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Biomedical subjects

Y Furusawa

Publications and source records attributed to Y Furusawa.

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

The dependence of p53 on the radiation enhancement of thermosensitivity at different let.

PURPOSE: The aim of this study is to investigate the dependence of p53-gene status on the radiation enhancement of thermosensitivity at different levels of linear energy transfer (LET). METHODS AND MATERIALS: We used two kinds of human glioblastoma transfectants of A-172 cells bearing the wild-type p53 gene, A-172/neo cells with control vector containing the neo gene and A-172/mp53 cells with both the dominant negative mutated p53 gene and neo gene. We exposed these cells to X-rays and accelerated carbon-ion (C-) beams (13-200 KeV/microm) followed by heating at 44 degrees C. Cellular sensitivities were determined using clonogenic assay. RESULTS: The radiation enhancement of thermosensitivity was LET-dependent for the A-172/neo cells, but this was not clearly demonstrated in the A-172/mp53 cells. The supraadditive radiation enhancement of thermosensitivity was observed in A-172/neo cells at the LET range of 13 to 70 KeV/microm, though only an additive effect was observed at higher LET. In A-172/mp53 cells, only an additive effect was observed through all the LET examined. CONCLUSION: These results indicate that the radiation enhancement of thermosensitivity is p53- and LET-dependent. Our results suggest that the combined use of high-LET radiation and hyperthermia brings useful application for cancer therapeutic purposes.

Cell Survival↗
PubMed2000

Complex-type chromosomal exchanges in blood lymphocytes during radiation therapy correlate with acute toxicity.

The new method of chemical-induced premature chromosome condensation combined with fluorescence in situ hybridization was used to analyze chromosomal damage in peripheral blood mononuclear lymphocytes of patients undergoing radiation treatment for esophageal cancer with high-energy X-rays or accelerated carbon ions at the National Institute of Radiological Sciences (Chiba, Japan). Total number of aberrant cells correlated with radiation field size, but no correlation was found with acute toxicity. A high frequency of complex-type exchanges were also recorded. This aberration type presented a high individual variability, and correlated well with the acute morbidity. Cytogenetic analysis by interphase chromosome painting is proposed as a useful tool for monitoring normal tissue effects during radiotherapy.

Aged↗
PubMed2000

Inhibitory effects of JTV-519, a novel cardioprotective drug, on potassium currents and experimental atrial fibrillation in guinea-pig hearts.

1. We investigated the effects of JTV-519 (4-[3-(4-benzylpiperidin-1-yl)propionyl]-7-methoxy-2,3,4, 5-tetrahydro-1,4-benzothiazepine monohydrochloride), a novel cardioprotective drug, on the repolarizing K(+) currents in guinea-pig atrial cells by use of patch-clamp techniques. We also evaluated the effects of JTV-519 on experimental atrial fibrillation (AF) in isolated guinea-pig hearts. 2. In atrial cells stimulated at 0.2 Hz, JTV-519 in concentrations of 0.3 and 1 microM slightly prolonged the action potential duration (APD). The drug also reversed the action potential shortening induced by the muscarinic agonist carbachol in a concentration-dependent manner. 3. The muscarinic acetylcholine receptor-operated K(+) current (I(K.ACh)) was activated by the extracellular application of carbachol (1 microM), adenosine (10 microM) or by the intracellular loading of GTP gamma S (100 microM). JTV-519 inhibited the carbachol-, adenosine- and GTP gamma S-induced I(K.ACh) with the IC(50) values of 0.12, 2.29 and 2.42 microM, respectively, suggesting that the drug may inhibit I(K.ACh) mainly by blocking the muscarinic receptors. 4. JTV-519 (1 microM) inhibited the delayed rectifier K(+) current (I(K)). Electrophysiological analyses indicated that the drug preferentially inhibits I(Kr) (rapidly activating component) but not I(Ks) (slowly activating component). 5. In isolated hearts, perfusion of carbachol (1 microM) shortened monophasic action potential (MAP) and effective refractory period (ERP), and lowered atrial fibrillation threshold (AFT). Addition of JTV-519 (1 microM) inhibited the induction of AF by prolonging MAP and ERP. 6. We conclude that JTV-519 can exert antiarrhythmic effects against AF by inhibiting repolarizing K(+) currents. The drug may be useful for the treatment of AF in patients with ischaemic heart disease.

