The Kitasato archives of experimental medicine最新文献

Oxygen free radicals and other oxygen derived species (Superoxide, O2-; Hydroperoxide, HOO; Singlet oxygen, 1O2-; Hydroxyl radical, OH; and Hydrogen peroxide, H2O2) including lipid peroxides have been suggested as important causative agents of aging and several human diseases, including cancer, multiple sclerosis, Parkinson's disease, autoimmune disease, ischemia, anemia, senile dementia, asbestosis and in thalassemia. This paper aims to communicate some of the theories and rationales in aging process and thalassemia.

We conducted an animal experiment to determine how dietary seaweeds rich in iodine and dietary fibers suppress radioactive iodine uptake by the thyroid, using mice and four kinds of experimental diets, three with 1% or 2% powdered fronds of the kelp Laminaria religiosa and 2% powdered laver Porphyra yezoensis, and one with cellulose. Iodine content of a hot-water extract of the kelp was 0.530 +/- 0.001%, and its dietary fiber (DF) values were 52.8 +/- 1.2%. Iodine in an extract of the laver was 0.008 +/- 0.001%, and its DF values were 41.4% +/- 0.7%. A statistically significant reduction of 125I uptake by the thyroid, 3 hours after intragastric administration of the radionuclide at a dosage of 18.5 kBq or 185 kBq in 0.3 ml aqueous solution per mouse, was observed in mice previously fed the experimental diets containing 1% and 2% kelp during periods varying from 24 hours to 7 days. The degree of the suppression was observed to depend on the amount of iodine in the diet or in the injected sample, no matter whether organic or inorganic, judging from the results of an additional experiment. Thus, we conclude that previously fed iodine-rich material, especially dietary seaweeds rich in iodine and other minerals, vitamins, and beta-carotene, such as kelps or laver supplemented with inorganic iodine, may be effective in prevention of internal radiation injury of the thyroid.

Relationship between depression of early protection against influenza virus infection and the decrease in the number of peripheral polymorphonuclear leukocytes in cyclophosphamide-treated mice was investigated using protein-bound polysaccharide (PSK), which had been shown to exert a potent restorative effect on leukocytopenia in immunocompromised hosts. Following intranasal inoculation with influenza virus (1.5 x 10(3) PFU) into untreated mice, the pulmonary virus titer progressively increased during 3 days and decreased gradually from the day 7 after infection. The treatment of mice with cyclophosphamide (150 mg/kg) 2 days before infection markedly enhanced the pulmonary virus multiplication from the early phase of infection, and the higher virus titer was maintained thereafter. When mice were given cyclophosphamide after PSK-treatment, virus titers from the early to late phases of infection were lower than those in untreated mice.

Two kinds of benzimidazoles, flubendazole and mebendazole were each administered at 10 mg/kg to rats harbouring the developing larvae of the rat lungworm, Angiostrongylus cantonensis 3 or 10 days post-infection and to those harbouring the adult worms 70 days post-infection. Almost all of the larvae were eliminated from the rats mediated 3 days post-infection. The larvicidal effects of the drugs administered 10 days post-infection were not so high as those 3 days post-infection. However, the growth of larvae in rats medicated 10 days post-infection were significantly inhibited as judged from their length, width and weight except the length of the larvae in rats given mebendazole. An inhibition of their growth was also demonstrated by the observation that no first-stage larvae were released from the rats medicated 10 days post-infection and examined 66 days post-infection at which the first-stage larvae were released from non-medicated rats. On the other hand, when the drugs were administered 70 days post-infection, no effects were seen on the number, body size and weight of recovered worms, and the release of the first-stage larvae. A sound conclusion was drawn that the developing larvae are more sensitive to the drugs than the adult worms.

The retinopathy (microaneurysm/small dot hemorrhage) is an early and specific biological indicator to quantitatively evaluate the CS2 exposure. The appearance of retinal lesions was observed among Yugoslavian, German and American workers exposed to CS2. However, among Finnish CS2 workers a positive result was not obtained. We suggested a different response to CS2 exposure between two ethnic populations. We had an opportunity to do a cross-sectional medical and occupational hygiene survey in a Chinese rayon staple plant. Cross-sectional medical examinations failed to show any chronic CS2 effects on the Chinese workers.

In our studies, it was demonstrated for the first time that HTLV-I gag and pX, and env and pX antigens are the target antigens recognized by CD8+ CTL in association with RT-1k and RT-1l class I antigens, respectively, in the rat system. Furthermore, the gag-expressing rVV and the env-expressing rVV were shown to have the potential to induce HTLV-I-specific CTL in WKA and LEW rats, respectively. These results suggest that, in general, HTLV-I structural and non-structural antigens can be recognized by CTL, and their immunogenicity for the induction of HTLV-I-specific CTL may be influenced by host MHC. Successful vaccination of mice against retrovirus tumorigenicity with the viral structural components has been demonstrated. As was the case with polyoma virus-induced tumors, utilization of rVV vectors containing HTLV-I genes for potential HTLV-I vaccines in humans may become possible if target antigens recognized by each recipient CTL can be identified prior to vaccination. Another vaccine candidate will be a synthetic peptide containing each CTL epitope. We are currently identifying the CTL epitopes, and recent results indicate that a major CTL epitope on the env-gene product is located between the env amino acids 101-112 (Tanaka et al., manuscript in preparation).

Two different types of monoclonal human immunoglobulins (M-components) with antistreptolysin-O (ASO) activity were investigated. The M-component FM with essential monoclonal gammopathy revealed to have an ASO activity, demonstrated not only by streptolysin-O neutralizing assay according to Ranz-Randall's method, but also by passive agglutination assays and precipitation on agar. The ASO activity was shown to reside in the Feb. These findings suggest that the M-component FM have a true antibody activity. On the other hand, ASO activity of M-component TT with multiple myeloma was detected only by streptolysin-O neutralizing assay, but the passive agglutinating assays and precipitation on agar showed no positive results. It has not been fully confirmed if the M-component TT behaves as a true antibody activity. Heterogeneity of the M-components with ASO activity was discussed.