We sent a questionnaire to members of Yokohama Medical Association and Departments of University Hospital to get an overview of leprosy patients in the clinic.
Yokohama Medical Association: The rate of collection was approximately 47%. Few doctors have taken medical care of Leprosy patients. Half of the doctors will take medical care, but they have little information about Leprosy. Aged doctors do not take medical care compared with young doctors.
Departments of University Hospital: The rate of collection was approximately 74%. Doctors in the University Hospitals do not hesitate to take medical care of leprosy patients. Dermatologists actively take medical care and have a chance of getting information about leprosy.
It is necessary to give doctors information about leprosy and its history of stigma.

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The relation between diaminodiphenylsulfone (called dapsone)-resistance and point mutations of the dihydropteroate synthase (DHPS) gene was analyzed using dapsone resistant Mycobacterium leprae isolates derived from Japanese leprosy patients. The mutation was found at amino acid residues 53 or 55 of the DHPS. This finding suggests that two specific mutations in the DHPS gene involved in dapsone resistance of M. leprae.

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DNA sequences of Mycobacterium leprae in particular regions of the gyrA, rpoB, and folP genes responsible for resistance to new quinolones, rifampicin and dapsone, respectively, were analyzed. Among 88 isolates of M. leprae from leprosy patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines, eleven isolates had mutational changes in 2 genes (resistance to 2 drugs), and 2 isolates (Shinsei-1 and Zensho-4) showed mutations in 3 genes (resistance to 3 drugs). These findings are suggesting emergence of multi-drug resistant M. leprae.

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Thalidomide was developed in the 1950s as a sedative having only a low toxicity. However, McBride and Lenz reported in 1961 a close correlation between oral administration of thalidomide by pregnant women and a particular deformity (phocomelia) of their babies. In the 1990s, the biological activities of thalidomide were determined to include the control of tumor necrosis factor-alpha production and inhibition of angiogenesis. In 1994, Folkman et al. reported that thalidomide exhibited a strong inhibition of angiogenesis in their experiments with rabbits and that this effect had a significant relationship to phocomelia. They suggested a utility of thalidomide as a therapeutic agent for diseases that involve angiogenesis, particularly tumorous diseases. Furthermore, in 1994, Vacca et al. reported that the bone marrow of multiple myeloma (MM) patients was rich in blood vessels and that there is a causal relationship between the activity of MM and marrow angiogenesis. According to these data, thalidomide was tested in many countries as a new therapeutic agent for MM. In this review, new pharmacological availability of thalidomide is described on the basis of our experiences.

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Multinucleated giant cells (MGC) are characteristic cells in granulomatous disorders such as sarcoidosis and leprosy. There are two types of MGC; foreign body-type and Langhans-type cells. The exact mechanisms of the formation and the functional significance of MGC are not determined, although their morphological features are well understood. MGC are also formed in vitro from peripheral blood mononuclear cells by stimulation with cytokines and lectins. Particularly IFN-γ is considered to play a pivotal role in monocyte fusion. IL-3, IL-4, IL-13, and GM-CSF are other reported cytokines involved in MGC formation. In addition to such inflammatory mediators, a factor derived from the pathogens of granulomatous disorders may be necessary for MGC formation. Muramyl dipeptide, a peptidoglycan portion of bacterial cell walls, is one of the candidates and can preferentially induce Langhans-type cells in in vitro MGC formation system. Although the exact mechanisms of in vitro MGC formation remains unknown, cell surface molecules such as P2X₇ receptor, integrins, CD98, and macrophage fusion protein are considered to be involved in fusion process. Monocytes of sarcoidosis patients expressed higher levels of P2X7 and had a higher ability to induce MGC than those of healthy controls. Effective agents for sarcoidosis such as tranilast, alloprinol, and captopril inhibited _{in vitro} MGC formation, suggesting their therapeutic effects through the direct effects on monocytes . Thus, an in vitro MGC formation model would be a useful tool to understand the relevance of MGC in granulomatous disorders.

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As an obligate intracellular pathogen, the principal host cells for Mycobacterium leprae are mononuclear phagocytes or macrophages. The macrophage is a primitive cell type being found in both early and advanced life forms, and possesses a variety of functions, such as phagocytosis of invaded bacteria, production of cytokines, antigen presentation and tumor killing. Hansen's disease is a chronic infectious disease characterized by specific host immune responses against M. leprae. In this article the macrophage is focused to dissect its functions in the disease.

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Mycobacterial diseases, including tuberculosis, leprosy, and disease due to nontuberculous mycobacteria, are the major cause of death from infectious diseases around the world. About one-third of the world population is latently infected with Mycobacterium tuberculosis. Over 8 million new cases and nearly 2 million deaths occur each year. Tuberculosis presents a significant health threat to the world. The pathogenicity of mycobacteria is related to their ability to escape killing by ingested macrophages, latent infection, and induce delayed type hypersensitivity. This has been attributed to several components of the mycobacterial cell wall, such as surface glycolipids, lipoarabinomannan, complement activation factor, heat-shock protein, and mycobacterial DNA binding protein. From the aspect of my research interests, I have focused on mycobacterial glycolipids and mycobacterial DNA binding protein in this article. Surface molecules of mycobacteria exert pleiotropic activities in both the microbe and host, and thus participate in the pathogenesis of mycobacterial diseases. The better understanding of mycobacterial pathogenicity may open the new avenue for the development of therapeutic and prophylactic interventions.

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