The Japanese journal of experimental medicine最新文献

Nonlethal thermal injury in mice results in rapid death by immediate injection of 10(3) viable P. aeruginosa in the skin of the burn sites. Resistance to the lethal burn combined with P. aeruginosa infection developed 24 h after initial thermal injury and reached maximal effect 7 days later; it then continued for at least 21 days. The optimal survival was achieved when the first thermal injury was made for 7 seconds at 350 degrees C. Increased resistance, but for a short period could also be obtained by injection of lipopolysaccharide (LPS) 1-4 days prior to the burn-P. aeruginosa infection. However, when the LPS was injected immediately after the burn-infection, the lethal effect was increased. The induction of late protection after thermal injury and bacterial infection was demonstrated with P. aeruginosa organisms only. Under similar schedule of thermal injury resistance was not induced by infection with Semliki forest virus. On the contrary viral infection increased the susceptibility of burned mice to a fatal outcome. Immune or natural antibodies were not elevated in the sera of post burn mice. Furthermore, delayed type hypersensitivity response, as evaluated by a footpad weight assay was inhibited and this inhibition persisted at least for 7 days post burn. The thymus weight and its lymphoid cell content in thermally injured mice decreased significantly 7 days post burn, whereas the weight of the spleen increased and it contained fewer lymphocytes per gram tissue. We suggest that endotoxin entering the systemic circulation post-burn might be one of the factors contributing to the early sensitivity and the late protection against the fatal P. aeruginosa burn-infection.

A cultured glioma cell line, SR-B10.A, which was derived from a brain tumor induced in an adult female B10.A mouse by Rous sarcoma virus (RSV), has been established. The morphological appearance of the tumor produced by s.c. inoculating SR-B10.A cells was analogous to an astrocytoma of human glioma. Glial fibrillary acidic protein as well as S-100 protein was positive in these SR-B10.A tumor cells. A population doubling time of the cultured cells was 18.5 hours. Chromosomal analysis revealed a defect in one of the sex chromosomes. Integration of RSV genome was proven to be positive in SR-B10.A cells. It was possible to generate cytotoxic effector cells in the syngeneic B10.A mouse against SR-B10.A. The tumor-bearing syngeneic hosts harbored a suppressor activity in the splenocytes. Although recombinant human tumor necrosis factor (rH-TNF) had no growth inhibitory effect on the SR-B10.A cells in vitro, the s.c. implanted and growing tumor regressed when rH-TNF was administered intratumorally several times. In addition, this anti-tumor effect was completely abrogated when the host mice were treated with wholebody x-ray irradiation prior to the tumor cells inoculation. In contrast, neither rH-TNF (i.v.) nor cyclophosphamide (i.p.) induced the regression of SR-B10.A, indicating that efficacy of the locally administered rH-TNF is dependent on the host immune mechanism. These results suggest that SR-B10.A is a potentially useful tumor model in evaluating efficacy of immunomodulators.

In a study of the role of atrial natriuretic peptide (ANP) in sodium homeostasis in experimental renal failure, we found that a infusion of ANP at 0.25 microgram/min for 15 min produced an increase in the glomerular filtration rate (GFR) and fractional excretion of sodium (FENa) in five-sixth nephrectomized (5/6 Nx) rats. Renal vascular resistance (RVR) was lower during the base-line period and did not change after the administration of 100 ng/ml ANP to isolated perfused kidney (IPK) from adriamycin-treated rats. Furthermore, fractional excretion of ANP (FEANP) by IPK decreased in kidneys from adriamycin-treated rats as compared to that in kidneys from control rats. Finally, after 5/6 Nx, levels of plasma immunoreactive ANP (ir-ANP) gradually increased but excretion of water and sodium did not change during normal intake of sodium. The increase in levels of ir-ANP was accompanied by an increase in the rates of excretion of water and sodium was observed 2 days later but these rates returned to the base-line values after 2 weeks. These findings suggest that ANP plays an important role in the adjustment of acute changes in the volume of extracellular fluid during experimental renal failure.

Ultrastructure of schistosomula of Schistosoma japonicum was studied in relation to the effect of mouse neutrophils in vitro. In the presence of antibody and complement, damage to the schistosomular tegument covered with many neutrophils began to appear within 1 h incubation. Exfoliation of the granular cytoplasm of the tegument, disorganization of the muscle layers and vacuolation in the inner tissues were seen in a part of neutrophil-attached parasites by 2 h incubation. However, the majority of schistosomula with fewer cells retained their integrity till 16 h. The cytochemical examination of schistosomula incubated with mouse neutrophils for 1 and 2 h demonstrated clearly the localization of the peroxidase activity on the surfaces of the cells and the parasites.

