Followup study of mercury pollution in indigenous tribe reservations in the Province of Ontario, Canada, 1975-2002.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
T Kizaki
Publications and source records attributed to T Kizaki.
Wide use of merthiolate may cause mercury poisoning in Mexico.
Explore the source record for details and available documents.
Adolescent↗
Contribution of the calcineurin signaling pathway to overload-induced skeletal muscle fiber-type transition.
Skeletal muscle is highly adaptable, being capable of undergoing changes in its structural and functional properties in response to physiological stimuli. The fast-to-slow muscle fiber-type transition is evoked by increased motor nerve activity. Recently, the calcineurin (CaN) signaling pathway has been implicated in the transcriptional regulation of slow muscle fiber genes. Here we investigated the effect of treatment with a CaN-specific inhibitor, FK506, on skeletal muscle fiber-type transition in functionally overloaded muscles. The overloaded plantaris muscle showed fast-to-slow muscle fiber type transition, i.e., a decrease in myosin heavy chain (MHC) IIb, an increase in MHCIIa+d/x, and new expression of MHCI. In the FK506-administered group, however, overload-induced muscle fiber-type transition was completely prevented. We have demonstrated, therefore, that the CaN signaling pathway is required for fast-to-slow skeletal muscle fiber-type transition. Furthermore, we also confirmed that the protein expression levels of downstream effectors of CaN signaling exhibit a transient increase in the early phase of the overloaded condition.
Animals↗
Genetic variation in hypoxia-inducible factor 1alpha and its possible association with high altitude adaptation in Sherpas.
Hypoxic stress at high altitude requires adaptations in several physiological functions to ensure the optimal oxygenation of all cells. Several lines of evidence suggested that high-altitude native populations such as Sherpas have been genetically adapted to their stressful environment. We investigated the genetic variation in the hypoxia-inducible factor (HIF)-1alpha gene in Sherpas as compared with Japanese, native lowlanders, and found a novel dinucleotide repeat polymorphism in intron 13 of the HIF-1alpha gene. GT15 allele was more frequent in Japanese than in Sherpas with statistical significance, while GT14 allele was significantly more frequent in Sherpas as compared with Japanese. A possible genetic variation in the HIF-1alpha gene might function in adaptation to living at high altitude. Because the activity of HIF-1 is regulated by multiple steps including the transcriptional level, the effect of the polymorphism in intron 13 on the cellular hypoxic responses remains to be elucidated.
Adaptation, Physiological↗
Intermittent hypobaric hypoxia increases the ability of neutrophils to generate superoxide anion in humans.
1. We investigated the effect of intermittent exposure to hypobaric hypoxia on the ability of neutrophils to generate.O2-. 2. Seven male volunteers were exposed intermittently to hypobaric hypoxia, equivalent to an altitude of 4500 m, for 7 successive days. Peripheral blood samples were collected before and after the 2 h course of hypobaric hypoxia on days 1 and 7 and neutrophils were subjected to a chemiluminescence assay for.O2- production. 3. On day 1, 2 h exposure to hypobaric hypoxia induced granulocytosis (P < 0.01), but the ability of neutrophils to generate.O2- was unchanged. 4. On day 7, such granulocytosis was not observed, suggesting acclimatization to hypobaric hypoxia. 5. The ability of neutrophils to generate.O2- was significantly increased on day 7 (P < 0.01), although there was no definite change in the mRNA expression of NADPH oxidase subunits in the cells. 6. The results suggest that the ability of neutrophils to generate.O2- may be gradually potentiated by intermittent exposure to hypobaric hypoxia, even after the number of neutrophils in peripheral blood stabilizes.
Adult↗
Negative regulation of LPS-stimulated expression of inducible nitric oxide synthase by AP-1 in macrophage cell line J774A.1.