Action Potentials↗
PubMed2000

WAF1 accumulation by carbon-ion beam and alpha-particle irradiation in human glioblastoma cultured cells.

PURPOSE: There have been no reports about the effects of heavy-ion beams on the expression of the WAF1 gene, although ionizing radiation such as y-rays and X-rays is well known to induce WAF1 (p21/CIP1/sdi1) gene expression in a p53-dependent manner. In the present study, it was examined whether WAF1 accumulation was induced after carbon-ion (C-) beam or alpha-particle irradiation in four glioblastoma cell lines. MATERIALS AND METHODS: A colony assay for radiosensitivity and Western blot analysis of WAF1 were applied to two human glioblastoma cell lines, A-172 bearing wild-type p53 (wtp53) and T98G bearing mutated p53 (mp53). A-172/neo and A-172/mp53 were transfected with a control vector (containing only a neo selection marker) and a mp53 expression vector respectively. RESULTS: The amount of WAF1 increased markedly after X-ray irradiation in A-172 and A-172/neo cells but not in T98G and A-172/mp53 cells. The level of WAF1 reached a plateau at 3-10 h after X-ray irradiation at 5 Gy in A-172 and A-172/neo cells. Likewise, the levels of WAF1 in A-172 and A-172/neo cells reached a plateau at 3-10 h and 6-24 h after C-beam (3.0 Gy) and alpha-particle (4.5 Gy) irradiation respectively. The amount of WAF1 increased markedly in a dose-dependent manner 10 h after X-ray, C-beam or alpha-particle irradiation in A-172 and A-172/neo cells but not in T98G or A-172/mp53 cells. In addition, cell survival assay showed that these cell lines were most sensitive to C-beams, less sensitive to alpha-particles and least sensitive to X-rays at 10% survival. There was no difference in sensitivity among these cell lines against C-beam and alpha-particle irradiation whereas wtp53 cells (A-172 and A-172/neo) were more sensitive to X-rays than mp53 cells (A-172/mp53 and T98G). CONCLUSIONS: These results indicate that C-beams and alpha-particles induce p53-dependent WAF1 accumulation as well as is the case with X-rays, suggesting that WAF1 protein accumulation may not contribute to cell killing.

Alpha Particles↗
PubMed2000

High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts.

PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.

Cell Line↗
PubMed2000

Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma.

PURPOSE: To investigate whether nitric oxide excreted from cells irradiated with accelerated carbon-ion beams modulates cellular radiosensitivity against irradiation in human glioblastoma A-172 and T98G cells. MATERIALS AND METHODS: Western-blot analysis of inducible nitric oxide synthase, hsp72 and p53, the concentration assay of nitrite in medium and cell survival assay after irradiation with accelerated carbon-ion beams were performed. RESULTS: The accumulation of inducible nitric oxide synthase was caused by accelerated carbon-ion beam irradiation of T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells after exposure to the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams, and the accumulation was abolished by the addition of an inhibitor for inducible nitric oxide synthase to the medium. The radiosensitivity of A-172 cells was reduced in the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams compared with conventional fresh growth medium, and the reduction of radiosensitivity was abolished by the addition of an inducible nitric oxide synthase inhibitor to the conditioned medium. CONCLUSIONS: Nitric oxide excreted from the irradiated donor cells with accelerated carbon-ion beams could modulate the radiosensitivity of recipient cells. These findings indicate the importance of an intercellular signal transduction pathway initiated by nitric oxide in the cellular response to accelerated heavy ions.

Blotting, Western↗
PubMed2000

LET dependency of heavy-ion induced apoptosis in V79 cells.