We have succeeded in the immunohistochemical demonstration of methamphetamine; and in the present study, we used this technique to determine the topographic distribution of exogenously administered methamphetamine in mouse major salivary glands. Positive reactions for methamphetamine were localized in the striated duct portion of the major salivary glands and granular duct in the submandibular glands. Time course of the decrease in immunohistochemical reactivity of the ducts was very similar to that for reported methamphetamine levels in plasma or saliva. These results show that through the striated ducts of the major salivary glands and the granular ducts of the submandibular glands, MA is excreted into saliva; however, the mechanism by which MA is excreted into saliva is unknown.

In the endemic area of schistosomiasis on Bohol Island, we succeeded in locating seven new colonies of the vector snail, Oncomelania quadrasi, four in Trinidad and three in Talibon, in addition to six locations from which the snails were previously recorded. We were led by the proximity of the snail habitat to the residence of the infected individuals. In northern Bohol the continuous wet season would appear to make the major differences between the places that do and those that do not support O. quadrasi. Twice-yearly weed clearance and applying chemical molluscicides (niclosamide and phebrol) for the control of O. quadrasi have been extensively in effect over the snail colonies, since July 1986. Although it has not yet yielded satisfactory results in certain colonies, snails have been eliminated from six habitats in a period of two and a half years.

A warm water-extract (ECS) prepared from dried Cordyceps sinensis (Berk.) Sacc., a Chinese traditional medicine, was tested for antitumor activity in vivo and in vitro. Ehrlich ascites carcinoma cells (EAC), allogeneic to ICR mice and Meth A fibrosarcoma (Meth A), syngeneic to BALB/c mice were used as the target tumor cell lines. Mice were inoculated i.p. with 1 x 10(6) EAC or 1 x 10(5) Meth A on Day 0, and ECS or saline (control) was injected i.p. to the mice from Day 1 to Day 4. ECS-treatment increased the median survival time of the allogeneic mice inoculated with EAC to 316% of the control. Eight of the 10 ECS-treated mice survived on the 60th day (Day 60) after EAC implantation. ECS-treatment also increased the median survival time of the syngeneic mice inoculated with Meth A to 312% of the control. Half of the ECS-treated mice survived on Day 60. On the other hand, no cytotoxic effect of ECS was found on either EAC or Meth A in vitro. The antitumor effect of ECS seen in the allogeneic mice was significantly reduced when the mice received whole body X-irradiation (5 Gy) before EAC implantation. These results suggest that the antitumor effect of ECS may be mediated through its immunomodulating action.

Ciclosporin A (CYA) is a newly developed immunosuppressant and has a sparing effect on suppressor cell regulatory mechanism. However, accumulation of experimental animal studies has not been enough for the administration of CYA to human autoimmune diseases such as lupus nephritis. In this study, the histopathological aspects of the kidney in (NZB x NZW)F1 mice after administration of CYA were analysed. A dose of 25 mg/kg/day of CYA was injected intraperitoneally so that serum level of CYA was controlled from 250 to 300 ng/ml with this dosage. Typical histopathological changes of lupus nephritis including wire-loop lesions were observed in the kidney of the non-treated control group. In contrast, only few lesions were demonstrated in the CYA-treated group. These results suggest that CYA prevented the renal deterioration in lupus mice.

Antibodies to group A streptococcal polysaccharide were estimated in the following groups of patients: (I) Patients with uncomplicated streptococcal pharyngitis: 10 patients, followed up for 3 months. (II) Patients with acute rheumatic fever: 8 patients with first attack followed up for one year. (III) Patients with reactivated rheumatic heart disease: 10 patients, followed up for one year. (IV) Patients with chronic rheumatic heart disease: followed up for one year. (V) normal controls without any history of sore throat/fever/vaccination/rheumatic disease: 10 patients followed up for one year. Group (I) patients did not show any significant elevation in anticarbohydrate antibodies by both ELISA and RIA. In the case of (III) and (IV), antibody levels were significantly higher as compared to group (V) and remained so till one year of follow up. In group (II) patients there was no significant rise in antibody levels. There was a good correlation between the ELISA and RIA used to detect the antibody levels. These findings suggest that the use of ELISA to detect anticarbohydrate antibody can be of help in diagnosing cases of rheumatic heart disease (both acute and chronic RHD).

Monoclonal antibodies (Mabs) were raised to components of a DNA binding protein fraction obtained by using native and denatured DNA-cellulose column chromatographies of chick embryo extract. Indirect immunofluorescence microscopic analysis revealed that 3 Mabs, Pr-28, Pr-123 (or Pr-122) and Pr-192 react to nuclear antigens of proliferating cells. Part of the cell nuclei in chick embryo fibroblast culture were stained in speckled patterns by all three of the Mabs. It seems however that they are different clones judging from the following criteria; 1. Pr-28 crossreacts to a P3U1 cell surface antigen but Pr-123 (or Pr-122) and Pr-192 do not. 2. The rate of nuclei stained by Pr-122 is different from that of Pr-192 in both growing and quiescent cultures.