The level of NOS II mRNA was markedly increased during 24 h lipopolysaccharide (LPS) stimulation, but showed no further increase thereafter. On the other hand, the level of NOS II mRNA in J774A.1 cells transfected with an expression vector containing the rat csk cDNA (J.Csk) was significantly increased during 3 h LPS stimulation, but rather decreased thereafter. Although no significant difference was observed in the activation of NF-kappaB by LPS among parental J774A.1, J774A.1 transfected with promoterless vector (J.pBK), and J.Csk cells, activity of c-Jun N-terminal kinase (JNK) and nuclear translocation of nuclear factor activator protein-1 (AP-1) were markedly upregulated in the J.Csk cells. Then luciferase reporter vectors containing NOS II promoter with mutations in two AP-1-like sites (U site, -1126 approximately -1120; L site, -524 approximately -518) were transiently transfected in J774A.1 cells. The promoter activity following LPS stimulation for 24 h was significantly increased by mutation at the L site, but not by mutation at the U site, suggesting that NOS II expression is negatively regulated, at least in part, through the AP-1-like L site in response to LPS.
Animals↗
Activation and apoptosis of murine peritoneal macrophages by acute cold stress.
Effects of acute cold stress (5 degrees C for 24 h) on the functions of peritoneal macrophages and the mechanisms for controlling host homeostasis were investigated in mice. Phagocytic activity and expression of the cell surface adhesion molecule CD11b/CD18 were markedly increased in peritoneal exudate cells by acute cold stress. These alterations were attributable to an increased number and phenotypical changes of adherent cells from acute cold-stressed mice. On the other hand, a lipopolysaccharide-induced activity of src-family tyrosine kinase Fgr, an expression of interleukin-1beta (IL-1 beta) mRNA, and a bioactivity of IL-1 in the culture supernatants of adherent cells from acute cold-stressed mice were markedly lower than those from control mice. A time course study revealed that the number of adherent cells in peritoneal exudate cells was markedly increased in mice exposed to cold for 24 h but returned to normal numbers when mice were exposed to cold for 72 h. DNA fragmentation and Annexin-V(+) cells were observed in peritoneal exudate cells from acute-cold stressed mice. Thus, cold stress activated macrophages but these macrophages were destined to be eliminated by apoptosis.
Animals↗
Wide use of skin-lightening soap may cause mercury poisoning in Kenya.
In a previous study, we speculated that some of the high mercury levels observed in head hair from a total of 14 subjects who resided around Lake Victoria, Tanzania, might be attributable to the habitual use of toilet soap containing considerable amounts of mercury (Harada et al. Sci Total Environ 1999;227:249-256). In August 1998, the current study was conducted to investigate if such mercury-containing soap was also available in the surroundings of Lake Victoria, Kenya, and if so, its toxic effects. A total of nine goldminers, 44 fishermen and their families, and 12 residents of Kisumu City, Kenya, volunteered for the study. Fourteen types of toilet soap were collected in Kisumu. Total mercury content was very significantly higher than in European-made soap (0.47-1.7%, as mercury iodide) compared with Kenya-made soap (0.41 x 10(-4)-6.2 x 10(-4)%). Indeed, all the subjects with a high hair mercury level (> 36.1 ppm) had made habitual use of European-made soap, accompanied by various symptoms, such as tremor, lassitude, vertigo, neurosthenia, and black and white blots, suggesting inorganic-mercury poisoning. On the other hand, any subject who had used soap other than the European-made soap, did not exceed a mercury level of 10 ppm in hair that is well within normal limits (Harada et al. Sci Total Environ 1999:227:249-256). The findings obtained suggest that the mercury-containing soap must be barred from circulation without delay, and that the residents' health in addition to the environmental pollution in Lake Victoria (Kenya as well as Tanzania) should be kept under close observation.
Adult↗
Mercury pollution in the Tapajos River basin, Amazon: mercury level of head hair and health effects.
