Receptor-interacting serine/threonine kinase 2(RIPK2) is an adaptor molecule involved in the signal pathway of TLRs. However, there is no report on association between RIPK2 expression and infectious disease including mycobacterial disease in which TLRs play main role on interaction of infection. We evaluated relationship between Mycobacterium leprae and RIPK 2 by real-time RT-PCR. This study revealed that RIPK2 expression was down-regulated in the footpads and skin but was up-regulated in the liver, lymph node, and spleen of Mycobacterium leprae-infected nu/nu mice compared with those of non-infected nu/nu mice. It was observed that the IL-12p40, IFN-gamma, and IL-18 involved in the susceptibility of Mycobacterium leprae were down-regulated in the skin and footpad but up-regulated in the liver. These results suggest that regulation of RIPK2 expression is tissue-specific and is associated with M. leprae infection.
Animals ; Communicable Diseases ; Interleukin-12 ; Interleukin-12 Subunit p40 ; Interleukin-18 ; Liver ; Lymph Nodes ; Mice ; Mycobacterium leprae* ; Mycobacterium* ; Phosphotransferases ; Signal Transduction ; Skin ; Spleen

Apoptosis is an unique physiologic process of programmed cell death, playing an important role in the development and homeostasis of both normal and pathologic tissues. In mycobacterial infections, apoptosis of the macrophage is an important defense mechanism, which prevents the spread of the infection. The purpose of this study is to investigate whether apoptosis occurs in leprosy, and whether a positive correlation occurs among caspase-1, 3, 8, IFN-gamma, and iNOS among normal tissue, BT, and LL lesions. TUNEL staining and double immunohistochemical staining with anti-CD8, CD68 antibodies were done in paraffin-embedded tissue sections of 10 cases of paucibacillary leprosy and 8 cases of multibacillary leprosy. The mRNA expression of caspase-1, 3, 8, IFN-gamma, and iNOS was detected by RT-PCR analysis. The results are summarized as follows: 1. The number of apoptotic cells was 3.5+/-1.6 in paucibacillary leprosy and 6.1+/-3.7 in multibacillary leprosy. The difference was statistically insignificant. 2. Caspase-1 mRNA was expressed in order of LL, BT, and normal skin, and the differences were statistically insignificant. 3. Caspase-3 mRNA was expressed in order of LL, BT, and normal skin. Between LL and normal skin, the difference was statistically significant. 4. Caspase-8 mRNA was expressed in order of LL, normal skin, and BT, and differences were statistically significant. Especially, between LL and BT, the difference was statistically significant. 5. IFN-gamma mRNA was expressed in order of LL, BT, and normal skin. Between LL and normal skin, the difference was statistically significant. 6. iNOS mRNA was expressed in order of LL, BT, and normal skin. Between LL and normal skin, the difference was statistically significant. 7. Statistically significant positive correlation between caspase-1 and IFN-gamma, caspase-3 and iNOS, and caspase-8 and iNOS was found in normal tissue, BT, and LL. Statistically significant positive correlation between caspase-1 and IFN-gamma was shown in BT and LL. In conclusion, apoptosis exists in leprosy lesions and apoptotic cells expressing CD8 and CD68 positivity. Number of apoptotic cells in multibacillary leprosy lesions was insignificantly more than that of paucibacillary lesions. Agents inducing apoptosis such as caspase-3, caspase-8, IFN-gamma, and iNOS significantly increased in leprosy lesions, especially in LL lesions comparing to normal tissues. Apoptosis in the LL lesions might rather be an additive result to macrophage activation than play a defense role. Only the mRNA expression of caspase-8 significantly increased in LL lesions more than in BT lesions. So caspase-8 might be a major player of the apoptotic pathway in LL.
Antibodies ; Apoptosis* ; Caspase 3 ; Caspase 8 ; Cell Death ; Homeostasis ; In Situ Nick-End Labeling ; Leprosy* ; Leprosy, Multibacillary ; Leprosy, Paucibacillary ; Macrophage Activation ; Macrophages ; RNA, Messenger* ; Skin

Many futurists state that the rate of change that has happened around the world over the past 10 years is greater than at all other period's of time. The leading factor, irrelevant of an individuals knowledge, is the popularization of the Internet. People now can get large amounts of information at a very low cost. Popularization of information technology has changed the economic competitiveness from existing physical production capacity to information collecting and information processing power. . In other words, advanced products that have high added value, generated by collecting and processing technical information, are superior to products that are made physically. With respect to Hansen's disease, after MDT was introduced in 1980's, and WHO started to eliminate leprosy in 1991, Hansen's disease situation has changed in most of the world. However, using only the traditional information systems that were used in the past, it is difficult to cope with this situation. To improve and keep the competitiveness, it is necessary to keep pace with available changes in technology, and it is essential to establish flexible information system about the disease. To do this, we have to create new services. To create a new paradigm for dealing properly with changes in the management of Hansen's disease in the information society, I would like to introduce an information system. As part of the development of this system, I would like to introduce new material resources including an information system, human resources, databases, and network.
Automatic Data Processing ; Humans ; Information Systems* ; Internet ; Leprosy*

