Biomedical subjects

Masahiko Satoh

Publications and source records attributed to Masahiko Satoh.

28 records · Page 2Linked to original sources

PubMed2003

Optimal administration schedule of cisplatin for bladder tumor with minimal induction of metallothionein.

PURPOSE: The metal binding protein metallothionein (MT) confers drug resistance when MT is induced in tumor tissues. Cisplatin is known to induce MT synthesis in tumor tissues, which may lead to drug resistance. We examined whether a difference in the administration schedule of cisplatin affect the efficiency of MT induction. MATERIALS AND METHODS: Balb/c nude mice were inoculated with NMB-1 human bladder tumor tissues and injected with cisplatin (total dose of 64 micromol/kg) in a single injection or fractioned daily injections. Tumor MT concentration was determined 24 hours after the last injection of cisplatin by mercury binding assay. The effect of pretreatment with ZnCl2 on antitumor activity of cisplatin was examined in NMB-1 bearing mice. RESULTS: Tumor MT levels increased significantly with the increase in the number of cisplatin injections. Pretreatment of NMB-1 bearing mice with ZnCl2 (200 micromol/kg x 2) caused the same level of MT induction (1.6-fold) as that of fractioned injections of cisplatin (4 x 16 micromol/kg). Pretreatment of NMB-1 bearing mice with ZnCl2 (200 micromol/kg x 2) depressed cisplatin antitumor activity by about 50%. CONCLUSIONS: The induction of MT to a moderate extent (1.6-fold) in NMB-1 tumor inoculated in mice conferred cisplatin resistance. This level of MT induction can be achieved by fractioned daily injections of cisplatin but not by a single injection. Therefore, it is preferable to administer cisplatin as a single injection rather than as fractioned injections to achieve effective antitumor activity with minimum MT induction.

Animals↗

PubMed2003

Embolic attack in patients with atrial fibrillation and atrial thrombus depends on the character of the thrombus.

It is very important to prevent embolisms from left atrial thrombi (LAT). The present study was a trial for the management of patients with AT using 122 patients with atrial fibrillation and LAT who were followed for 1 year after transesophageal echocardiography. LAT were classified by their shape and mobility into the mobile ball type (MB, n=28), fixed ball type (FB, n=32) and mountain type (MO, n=42). The patients were given warfarin (INR: 1.5-2.0, n=43), aspirin 81 mg (n=74) and/or ticlopidine 200 mg/day (n=31). The embolic rate (ER) in the MB group was significantly higher than in the other groups [ie, MB 39.3% vs FB 15.6% (p<0.05), vs MO 2.4% (p<0.05)]. The ER in the FB group was significantly higher than in the MO group (p<0.05). Therapy with a combination of ticlopidine and aspirin reduced the ER in the patients with ball thrombi. The ER of the ball thrombus type group, especially the MB group, was very high in spite of therapy with anti-coagulants and/or anti-platelet agents, and such patients should be treated by early surgical intervention. However, the combination of ticlopidine and aspirin may be useful for preventing embolism.

Aged↗

PubMed2003

[Low dose exposure to cadmium and its health effects. (3) Toxicity in laboratory animals and cultured cells].

We have reviewed studies on cadmium (Cd) toxicity in laboratory animals and cultured cells with special attention to the disruption in cellular signal transduction, involvement in apoptosis of Cd, the cellular transport system for Cd and roles of metallothionein as a protective factor against Cd. Cd affects cellular functions by perturbing signal transductions, such as protein kinase C, mitogen-activated protein kinase and cyclic AMP pathways, but how the disruption of these pathways by Cd leads to the manifestation of toxicity in vivo is largely unknown. Exposure to cadmium at relatively high and low levels causes necrosis and apoptosis, respectively, which suggests that the mode of cell death by cadmium is dependent upon its exposure level. On the other hand, utilization of Ca2+ channels, DMT1 (divalent metal transporter 1) and a novel transport system having high-affinity for Mn2+ and Cd2+ were found to act as Cd transport systems via the cellular membrane. Metallothionein-I/II-null mice are highly susceptible to renal toxicity, hepatotoxicity, bone injury, hematotoxicity and immunotoxicity caused by chronic Cd exposure. Thus, metallothionein plays an important role in detoxification of Cd toxicity.

