The Kitasato archives of experimental medicine最新文献

Immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the rat forebrain were analyzed quantitatively as a possible model for the hypertension mechanism. The brain slices of spontaneously hypertensive rats (SHR) at 12 weeks of age were stained immunohistochemically for tyrosine hydroxylase and for calmodulin, and the distributions and amounts of these proteins were measured at 40-microns intervals by a fluorescence microphotometry system in comparison with those in normotensive control, Wistar Kyoto rats (WKY, the parent strain of SHR). Tyrosine hydroxylase levels in the neostriatum, nucleus accumbens, nucleus septi lateralis and tractus diagonalis, and calmodulin levels in the medial part of the neostriatum of SHR were lower than those in WKY. We reported previously that the decrease of the serum calcium level in SHR causes a decrease of the dopamine levels in the neostriatum and nucleus accumbens regions through a calmodulin-dependent system, and subsequent low levels of dopamine in the brain which may produce an increase in blood pressure. Combining this finding and our previous reports, we also suggest that the lower dopamine levels seen in the neostriatum and nucleus accumbens regions of SHR may result from the decrease in tyrosine hydroxylase and/or calmodulin levels in these regions in addition to the abnormality of calcium metabolism, and low levels of dopamine may produce an increase in blood pressure through functions of cerebral dopaminergic neurons and peripheral sympathetic nerves.

Characteristics of peritoneal macrophages recovered from mice infected with two attenuated strains SER and Jena of Salmonella enteritidis were compared. Strong resistance against lethal infection with a virulent strain 116-54 of S. enteritidis was seen in a group of mice immunized with strain SER, but not in a group of mice immunized with strain Jena as well as in a control group. Peritoneal macrophages from mice immunized with strain SER showed an enhanced Salmonella-killing activity, an increased generation of O2- and an increased expression of Ia antigen on 7 to 14 days after infection when compared with those from mice immunized with strain Jena and thioglycollate(TG)-elicited macrophages as a control. The bacterial number of strain Jena in organs decreased more rapidly than that of strain SER after day 4 of infection. These observations suggest that the survival of an attenuated Salmonella bacilli at reticulo-endothelium is essential to increase of their activities of macrophages. Macrophages from mice injected with recombinant interferon(IFN)-gamma for 3 days induced the activated stage of the same characteristics as noted in activated macrophages from mice immunized with strain SER. Effect of oxygen intermediates (OI) scavengers such as superoxide dismutase and catalase on Salmonella-killing activity of activated macrophages was not seen at all. These results suggest that an increased generation of OI may be not primarily responsible for the ability to inhibit the intracellular growth of a virulent strain of S. enteritidis in macrophages activated by immunization with live, attenuated strains and injection with rIFN-gamma.

A cytotoxic effect of antitumor agents (mitomycin C;MMC, adriamycin;ADM, bleomycin;BLM, 5-fluorouracil;5-FU, and cisplatin;CDDP) on ciliated epithelial cells of mouse tracheal organ cultures was studied in transmission electron microscopy. Mouse tracheal rings incubated with each agent in a concentration of 1 microgram/ml or 10 micrograms/ml were observed after 1, 2, and 20 hr of the incubation. After 2 hr, the ciliated epithelial with MMC or ADM of 1 microgram/ml exhibited appearance of lipid droplets in the nonciliated cells and the swelling of mitochondria and epithelial cells. Further incubation of 20 hr with those agents resulted in the pronounced degeneration including the ciliary subsidence into intracellular spaces, balloon-like ciliary swelling, and cellular destruction. Whereas, the ciliated epithelia with 5-Fu, BLM or CDDP did not show any notable change within 2 hr. After 20 hr, these exhibited the swelling of mitochondria, cilia and epithelial cells. The ciliated epithelia incubated with MMC or ADM of a greater concentration of 10 micrograms/ml showed remarkable cytotoxic effects after 1 hr of the incubation. The morphological changes in the epithelial cells with 1 hr incubation were almost similar to those of 20 hr incubation with the 1 microgram/ml. After 20 hr, the cellular degeneration proceeded to extremely flattened epithelial cells with disappearance of cilia and appearance of numerous vacuoles. Those with 5-FU, BLM or CDDP of 10 micrograms/ml exhibited ciliary swelling after 2 hr, but the morphological changes of 5-FU were more remarkable than those of BLM or CDDP. After 20 hr, the pronounced degeneration was observed, and it was similar to one of MMC or ADM of 2 hr incubation.

The intracellular potentials (ICP) of 42 visceronociceptive neurons related to stimulating greater splanchnic nerve (SPL) in Posterior group of thalamic nuclei (PO) were investigated. We analyzed the electrophysiological features, such as amplitude of resting potentials and action potentials of the neurons. Following acquisition of electrophysiological data, (HRP) was injected into 3 neurons, whose responses were inducted by stimulating SPL (related neurons) and able to be inhibited by morphine intravenously. Two neurons revealing spontaneous discharges but are not able to evoke response by stimulating SPL (non-related neurons), also were stained by HRP. Two kinds of neurons, related and non-related ones, display different dendrite branching patterns.

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.