We investigated the relationship between the LET values and cell death, defined as either apoptosis or loss of reproductive integrity (reproductive death), using Chinese hamster V79 cells. The cells were irradiated with X-rays or carbon-ion beams from the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS). Apoptosis was defined based on the morphological change upon treating of cells with caffeine. The apoptotic index, the ratio of apoptotic cells to the total, after exposure to 2 Gy of X-rays was 0.043. Upon irradiation with carbon-ion beams, the index was gradually increased with increasing LET values, reaching a maximum of 0.076 at 110 keV/micron, and then decreased to 0.054 at 237 keV/micron. An analogous pattern of the LET dependence was observed between reproductive death and apoptotic death. The cell-survival values obtained after 2 Gy exposure (SF2) were 0.64, 0.13, and 0.24, respectively. A similar trend was found for the RBE values calculated from the initial slope for both apoptosis and reproductive death. These results strongly suggest that the target for both types of cell death is the same.

Animals↗
PubMed2000

Inactivation of aerobic and hypoxic cells from three different cell lines by accelerated (3)He-, (12)C- and (20)Ne-ion beams.

The LET-RBE spectra for cell killing for cultured mammalian cells exposed to accelerated heavy ions were investigated to design a spread-out Bragg peak beam for cancer therapy at HIMAC, National Institute of Radiological Sciences, Chiba, prior to clinical trials. Cells that originated from a human salivary gland tumor (HSG cells) as well as V79 and T1 cells were exposed to (3)He-, (12)C- and (20)Ne-ion beams with an LET ranging from approximately 20-600 keV/micrometer under both aerobic and hypoxic conditions. Cell survival curves were fitted by equations from the linear-quadratic model and the target model to obtain survival parameters. RBE, OER, alpha and D(0) were analyzed as a function of LET. The RBE increased with LET, reaching a maximum at around 200 keV/micrometer, then decreased with a further increase in LET. Clear splits of the LET-RBE or -OER spectra were found among ion species and/or cell lines. At a given LET, the RBE value for (3)He ions was higher than that for the other ions. The position of the maximum RBE shifts to higher LET values for heavier ions. The OER value was 3 for X rays but started to decrease at an LET of around 50 keV/micrometer, passed below 2 at around 100 keV/micrometer, and then reached a minimum above 300 keV/micrometer, but the values remained greater than 1. The OER was significantly lower for (3)He ions than the others.

Acceleration↗
PubMed1999

Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy.

PURPOSE: The irradiation system and biophysical characteristics of carbon beams are examined regarding radiation therapy. METHODS AND MATERIALS: An irradiation system was developed for heavy-ion radiotherapy. Wobbler magnets and a scatterer were used for flattening the radiation field. A patient-positioning system using X ray and image intensifiers was also installed in the irradiation system. The depth-dose distributions of the carbon beams were modified to make a spread-out Bragg peak, which was designed based on the biophysical characteristics of monoenergetic beams. A dosimetry system for heavy-ion radiotherapy was established to deliver heavy-ion doses safely to the patients according to the treatment planning. A carbon beam of 80 keV/microm in the spread-out Bragg peak was found to be equivalent in biological responses to the neutron beam that is produced at cyclotron facility in National Institute Radiological Sciences (NIRS) by bombarding 30-MeV deuteron beam on beryllium target. The fractionation schedule of the NIRS neutron therapy was adapted for the first clinical trials using carbon beams. RESULTS: Carbon beams, 290, 350, and 400 MeV/u, were used for a clinical trial from June of 1994. Over 300 patients have already been treated by this irradiation system by the end of 1997.

Calibration↗
PubMed1999

Measurements of the equivalent whole-body dose during radiation therapy by cytogenetic methods.