There is increasing concern about the potential neurotoxic effects of exposure to methylmercury for the 6 million people living in the Amazon, even in regions situated far away from the gold mines (garimpos), considered to be the major source of mercury pollution. In November 1998, a spot investigation on mercury contamination was conducted in three fishing villages (Barreiras, Rainha, and Sao Luiz do Tapajos) on the Tapajos River, an effluent of the Amazon, situated several hundred kilometers downstream from the gold-mining areas. A total of 132 fishermen and their families volunteered for the current study. As was anticipated, the total mercury levels in the head hair collected from the fishing villages were relatively high (14.1-20.8 ppm on the average) and the number of subjects with a high total mercury level over 10 ppm (the least upper bound of a normal value) was 103 (78.0%) in total, along with various symptoms, thereby suggesting wide mercury contamination in the Tapajos River basin. Moreover, in view of the absence of other diseases (e.g., alcoholism or malaria), a high intake of fish containing a methylmercury level, and high hair mercury levels in addition to the various symptoms such as sensory disturbance (especially glove-and-stocking type, which is characteristic of Minamata disease), tremor, failure in two-point discrimination, and slight balancing failure, several subjects examined were diagnosed with mild Minamata disease. The findings obtained suggest, thus, that the mercury pollution in the Amazon should be crucially observed for head hair mercury level and health in a much broader region.
Adolescent↗
Changes in the tissue and plasma superoxide dismutase (SOD) levels in a burned rat model.
To examine whether thermal injury alters the superoxide dismutase (SOD) concentrations in various types of tissue or plasma, we studied the plasma and tissue Mn- and Cu/Zn-SOD levels in a rodent burn model. The animals were resuscitated with saline (50 mg/kg, i.p.) immediately following thermal injury and thereafter were sacrificed at either 6 or 24 hours post-burn. The Mn- and Cu/Zn-SOD levels were measured using an enzyme-linked immunosorbent assay (ELISA). The plasma Mn- and Cu/Zn-SOD concentrations significantly increased 6 hours after the injury and positively correlated with the burn size. The kidney Mn-SOD concentrations were significantly higher 24 hours after the injury in the animals with 30% burns than in those with either sham or 50% burn injuries. The lung Cu/Zn-SOD concentrations were also significantly higher 6 hours after the injury in animals with 30% burns than in the other two types above. These findings suggest that the changes in the SOD concentrations after burn injury vary according to the type of SOD and also the type of tissue. As a result, the SOD concentrations may play some role in the early response to thermal trauma.
Animals↗
Inhibition of adipocyte lipolysis by papaverine: papaverine can inhibit the redistribution of hormone-sensitive lipase.
Papaverine, despite being a potent phosphodiesterase inhibitor, actually blocks adipocyte lipolysis. The present study was designed to clarify the mechanism of the inhibitory effect of papaverine on lipolysis. Lipolysis, stimulated by either 10 microM isoproterenol or 5 mM dibutyryl cAMP, was significantly inhibited by papaverine (100 microM and above). Papaverine, however, did not affect the isoproterenol-induced increase in the protein kinase A (A-kinase) activity ratio. In cell-free extract from non-stimulated adipocytes, cAMP-stimulated A-kinase activities were almost completely blocked by H-89, a potent inhibitor of A-kinase, but not by papaverine. Thus, the inhibitory effect of papaverine on lipolysis could be responsible for a deficit in step(s) distal to A-kinase activity. Hormone-sensitive lipase activities in the infranatant fraction of centrifuged homogenates of cells, which were maximally stimulated with isoproterenol were significantly reduced. This result indicates that hormone-sensitive lipase redistributes from cytosol to its substrate in lipolytically stimulated cells. Papaverine completely blocked the isoproterenol-induced decrease in lipase activity in the infranatant fraction. These results suggest that papaverine blocks lipolysis through its inhibitory effect on the redistribution of hormone-sensitive lipase.
Adipocytes↗
Epstein-Barr virus-negative high grade B cell lymphoma of donor origin developing 19 months after unrelated allogeneic bone marrow transplantation.
