Tsuguyoshi Suzuki

Migration of granule neurons in cerebellar organotypic cultures is impaired by methylmercury

To examine whether abnormal migration of granule cells in the external granular layer during cerebellar development is in part of the etiology of fetal Minamata disease, organotypic culture of rat cerebellar slice was established. Migration of external granule cells pulse-labeled with bromodeoxyuridine (BrdU) toward the internal granular layer was inhibited by the presence of methylmercury (0-10 microM) in a dose-dependent manner. Nuclear condensation and DNA fragmentation visualized by the indirect immunofluorescence method with anti-BrdU antibody and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method indicated that a large fraction of cells in the external granular layer underwent apoptotic death in the slices treated with 10 microM methylmercury. Thus, methylmercury inhibits the migration of cerebellar granule cells in a model system for neural development. The impaired migration was a possible cause of the apoptotic death of external granule cells.

Trace elements in ribs of elderly people and elemental variation in the presence of chronic diseases.

Element concentrations in ribs obtained from elderly Japanese people (17 males and 28 females; mean age, 81.5 years) were determined by atomic absorption spectrometry (AAS), inductively coupled plasma atomic emission spectrometry (ICP-AES), and ICP mass spectrometry (ICP-MS). Nine elements--Na, Mg, P, K, Ca, Fe, Zn, Sr, and Pb--were determinable in most of the subjects by a combination of AAS and ICP-AES. The levels of these elements were generally comparable with those obtained in our previous study on ribs from younger Japanese. By the use of ICP-MS, Sn (median, 0.79 micrograms/g dry bone) and Ba (1.3 micrograms/g) were determinable in all of the subjects analysed (n = 35) and 18 other elements at lower concentration levels were also detected in some of the subjects. An exploratory statistical analysis was carried out to find element(s) of which level(s) in rib vary in the presence of degenerative chronic diseases, using information obtained from pathological autopsy reports and medical histories of the present subjects. It indicated that (i) Pb and Zn, (ii) Ba, and (iii) Sr levels in the ribs varied in the presence of cancer, cerebrovascular damage, and bone problems, respectively. The present results were discussed in relation to the results of the previous epidemiologic and experimental studies.

High Hair and Urinary Mercury Levels of Fish Eaters in the Nonpolluted Environment of Papua New Guinea

Hair and mercury concentrations of 134 fish-eating subjects in the Lake Murray area and 13 non-fish-eating subjects in the upper-Strickland area, Papua New Guinea, were studied. Hair mercury levels among the subjects in the Lake Murray area (mean = 21.9 micrograms/g, range = 3.7-71.9 micrograms/g) and urinary mercury levels (mean = 7.6 micrograms/g creatinine, range = 1.4-25.6 micrograms/g creatinine) were markedly higher than levels found in subjects from the upper-Strickland area (mean hair mercury = 0.75 micrograms/g, mean urinary mercury = 0.48 micrograms/g creatinine). Mercury intake of the fish eaters, estimated from mercury concentrations found in fish and from the observed amounts of fish consumed, was approximately 73 micrograms/d. Hair and urinary mercury concentrations were correlated significantly (r = .59), indicating that urinary mercury excretion was elevated because fish consumption was very high.

Cadmium-bound metallothionein induces apoptosis in rat kidneys, but not in cultured kidney LLC-PK1 cells.

