To activate naïve T cells convincingly using Mycobacterium bovis BCG (BCG), rBCG (BCG-D70M) that was deficient in urease, expressed with gene encoding the fusion of BCG-derived heat shock protein (HSP) 70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed. BCG-D70M was more potent in activation of both CD4+ and CD8+ subsets of naïve T cells than rBCGs including urease-deficient BCG and BCG-70M secreting HSP70-MMP-II fusion protein. BCG-D70M efficiently activated dendritic cells (DC) to induce cytokine production and phenotypic changes, and activated CD4+ T cells even when macrophages were used as APCs. The activation of both subsets of T cells was MHC and CD86 dependent. Pre-treatment of DC with chloroquine inhibited both surface expression of MMP-II on DC and the activation of T cells by BCG-D70M-infected APCs. The naïve CD8+ T cell activation was inhibited by treatment of DC with brefeldin A and lactacystin so that the T cells was activated by TAP- and proteosome-dependent cytosolic cross-priming pathway. From naïve CD8+ T cells, effector T cells producing perforin and memory T cells having migration markers, were produced by BCG-D70M stimulation. BCG-D70M primary infection in C57BL/6 mice produced T cells responsive to in vitro secondary stimulation with MMP-II and HSP70, and more efficiently inhibited the multiplication of subsequently challenged M. leprae than vector control BCG. These results indicate that the triple combination of HSP70, MMP-II and urease depletion may provide useful tool for inducing better activation of naïve T cells.
{"title":"[Enhanced activation of T lymphocytes by urease-deficient recombinant bacillus Calmette-Guérin producing heat shock protein 70-major membrane protein-II fusion protein].","authors":"Masahiko Makino, Tetsu Mukai","doi":"10.5025/hansen.81.199","DOIUrl":"https://doi.org/10.5025/hansen.81.199","url":null,"abstract":"<p><p>To activate naïve T cells convincingly using Mycobacterium bovis BCG (BCG), rBCG (BCG-D70M) that was deficient in urease, expressed with gene encoding the fusion of BCG-derived heat shock protein (HSP) 70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed. BCG-D70M was more potent in activation of both CD4+ and CD8+ subsets of naïve T cells than rBCGs including urease-deficient BCG and BCG-70M secreting HSP70-MMP-II fusion protein. BCG-D70M efficiently activated dendritic cells (DC) to induce cytokine production and phenotypic changes, and activated CD4+ T cells even when macrophages were used as APCs. The activation of both subsets of T cells was MHC and CD86 dependent. Pre-treatment of DC with chloroquine inhibited both surface expression of MMP-II on DC and the activation of T cells by BCG-D70M-infected APCs. The naïve CD8+ T cell activation was inhibited by treatment of DC with brefeldin A and lactacystin so that the T cells was activated by TAP- and proteosome-dependent cytosolic cross-priming pathway. From naïve CD8+ T cells, effector T cells producing perforin and memory T cells having migration markers, were produced by BCG-D70M stimulation. BCG-D70M primary infection in C57BL/6 mice produced T cells responsive to in vitro secondary stimulation with MMP-II and HSP70, and more efficiently inhibited the multiplication of subsequently challenged M. leprae than vector control BCG. These results indicate that the triple combination of HSP70, MMP-II and urease depletion may provide useful tool for inducing better activation of naïve T cells.</p>","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30934050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
From among the materials of Masao Ota, in the Library of Tokyo University, a letter (1931) was found from Isamu Miyake, prof. of Dermatology, Kumamoto Medical College. Its contents was some information on Kaisyun Hospital (The Kumamoto Hospital of the Resurrection of Hope, leprosy hospital), A calendar (the 1930s) of Kaisyun Hospital was also found in Riddell & Wright's Memorial Museum. This calendar was written in English, and it was to ask for the British and American sponsors to contribute. It includes a lot of articles related to leprosy like Riddell's article. Some new findings related to leprosy at that time were recognized from this calendar.