Estimates of equivalent whole-body dose following partial body exposure can be performed using different biophysical models. Calculations should be compared with biodosimetry data, but measurements are complicated by mitotic selection induced in target cells after localized irradiation. In this paper we measured chromosomal aberrations in peripheral blood lymphocytes during radiotherapy, and estimated the equivalent whole-body dose absorbed, by using the novel technique of interphase chromosome painting. Premature chromosome condensation was induced in stimulated lymphocytes by incubation in calyculin A, and slides were hybridized in situ with whole-chromosome DNA probes specific for human chromosomes 2 and 4. Reciprocal exchanges were used to estimate the equivalent whole-body dose, based on individual pre-treatment in vitro calibration curves. Equivalent whole-body dose increased as a function of the number of fractions, and reached a plateau at high fraction numbers. Chromosomal aberration yields were dependent on field size, tumour position and concurrent chemotherapy. Results suggest that interphase chromosome painting is a simple technique able to give a reliable estimate of the equivalent whole-body dose absorbed during therapeutic partial-body irradiation.

Aged↗
PubMed1999

Cell cycle and LET dependence for radiation-induced mutation: a possible mechanism for reversed dose-rate effect.

A previous study of the mutagenic action of 252Cf radiation in mouse L5178Y cells showed that the mutation frequency was higher when the dose was chronic rather than acute, which was in sharp contrast to the effects reported for gamma-rays (Nakamura and Sawada, 1988). A subsequent study using synchronized cells revealed that the cells at the G2/M stage were uniquely sensitive to mutation induction by 252Cf radiation but not to gamma-rays (Tauchi et al., 1993). A long phase cell population was first subjected to conditioning gamma or 252Cf radiation doses at different dose-rates. The cell cycle distribution of these cells was then observed, and they were then exposed to 252Cf radiation, and the mutation rate was determined. The G2/M fraction increased by 3- to 4-fold when the conditioning doses (2 Gy of gamma or 1 Gy of 252Cf radiation) were delivered chronically over 10 h, but only slightly when the same doses were delivered over a 1 h period or less. Subsequent 252Cf irradiation gave higher mutation frequencies in the cells pre-irradiated with gamma-rays over a protracted period of time than in those exposed with the higher dose-rate gamma-rays. These results suggest that the radiation-induced G2 block could be at least partly (but not totally) responsible for this reverse dose-rate effect (Tauchi et al. 1996). Possible factors which cause the hyper-sensitivity of G2/M cells to mutation induction by neutrons will be discussed.

Animals↗
PubMed1999

Association between G2-phase block and repair of radiation-induced chromosome fragments in human lymphocytes.

We have studied the induction of chromosomal aberrations in human lymphocytes exposed in G0 to X rays or carbon ions. Aberrations were analyzed in G0, G1, G2 or M phase. Analysis during the interphase was performed by chemically induced premature chromosome condensation, which allows scoring of aberrations in G1, G2 and M phase; fusion-induced premature chromosome condensation was used to analyze the damage in G0 cells after incubation for repair; M-phase cells were obtained by conventional Colcemid block. Aberrations were scored by Giemsa staining or fluorescence in situ hybridization (chromosomes 2 and 4). Similar yields of fragments were observed in G1 and G2 phase, but lower yields were scored in metaphase. The frequency of chromosomal exchanges was similar in G0 (after repair), G2 and M phase for cells exposed to X rays, while a lower frequency of exchanges was observed in M phase when lymphocytes were irradiated with high-LET carbon ions. The results suggest that radiation-induced G2-phase block is associated with unrejoined chromosome fragments induced by radiation exposure during G0.

Adult↗
PubMed1999

[Sense of coherence, stressful life events and psychological health].