Animals↗

PubMed2003

[Low dose exposure to cadmium and its health effects. (4) Body burden, critical concentration and life expectancy].

As the last manuscript in our series of review articles on cadmium (Cd) and health effects, we reviewed research articles on epidemiologic and experimental studies on exposure levels of Cd in occupational and environmental settings in various countries, disposition and body burden of Cd, critical concentrations of Cd in the kidney of humans and animals with a focus on biomarkers for renal dysfunction, and life expectancy in Cd-polluted areas and reference areas. After this manuscript was compiled, cadmium levels in rice crops received significant attention, since the risk assessment of cadmium is now under review and discussion by the Joint Expert Committee of Food Additives and Contaminants organized by the Food Agricultural Organization and World Health Organization in 2003. We hope that the information compiled in this review may provide directions for future studies on the health risk assessment of Cd.

Animals↗

PubMed2003

Interleukin-6 protects skin lesion caused by 7,12-dimethylbenz[a]anthracene.

Interleukin-6 (IL-6) regulates essential physiological functions such as acute phase reaction, immune response and hematopoiesis. We here studied possible protective effects of IL-6 on skin damage caused by 7,12-dimethylbenz[a]anthracene (DMBA) by using IL-6 null mice. The mice were topically applied with a single dose of DMBA (500 microg /mouse) on the dorsal skin. Osmotic pumps filled with recombinant human IL-6 (rhIL-6) were implanted subcutaneously on the ventral side of the mice. Control mice received PBS instead of rhIL-6 by the pump. Severe skin damage was observed in IL-6-null mice, whereas only epidermal hyperplasia was observed in the wild-type mice. Recombinant hIL-6 treatment to DMBA-treated IL-6-null mice suppressed the occurrence of the skin damage, indicating.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

Maternal-to-fetus transfer of mercury in metallothionein-null pregnant mice after exposure to mercury vapor.

This study examined the role of placenta metallothionein (MT) in maternal-to-fetal mercury transfer in MT-null and wild-type mice after exposure to elemental mercury (Hg(0)) vapor. Both strains were exposed to Hg(0) vapor at 5.5-6.7 mg/m(3) for 3 h during late gestation. Twenty-four hours after exposure to Hg(0) vapor, accumulation of mercury in the major organs, except the brain, of MT-null maternal mice was significantly lower than that in organs of wild-type mice. In contrast to mercury levels in maternal organs, fetal mercury levels were significantly higher in MT-null mice than in wild-type mice. In placenta, mercury concentrations were not significantly different between the two strains. Although MT levels in major organs, except the brain, of wild type mice were markedly elevated after the exposure to Hg(0) vapor, the placental MT levels were not elevated. However, endogenous MT level in the placenta is significantly higher than that in other organs, except the liver. Gel filtration profile of the placental cytosol in the wild-type mice revealed that a large amount of placental mercury was associated with MT. In MT-null mice, mercury in placental cytosol appeared mainly in the high-molecular-weight protein fractions. Mercury in the placenta was localized mainly in the yolk sac and decidual cells in the deep layer of the decidua in both mouse strains. The similar localization of MT was found in the placenta of wild type mice. These results suggest that MT in the placenta has a defensive role in preventing maternal-to-fetal mercury transfer.

Administration, Inhalation↗

PubMed2002

[Low dose exposure to cadmium and its health effects (1). Genotoxicity and carcinogenicity].

We reviewed studies on genotoxicity and carcinogenicity of cadmium (Cd). Salmonella typhimurium and Escherichia coli exposed to Cd did not show mutagenicity, whereas cultured mammalian cells exposed to Cd showed mutation, DNA strand breaks, and chromosomal aberrations. Carcinogenicity tests showed that exposure to Cd increased the occurrence of tumors in testis, lung, prostate, hematopoietic tissues, and injection sites. On the other hand, recent epidemiologic studies are not supportive of earlier observations on the association between Cd and prostate cancer. The US NIOSH data on a possible association between Cd and lung cancer may need reevaluation. No studies which show a positive relationship between oral Cd exposure and carcinogenesis have been reported. All available data suggest that Cd should be reassigned to IARC Group 2A (probably carcinogenic to humans) from the current Group 1.