The ability of cadmium-bound metallothionein(Cd-MT) to induce apoptosis was investigated in vivo and in vitro. Administration of purified Cd-MT (0.15 mg MT bound Cd per kg body weight) to the rat induces DNA fragmentation, a biochemical characteristic of apoptosis in the kidney at 16 h, which was detectable by ethidium bromide staining on an agarose gel. It was still detected 24 h after administration. Induction of apoptosis by Cd-MT was specific to kidney; it was not observed in cerebrum, cerebellum, heart, lung, liver, testis, dorsolateral prostate, and ventral prostate. In contrast, addition of Cd-MT (0.01-100 microM) to the cultured porcine kidney LLC-PK1 cells failed to induce apoptosis under the condition where cadmium chloride (10 microM) did. There was no additivity of induction of apoptosis by CdCl2 (10 microM) in the presence of Cd-MT (0.01-100 microM). To examine the effect of intracellular MT on cadmium-induced apoptosis in cultured cells, new cell lines were established, which constitutively produce MT, being termed as Cd(r)-LLC-PK1 cells since Cd-MT exogenously added had much less permeability to the cultured cells. Followed by exposure of wild-type LLC-PK1 cells to 50 microM CdCl2 for 24 h, the surviving cells(Cd(r)-LLC-PK1 cells) induce MT at the level of 1.9 microg/2 x 10(6) cells. In Cd(r)-LLC-PK1 cells, 10 microM CdCl2 failed to induce apoptosis, but 60 microM CdCl2 could exert the apoptotic response, indicating that intracellular MT which was induced by CdCl2 did not facilitate CdCl2-elicited apoptosis. Furthermore, chromatin in rat kidneys was condensed by Cd-MT, but not that in LLC-PK1 cells. Thus, Cd-MT induces apoptosis in rat kidneys, but not in the cultured renal cells, suggesting that the ionic form of cadmium was required for programmed cell death.

C-myc is not involved in cadmium-elicited apoptotic pathway in porcine kidney LLC-PK1 cells

Cadmium chloride can induce DNA fragmentation, a biochemical characteristics of apoptosis in renal epithelial LLC-PK1 cells. Studies of cadmium cytotoxicity demonstrated that cadmium activates c-myc transcription. In this study, we investigated whether c-myc is a necessary component of cadmium-induced apoptosis. By kinetic analysis, transient activation of c-myc transcript by cadmium occurred before DNA fragmentation was induced by the metal, indicating an apparent correlation between induction of c-myc mRNA and promotion of apoptosis. However, even when using actinomycin D to block transcriptional activation of c-myc, or antisense oligodeoxynucleotide complementary to c-myc to block translation of c-myc, cadmium could still induce apoptosis. Thus, our data show that cadmium elicits apoptosis by a mechanism other than regulation of c-myc expression: transcriptional activation of c-myc during apoptosis is not always involved in the cell-death events.

Lead in prehistoric, historic and contemporary Japanese: stable isotopic study by ICP mass spectrometry

Abstract Lead concentration and isotopic composition of prehistoric (middle and latest Jomon era, 2000–4500xa0BP, n =6), historic ( Edo era, 130–400xa0BP, n =10), and contemporary (died in 1987–88, n =15) Japanese bones, and deciduous teeth from contemporary Japanese children born during 1985–88 ( n =17) were analyzed by inductively coupled plasma mass spectrometry. Lead concentration was lowest in Jomon bones and was higher in rural Edo , contemporary, and urban Edo , in that order. Elevated Pb concentration in historic Edo people, as reported previously, was reconfirmed. The average isotopic ratios ( 207 Pb/ 206 Pb and 208 Pb/ 206 Pb) in excavated (prehistoric and historic) bones, contemporary bones, and deciduous teeth were different from each other. The contemporary bones had the least radiogenic composition (mean 207 Pb/ 206 Pb: 0.879; mean 208 Pb/ 206 Pb: 2.126) while the excavated bones the most (0.848; 2.098), and teeth intermediate (0.866; 2.111). The comparison with the literature data of isotopic compositions of environmental samples showed that the isotopic composition of the excavated bones was within the range of Japanese ores, rocks and soils, indicating the absence of foreign Pb sources in preindustrialized Japan. That of the contemporary bones was closer to the average gasoline Pb, the use of which had been banned in the late 1970s, than to the Pb in airborne particulate matter or refuse incineration ash of 1980s. The average Pb isotopic ratios in the deciduous teeth was close to the isotopic ratios of Pb in airborne particulate matter and refuse incineration ash. These data indicated that the contemporary Japanese population was exposed to foreign Pb which had different isotopic composition from domestic Pb. Exposure to Pb of foreign origin was particularly evidently recorded in people born before the leaded gasoline ban. The history of human Pb contamination in Japan is discussed based on the present results and other previously published data.

