[Mutation of virulence in pathogenic bacteria].
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Biomedical subjects
Publications and source records attributed to K Kanai.
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Intraacinar regionality in glycogen withdrawal during fasting was studied in the liver of the mouse. When animals were fasted from 10.00 a.m. onwards, glycogen withdrawal began in zone 1, spreading gradually to zone 3, and after 12 h glycogen disappeared throughout the acinus. After 24 h new glycogen accumulated in various portions of the acinus. However, when animals were fasted from 10.00 p.m. or 12 midnight to the following morning, glycogen was withdrawn evenly throughout the lobule. After 24 h glycogen disappeared throughout the acinus. These results show that there is a heterogeneity in the hepatocyte with respect to glycogen withdrawal during fasting by day but not by night. Therefore, the discrepancy in reported results on the intraacinar distribution of glycogen during fasting is probably due to the time of sacrificing animals.
The experience in Japan that pertussis was controlled by the nation-wide regular vaccination and that the reincrease of case notification occurred recently after the decrease of vaccine acceptance rate upholds the view that pertussis vaccine produced under the national control system is fully protective. Though the recent decrease of the vaccine acceptance rate was due to the public reaction to rather imbalaanced arguments concerning the vaccine risk, it is also true that a more potent and less toxic component vaccine is urgently needed at this moment.
Two kinds of fungal glucan, particulate yeast glucan (PYG) and lentinan, were examined for their immunopotentiating effect illustrated by reduced frequency of post-chemotherapy relapse in experimental mouse tuberculosis. Infected mice were treated by intensive chemotherapy with a three-drug combination [Streptomycin (SM) + isoniazid (INH) + rifampicin (RFP), ethambutol (EB) + INH + RFP, or SM + INH + pyrazinamide (PZA)] for 5 months. After termination of chemotherapy, the mice of each treated group were divided into three subgroups to receive or not to receive glucan for 4 weeks and again for 4 weeks after a month interval. During this 3-month period and the succeeding 5 months, the mice were subjected to occasional sacrifice to examine the growth of latent tubercle bacilli in the lung and spleen by cultivation of tissue homogenates. The results indicated that the regimens with SM + INH + RFP and EB + INH + RFP were highly effective in eliminating persistent tubercle bacilli down to undetectable levels. However, later multiplication of the latent bacilli was observed during the advanced postchemotherapy period. The application of PYG was most effective in prevention of this type of relapse in the spleen, but not so in the lung. Lentinan effect was manifested in the lung, but not in the spleen.
Tubercle bacilli were preincubated with the membrane fraction separated from casein-induced peritoneal exudate cells of guinea pigs, and subsequently exposed to exogenous phospholipase A2. Marked reduction in viable counts occurred in the incubation mixture at pH 5.6. The additional presence of cholesterol esterase, which alone was inactive, enhanced greatly the phospholipase A2-induced mycobactericidal activity of the fraction. Lipid analysis revealed degradation of phospholipids. The use of cell sap, in place of the membrane fraction, was not only ineffective in the same experimental system, but also neutralized the enzyme-induced activity of the latter. Bacteriostatic effect was also demonstrated in the enzyme-containing Kirchner semi-solid agar medium into which the bacilli were inoculated after being preincubated with the membrane fraction. An additional observation was that the mycobactericidal effect was also revealed when the artificial biomembrane (liposomes) prepared with phospholipids extracted from the exudate cells was used in place of the membrane fraction. These results support such an assumption that toxic fatty acids released from membrane phospholipids have an opportunity to kill the mycobacteria which are in close contact with the membrane.
The effect of BCG, an immunopotentiator, on the hepatocarcinogenesis of the rat induced by 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) was investigated. After administration of 3'-Me-DAB for 6 weeks, BCG was injected to the rats at 2-week intervals for 50 weeks and the serial determinations of serum alpha-fetoprotein and morphological examination of the liver were made. In the control group, the second rise of serum alpha-fetoprotein, which reflected the occurrence of hepatoma, was seen at about 12 weeks after discontinuance of 3'-Me-DAB. On the other hand, the second rise of serum alpha-fetoprotein in the group treated with BCG was delayed about 10 weeks compared to control group, although there was no significant difference in the final incidence of hepatomas between these two groups. Infiltration of the lymphocytes was observed in the liver of rats treated with BCG without hepatoma. BCG seems to have an inhibitory effect on 3'-Me-DAB carcinogenesis of the rat, possibly by stimulating the cell-mediated immunity, although it is not strong enough to prevent the occurrence of hepatoma completely.
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Hydrophobic protein (H protein) was isolated from membrane fractions of Bacillus subtilis and constituted into artificial membrane vesicles with lipid of B. substilis. Glutamate was accumulated into the vesicle when a Na+ gradient across the membrane was imposed. The maximum effect of Na+ on the transport was achieved at a concentration of about 40 mM, while the apparent Km for Na+ was approximately 8 mM. On the other hand, Km for glutamate in the presence of 50 mM Na+ was about 8 micro M. Increasing the concentration of Na+ resulted in a decrease in Km for glutamate, maximum velocity was not affected. The transport was sensitive to monensin (Na+ ionophore). Glutamate was also accumulated when pH gradient (interior alkaline) across the membrane was imposed or a membrane potential was induced with K+-diffusion potential. The pH gradient-driven glutamate transport was sensitive to carbonylcyanide m-chlorophenylhydrazone and the apparent Km for glutamate was approximately 25 microM. These results indicate that two kinds of glutamate transport system were present in H protein: one is Na+ dependent and the other is H+ dependent.
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Electron microscopic examination of the lung of mice infected with a virulent strain of M. bovis (Ravenel) revealed marked alterations in the alveolar epithelial cells, particularly Type 2 cells (granular pneumocytes), in addition to the development of interstitial and intra-alveolar granuloma. Unlike the feature in uninfected mice, more than one Type 2 epithelial cells were often found adjacent to one another within a single alveolus. Some of these cells showed mitotic figures. Their characteristic lamellar inclusions were morphologically altered.