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Papers by motoyasu ohsawa
The Journal of Immunology
Adjuvant arthritis (AA) is an experimental model of autoimmune disease in rats induced by immuniz... more Adjuvant arthritis (AA) is an experimental model of autoimmune disease in rats induced by immunization with Mycobacterium tuberculosis (MT). Induction of AA in other species, including mice, has been shown to be difficult. In the present study, we found that AA could be induced in mice if the animals were treated with a mAb (11B11 mAb) against IL-4. Histologically, the joints exhibited synovial edema with infiltration of many neutrophils in the early phase of inflammation. In its late phase, there were proliferation of synovium, cell infiltrate in which mononuclear cells predominated, and destruction of cartilage and subchondral bone. The joint inflammation was passively transferred to normal syngeneic recipient mice with lymphoid cells but not with sera from mice immunized with MT followed by treatment with the anti-IL-4 Ab. Delayed-type hypersensitivity (DTH) and proliferative responses of lymphoid cells to purified protein derivative were markedly augmented in 11B11 mAb-treated m...
Mutation Research/Environmental Mutagenesis and Related Subjects, 1984
The Journal of Toxicological Sciences, 1982
Toxicology Letters, 1983
Zinc added to the culture medium caused a dose-related suppression of the proliferative response ... more Zinc added to the culture medium caused a dose-related suppression of the proliferative response of human lymphocytes to cultured allogeneic HeLa cells without any significant decrease in cell viability. In contrast to the response to HeLa cells, this metal ion moderately enhanced T lymphocyte response to mitogens such as pb~~ohemagglutinin (PHA), concanavalin A (ConA) and 12-~-tetrad~a~oylphorbol-13-acetate (TPA). These findings seem to indicate that zinc may be a crucial factor for the modulation of the T Iymphocyte function. It can also be considered that the different effect of zinc on the proliferative responses of lymphocytes to allogeneiz HeLa cells and to some soluble mitogens might reflect a difference in mechanisms between the two proliferative responses.
![Research paper thumbnail of Involvement of DNA polymerases in the repair of DNA damage by benzo[a]pyrene in cultured Chinese hamster cells](https://attachments.academia-assets.com/104531689/thumbnails/1.jpg)
](Mutation Research/DNA Repair Reports, 1987
Journal of Toxicological Sciences, Oct 17, 2001
Journal of Toxicological Sciences, Oct 26, 1999
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1986
The effect of 3-aminobenzamide, a potent inhibitor of poly(ADP-ribosyl)ation, on UV-induced DNA e... more The effect of 3-aminobenzamide, a potent inhibitor of poly(ADP-ribosyl)ation, on UV-induced DNA excision repair was investigated. HeLa cells were treated with DNA replication inhibitors, hydroxyurea (HU) and 1-beta-D-arabinofuranosyl cytosine (araCyt), before and after ultraviolet light (UV) irradiation, to accumulate DNA single-strand breaks. The activity of poly(ADP-ribosyl)ation measured in the permeable cell system of HeLa cells was enhanced in a UV dose-dependent manner after the combined treatment with HU and araCyt in vivo. However, DNA repair synthesis in vitro was not affected by addition of 1 mM 3-aminobenzamide or nicotinamide, while incorporation of [3H]NAD in the same system was completely inhibited. Furthermore, neither the magnitude of UV-induced DNA single-strand breaks accumulated by the combined treatment of HU and araCyt nor the rate of their rejoining after release from the HU and araCyt block were influenced even in the presence of 10 mM 3-aminobenzamide. As the cytotoxicity of UV irradiation was significantly potentiated by 5 mM 3-aminobenzamide, these results suggest that poly(ADP-ribosyl)ation is involved in a process other than DNA excision repair induced by UV irradiation.
Endocrinologia Japonica, 1973
In an attempt to analyze the pathogenesis of hereditary vasopressin-resistant diabetes insipidus ... more In an attempt to analyze the pathogenesis of hereditary vasopressin-resistant diabetes insipidus (DI) in mice associated with oligosyndactily (Os), possible participation of adenyl cyclase of the kidney cells in the mechanism of diuresis was examined. In DI Os/+ mice with severe diuresis intraperitoneal injection of adenosine 3',5'-monophosphate (cyclic AMP) but not exogenous vasopressin delayed the onset of diuretic response to water load, while the reverse was true in DI +/+ mice with mild diuresis. Urinary osmolarity, moreover, was increased by cyclic AMP but not by vasopressin in Os/+ mice, whereas the reverse was the case with +/+ sibs. Although lack or defect of vasopressin-sensitive adenyl cyclase of the kidney cells might be assumed in the severely diuretic mice, both the basal and vasopressin-activated adenyl cyclase activities in vitro were similar between Os/+ and +/+ animals. The defect of vasopressin-sensitive adenyl cyclase in the kidney thus does not seem to be responsible for the hereditary nephrogenic diuresis of mice.