The method of cell lysate preparation of M. leprae is an important technique in the study of leprosy. This report describes the optimization of method for cell lysate preparation of M. leprae obtained from infected nude mouse. After M. leprae isolated from nude mouse foot-pad was disrupted by sonication, it was centrifuged and then whole lysate was prepared. With this method it was possible to isolate 0.3 mg whole cell lysate using 20 mg of M. leprae. By SDS-PAGE and Coomassie blue staining, the number of protein in M. leprae is less than that of other bacteria, for example, E. coli and M. smegmatis. It is likely that this is due to the small genome size. This work will contribute to the analysis of new protein antigen of M. leprae and the basic study for the development of vaccine in leprosy.
Animals ; Bacteria ; Electrophoresis, Polyacrylamide Gel ; Genome Size ; Leprosy ; Mice ; Mice, Nude* ; Sonication

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, which is an obligate intracelluar pathogen. It presents broad spectrum of clinical manifestations depending on the host's specific cell-mediated immune response to M. leprae. Especially, type I Th cells and macrophages are important in defense mechanism to M. leprae, and the immune response is regulated by cytokines secreted by immune cells. Recent investigations showed nitric oxide(NO) was the key molecule in the killing activity of macrophages, which was enhanced by IFN-gamma but suppressed by TGF-beta1 and IL-10. Since cytokine is secreted by activated immune cells with antigenic stimulation, decreased antigens by treatment modulates the expression of cytokines in leprosy. In this study, we observed the dynamics of cytokines expression using RT-PCR, such as TGF-beta1 and IL-10, which suppress the activity of macrophages, IFN-gamma, which activates macrophages, and iNOS, which represents the killing activity of macrophages, in the lesions taken from fifteen borderline lepromatous leprosy patients before and after multiple drug therapy for 4 weeks. The results are summarized as follows: 1. Before treatment, cytokines were expressed in order of IL-10, iNOS, TGF-beta1 and IFN-gamma(p>0.05). 2. After 4 weeks treatment, cytokines were expressed in order of iNOS, IL-10, TGF-beta1 and IFN-gamma(p<0.05). 3. Fifty-four percent of patients showed a non-polarized Th 0 pattern, 33% a polarized Th 1 pattern, and 20% Th-negative. Th 2 pattern was not observed. 4. The changes of cytokines expression after 4 weeks treatment were not significant, although mRNA of IL-10, TGF-beta1 and IFN-gamma were somewhat decreased. 5. There was negative correlation between TGF-beta1 and iNOS(gamma(2)=0.499, p<0.05, before treatment), positive correlation between TGF-beta1 and IFN-gamma(gamma(2)= 0.622, p<0.05, before treatment), and positive correlation between IFN-gamma and IL-10(gamma(2)= 0.935, p<0.05, before treatment; gamma(2)= 0.937, p<0.05, after treatment). In conclusion, these results suggest that TGF-beta1 and IL-10 may contribute to immune suppression in multibacterial leprosy patients, and that TGF-beta1 suppresses iNOS expression in macrophages. With 4 weeks treatment, the significant changes in cytokines expression were not observed. Interestingly, the majority of BL patients showed Th 0 pattern of cytokine, and none of Th 2 pattern.
Cytokines ; Drug Therapy ; Granulomatous Disease, Chronic ; Homicide ; Humans ; Interleukin-10* ; Leprosy* ; Leprosy, Multibacillary* ; Macrophages ; Mycobacterium leprae ; RNA, Messenger* ; Transforming Growth Factor beta1*

Leprosy is chronic infectious disease caused by Mycobacterium leprae, a microorganism to which only a small portion of any given population is susceptible. Although M. leprae can be found nearly anywhere in the body outside the central nervous system, even in the more severe types of leprosy it produces significant damage only in the superficial nerves, the skin, the anterior third of eye, the upper respiratory tract, and testis. Bacillary invasion of peripheral nerve commonly occur in leprosy patients and lepromatous neuropathy is treatable neuropathy in the world. So early detection of lepromatous neuropathy is important for social adaptation and prevention of life threatening complications. For differential diagnosis with other peripheral neuropathies, general overviews of peripheral neuropathies about anatomical, clinical, laboratory and diagnostic aspects of peripheral nervous system.
Central Nervous System ; Communicable Diseases ; Diagnosis, Differential ; Humans ; Leprosy ; Mycobacterium leprae ; Peripheral Nerves ; Peripheral Nervous System ; Peripheral Nervous System Diseases ; Respiratory System ; Skin ; Testis