{"title":"[Prof. Masao Ota was interested in Kaisyun Hospital of Kumamoto].","authors":"Tomomichi Ono","doi":"10.5025/hansen.81.209","DOIUrl":"https://doi.org/10.5025/hansen.81.209","url":null,"abstract":"<p><p>From among the materials of Masao Ota, in the Library of Tokyo University, a letter (1931) was found from Isamu Miyake, prof. of Dermatology, Kumamoto Medical College. Its contents was some information on Kaisyun Hospital (The Kumamoto Hospital of the Resurrection of Hope, leprosy hospital), A calendar (the 1930s) of Kaisyun Hospital was also found in Riddell & Wright's Memorial Museum. This calendar was written in English, and it was to ask for the British and American sponsors to contribute. It includes a lot of articles related to leprosy like Riddell's article. Some new findings related to leprosy at that time were recognized from this calendar.</p>","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30934052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The polymorphism of TTC repeats in Mycobacterium leprae was examined using bacilli from slit skin samples of leprosy patients attending at Central Special Skin Clinic, Yangon General Hospital and nasal swabs of their contacts to elucidate the possible mode of leprosy transmission. It was found that bacilli with different TTC genotypes were distributed among same household contacts and also harbored bacilli in patients were different TTC genotype from that harbored on the nasal mucus of the healthy contacts. Genotypes of TTC repeats were found to differ between husband under treatment and his wife and also mother under treatment and her sons living in same house. This study revealed that TTC genotype of bacilli harbored by household contacts was different with the TTC genotype by index cases. These results indicate that the family members get transmission from outside the dwellings rather than from commonly supposed their MB index cases. There might have been some infectious sources to which the populace had been commonly exposed outside the dwellings.
{"title":"Genotyping of Mycobacterium leprae in Myanmar and possible transmission modes.","authors":"Khin Saw Aye, Yin Thet Nu Oo, Kyaw Kyaw, Aye Aye Win, Masanori Matsuoka","doi":"10.5025/hansen.81.191","DOIUrl":"https://doi.org/10.5025/hansen.81.191","url":null,"abstract":"<p><p>The polymorphism of TTC repeats in Mycobacterium leprae was examined using bacilli from slit skin samples of leprosy patients attending at Central Special Skin Clinic, Yangon General Hospital and nasal swabs of their contacts to elucidate the possible mode of leprosy transmission. It was found that bacilli with different TTC genotypes were distributed among same household contacts and also harbored bacilli in patients were different TTC genotype from that harbored on the nasal mucus of the healthy contacts. Genotypes of TTC repeats were found to differ between husband under treatment and his wife and also mother under treatment and her sons living in same house. This study revealed that TTC genotype of bacilli harbored by household contacts was different with the TTC genotype by index cases. These results indicate that the family members get transmission from outside the dwellings rather than from commonly supposed their MB index cases. There might have been some infectious sources to which the populace had been commonly exposed outside the dwellings.</p>","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30934049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The objectives of this paper are to grasp the current status of an endemic disease in the Republic of Ghana known as Buruli ulcer(BU) and to clarify relationships between the National Health Insurance Scheme(NHIS) and the health care system. As for the method of the study, I have adopted field investigations conducted in Ghana in March, 2009 and August, 2011. All the counter-measurements on BU taken either by the very government or international NGOs have been administered and controlled the disease in accordance with the National Buruli ulcer Control Programme(NBUCP) under the guidance of Global Buruli ulcer Initiative which was established in Geneva, Switzerland in 1998 as an advisory committee of the World Health Organization. BU patients can receive treatments free. The government sponsored NBUCP and direct and indirect donations from various NGOs provide the cost of medical treatments. The Ghanian NHIS of 2003 aimed to ease and improve the health situations of the people. Some of serious endemic diseases like BU, however, are excluded from the schemes. While the NHIS remains ineffective to the diseases like BU, the burden of treatment costs puts the strain on NBUCP. The field researches indicate that the budgets provided by the NBUCP often faile to cover the fundamental medical supplies like bandages. This causes to give an extra burden on the already constrained hospital budgets. Only reliefs the hospitals can rely on are the international aids which often determine the fate of the national disease control. The research reveals that the region's health system remains unsound. Ghana represents such realities of West Africa as a whole.