Endocrinologia Japonica, 1969
YAKUGAKU ZASSHI, 2007
Transcriptional activation of metallothionein (MT) genes by heavy metals is a valuable system for... more Transcriptional activation of metallothionein (MT) genes by heavy metals is a valuable system for understanding the functions of MT as well as the cellular response against heavy metals. Although it is now known that heavy metal signals culminating in MT induction converge upon a transcription factor MTF-1, the mechanism underlying the MTF-1 response to heavy metals has not been elucidated. To address this issue, we investigated various aspects of the in vivo response of MTF-1 against heavy metals. Chromatin immunoprecipitation assay showed that heavy metal-dependent DNA binding of MTF-1 is the critical step in vivo. MTF-1 is primarily localized in the nucleus so that heavy metal-dependent nuclear translocation demonstrated by other groups does not seem to be universal and hence may not be critical for activation of MTF-1. In the six Znˆnger motifs, the hallmark of MTF-1, the third and the fourthˆngers are essential for the nuclear localization of MTF-1. Furthermore, allˆngers except the last are important for transcriptional activation function of MTF-1, suggesting their key role for MTF-1 function. Also, a cysteine cluster structure located in the C-terminal region of MTF-1 is critical for transactivating function of MTF-1. These results suggest a central role of the Znnger domain and intramolecular cooperation through a structural change of MTF-1 for its response to heavy metal challenge.
JOURNAL OF HEALTH SCIENCE, 2002
INDUSTRIAL HEALTH, 1974
Ca, and P in plasma were measured once a week on rabbits injected subcutaneously with 0.5 and 1.0... more Ca, and P in plasma were measured once a week on rabbits injected subcutaneously with 0.5 and 1.0 mg Cd/kg daily for 11 weeks respectively, and Cd, Cu, Mn, and Zn contents in organs were determined at the termination of the experiment. Prostatic Ac-P activity, cholesterol, and free fatty acid levels in plasma rose in the early stage of administration, and GOT, GPT, LDH, and Al-P activities rose in the latter stage of administration. Ca and P levels in plasma did not change in all periods of the experiment. From these results, it could be concluded that a measurement of prostatic Ac-P, cholesterol, and free fatty acid is available for knowing an excess intake of Cd.
INDUSTRIAL HEALTH, 1993
Metallothionein (MT) is thought to play a central role in the detoxification of heavy metals, and... more Metallothionein (MT) is thought to play a central role in the detoxification of heavy metals, and thus studies on its regulation are toxicologically important. Heavy metal-dependent induction of MT genes is mediated by metal responsive elements (MREs) located upstream of the genes. Zinc regulatory factor (ZRF) is a zinc-dependent MRE-binding protein that was originally detected in HeLa cell nuclear extracts using the most proximal MRE of the human MT-IIA gene (hMREa) as a probe. We show that ZRF in HeLa cell nuclear extracts can also bind to the most potent MRE of the mouse MT-I gene (mMREd). This finding was further confirmed by using partially purified ZRF. Moreover, cadmium could not promote complex formation between ZRF and mMREd at any concentration tested, as is also the case with ZRF and hMREa. These observations suggest that the transcriptional regulatory system of MT genes by zinc is conserved beyond species.