Selective down-regulation of 440 kDa ankyrinB associated with neurite retraction.

BRAlN-specific isoforms of ankyrin, 440 kDa and 220 kDa ankyrinB, which are generated from a single gene by alternative splicing of pre-mRNA, are both expressed in human neuroblastoma NB-1 cells and the expression of the larger isoform is increased upon induction of neurite outgrowth. Exposure to methylmercury, a potent neurotoxic substance, at a sublethal dose induced dramatic retraction of neurites in NB-1 cells. Concomitantly, synthesis of 440 kDa ankyrinB polypeptide and mRNA were selectively attenuated in methylmercurytreated cells, while the 220 kDa isoform was not affected. These results indicate that the expression of 440 kDa ankyrinB is intimately associated not only with the neurite outgrowth but also with neurite retraction in neuronal cells, and is regulated at mRNA level.

Selenium intake status in an Andean highland population

Abstract Nutritional selenium (Se) status in an Andean population living at high altitude (4000 m above sea level) was examined using dietary Se (DSe) intake. Mean (±SD) DSe intake was 47.7±16 μg/day for adult males (19 years old and above), and 36.6±13 μg/day for adult females. Two-thirds of the subjects were found to consume less Se than the U.S. Recommended Dietary Allowance values. The DSe levels among the subjects examined were marginally lower compared to values reported from other areas of the world. Their blood Se (whole blood Se, erythrocyte Se and serum Se), however, appeared to be maintained at a relatively high level with respect to the marginally lower DSe intake.

Iron nutrition and anaemia in a malaria-endemic environment : haematological investigation of the Gidra-speaking population in lowland Papua New Guinea

Blood examination was conducted for the four Gidra-speaking village groups in Papua New Guinea, who were characterized by high Fe intake and high malaria prevalence with marked inter-village differences. The northern riverine villagers, whose Fe intake was higher than the other three village groups, did not suffer from Fe-deficiency anaemia in their malaria-endemic environment; nor did the inland villagers, with their second highest Fe intake and their malaria-free environment, suffer from Fe-deficiency anaemia. However, several individuals of the southern riverine village suffered from anaemia in a malaria-endemic environment, although their Fe intake was almost the same as the inland villagers. A considerable proportion of the coastal villagers were anaemic, reflecting the lowest Fe intake and the highest malaria prevalence. An inter-village comparison of the relationships between haemoglobin levels and transferrin saturation revealed that the southern riverine villagers needed smaller amounts of circulating Fe for erythropoiesis than the northern riverine and inland villagers, reflecting the long-term human-environment conditions such as the density of malaria vectors and the peoples dietary habits. Fe supplementation was not judged effective against hypoferraemia and/or anaemia in such a population. As the incidence of malaria had no significant long-lasting effect on Fe stores or circulating Fe concentration, but did have an effect on anaemia, the hypothesis that malaria causes a transfer of Fe from the blood to parenchymal tissues as a defence against infectious diseases was not supported.

Health Status Comparison by Urinalysis (Dipstick Test) Among Four Populations in Papua New Guinea

The health status of four populations depending on traditional subsistence in Papua New Guinea was compared by the dipstick test urinalysis. Conspicuous inter-population difference in the distribution of urinary pH was attributed to the levels of protein intake and the balances of sodium and potassium intake. The percentage of positive findings on protein differed by population along with the percentages of urobilinogen and bilirubin; the higher percentage of protein positives (12-16%) found in less urbanized populations suggests a high risk of hepatic and/or renal disorders in traditional societies. The very low percentage, 0.3 percent, of positive findings on glucose among 1, 132 urine samples tested indicated that diabetes mellitus was not yet the major problem. Simultaneously, however, the fact that glucose positives were found only in the most urbanized villages indicates increasing risk of diabetes even in the traditional populations during future urbanization. Asia Pac J Public Health1994; 7(3): 165-72.