To assess the toxicity of the C1 compounds methanol and formaldehyde, gene expression profiles of treated baker's yeast were analyzed using DNA microarrays. Among approximately 6,000 open reading frames (ORFs), 314 were repressed and 375 were induced in response to methanol. The gene process category "energy" comprised the greatest number of induced genes while "protein synthesis" comprised the greatest number of repressed genes. Products of genes induced by methanol were mainly integral membrane proteins or were localized to the plasma membrane. A total of 622 and 610 ORFs were induced or repressed by formaldehyde, respectively. More than one-third of the genes found to be strongly repressed by formaldehyde belonged to the "protein synthesis" functional category. Conversely, genes in the subcategory of "nitrogen, sulfur, and selenium metabolism" within "metabolism" and in the category of "cell rescue, defense, and virulence" were up-regulated by exposure to formaldehyde. Our data suggest that membrane structure is a major target of methanol toxicity, while proteins were major targets of formaldehyde toxicity.
The effect of the heavy metal copper on the expression of a wide spectrum of genes was analyzed by using a DNA microarray. The gene expression profile of baker's yeast Saccharomyces cerevisiae grown in a medium containing a sublethal concentration of cupric sulfate was compared with that of yeast grown in a normal medium. Among approximately 6000 yeast ORFs, 143 ORFs were induced more than twofold to resist copper toxicity after exposure to copper. Copper metallothionein CUP1-1 and CUP1-2 were induced more than 20-fold. Some genes related to sulfur metabolism and oxidative stress response were also up-regulated. This DNA microarray analysis identified several molecular targets of copper toxicity.
Lactobacillus plantarum HOKKAIDO (HOKKAIDO strain) was isolated from well-pickled vegetables in Hokkaido, Japan. We report a randomized, double-blind, placebo-controlled study evaluating the effects of L. plantarum HOKKAIDO on immune function and stress markers in 171 adult subjects. Subjects were divided into three groups: the L. plantarum HOKKAIDO yogurt group, the placebo-1 group who ingested yogurt without the HOKKAIDO strain, and the placebo-2 group who ingested a yogurt-like dessert without the HOKKAIDO strain. Hematological tests and body composition measurements were performed before and after 4 and 8 weeks of blinded ingestion. Although no significant differences in natural killer cell activity were observed, it was found that neutrophil ratio significantly decreased and lymphocytes tended to increase in the HOKKAIDO strain yogurt group compared with the yogurt-like dessert group. In addition, the neutrophil-to-lymphocyte ratio, a stress marker, tended to improve in the HOKKAIDO strain yogurt group compared with the yogurt-like dessert group. These results suggest that the ingestion of HOKKAIDO strain yogurt tends to improve immune activity and decrease stress markers.
Recently, a series of cases of a central nervous system disease of unknown cause with extrapyramidal tract abnormalities as the most prominent feature occurred, mainly in fishermen's communities, on the periphery of Minamata City. Because the symptoms of the disease were unique and severe, and its prognosis was extremely poor, the disease caught immediate attention. In response to the request from the local Minamata Strange Disease Countermeasures Committee to investigate this disease, we visited this area many times since September 1956 and conducted a detailed epidemiological study, including face-toface interviews of 40 households with patients and 68 adjacent households without patients as control households. The results of the study are described below.
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