Bioassay for neutron-dose estimations of three patients in the JCO criticality accident in Tokai-mura by measuring beta-ray emitters.

The measurement of beta-emitters in biological samples (hair, urine and bone) from three patients in the JCO criticality accident was performed to assess the neutron dose to individuals. The result of the measurements of 32P in hair and urine collected immediately after the accident showed that sufficient 32P activities had been induced in the hair by fast neutrons and in the urine by thermal neutrons to know the severity of the exposure to the individuals and to the position. From the measurement of 32P and 45Ca in bone from various anatomical parts of two patients who died 82 and 210 days after the accident, it was suggested that the distribution of the induced beta-emitters activities could prove the position and posture of the patients at the moment of exposure.

Decrease of erythropoiesis in the fetal liver of X-ray irradiated pregnant mice.

To accumulate fundamental knowledge about a possible relationship between severe mental retardation caused by in utero radiation exposure and impaired oxygen transport to fetal brain, the effect of X-ray irradiation on erythropoietic activity in fetal liver of C57BL/6J mice was studied in vivo and in vitro by measuring 59Fe uptake into heme and nonheme fractions of fetal liver. For the in vitro experiments, the mice were irradiated with X-rays at a dose of 189 cGy on day 9, 11, 13 or 15 of gestation. The day after irradiation, fetal livers were dissected, homogenated, and incubated with 59Fe-labeled mouse plasma. 59Fe uptake into the heme fraction of fetal liver was markedly reduced, depending both on the fetal developmental stage at the time of irradiation and the time that had elapsed since irradiation. In the in vivo experiments, pregnant mice were irradiated with X-rays at doses of 24 to 284 cGy on day 15 of gestation. The ratios of the amounts of 59Fe incorporated in the heme and nonheme fractions significantly decreased when mice were irradiated with more than 1 Gy. These results suggested that the necessary amount of oxygen may not be transferred to the fetal brain at the time required. The possible relationship between decreased fetal liver erythropoiesis and severe mental retardation is described.

The effect of OK-432 upon erythropoietic recovery in sub-lethally irradiated mice: a preliminary report.

OK-432, a multicytokine inducer and clinically used as an immunopotentiating anti-cancer agent, is known to induce IL-1 and TNF-alpha. The suppressive effect of IL-1 and TNF-alpha on erythropoiesis could limit the clinical use of OK-432 in cancer treatment, especially when combined with radiotherapy. In this study, the effect of OK-432 on normal and X-ray impaired erythropoiesis was examined. C57BL/6J mice were injected with a single dose of OK-432 (5.0 KE). Erythropoietic activity was measured by 59Fe incorporation into circulating erythrocytes and the heme iron fraction of erythropoietic tissue. When irradiated with 662 cGy of X-rays, OK-432 prolonged the survival of mice. No significant change in erythropoiesis was observed when normal mice were treated with OK-432. When treated with OK-432, the recovery of erythropoiesis after irradiation was promoted as judged by the uptake of 59Fe into erythrocytes. This promotion was observed when OK-432 was injected within 1 day before or within 3 hours after the irradiation with 284 cGy of X-rays. This promoting effect, however, appeared to be limited to the spleen. Whether the combination of OK-432 with radiotherapy has the potential to improve the treatment of malignant tumors is still a subject of controversy. The present results, nevertheless, suggest that when combined with radiotherapy, OK-432, at the very least, may have no adverse effects on erythropoiesis.

Pathology of rats intranasally inoculated with the cilia-associated respiratory bacillus.

Five-week-old Wistar/Ms rats were inoculated intranasally with a lung homogenate containing a strain of cilia-associated respiratory (CAR) bacillus and were examined on days 4, 7, 14, 21, 28 and 56 postinoculation (PI). Some rats showed clinical signs with wheezing and considerable body weight loss from day 21 PI. Gross lesions, including enlargement of lungs with focal atelectasis, bronchiectasis and emphysema, were observed from day 21 PI. Histologically, round cell infiltration was first present in the lamina propria of the nasal respiratory mucosa on day 7 PI. From day 14 PI, colonization of the CAR bacillus (4-8 micron in length), associated with round cell infiltration in the lamina propria and the peripheral regions, was observed in the ciliated mucosa of the bronchioles, bronchi, trachea and nasal cavities. Generally, the lesions progressed and expanded from upper to lower airways with time. Sporadic mucopurulent bronchopneumonia was observed from day 21 PI in some rats. The CAR bacilli (0.2-0.25 micron in diameter) were also demonstrated electron-microscopically in the ciliated epithelium of the intrapulmonary airways. The CAR bacillus antigen was demonstrated on the ciliated mucosa of the affected airways by the indirect immunofluorescence assay technique. Microbiological examination revealed that the rats used in this study were free from other known respiratory pathogens throughout the experimental period. Thus, it is suggested that the CAR bacillus alone can produce a murine respiratory disease. Fourteen days were needed for pathological lesions to develop.

Transmission experiments of cilia-associated respiratory bacillus in mice, rabbits and guineapigs.

Transmission experiments of cilia-associated respiratory (CAR) bacillus were performed in mice in order to clarify the principal route of the infection, and in rabbits and guineapigs in order to examine their susceptibility. Determination of the infection was evaluated serologically by the indirect immunofluorescence assay (IFA) technique and histologically by the presence of CAR bacillus in the airways. BALB/c mice were intranasally inoculated with the SMR strain of CAR bacillus. The IFA antibody to the bacteria in these mice rose to more than 1:160 at 4 weeks postinoculation (PI) and the mice were utilized as transmitters for the following experiments. One out of 15 uninfected mice kept in intracage contact with infected mice became infected from 4 weeks after contact. Incidence of contact infection increased thereafter. On the other hand, there was no evidence of infection in the uninfected mice housed in the separate cages from the cage in which infected mice were housed throughout the 12-week observation period. The primary method of CAR bacillus transmission seems to be direct contact with infected mice or fomites contaminated by infected mice; airborne transmission appears to be of little importance. Rabbits and guineapigs were also intranasally inoculated with the SMR strain of CAR bacillus. IFA antibodies were positively detected by 4 weeks PI, but no CAR bacillus nor histological changes relating to the infection were observed in the airways of either species. It is suggested that rat origin CAR bacillus can transmit to rabbits and guineapigs, and that the infection can spread to other species of rodents and rabbits.

Serodiagnosis of cilia-associated respiratory bacillus infection by the indirect immunofluorescence assay technique.

Antibody to cilia-associated respiratory (CAR) bacillus was detected by the indirect immunofluorescence assay (IFA) technique using tracheal sections of infected mice as antigen in serum samples collected from rats infected naturally and experimentally. Nine of 23 cases of natural infection were positive in IFA antibody, with titres ranging from 1:10 to 1:80, and all these antibody-positive cases were also histologically positive. The remaining 14 cases were negative in both IFA antibody and histological diagnosis, even though some of them were infected with Sendai virus and Mycoplasma pulmonis. In the experimental infection, serum samples collected from 18 rats on days 4, 7, 14, 21, 28 and 56 post-inoculation (PI) (three rats for each point) and examined for IFA antibody revealed that seroconversion occurred in one rat on day 14 PI and in three rats on day 21 PI. Antibody titres of 1:80 to 1:160 remained to the termination of the experiment. The IFA technique was useful for the diagnosis of CAR bacillus infection except in the early stage of the infection.