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S Antoku

Publications and source records attributed to S Antoku.

At least 19 recordsLinked to original sources
PubMed2006

Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B.

The Nck family of Src homology (SH) 2/SH3 domain adaptors functions to link tyrosine phosphorylation induced by extracellular signals with downstream regulators of actin dynamics. We investigated the role of mammalian Nck adaptors in signaling from the activated platelet-derived growth factor (PDGF) receptor (PDGFbetaR) to the actin cytoskeleton. We report here that Nck adaptors are required for cytoskeletal reorganization and chemotaxis stimulated by PDGF-B. Analysis of tyrosine-phosphorylated proteins demonstrated that Crk-associated substrate (p130(Cas)), not the activated PDGFbetaR itself, is the major Nck SH2 domain-binding protein in PDGF-B-stimulated cells. Both Nck- and p130(Cas)-deficient cells fail to display cytoskeletal rearrangements, including the formation of membrane ruffles and the disassembly of actin bundles, typically shown by their WT counterparts in response to PDGF-B. Furthermore, Nck and p130(Cas) colocalize in phosphotyrosine-enriched membrane ruffles induced by PDGF-B in NIH 3T3 cells. These results suggest that Nck adaptors play an essential role in linking the activated PDGFbetaR with actin dynamics through a pathway that involves p130(Cas).

Actins↗
PubMed2001

Organ doses from radiation therapy in atomic bomb survivors.

Previous surveys of radiation therapy among the Life Span Study (LSS) population at the Radiation Effects Research Foundation (RERF) revealed that 1,670 (1.4%) of the LSS participants received radiation treatments before 1984. The data on therapeutic radiation doses are indispensable for studying the relationship between radiation treatments and subsequent cancer occurrences. In this study, the radiation treatments were reproduced experimentally to determine the scattered radiation doses. The experiments were conducted using a female human phantom and various radiation sources, including a medium-voltage X-ray machine and a (60)Co gamma-ray source. Doses were measured using thermoluminescence dosimetry and ionization chambers. Radiation doses were determined for the salivary glands, thyroid gland, breast, lung, stomach, colon, ovary and active bone marrow. The results have been used for documenting the organ doses received by patients in previous surveys. The contribution of therapeutic irradiation to the occurrence of chromosome aberrations was studied using data on doses to active bone marrow from both radiation treatments and atomic bomb exposures in 26 RERF Adult Health Study participants. The results suggest that radiation treatments contributed to a large part of their frequencies of stable-type chromosome aberrations. The therapeutic radiation doses determined in the present study are available for investigating the effects of therapeutic irradiation on the subsequent primary cancers among atomic bomb survivors who received radiation treatments.

Chromosome Aberrations↗
PubMed1999

Synthesis and characterization of lipophilic 1-[18F]fluoroalkyl-2-nitroimidazoles for imaging hypoxia.

In order to develop new imaging markers for brain hypoxia, two lipophilic nitroimidazoles, 1-(3-fluoropropyl)-2-nitroimidazole (FPN) and 1-(8-fluorooctyl)-2-nitroimidazole (FON) were synthesized and labeled with fluorine-18. The octanol/water partition coefficients were measured as an indication of lipophilicity, giving values of logP=0.28 for FPN and logP=2.72 for FON, respectively, which are in the range thought to be optimal for the diffusion of molecules across the blood-brain barrier. It was suggested from a comparative study of in vitro radiosensitization in V79 cells that these lipophilic analogs may have reduction potentials close to those of fluoromisonidazole (FMISO) and misonidazole (MISO), known hypoxic cell radiosensitizers. The preparation of 18F-labeled FON (18FON) and FPN (18FPN) was achieved via two-steps through [18F]fluoride ion displacement of tosylate precursors, in reasonable radiochemical yields. Tissue distribution of 18FPN and 18FON in normal rats and tumor-bearing mice after intravenous injection was investigated and compared to the behavior of 18F-labeled FMISO (18FMISO), a proven hypoxic imaging agent. The high lipophilicity of 18FON and 18FPN resulted in increased initial uptake into normal rat brain, relative to 18FMISO, followed by a rapid washout from brain. Both of these lipophilic analogs had significantly lower tumor uptake and lower tumor-to-blood ratios than 18FMISO, suggestive of a poor trapping mechanism within the tumor tissue. Neither 18FON or 18FPN offers improved biological properties over 18FMISO as a potential agent for use in brain hypoxic imaging.

