Animal (mouse and guinea pig) pulmonary tuberculosis models were established, using an automated inhalation exposure apparatus (Glas-Col Corp., USA, Model 099CA-4212). This apparatus includes four steps-preheating, nebulization, cloud decay and decontami nation. The optimal conditions for M. tuberculosis H37Rv strain infection experiments were as follows: 105-6 colony forming unit (cfu) tubercle bacilli ; preheating for 15 min., nebulization for 90min.; cloud decay for 15 min. and decontamination foi 5 min. When 104cfu M. tuberculosis H37Rv strain were introduced into the lungs of interferon (IFN)-gamma knockout mice, using the inhalation exposure apparatus and were followed up for 9 months, the primitive cavitary lesions were observed. This apparatus was also useful for inhalation exposure experiments of guinea pigs. This apparatus can also be utilized for animal inhalation experiments of allergens.

抄録全体を表示

Annual incidence of Mycobacterium avium complex (MAC) pulmonary disease has beengradually increasing in the last 10 years in Japan, however, the optimal therapeuticregimen for the disease has not yet established. We investigated the effect of our newregimen in twenty seven cases of pulmonary MAC infection without HIV infection, diagnosed according to the American Thoracic Sociey criteria during the period fromJanuary 1996 to October 1997 at our hospital.These patients wee treated with rifampicin (RFP), ethambutol (EB) and clarithromycin (CAM) for more than 12 months, together with streptomycin (SM) initially (first 2-3months), except one patient who was treaed for 11 months only. Twenty-four monthsafter the therapy, sputum cultures converted from positive to negative in 13 patients andthe amount of bacilli in sputum reduced in two patients.The radiological findings improved in 10 patients, showed no significant changes in 11patients, while worsened in the remaining 6 patients. As to adverse reactions 1 case ofliver damage, 3 cases of skin disorders, 4 cases of gastrointestinal malfunctions, and 1case of optic neuritis were observed. This regimen was safe and tolerable even in theelderly outpatients, but not so effective against MAC pulmonary disease compared withthe results of recent reports from the U.S. and Europe. Size of pulmonary lesions wasclosely associated with the effectiveness in this study. However, five bacteriologicallyconverted cases did not show radiological improvement, and the reasons behind this factremain to be investigated.

抄録全体を表示

We examined profiles of intramacrophagial growth of M. tuberculosis (MTB) when mouse peritoneal macrophages (MφOs) were infected with the organisms at day 0 or day 7 after in vitro precultivation, and obtained the following results. First, the growth rate of the virulent MTB H37Rv strain as well as attenuated H37Ra strain was slower in MO s which had been precultured for 7 days (MφOs [day 7]) than in freshly prepared Mφs without precultivation (MφOs [day 0]). The doubling time of MTB H37Rv was 2.2 and 2.9 days in MφOs [day 0] and MφOs [day 7], respectively, and that of MTB H37Ra was 2.9 and 3.6 days in MφOs [day 0] and MφOs [day 7], respectively. Second, MTBφmediated cytotoxicity in terms of the LDH release from infected MφOs was less marked in MφOs [day 7] than in MφOs [day 0], when they were infected with MTB of either the H37Rv or H37Ra strain. MTB H37Ra strain exhibited much weaker cytotoxic effects on host Mφs than did H37Rv strain. Third, when Mφs [day 7] were infected with MTB of either the H37Rv or H37Ra strain, they showed markedly lowered levels of reactive oxy gen intermediate (ROI) production than did Mφs [day 0]. In contrast, the reactive nitrogen intermediate (RNI) producing ability of MO s in response to MTB infection was not so markedly reduced in MφOs [day 7] from that of MφOs [day 0]. As mentioned above, the MφOs [day 7] did not permit accelerated growth of infected MTB, comparedto the MTB growth in the MφOs [day 0]. It thus appears that ROI played a trivial rolein the antimicrobial activity against MTB of murine peritoneal Mφs which had beenprecultured for long periods. Although it is regarded that RNI played more critical rolesin MφOanti-MTB activity than did ROI, the present results also suggest that other kindsof antimicrobial effectors are required in MφO antimicrobial activity against MTB organisms, particularly in the case of MφO s after prolonged in vitro cultiv

抄録全体を表示

I have engaged in the research on tuberculosis for 50 years, and lessons I have learnt during this period could be summarized in the following ten topics. First is great re search achievements by our predecessors on the establishment of socalled primary infec tion theory on the pathogenesis of TB, planning of TB control principles based on the theory and development of new technologies used for TB control, such as mass miniature Xray examination and BCG vaccination in 1920s and 1930s. TB control law was en forced in 1951, and the modern TB programme was initiated.Second, the field is a treasure house of interesting data. Several interesting data on TB soon after the World War II in Tokyo and a rural area were collected and analyzed from the mass health examination. Third, looking at the increase of tuberculin positivity with age, it was found that the tuberculin negativity decreased as the exponential function of age, and the current concept of the annual risk of TB infection was already developed in late 1940s. It was 18.1% in male and 11.6% in female in Tokyo in late 1940s. Based on this concept, age specific TB mortality was analyzed by the type of TB, and the rates of miliary TB and TB meningitis were similar to the rate of newly infected to the total population, while the rate of all forms could be divided into early and late death as shown in Fig. 1. Fourth, I suffered from TB by myself from 1951 to 1953, receiving first thoracoplasty in two stages under local anaesthesia, then right upper lobectomy and segmentectomy of superior segment of right lower lobe. From this experience, I learnt a lot about the psy chology and suffering of TB patients.Fifth, the importance of recognition of real magnitude of the problem in such a diseaseas TB in which many TB cases did not aware of their disease. The answer to this was thefirst TB prevalence survey in 1953 using stratified random sampling method, and based on the results of the survey, the mass health examination originally focussed on youth was expanded to the total adult population of Japan. Sixth, TB could be reduced rapidly by applying appropriately planned control programme. In big enterprises, the application of intensive casefinding programme brought about the rapid decline of severe TB cases, contributed to the increase of the productivity of the enterprises, thus to the rapidincrease of GDP of whole Japan, and the growing spiral between the improvement of health and the economic development was formed by successful TB control. In addition to the mass health examination, BCG vaccination and spread of appropriate treatment in the original TB control law, the registration and case management system and the more extensive application of hospitalization for infectious cases were introduced in early 1960s. Observing the proportion of TB care expenditure to the national medical expendi ture, it was 28% in 1954, and it dropped down to 0.4% in recently as shown in Fig. 2. The decline of TB in Japan during 1950s and 1960s was one of fastest in the world. Seventh, there had been marked differences in the prevalence of TB as well as the cover age and quality of TB programmes in several areas of Japan though it was often saidthat Japan is homogeneous country. To know the real status in various areas of Japan, a chart to express graphically the magnitude of TB and coverage and quality of TB pro grammes was developed (Fig. 3), and it was finally refined to the current form. Eighth, difficulty in changing existing programmes, and we are grateful for kind cooperation of Niigata Prefecture for making several new attempts.

抄録全体を表示