INDUSTRIAL HEALTH, 1981
ACCELERATED ACCUMULATION OF METHLYMERCURY IN THE RAT FETUS AT THE LATE PREGNANT STAGE Methylmercu... more ACCELERATED ACCUMULATION OF METHLYMERCURY IN THE RAT FETUS AT THE LATE PREGNANT STAGE Methylmercury is readily absorbed through the gastrointestinal tract and crosses the blood-brain barrier1) and placental barrier.2). Exposure of the pregnant females to methylmercury has been shown to involve a greater risk of damage to the fetus than to the mother in humans,3) rats4) and mice.5)6) In rats exposed to methylmercury the mercury concentrations in the fetal brain were found to be much higher than those in the maternal brain.7)-9) The concentration of mercury in the fetus of mice seems to become higher with fetal age at the time of a single injection of methylmercury during Day 7 to Day 13 of gestation.10) In the present study, moreover, we found that the placental transfer
The Journal of Immunology
Adjuvant arthritis (AA) is an experimental model of autoimmune disease in rats induced by immuniz... more Adjuvant arthritis (AA) is an experimental model of autoimmune disease in rats induced by immunization with Mycobacterium tuberculosis (MT). Induction of AA in other species, including mice, has been shown to be difficult. In the present study, we found that AA could be induced in mice if the animals were treated with a mAb (11B11 mAb) against IL-4. Histologically, the joints exhibited synovial edema with infiltration of many neutrophils in the early phase of inflammation. In its late phase, there were proliferation of synovium, cell infiltrate in which mononuclear cells predominated, and destruction of cartilage and subchondral bone. The joint inflammation was passively transferred to normal syngeneic recipient mice with lymphoid cells but not with sera from mice immunized with MT followed by treatment with the anti-IL-4 Ab. Delayed-type hypersensitivity (DTH) and proliferative responses of lymphoid cells to purified protein derivative were markedly augmented in 11B11 mAb-treated m...
Mutation Research/Environmental Mutagenesis and Related Subjects, 1984
The Journal of Toxicological Sciences, 1982
Toxicology Letters, 1983
Zinc added to the culture medium caused a dose-related suppression of the proliferative response ... more Zinc added to the culture medium caused a dose-related suppression of the proliferative response of human lymphocytes to cultured allogeneic HeLa cells without any significant decrease in cell viability. In contrast to the response to HeLa cells, this metal ion moderately enhanced T lymphocyte response to mitogens such as pb~~ohemagglutinin (PHA), concanavalin A (ConA) and 12-~-tetrad~a~oylphorbol-13-acetate (TPA). These findings seem to indicate that zinc may be a crucial factor for the modulation of the T Iymphocyte function. It can also be considered that the different effect of zinc on the proliferative responses of lymphocytes to allogeneiz HeLa cells and to some soluble mitogens might reflect a difference in mechanisms between the two proliferative responses.
Mutation Research/DNA Repair Reports, 1987
Journal of Toxicological Sciences, Oct 17, 2001
Journal of Toxicological Sciences, Oct 26, 1999
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1986
The effect of 3-aminobenzamide, a potent inhibitor of poly(ADP-ribosyl)ation, on UV-induced DNA e... more The effect of 3-aminobenzamide, a potent inhibitor of poly(ADP-ribosyl)ation, on UV-induced DNA excision repair was investigated. HeLa cells were treated with DNA replication inhibitors, hydroxyurea (HU) and 1-beta-D-arabinofuranosyl cytosine (araCyt), before and after ultraviolet light (UV) irradiation, to accumulate DNA single-strand breaks. The activity of poly(ADP-ribosyl)ation measured in the permeable cell system of HeLa cells was enhanced in a UV dose-dependent manner after the combined treatment with HU and araCyt in vivo. However, DNA repair synthesis in vitro was not affected by addition of 1 mM 3-aminobenzamide or nicotinamide, while incorporation of [3H]NAD in the same system was completely inhibited. Furthermore, neither the magnitude of UV-induced DNA single-strand breaks accumulated by the combined treatment of HU and araCyt nor the rate of their rejoining after release from the HU and araCyt block were influenced even in the presence of 10 mM 3-aminobenzamide. As the cytotoxicity of UV irradiation was significantly potentiated by 5 mM 3-aminobenzamide, these results suggest that poly(ADP-ribosyl)ation is involved in a process other than DNA excision repair induced by UV irradiation.
Endocrinologia Japonica, 1973
In an attempt to analyze the pathogenesis of hereditary vasopressin-resistant diabetes insipidus ... more In an attempt to analyze the pathogenesis of hereditary vasopressin-resistant diabetes insipidus (DI) in mice associated with oligosyndactily (Os), possible participation of adenyl cyclase of the kidney cells in the mechanism of diuresis was examined. In DI Os/+ mice with severe diuresis intraperitoneal injection of adenosine 3',5'-monophosphate (cyclic AMP) but not exogenous vasopressin delayed the onset of diuretic response to water load, while the reverse was true in DI +/+ mice with mild diuresis. Urinary osmolarity, moreover, was increased by cyclic AMP but not by vasopressin in Os/+ mice, whereas the reverse was the case with +/+ sibs. Although lack or defect of vasopressin-sensitive adenyl cyclase of the kidney cells might be assumed in the severely diuretic mice, both the basal and vasopressin-activated adenyl cyclase activities in vitro were similar between Os/+ and +/+ animals. The defect of vasopressin-sensitive adenyl cyclase in the kidney thus does not seem to be responsible for the hereditary nephrogenic diuresis of mice.