Animals↗

PubMed2002

[Low dose exposure to cadmium and its health effects (2). Life-cycle related diseases and reproductive toxicity].

We have reviewed earlier studies on the possible involvement of cadmium in life-cycle related diseases and the reproductive toxicity of Cd including environmental disrupting actions. Experimental studies have suggested that Cd may be involved in the aggravation of life-cycle related diseases and the occurrence of reproductive toxicity. On the other hand, epidemiological studies did not necessarily support the experimental observations. Thus, we conclude that it is necessary to investigate further to determine whether Cd is responsible for the aggravation of life-cycle related diseases or has the capability to act as an environmental endocrine disrupter in humans.

Animals↗

PubMed2002

Perspectives on cadmium toxicity research.

Since there are a plethora of studies on cadmium toxicity and poisoning in laboratory animals and humans, we have limited this review to studies that are relevant to human health issues by focusing on carcinogenicity, genotoxicity, circulatory disease, nephrotoxicity and life expectancy. Cadmium exposure has been established to induce cancer in various tissues of laboratory animals. Contrary to early findings of the lack of genotoxicity by cadmium, recent findings of mammalian cell culture studies have revealed genotoxic effects. Furthermore, cadmium exposure at relatively low doses induces circulatory diseases in laboratory animals. Despite such results of various cadmium toxicities in animal studies, data from human studies are lacking and insufficient to support the cause-effect relationship. Although cadmium is currently considered to be a human carcinogen by the International Agency for Research and Cancer, it is inappropriate to conclude that sufficient evidence on the carcinogenicity of cadmium in humans exists. It is also thought that epidemiological studies so far reported do not support the occurrence of cadmium-induced circulatory disease in humans. Since there are inconsistent reports on the relationship of cadmium exposure with the life expectancy of people living in cadmium-polluted areas, further studies are needed for clarification. It is also necessary to examine apparent discrepancies in result between humans and experimental animals. It has been established that long-term exposure to cadmium causes renal dysfunction in both humans and experimental animals, and whether there are any differences in the inducibility of metallothionein in the kidney warrants further study.

Animals↗

PubMedDate not supplied

Ultrastructural demonstration of mercury granules in the placenta of metallothionein-null pregnant mice after exposure to mercury vapor.

The placenta plays an important role in the regulation of maternal to fetal transfer of toxic substances, including nonessential metals. Metallothioneins (MTs), which are known to have protective effects against heavy metal toxicity, exist in the placenta, but the exact localization of placental MTs (both MT-I and MT-III) and their physiological role in the placenta exposed to mercury are unclear. The present study was performed to examine the localization of MTs and mercury granules in the placenta of mice exposed to mercury vapor. On gestational day 16, MT-I & II-null and wild-type mice were exposed to mercury vapor at 4.9 to 5.9 mg/m3 for 2 hours. At 24 and 48 hours after exposure, the placentas were examined for mercury distribution (autometallography), MT immunoreactivity, and MT mRNA expression (in situ hybridization). No histological changes were observed in the placentas of either MT-null or wild-type mice. Mercury deposition was demonstrated along the boundary between the junctional zone and the labyrinth zone, as well as in the yolk sac, maternal decidual cells, and labyrinth trophoblasts of both MT-null and wild-type mice. MT-I & -II immunoreactivity, which was confined to wild-type mice, was demonstrated in the yolk sac and decidual cells; mercury was also shown in both structures, suggesting that mercury granules were bound to MTs. MT-III mRNA expression was observed in the yolk sac, decidual cells, and spongiotrophoblasts in both MT-null and wild-type mice. There was, however, no evidence of MT at the boundary between the junctional and labyrinth zones, where substantial mercury deposits were demonstrated. These results suggest that placental MTs and the other unknown molecules may be related to the barrier to the placental transfer of mercury.

Administration, Inhalation↗