suicide rate in an autoregressive model. On the other hand, significant relationships with female suicide rate were not found. Policies designed to reduce tobacco consumption are consistent with a benefit of reducing suicides, particularly for men in this sample.

Adolescent↗

[A case of chronic obstructive pulmonary disease (COPD) successfully treated by acupuncture].

Chronic obstructive pulmonary disease (COPD) involves a decrease in respiratory function and limits daily activities. We report a COPD patient whose respiratory symptoms were improved by acupuncture treatment. A 66-year-old man visited Gifu University Hospital with breathlessness on exercise. Despite medication, his general condition worsened. A series of acupuncture treatments was subsequently started on October 27, 2001. He had level III breathlessness on JRS classification prior to acupuncture treatment, and his respiratory function parameters were VC: 3.54 L, FEV1: 1.19 L, FEV1% (G): 33.6% and %FEV1: 45%. The basic meridian points used were KI 3 (Fuliu), LU 9 (Taiyuan), LU 1 (Zhongfu), CV 12 (Zhongwan), CV 4 (Guanyuan), BL 13 (Feishu), and BL 23 (Shenshu). The acupuncture needles were retained for ten minutes in each session. This research design was used to detect the specific efficacy of acupuncture treatment After ten acupuncture treatments over two months, his walking distance, Borg scale and respiratory function were improved compared with before treatment. These findings suggest that acupuncture treatment may be efficacious for advanced cases of COPD.

Acupuncture Points↗

Genotoxicity in the eyes of bystander cells.

The controversial use of a linear, no threshold extrapolation model for low dose risk assessment has become even more so in light of the recent reports on the bystander phenomenon. The answer to the question as to which of the two phenomena, bystander versus adaptive response, is more important has practical implication in terms of low dose radiation risk assessment. In this review, genotoxicity is used as an endpoint to introduce the two phenomena, provide some insight into the mechanisms of bystander effect and to bridge the two low dose phenomena which operate in opposite directions: the bystander effect tends to exaggerate the effect at low doses, by communicating damage from hit to non-hit cells whereas the adaptive response confers resistance to a subsequent challenging dose by an initial low priming dose.

Alpha Particles↗

Efficacy of glimepiride in Japanese type 2 diabetic subjects.

We investigated the efficacy of glimepiride, a third-generation sulfonylurea (SU), in Japanese type 2 diabetic patients in whom glycemic control had been inadequate with a conventional SU, gliclazide or glibenclamide. A total of 172 Japanese type 2 diabetic patients (HbA1C > or = 7.0%), maintained on a conventional SU, were randomly assigned to the 3rd SU group (SU treatments switched to glimepiride) or the 2nd SU group (treatments not changed). The conventional SU was switched to the indicated doses of glimepiride (gliclazide 40 mg = glimepiride 1 mg, glibenclamide 2.5 mg = glimepiride 2 mg). After 6 months, glycemic control (HbA1C and fasting plasma glucose) had not changed significantly in either the 2nd or the 3rd SU group. The homeostasis assessment model of insulin resistance (HOMA-IR) in the 3rd SU group was decreased by more than 10% (p = 0.015), whereas no change was observed in the 2nd SU group. The triglyceride level was decreased by approximately 10% in the 3rd SU group, not a significant change (p = 0.080). Patients who had been treated with only SU, or treated with SU for a short time (less than 5 years), and who were also obese (BMI > or = 25) or had a high HOMA-IR (HOMA-IR > or = 3), showed significantly reduced insulin resistance. According to logistic regression analysis, high BMI ( > or = 25) was the only variable predicting that glimepiride would more effectively improve HbA1C than conventional SU treatment. In conclusion, switching conventional SUs to glimepiride reduced insulin resistance without improving glycemic control. A notable finding of this study is that glimepiride was more beneficial in obese than in non-obese Japanese type 2 diabetic patients.

Aged↗

Screening cost for abdominal aortic aneurysms: Japan-based estimates.

PURPOSE: The aim of this study was to evaluate the screening procedures in Japan economically focusing on the screening costs and the hospital costs for abdominal aortic aneurysm (AAA) surgery. METHODS: A total of 10,057 residents, 60 years of age or older, including 4 247 men and 5 810 women, participated in the screening test for AAA using ultrasound. RESULTS: Aneurysms were detected in 34 participants, including 32 men and 2 women. The detection rate of AAA was 0.8% in men, 0.03% in women, and 0.3% in total. It cost 8 US dollars to screen each participant, and the cost to detect each aneurysm was thus estimated at 1,250 dollars in men, 23,240 dollars in women, and 2,366 dollars in total. The difference in the mean hospital cost between ruptured and nonruptured AAA was 21,833 dollars in our recent cases. Obesity, male sex, and smoking habits were all significant risk factors for AAA. CONCLUSION: Screening for AAA using ultrasound is useful not only for the early detection of AAA but also for a reduction in the overall medical cost.

Aged↗

Solid-liquid phase behavior of binary fatty acid mixtures. 1. Oleic acid/stearic acid and oleic acid/behenic acid mixtures.