Animals↗
PubMed1998

Radiation therapy among atomic bomb survivors, Hiroshima and Nagasaki.

As a follow-up to the two previous surveys of radiation therapy among the atomic bomb survivors, a large-scale survey was performed to document (1) the number of radiation therapy treatments received by the atomic bomb survivors and (2) the types of radiation treatments conducted in Hiroshima and Nagasaki. The previous two surveys covered the radiation treatments among the Radiation Effects Research Foundation Adult Health Study (AHS) population, which is composed of 20,000 persons. In the present survey, the population was expanded to include the Life Span Study (LSS), including 93,611 atomic bomb survivors and 26,517 Hiroshima and Nagasaki citizens who were not in the cities at the times of the bombings. The LSS population includes the AHS population. The survey was conducted from 1981 to 1984. The survey teams reviewed all the medical records for radiation treatments of 24,266 patients at 11 large hospitals in Hiroshima and Nagasaki. Among them, the medical records for radiation treatments of 1556 LSS members were reviewed in detail. By analyzing the data obtained in the present and previous surveys, the number of patients receiving radiation therapy was estimated to be 4501 (3.7%) in the LSS population and 1026 (5.1%) in the AHS population between 1945-1980. During 1945-1965, 98% of radiation treatments used medium-voltage X rays, and 66% of the treatments were for benign diseases. During 1966-1980, 94% of the radiation treatments were for malignant neoplasms. During this period, 60Co gamma-ray exposure apparatus and high-energy electron accelerators were the prevalent mode of treatment in Hiroshima and in Nagasaki, respectively. The mean frequency of radiation therapy among the LSS population was estimated to have been 158 courses/year during 1945-1965 and 110 courses/year during 1966-1980. The present survey revealed that 377 AHS members received radiation therapy. The number was approximately twice the total number of cases found in the previous two surveys. Thus the data on radiation therapy in the AHS members have been updated well by this survey, and will provide information for more precise dose-response analyses of radiation effects in the AHS population. The information extracted from the medical records of the hospitals consisted of hospital names, treatment periods, body sites treated, diagnoses, treatment doses, radiation sources, the field sizes of the exposures and the data for identification of the patients. These data will be essential in estimating the organ doses from scattered radiation and in evaluating the effects of therapeutic radiation.

Adolescent↗
PubMed1997

[Protection of cultured mammalian cells by rebamipide].

Rebamipide which is used as a drug for gastritis and stomach ulcer has large capability for OH radical scavenging. It is expected that rebamipide has protective effect against ionizing radiations. The present paper deals with protective effect of rebamipide for cultured mammalian cells exposed to ionizing radiations. As rebamipide is insoluble in water, three solvents were used to dissolve. Rebamipide dissolved in dimethyl sulfoxide (DMSO), dimethyl formamide (DMFA) and 0.02 N NaOH was added to the cells in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum and the cells were irradiated with X-rays. After irradiation, the cells were trypsinized, plated in MEM with 10% fetal calf serum and incubated for 7 days in a CO2 incubator to form colonies. Rebamipide dissolved in 0.02 N NaOH exhibited the protective effect expected its OH radical scavenging capability. However, the protective effect of rebamipide dissolved in DMSO was about half of that expected by its radical scavenging capability and that of rebamipide dissolved in DMFA was not observed. Uptake of rebamipide labeled with 14C increased with increasing contact time with rebamipide. These rebamipide mainly distributed in nucleous rather than cytoplasm.

Alanine↗
PubMed1996

Promotion of heat-induced apoptosis in FM3A cells by protease inhibitors.