Leprosy has turned out to be a minor health problem in Korea due to implementation of multidrug therapy, intensive case detection and mobile works for the villages for last 20 years. Even we have 20 new cases a year and national registry of 18,000, elimination of leprosy in Korea will require more decades in comparison with Japan, which seems to be an advanced country in leprosy work but still has new cases not more than 10 a year. As genome of M. leprae has unravelled to public in 2001, molecular biologic and genetic research work in leprosy area will progress rapidly near future. Range of leprosy research depends on the state of personal and grant resources in the nation. As Korea has only limited scientist, clinicians and financial support for research work to solve problems in leprosy. To maintain research capabilities and man powers in leprosy, it is reasonable to adjust our research works for priorities of the problems in leprosy work in Korea. Diagnosis, follow up and detection of drug resistance in new cases using molecular epidemiologic and genetic tools are one of high priorities in Korea. Management of neuritis and prevention of deformities on eyes, hands and foot of post-period of multidrug therapy appear to be an important area to improve the quality of life of the treated patients. Collaboration with researchers in tuberculosis, adoption of methods from them can expand research capacity and keep leprosy research alive in Korea.
Congenital Abnormalities ; Cooperative Behavior ; Diagnosis ; Drug Resistance ; Financial Support ; Financing, Organized ; Foot ; Genetic Research ; Genome ; Hand ; Humans ; Japan ; Korea ; Leprosy* ; Neuritis ; Quality of Life ; Tuberculosis

In 2005, we find 7 new cases and 5 relapse cases, diagnosis by the clinical finding, skin smear, skin biopsy, lepromin test, ELISA for PGL-I antibody, and DNA-PCR. The results obtained were summarized as follows: 1. In new cases, the mean age is 54.6, mean BI is 4.1+,and mean O.D. of PGL-I antibody is 0.866, and numbers of TTC repeat are 10(3 cases), 12(3 cases), and 11(1 case), and of GACATC repeats are 4(all Korean 5 cases) and 3(all foreigners 2cases). 2. In relapse case, the mean age is 65.0, mean BI is 4.6+,and mean O.D. of PGL-I antibody is 1.19, and numbers of TTC repeat are 11(2 cases), 12(1 cases), 13(1 case) and unknown(1 case), and of GACATC repeats are 4(all Korean 4 cases) and unknown(1 case).
Biopsy ; Diagnosis ; Emigrants and Immigrants ; Enzyme-Linked Immunosorbent Assay ; Humans ; Lepromin ; Leprosy ; Recurrence ; Skin

Claw hand deformity is caused by the lost function of intrinsic muscles and it is due to low median nerve and ulnar nerve palsy. Traumatic nerve injury and leprosy are the common cause of that deformity. Sensory loss is accompanied with claw hand deformity and the joint get stiffened by frequent trauma and it is followed by mutilated fingers. Surgical treatment of the claw hand restored the lost function of hand as well as recovered the inferiority complex of the deformed patient. The purpose of surgery is stabilized the hyperextended MP joint and Stiles-Bunnel and Brand operation are useful method.
Animals ; Congenital Abnormalities* ; Fingers ; Hand ; Hand Deformities ; Hoof and Claw ; Humans ; Joints ; Leprosy ; Median Nerve ; Muscles ; Ulnar Neuropathies

Chemotherapy is a main component of treatments for leprosy. The World Health Organization (WHO) recommends multiple-drug therapy (MDT) consisting of dapsone, clofazimine and monthly rifampin as the first-line drugs against leprosy. Minocycline, clarithromycin and certain fluoroquinolones can be used as substitutes in dapsone or clofazimine. For management of reactions, type I reactions should be treated with corticosteroids while thalidomide is the drug of choice for type II reaction. This review summarizes pharmacologic effects of drugs being used in leprosy including mechanisms of action, side effects, drug interactions and drug resistance.
Adrenal Cortex Hormones ; Clarithromycin ; Clofazimine ; Dapsone ; Drug Interactions ; Drug Resistance ; Drug Therapy ; Fluoroquinolones ; Leprosy* ; Minocycline ; Rifampin ; Thalidomide ; World Health Organization