Aaron Antonovsky's Sense of Coherence (SOC), as a stable disposition of personality that serves as a major coping resource for the preservation of health, has been widely used in many studies. However, few empirical studies are conducted on the concept of SOC. We examined the stability of SOC and the buffering effect of SOC on the psychological health in dealing with stressful life events. The subjects were 200 adults randomly selected in Tokyo, and follow-up survey was conducted one year after the first survey. Goldberg's General Health Questionnaire (GHQ) was used for assessing psychological health. Antonovsky's SOC scale was translated into Japanese (and reverse translated) in this study. The test-retest reliability of SOC scale was 0.78. Cronbach's alpha was 0.91. The factors related to the SOC supported previous findings and Antonovsky's theory about the positive correlation with educational and economic status. In the follow-up survey, the subjects were also asked about the experience of 56 stressful life events (SLE) composed of four aspects of life during the previous year: personal, family, work and environment. The SLE was assessed through the total number and the weighted score. Contrary to the theory, the results showed that the SOC score has no intra-individual stability. The mean score of SOC in 1998 was 131.1 +/- 23.9, significantly lower than that in the previous year. When the subjects were divided into two groups based on a median 1997 score, the effect of SLE negatively affected SOC scores after one year among those who had a low SOC, although this effect was not observed among those who had a high SOC. The effect of SLE on changes of SOC was stronger among men compared to women. Also, the results showed the SOC was positively related to psychological health, and the buffering effect of SOC on the psychological health in dealing with stressful life events was only observed among men. Findings in this study suggest that SOC is variable for those with weak SOC if they experienced stressful life events. Also, the stressful life events differentially affect the SOC among men and women. The buffering effect was not sufficiently proven in this study. Methodological issues to confirm Antonovsky's theory are also presented.

Adult↗
PubMed1998

Evidence for mRNA expression of vascular endothelial growth factor by X-ray irradiation in a lung squamous carcinoma cell line.

Vascular endothelial growth factor (VEGF) is a multipotent cytokine which plays an important role in various angiogenic conditions as well as in some tumor behaviors. Here we examined the induction of VEGF mRNA by X-ray irradiation in a lung squamous cell carcinoma cell line (RERF-LC-AI). Irradiating the cells with 15 Gy X-rays significantly increased the mRNA expression up to 2.5-fold of control at a post-irradiation time of 16-24 h. The induction of VEGF mRNA by X-ray irradiation was completely blocked by treating cells with either genistein (Src tyrosine kinase inhibitor) or H7 (protein kinase C inhibitor). This suggests that the mechanism of induction might be concerned with the pathway which triggers Src tyrosine kinase of the cell surface and the protein kinase C pathway.

Antineoplastic Agents↗
PubMed1998

An increase in [3H]QNB binding by proton-beam irradiation in intact rat brain: an apparent positive cooperativity of binding.

After focal irradiation of rat brains with a beam of proton (dose, 30 Gy), [3H]quinuclidinyl benzilate (QNB) binding, both in vitro and in vivo, was measured, using either autoradiographic or tissue-dissection methods. No changes in in vitro [3H]QNB binding were seen in autoradiograms of brain slices from irradiated rat. The irradiated side of the brain showed a significant increase in [3H]QNB binding in vivo in the striatum and cerebral cortex 24 h after irradiation. This increase in binding was transient, and had almost disappeared 2 weeks after irradiation. These results indicate that early changes in receptor function as a results of radiation damage are only detected in in-vivo conditions. In the striatum of the intact rat brain, an apparent positive cooperativity of binding was observed, which was more pronounced on the irradiated side.

Animals↗
PubMed1998

Evaluation of ischemic damage in the skeletal muscle with the use of electrical properties.

We performed experimental and clinical studies with measurement of electrical character in the skeletal muscle to assess ischemic damage and reperfusion injury in lower limbs. In 14 dogs, the bilateral hind limbs were squeezed at the inguinal region to make ischemia and they were reperfused after various intervals. Conductivity (G) of the skeletal muscles in hind limbs was measured with an LCR meter, which is an impedance analyzer. Change of G from 0 to 3 h of reperfusion (Delta3G) was calculated. G was decreased during ischemia and increased after reperfusion. In those whose Delta3G as more than 2.1 mS/cm, serum creatine kinase and aldolase at 10 h after reperfusion were correlated significantly (P < 0.01) to Delta3G. In patients with an abdominal aortic aneurysm (N = 3), arteriosclerosis obliterans (N = 1), or acute arterial occlusion (AAO, N = 1), G of lower extremities was measured from arterial clamp to declamp. Conductivity markedly increased after reperfusion and serum creatine kinase was the highest in the patient with AAO. We suggested that measurement of G may provide monitoring of ischemic and reperfused phase injury in the skeletal muscle and may be applicable to prediction of the skeletal muscular reperfusion injury.

Animals↗