Although it has been shown that proteases may play a positive role in in causing apoptosis of some cells, we report here that, on the contrary, protease inhibitors can promote heat-induced apoptosis in FM3A cells. Cysteine protease inhibitor, trans-Epoxy-succinyl-L-leucylamido-(4-guanidino)butane (E-64, 100 micrograms/ml) and aspartate protease inhibitor, pepstatin-A (100 micrograms/ml) were used to test hyperthermic effect on FM3A cells and showed remarkable cytotoxicity when they were present in cell suspension during heating at 44 degrees C. The cytotoxicity was due to promotion of heat-induced apoptosis as judged by DNA agarose electrophoresis. Furthermore, using flow cytometric analysis, we observed a decrease in the G0/G1 phase cell and an increase in the S phase cell as well as increased apoptosis after heat shock. E-64 and pepstatin-A exhibited a promotive effect on the changes of cell cycle induced by heat. The data presented suggest that the enhancement of hyperthermic cell killing by protease inhibitors may be related to promotion of heat-induced apoptosis and changes of cell cycle.

Animals↗
PubMed1995

Enhancement of hyperthermic killing in L5178Y cells by protease inhibitors.

We have investigated the effect of protease inhibitors on hyperthermic cell killing using cultured mammalian cells (L5178Y) and found that protease inhibitors were potent hyperthermia sensitizers. At 37 degrees C, phenylmethylsulfonyl fluoride (PMSF), a serine protease inhibitor, was not cytotoxic at the concentration of 400 micrograms/ml for up to 6 h. When cells were exposed to PMSF (200-400 micrograms/ml) during heating at 43 degrees C, significant potentiation of hyperthermic cell killing was observed. Other protease inhibitors, such as chymostatin and diisopropylfluorophosphate (both are serine protease inhibitors); (2S,3S)-trans-epoxy-succinyl-L-leucylamido-3-methylbutane ethyl ester (cysteine protease inhibitor) and pepstatin-A (aspartate protease inhibitor) showed similar effects. However, when cells were heated at 43 degrees C in the presence of cycloheximide (a protein synthesis inhibitor) together with PMSF, hyperthermic enhancement by PMSF decreased markedly. A decrease in potentiating the effect of PMSF was also noted with thermotolerant cells. These facts suggest that protease inhibitors may exert their hyperthermic cell killing by inhibiting proteases and ubiquitin, which are necessary to degrade denatured proteins induced by heat.

Animals↗
PubMed1994

Enhancement of X-ray cell killing in cultured mammalian cells by the protein phosphatase inhibitor calyculin A.

Effects of calyculin A, a potent inhibitor of protein phosphatases 1 and 2A, on X-ray cell killing and chromatin structure were studied using cultured mammalian cells (BHK21). Calyculin A at concentrations of 2.5-20 nM enhanced X-ray cell killing when exponentially growing BHK21 cells were treated with calyculin A for 30 min after X-irradiation. A 30-min treatment with this drug induced chromatin condensation transiently. These results suggest that the enhancement of X-ray cell killing by calyculin A is caused by the events associated with chromatin condensation. Protein phosphatase-targeting drugs may represent a new class of radiation sensitizers.

Animals↗
PubMed1994

Increase in postirradiation survival of rat 3Y1 fibroblasts by a protein kinase inhibitor, staurosporine.

Protein kinases play an important role in the response of mammalian cells to ionizing radiation. In this study, we examined the effect of staurosporine, a potent inhibitor of protein kinases, on cell survival after X-irradiation, using the normal rat fibroblast line 3Y1. Treatment with 30 ng/ml staurosporine 1 h before irradiation resulted in the increase in survival of 3Y1 cells. This phenomenon was drug dose-dependent and maximal reduction of radiation-induced cell killing occurred when more than, or equal to, 30 ng/ml staurosporine was added. In contrast, treatment with 30 ng/ml staurosporine after irradiation did not increase cell survival. There was no change in cell cycle distribution by treatment for 1 h with 30 ng/ml staurosporine. These data suggest that the inhibition of protein kinase activities by staurosporine influences the radiosensitivity of 3Y1 cells.

Alkaloids↗
PubMed1991

Organ doses received by atomic bomb survivors during radiological examinations at the Radiation Effects Research Foundation.