A 22-year-old man, in first complete remission of acute myelogenous leukemia, developed a high grade B cell lymphoma 19 months after an allogeneic bone marrow transplant (allo-BMT) from an HLA-identical unrelated donor. Biopsy of a cervical lymph node revealed a lymphoma that was negative for Epstein-Barr virus-encoded small nuclear RNAs (EBERs) in situ hybridization. Genotypic analyses identified the lymphoma to be of donor origin, and there was no evidence of the Epstein-Barr virus (EBV) DNA in the lymphoma by Southern blot analysis. The lymphoma went into complete remission, following four courses of combination chemotherapy, but relapsed after a month and the patient died of congestive heart failure. The patient was thought to be persistently immunosuppressed 11 months after cessation of immunosuppressants, and the lymphoma was thought to be induced by one or more factors other than EBV.
Adult↗
Effects of ageing on generation of ED2high major histocompatibility complex class II+ macrophages during cold stress.
The effects of cold stress (5 degrees C, 24 h) were investigated on the function and surface phenotype of peritoneal cells in the monocyte/macrophage lineage from young (8-10-week-old) and old (22-24-month-old) rats. The role of glucocorticoid (GC) in the immunomodulation by cold stress was also examined. The proportion of cells with a high density of ED2 (ED2high cells), expressing major histocompatibility complex (MHC) class II molecules, was significantly increased in peritoneal cells during cold stress in young, but not in old, rats. Antigen-presenting function was significantly higher in ED2high cells than in cells with a low density of ED2 (ED2low cells), thereby indicating that ED2high cells are at a functionally high level. While serum corticosterone concentration in old rats increased markedly after 3 h of cold stress, that in young rats did not vary substantially, and was followed by a significant decrease in both groups of rats after 24 h of cold stress. Administration of dexamethasone to young rats completely inhibited the increase of ED2high cells caused by cold stress. Meanwhile, the proportion of ED2high cells in young rats was significantly increased by adrenalectomy. Furthermore, nuclear translocation of a large amount of the GC receptor was observed in ED2low cells. These results suggest that cold stress enhances immune function in young rats, but not in old rats, and that the generation of ED2high cells are partly regulated by circulating GC level.
Adrenalectomy↗
Anaplastic osteosarcoma with abundant eosinophilic cytoplasm and minimal osteoid production.
A case of osteosarcoma with unusual microscopic features, occurring in the right proximal tibial metaphysis of a 12-year-old boy is reported. Radiographically, the tumor was ill-defined and purely osteolytic. On gross examination, the tumor was soft, fragile, spongy and red to brown in color. Microscopically, the tumor consisted of pleomorphic cells possessing abundant eosinophilic cytoplasm, including cells larger than 100 microm in diameter. The cells were arranged in a sheet, with few extracellular collagen fibers. Multiple sectioning of the specimens revealed a small amount of osteoid production. Immunohistochemical study revealed a positive reaction for vimentin and osteocalcin. Electron microscopic study suggested the fibroblastic or osteoblastic origin of the cells.
Antineoplastic Combined Chemotherapy Protocols↗
Extracellular superoxide dismutase in tissues from obese (ob/ob) mice.
We have examined the protein content and gene expression of three superoxide dismutase (SOD) isoenzymes in eight tissues from obese ob/ob mice, particularly placing the focus on extracellular-SOD (EC-SOD) in the white adipose tissue (WAT). Obesity significantly increased EC-SOD level in liver, kidney, testis, gastrocnemius muscle, WAT, brown adipose tissue (BAT), and plasma, but significantly decreased the isoenzyme level in lung. Tumor necrosis factor-alpha and interleukin-1beta contents in WAT were significantly higher in obese mice than in lean control mice. Immunohistochemically, both WAT and BAT from obese mice could be stained deeply with anti-mouse EC-SOD antibody compared with those from lean mice. Each primary culture per se almost time-dependently enhanced EC-SOD production, and overtly expressed its mRNA. The loss of heparin-binding affinity of EC-SOD type C with high affinity for heparin occurred in kidney of obese mice. These results suggest that the physiological importance of this SOD isoenzyme in WAT may be a compensatory adaptation to oxidative stress.