Solid-liquid phase behavior of binary fatty acid mixtures was investigated by means of differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) for the mixture composed of oleic acid (OA) and stearic acid (SA) and that composed of OA and behenic acid (BA). The DSC results provided a monotectic type T-X phase diagram for these mixtures, from which it was suggested that the two fatty acid species are completely immiscible in a solid phase regardless of the two polymorphs of OA, i.e., alpha-form or gamma-form. The solid phase immiscibility was confirmed by the FT-IR observation that the spectra obtained for the mixtures correspond to the superposition of the two spectra for respective components. Thermodynamic analysis of liquidus line demonstrated that OA and SA form an ideal mixture in a liquid phase, whereas the mixing of OA and BA in a liquid phase is slightly non-ideal.

Calorimetry, Differential Scanning↗

Solid-liquid phase behavior of binary fatty acid mixtures. 2. Mixtures of oleic acid with lauric acid, myristic acid, and palmitic acid.

Solid-liquid phase behavior was investigated for binary fatty acid mixtures composed of oleic acid (OA; cis-9-octadecenoic acid) and saturated fatty acids, lauric acid (LA; dodecanoic acid), myristic acid (MA; tetradecanoic acid), and palmitic acid (PA; hexadecanoic acid), by means of differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). When the mixture was heated immediately after the solidification from the melt, the heat effect due to the gamma-to-alpha transformation of OA varied depending on the composition of the mixture. However, the mixture subjected to an annealing at the temperature slightly below the melting temperature provided the transformation at constant temperature which corresponds to the gamma-to-alpha transformation temperature of pure OA. This suggests that a solid phase formed by cooling of the melt of the mixture is not in an equilibrium state, but it relaxes to a stable solid during the annealing process. The T-X phase diagrams of these mixtures constructed from the DSC measurements demonstrate that the two fatty acid species are completely immiscible in a solid phase regardless of the type of polymorphs of OA, alpha- or gamma-form. According to a thermodynamic analysis of liquidus line basing on the regular solution model for the melt, the non-ideality of mixing tends to increase with the decrease in the acyl chain length of the saturated fatty acid, although the mixing is rather close to ideal.

Calorimetry, Differential Scanning↗

Solid-liquid phase behavior of binary fatty acid mixtures 3. Mixtures of oleic acid with capric acid (decanoic acid) and caprylic acid (octanoic acid).

Solid-liquid phase behavior of binary mixtures of oleic acid (OA)/capric acid (C10A) and OA/caprylic acid (C8A) were investigated by means of differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction. The phase diagram of OA/C10A mixture constructed from the DSC results suggested that a molecular compound with the composition of OA:C10A = 3:2 is formed in a solid phase, and OA and the molecular compound are miscible, while C10A and the molecular compound are completely immiscible. The formation of the molecular compound was supported by the IR spectroscopic observation, and a possible model of the structure was proposed on the basis of X-ray diffraction spectrum in small angle region. This compound formation is characteristic of the OA/C10A mixture, and may be attributed to the similarity of the acyl chain length of C10A to the lengths of Delta- and omega-chains of OA (i.e., the chain segments divided by cis-double bond). The mixture of OA and C8A, whose chain length is close to but shorter than the two chain segments of OA, provided a eutectic-type phase diagram showing a partial mixing of the two components in OA-rich region. Thermodynamic analysis of the liquidus line in the phase diagram exhibits a systematic trend for the non-ideality parameter of mixing with the variation of the chain length difference between OA and saturated fatty acid species.

Calorimetry, Differential Scanning↗

Structural study on polymorphism of long-chain dicarboxylic acids using oblique transmission method for micro FT-IR spectrometers.

Polymorphism and higher-order structures of even-number dicarboxylic acids from hexadecanedioic acid to eicosanedioic acid have been studied by micro-FTIR spectroscopy and microscopic observation. In order to obtain the three-dimensional structural information, the oblique transmission method was incorporated into a micro-FTIR spectrometer equipped with a couple of Cassegrain lenses. The IR spectra showed that the solid states of dicarboxylic acid bore a marked structural similarity to those of n-saturated fatty acids. It was found that a solution-grown single crystal of dicarboxylic acids was an aggregate of lamellae whose thickness exceeded by far their molecular length. The surfaces of lamellae were covered with hydrocarbon segments taking a hairpin structure, and the linkage of hydrogen-bonded dicarboxylic acids formed a folded chain structure. The result of oblique transmission measurements showed that the stacking mode of lamellae varied depending on crystallization conditions.

Biophysical Phenomena↗

Frequency measuring system using mirror gap stabilized Fabry-Perot interferometer.

The mirror gap of a Fabry-Perot interferometer was stabilized with two laser diodes; one locked to the line frequency 385,243,555.14445 MHz of the F=3<--1 in 5D(3/2)<--5S(1/2) (87Rb) and the other to the 385,284,566.3663 MHz of the F=4<--2 in 5D(5/2)<--5S(1/2) (87Rb) [Opt. Commun. 102 (1993) 432]. The length of the mirror gap was adjusted to generate the zero-cross points simultaneously at both of the two line positions. The fringe signals obtained from an interferometer thus stabilized can be used as frequency markers having accuracies of the order of 10(10) depending on the finesse of the interferometer used. Based on measurement using Cs D1 hyperfine lines reported by Udem et al. [Phys. Rev. Lett. 82 (1999) 3568], the uncertainty of markers in the region 50 THz apart from the reference lines is +/- 5 MHz.

Data Interpretation, Statistical↗