When evaluating the risks of oncogenesis and cancer mortality following exposure to the radiations of the atomic bombs (A-bombs), the medical X-ray doses received by the A-bomb survivors must also be estimated and considered. Using a human phantom, dosimetry was performed to estimate the X-ray doses received by A-bomb survivors during medical examinations at the Radiation Effects Research Foundation (RERF) as part of the long-term follow-up on the Adult Health Study (AHS). These examinations have been estimated to represent nearly 45% of the survivors' cumulative medical irradiation dose. Doses to the salivary glands, thyroid gland, lung, breast, stomach and colon were measured using thermoluminescent dosimeters. The results, which are reported here, will aid in estimating organ doses received by individual AHS participants.

Abdomen↗
PubMed1991

Organ doses to atomic bomb survivors during photofluorography, fluoroscopy and computed tomography.

Doses to the salivary glands, thyroid gland, breast, lung, stomach and colon during mass radiological gastric screening, mass radiographic chest screening, upper gastrointestinal series and computed tomography were determined by exposing a female human phantom to simulated radiological X-ray examinations as performed in community hospitals. The doses were measured using thermoluminescent dosimeters, and the results will be used to document organ doses received by participants in the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation Adult Health Study.

Adult↗
PubMed1990

Enhancement of radiosensitivity of cultured mammalian cells by neocarzinostatin. I. Inhibition of the repair of sublethal damage.

The enhancement of radiosensitivity by neocarzinostatin (NCS), an antitumour drug, was studied using three strains of cultured mammalian cells with different repair capabilities for sublethal damage. NCS enhanced the radiosensitivity of the cells when applied both during and after X-irradiation under aerobic conditions. The enhancement ratios of NCS during X-irradiation were 1.25, 1.27 and 1.38 for mouse lymphoma L5178Y, Chinese hamster V79 and mouse mammary tumour FM 3A cells, respectively. The corresponding ratios after X-irradiation were 1.18, 1.27 and 1.38, respectively. These ratios were proportional to the repair capabilities of the cells for sublethal damage. NCS completely inhibited the repair of sublethal damage regardless of the repair capabilities of the cells for sublethal damage. NCS was equally effective for hypoxic cells. These results suggested that NCS enhanced the radiosensitivity of the cells probably by interacting with the residual damage after X-irradiation, thereby converting the sublethal damage or potentially lethal damage into lethal damage.

Animals↗
PubMed1990

Enhancement of radiosensitivity of cultured mammalian cells by neocarzinostatin. II. Fixation of potentially lethal damage.

The effects of neocarzinostatin (NCS), an anti-tumour drug, on the repair of potentially lethal damage (PLD) were studied using cultured Chinese hamster V79, malignant human melanoma and mouse lymphoma L5178Y cells in the stationary phase. The repair of PLD was observed in the melanoma and L5178Y cells but no such repair was observed in the V79 cells, when studied by delayed plating. NCS added to the culture medium immediately after X-irradiation evoked fixation of PLD within 10 min of the addition of NCS. The ratios of D0 values of the survival curves of the cells treated with NCS to those plated immediately after X-irradiation were 0.78, 0.88 and 0.85 for V79, melanoma and L5178Y cells, respectively. The extent of the fixation by NCS was similar to that caused by 0.5 M NaCl solution. The results in the present study and the inhibition of sublethal damage (SLD) by NCS reported previously, suggest that NCS might react with the DNA damage induced by radiation and modify it to lethal damage. The study indicates that SLD and PLD appear to be closely related to one another.

Animals↗
PubMed1989

Dental radiography exposure of the Hiroshima and Nagasaki populations.

Dental radiography doses in Hiroshima and Nagasaki were estimated on the basis of survey data from dental hospitals and clinics in Hiroshima and Nagasaki, and doses were measured by thermoluminescent dosimeters and a phantom. Doses to organs, including the lens, pituitary fossa, thyroid gland, and skin were calculated from data obtained during a 2-week survey in both cities. The mean caput doses were calculated from the data indicating frequency per year and were tabulated by organs, age, teeth examined, type of examination, population, sex, and city. No significant difference was observed by age, population, sex, or city. Currently the doses incurred during dental radiography may not be sufficiently high to cause bias in the assessments for late radiation effects among atomic-bomb survivors. However, the mean caput thyroid doses of 62 mrad and 67 mrad in Hiroshima and Nagasaki, respectively, cannot be ignored from the standpoint of their potential in contributing to radiation-induced carcinogenesis.