Adipose Tissue↗
Swimming training prevents generation of suppressor macrophages during acute cold stress.
PURPOSE: Acute cold stress induces suppressor macrophages expressing large numbers of receptors to Fc portion of immunoglobulin G (MAC-1+ Fc gammaRII/IIIbright cells), resulting in suppression of splenocyte mitogenesis. The generation of MAC-1+ Fc gammaRII/IIIbright cells is partly mediated by increased glucocorticoid levels during acute cold stress. The aim of the current study was to investigate the effect of swimming training on the generation of the MAC-1+ Fc gammaRII/IIIbright suppressor macrophages by acute cold stress. METHODS: The trained mice underwent a 6-wk endurance swimming training (5 times/wk) in water at 35-36 degrees C for 90 min. The swimming training significantly increased brown adipose tissue mass, suggesting improved cold tolerance. Actually, when the swimming-trained mice were exposed to 5 degrees C for 3 h (acute cold stress), the rectal temperature was not decreased. The proportion of MAC-1+ Fc gammaRII/IIIbright cells in peritoneal exudate cells from swimming-trained mice was significantly lower than that from control mice. In addition, the proportion of MAC-1+ Fc gammaRII/IIIbright cells in peritoneal exudate cell population from swimming-trained mice was unaffected by the acute cold stress. The swimming training significantly attenuated the increases in serum corticosterone levels in response to acute cold stress. These results suggested that swimming training not only improves cold tolerance but also inhibits the generation of suppressor macrophages under acute cold stress as well as under normal conditions.
Acclimatization↗
Effects of swimming training on three superoxide dismutase isoenzymes in mouse tissues.
The purpose of the present study was to investigate the effects of swimming training on the changes in three superoxide dismutase (SOD) isoenzymes in mice. The trained mice underwent a 6-wk swimming program (1 h/day, 5 days/wk) in water at 35-36 degrees C. Immunoreactive extracellular SOD (EC-SOD), copper- and zinc-containing SOD (CuZn-SOD), and manganese-containing SOD (Mn-SOD) contents and their mRNA abundance were determined in serum, heart, lung, liver, kidney, and gastrocnemius muscle. EC-SOD content in liver and kidney was significantly increased with training. After training, CuZn-SOD content rose significantly only in kidney but decreased significantly in heart, lung, and liver. Mn-SOD content showed a significant increase in lung, kidney, and skeletal muscle but a significant decrease in liver. In most tissues, however, the changes in SOD isoenzyme contents were not concomitant with those in their mRNA levels. The results obtained thus suggest that, except for kidney, the responses in mouse tissues of three SOD isoenzymes (protein levels and mRNA abundance) to swimming training are different and that kidney may be one of the most sensitive organs to adapt to oxidative stress during physical training, although the mechanism remains vague.
Animals↗
Age-associated increase of basal corticosterone levels decreases ED2high, NF-kappaBhigh activated macrophages.
The proportion of cells with a high density of ED2 (ED2high cells) in peritoneal cells from old rats was significantly lower than that from young rats. The expression of major histocompatibility complex class II (MHC class II) molecules, the antigen presentation, production of interleukin (IL)-1beta and IL-6, and nuclear factor-kappaB activity in ED2high cells were markedly higher than those in cells with a low density of ED2 (ED2low cells), although no significant difference was observed in the expression of MHC class II molecules and the antigen presentation between ED2high cells from young and old rats. Meanwhile, basal corticosterone concentration in serum and glucocorticoid (GC) receptor mRNA expression in peritoneal cells increased significantly in old rats. The proportion of ED2high cells was increased by adrenalectomy in young rats. Furthermore, nuclear translocation of GC receptor was observed in ED2low cells, whereas GC receptor was detected in cytoplasmic extracts from ED2high cells. These results suggest that the decrease in functional ED2high macrophages with age results in the age-associated decline of immune responses, which is regulated, in part, by the basal GC concentration.
Adrenalectomy↗