Endocrinologia Japonica, 1969
YAKUGAKU ZASSHI, 2007
Transcriptional activation of metallothionein (MT) genes by heavy metals is a valuable system for... more Transcriptional activation of metallothionein (MT) genes by heavy metals is a valuable system for understanding the functions of MT as well as the cellular response against heavy metals. Although it is now known that heavy metal signals culminating in MT induction converge upon a transcription factor MTF-1, the mechanism underlying the MTF-1 response to heavy metals has not been elucidated. To address this issue, we investigated various aspects of the in vivo response of MTF-1 against heavy metals. Chromatin immunoprecipitation assay showed that heavy metal-dependent DNA binding of MTF-1 is the critical step in vivo. MTF-1 is primarily localized in the nucleus so that heavy metal-dependent nuclear translocation demonstrated by other groups does not seem to be universal and hence may not be critical for activation of MTF-1. In the six Znˆnger motifs, the hallmark of MTF-1, the third and the fourthˆngers are essential for the nuclear localization of MTF-1. Furthermore, allˆngers except the last are important for transcriptional activation function of MTF-1, suggesting their key role for MTF-1 function. Also, a cysteine cluster structure located in the C-terminal region of MTF-1 is critical for transactivating function of MTF-1. These results suggest a central role of the Znnger domain and intramolecular cooperation through a structural change of MTF-1 for its response to heavy metal challenge.
JOURNAL OF HEALTH SCIENCE, 2002
INDUSTRIAL HEALTH, 1974
Ca, and P in plasma were measured once a week on rabbits injected subcutaneously with 0.5 and 1.0... more Ca, and P in plasma were measured once a week on rabbits injected subcutaneously with 0.5 and 1.0 mg Cd/kg daily for 11 weeks respectively, and Cd, Cu, Mn, and Zn contents in organs were determined at the termination of the experiment. Prostatic Ac-P activity, cholesterol, and free fatty acid levels in plasma rose in the early stage of administration, and GOT, GPT, LDH, and Al-P activities rose in the latter stage of administration. Ca and P levels in plasma did not change in all periods of the experiment. From these results, it could be concluded that a measurement of prostatic Ac-P, cholesterol, and free fatty acid is available for knowing an excess intake of Cd.
INDUSTRIAL HEALTH, 1993
Metallothionein (MT) is thought to play a central role in the detoxification of heavy metals, and... more Metallothionein (MT) is thought to play a central role in the detoxification of heavy metals, and thus studies on its regulation are toxicologically important. Heavy metal-dependent induction of MT genes is mediated by metal responsive elements (MREs) located upstream of the genes. Zinc regulatory factor (ZRF) is a zinc-dependent MRE-binding protein that was originally detected in HeLa cell nuclear extracts using the most proximal MRE of the human MT-IIA gene (hMREa) as a probe. We show that ZRF in HeLa cell nuclear extracts can also bind to the most potent MRE of the mouse MT-I gene (mMREd). This finding was further confirmed by using partially purified ZRF. Moreover, cadmium could not promote complex formation between ZRF and mMREd at any concentration tested, as is also the case with ZRF and hMREa. These observations suggest that the transcriptional regulatory system of MT genes by zinc is conserved beyond species.
INDUSTRIAL HEALTH, 1981
ACCELERATED ACCUMULATION OF METHLYMERCURY IN THE RAT FETUS AT THE LATE PREGNANT STAGE Methylmercu... more ACCELERATED ACCUMULATION OF METHLYMERCURY IN THE RAT FETUS AT THE LATE PREGNANT STAGE Methylmercury is readily absorbed through the gastrointestinal tract and crosses the blood-brain barrier1) and placental barrier.2). Exposure of the pregnant females to methylmercury has been shown to involve a greater risk of damage to the fetus than to the mother in humans,3) rats4) and mice.5)6) In rats exposed to methylmercury the mercury concentrations in the fetal brain were found to be much higher than those in the maternal brain.7)-9) The concentration of mercury in the fetus of mice seems to become higher with fetal age at the time of a single injection of methylmercury during Day 7 to Day 13 of gestation.10) In the present study, moreover, we found that the placental transfer