Adolescent↗
PubMed1988

Soft X-ray dosimetry and RBE for survival of Chinese hamster V79 cells.

Dosimetry and biological effects of 40 and 50 keV low-energy X-rays generated by a SOFTEX Model CMBW-2 apparatus were studied. Doses were measured using a thin-window parallel-plate ionization chamber; beam quality was assessed using aluminum absorbers; exposure rates per unit current were determined according to the X-ray tube current and exposure times; and thermoluminescent (BeO chip) dosimeters were used to ascertain dose distributions in the irradiation field. The average correction factors for nonuniformity were calculated from the measured dose distributions. The means for ascertaining accurate exposures and doses using these methods are discussed. The dose-survival relationship of Chinese hamster V79 cells were assessed by irradiating them with 40 and 50 kV soft X-rays, 180 kV X-rays, and 60 Co gamma rays. Soft X-rays with three distinct effective energies were tested by changing the tube voltage kV and aluminium filter thicknesses; namely (1) 40 kV without filter, (2) 40 kV with a 0.2 mm thick aluminium filter and (3) 50 kV with a 0.7 mm thick aluminium filter. The effective energies obtained according to attenuation measurements using aluminium for these soft X-rays were 8.1, 11.7 and 18.5 kV, respectively. In this study the relative biological effectiveness (RBE) at 10 per cent survival compared with 60Co gamma rays ranged from 1.5 to 1.6. The RBE of 180 kV X-rays relative to 60Co gamma rays was 1.29. This study provided experimental data for the RBE of V79 cells in the intermediate energy range between hard and ultrasoft X-rays, data for which were previously reported by Goodhead and co-workers (1977, 1979, 1981).

Aluminum↗
PubMed1988

Medical x-ray exposure doses as contaminants of atomic bomb doses.

Since 1967 at the times of their biennial ABCC/RERF radiological examinations, all Adult Health Study (AHS) subjects have been interviewed to determine the exposures to medical x-rays they experienced in institutions other than RERF in order to estimate the numbers of examinations and corresponding doses which they received. These data have been stored on computer tapes together with the doses these subjects received during their radiological examinations in the ABCC/RERF Department of Radiology. Thus, their medical x-ray doses are available along with their atomic bomb doses (tentative 1965 doses revised, T65DR) for assessment of the role of ionizing radiation in the development of diseases. The medical x-ray doses incurred at RERF were assessed by means of phantom dosimetry. Those at other institutions were determined using phantom dosimetry data and results of surveys for trends in radiological examinations in Hiroshima and Nagasaki. By the end of 1982, the average medical x-ray doses to the active bone marrow were 12.04 mGy for A-bomb exposed groups and 8.92 mGy for control groups (not-in-cities); to the male gonads, 2.26 mGy and 1.89 mGy, respectively; and to the female gonads, 17.45 mGy and 12.58 mGy, respectively. Results for Hiroshima and Nagasaki were similar. The main impact of medical x-ray doses was in the lowest T65DR group. Medical x-ray active bone marrow doses ranged from 0.05-500% (mean, 35%) of A-bomb doses in the 10-99 mGy T65DR group. In the 100-999 mGy T65DR group, medical x-ray active bone marrow doses ranged from 0.005-50% (mean, 5%) of their T65DR. In the greater than 1,000-mGy T65DR group, medical x-ray exposures were proportionally less. Female active bone marrow and gonad doses were similar in magnitude to the male active bone marrow doses. Medical x-ray exposures produced smaller doses to the gonads of males than to those of the females. The use of medical x-rays is steadily increasing. Careful consideration of doses from medical sources is essential for reliable assessments of the effects from exposures to the atomic bombs.

Adult↗