[in Japanese]

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Infectious diseases account for more than 30% of deaths throughout the world, and we are increasingly faced with new and reemerging disease challenges. Infections caused by mycobacteria are the leading cause of death from infectious diseases around the world. Leprosy/Hansen's disease, caused by Mycobacterium leprae, primarily involves the peripheral nervous system and skin. Tuberculosis remains an important global health problem with approximately 1.9 billion people presently infected with M. tuberculosis. Infections with nontuberculous mycobacteria such as M. avium complex (MAC)constitute an important health problem, because most strains of MAC are resistant to antituberculous drugs. Mycobacteria are intracellular microbial pathogens. The infect macrophages cause chronic inflammation, such as granulomatous inflammation, and progressive scarring. Host defense against mycobacterial infection is controlled predominantly by the macrophage-cytokine-type 1 helper T (Th1) cell axis resulting in the expression of cell-mediated immunity. Development of cell-mediated, Th1 protective immunity to mycobacteria is considered a two-edged response, contributing to both clear-ance of infecting agents and tissue damage. In the second half of the 20th century, the conceptual approach to the management of established infectious diseases is antimicrobial chemotherapy. However, the successful implementation of antimicrobial chemotherapy is becoming increasingly difficult because of (1) an epidemic of immunocompromised patients, for whom antimicrobial therapy is less effective; (2) the emergence of new pathogens and the reemergence of old pathogens; and (3) widespread drug resistance. Antiinfective immunotherapy will be a new control strategy for mycobacterial diseases. It is also conceivable that therapeutic interventions to enhance the host immunity will be as effective as and possibly synergistic with antimicrobial drugs. We believe that the immune-based strategies will contribute to elimination of mycobacterial diseases.

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Leprosy in Federated States of Micronesia is still endemic with incidence rate 221/100, 000 and prevalence 33/10, 000 in 1996. The disease was introduced by the patients from Nauru. Epidemic of the disease was observed in Pingelap during the 1960's and Kpingamarangi sincel966.
Special project for the elimination of the disease by the chemoprophylaxis was launched in 1996. The preventive therapy is consist of one dose of an association of 3 antibiotics (rifampicin, ofloxacine and minocyclin) for adults and rifampicin alone for children. The project is completed for two years and followed by evaluation for 6 years. It is expected to reach the elimination level before year 2000.

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We examined the morphological changes of median nerve regeneration which situated to pass through degenerative latissimus dorsi and brachial triceps muscles in rabbits. Morphological observation was performed at 7, 14, 28, 45, 60 and 180 days after the creation of defect of the bilateral median nerves. Regenerative nerve fibers were observed in the residual tubes of left degenerative muscle bridges. In this respect the regenerative effect of the latissimus dorsi was better than that of the brachial triceps. These results suggest that regular and longer muscle fibers as those of latissimus dorsi may contribute to the effective regeneration of nerve.

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Not only in the experimental leprosy, primary aim to make every experimental model crucial for the medical research has been the simulation of the aspect of disease encountered in human case by the simplest possible way. The present study was conducted to do so making some variations in addition to the experimental lepromata, produced in nude mice by Sasaki et al, and by Hamit, utilizing a leproma-derived and cultivated Mycobaceterium HI 75 (HI-75). In this study HI-75, Mycobacterium bovip BCG (BCG) and female SPF ddY(ddY) were utilized to make experimental models. In addition to these combinations, the effect of the immunization of beta-glucuronidase binding protein (BGBP) to the lesion was also examined. The BGBP extracted from pisum sativum and utilized in this study shows cross-immunoreactivity with those of HI-75 and M Ieprae.
As the results, the lesions caused by HI-75 and BCG were somewhat resembling though HI-75 caused a little more extensive lesions especially in lymphocytic and monocytic infiltration. Also HI-75 caused distinct nerve lesions(NL) in which the bacilli were often encountered in the endoneurium but not in those by BCG. Contrarily in mice immunized with BGBP, the lesions were only a little milder and the affected tissue was a little fibrosed. However, in NL the solid form HI-75 were more often observed in the endoneurium.
The results indicated that the effect of BGBP immunization on the HI-75 induced lesion was not very clear by the present study alone, however, the proposed models itself should be and will become very useful, for experimental leprology with only slight modifications.

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The sequence of the polymerase chain reaction (PCR) product of 16S ribosomal RNA (l6S rRNA) of the leproma-derived and cultivable Mycobacterium HI-75 (M. HI-75) which was obtained from the infected regions of inoculated mice, was examined and compared with that of the cultured bacteria by the direct sequencing techniques. The sequence was completely consistent with the cultured bacilli in the comparable 837 bases of 16S rRNA. The mycobacterium examined in this study was originally isolated as M. leprae (ML) by Skinsnes, et al. in 1975 from leproma of a lepromatous type Hansen's disease patient and therefore named as Mycobacterium leprae HI-75 by them, and was maintained from 1984 using either Ogawa's or Sauton's media in the beginning and Ogawa's medium enriched with glucronic acid and N-acetyl-D- glucosamine recently. Sasaki and Hamit reported the nerve invasion and the growth of the inoculated bacilli either to the nude mice or the I131 treated immunocompromised Swiss mice. We previously reported that cultured HI-75 was most similar to M scrofulaceum by the direct sequencing of the gene of 16S rRNA. The 16S rRNA obtained from the mouse tissue in the present study indicated that M. HI-75 would be a variant of M. scrofulaceum possessing an ability to invade into peripheral nerve. The results suggest that the HI-75 strain claims a nature as a pathogen to develop a leproma-like lesion.

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An infection experiment with M. leprae was carried out using 20 nine-banded armadillos. As a result, the development of leprous lesions and a marked multiplication of AFB were confirmed in a high rate of 13 out of 15 cases (86.8%) in the inoculated groups. These changes were found to be progressing at post mortem of one case even with the shortest life period for 7.5 months and were very serious in one case with the longest life period for 33 months, suggesting the continuation of symptoms, though it is an expression neglecting the individual difference in susceptibility to leprosy.
Among infected viscera with AFB, the most conspicuous lesions were found in the liver and spleen. The developed lesions were found in the lung, stomach and kidney which had been never seen in HD in human cases, and so, which may characterize armadillos' leprosy.
The change in the peripheral nerve was not so severe when compared with that in HD in human cases. This difference will remain as a future pathological problem to be solved.

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Geriatric diseases have become significant problems in Japanese leprosariums. In particular, male osteoporosis seems to be more frequent in elderly leprosy patients than in non-leprosy elders. In 1987 we measured the cortical thickness of the 2nd metacarpal bone (MCI: metacarpal index) in 499 leprosy patients who were under medical treatment for osteoporosis. Of these patients, 139 were female patients with lepromatous leprosy (FL), 58 were female patients with tuberculoid leprosy (FT), 238 were male patients with lepromatous leprosy (ML) and the remaining 64 were male patients with tuberculoid leprosy (MT). The results were that the MCI of 238 ML was lower than 139 FL in the 4th, 5th 6th, and 7th decade of life. Furthermore the decreasing ratio of MCI peaked in the 4th decade was 70.6% between the ages of the 8th decade in ML. We conclude that this is a manifestation of leprosyspecific osteoporosis, which is associated with testicular dysfunction in elderly male patients with lepromatous leprosy.

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