{"title":"[Buruli ulcer and the National Health Insurance Scheme in Ghana].","authors":"Tomoki Niiyama","doi":"10.5025/hansen.81.185","DOIUrl":"https://doi.org/10.5025/hansen.81.185","url":null,"abstract":"<p><p>The objectives of this paper are to grasp the current status of an endemic disease in the Republic of Ghana known as Buruli ulcer(BU) and to clarify relationships between the National Health Insurance Scheme(NHIS) and the health care system. As for the method of the study, I have adopted field investigations conducted in Ghana in March, 2009 and August, 2011. All the counter-measurements on BU taken either by the very government or international NGOs have been administered and controlled the disease in accordance with the National Buruli ulcer Control Programme(NBUCP) under the guidance of Global Buruli ulcer Initiative which was established in Geneva, Switzerland in 1998 as an advisory committee of the World Health Organization. BU patients can receive treatments free. The government sponsored NBUCP and direct and indirect donations from various NGOs provide the cost of medical treatments. The Ghanian NHIS of 2003 aimed to ease and improve the health situations of the people. Some of serious endemic diseases like BU, however, are excluded from the schemes. While the NHIS remains ineffective to the diseases like BU, the burden of treatment costs puts the strain on NBUCP. The field researches indicate that the budgets provided by the NBUCP often faile to cover the fundamental medical supplies like bandages. This causes to give an extra burden on the already constrained hospital budgets. Only reliefs the hospitals can rely on are the international aids which often determine the fate of the national disease control. The research reveals that the region's health system remains unsound. Ghana represents such realities of West Africa as a whole.</p>","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5025/hansen.81.185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30934048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with highly bacillated lepromatous leprosy (LL) essentially lack T cell-mediated immune responses specific to Mycobacterium leprae (ML) antigens, resulting in severely impaired host resistance to leprosy bacilli. Such type of immune unresponsiveness characteristic of LL patients is mainly attributable to markedly depressed T cell ability to activate/expand in response to ML antigens. In this study, we examined profiles of antimycobacterial activity of macrophages, which phagocytized leprosy bacilli, because there is another possibility that, in LL patients, host macrophages in the leprosy lesions are impaired in their antimicrobial activity due to their interaction with infected leprosy bacilli, particularly cellular events through binding with and/or internalization of the pathogens, thereby causing the reduction in host resistance to ML pathogens. The present study indicated the following. First, the anti-M. avium complex activity of murine peritoneal macrophages was significantly reduced when they had phagocytosed heat-killed leprosy bacilli. Second, infection of macrophages with leprosy bacilli did not affect macrophage-mediated suppressor activity against T cell proliferative response to Concanavalin A. These findings indicate that macrophage's intracellular signaling pathways that are up-regulated in response to phagocytosis of leprosy bacilli are linked to the signaling cascades participating in macrophage antimicrobial functions, but not cross-talk with those allowing the expression of macrophage's suppressor activity against T cell functions.
{"title":"[Phagocytosis of Mycobacterium leprae down-regulates anti-microbial activity of murine macrophages against Mycobacterium intracellulare].","authors":"Yutaka Tatano, Chiaki Sano, Masako Emori, Hajime Saito, Katsumasa Sato, Toshiaki Shimizu, Haruaki Tomioka","doi":"10.5025/hansen.81.175","DOIUrl":"https://doi.org/10.5025/hansen.81.175","url":null,"abstract":"<p><p>Patients with highly bacillated lepromatous leprosy (LL) essentially lack T cell-mediated immune responses specific to Mycobacterium leprae (ML) antigens, resulting in severely impaired host resistance to leprosy bacilli. Such type of immune unresponsiveness characteristic of LL patients is mainly attributable to markedly depressed T cell ability to activate/expand in response to ML antigens. In this study, we examined profiles of antimycobacterial activity of macrophages, which phagocytized leprosy bacilli, because there is another possibility that, in LL patients, host macrophages in the leprosy lesions are impaired in their antimicrobial activity due to their interaction with infected leprosy bacilli, particularly cellular events through binding with and/or internalization of the pathogens, thereby causing the reduction in host resistance to ML pathogens. The present study indicated the following. First, the anti-M. avium complex activity of murine peritoneal macrophages was significantly reduced when they had phagocytosed heat-killed leprosy bacilli. Second, infection of macrophages with leprosy bacilli did not affect macrophage-mediated suppressor activity against T cell proliferative response to Concanavalin A. These findings indicate that macrophage's intracellular signaling pathways that are up-regulated in response to phagocytosis of leprosy bacilli are linked to the signaling cascades participating in macrophage antimicrobial functions, but not cross-talk with those allowing the expression of macrophage's suppressor activity against T cell functions.</p>","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5025/hansen.81.175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30934047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
New case detection in Japan has been markedly decreased and same trends have been also shown in Korea. Despite of unfavorable circumstances, research activities are still continuing and we have the accumulation of knowledge on leprosy both in Japan and Korea. Following basic studies for leprosy on going in Japan were reviewed. 1. Analysis of drug resistance mechanism and its application for clinical samples. 2. Establishment of early diagnostic technique. 3. Clarification of mechanisms of neuropathy. 4. Analysis of in vivo growth mechanisms of Mycobacterium leprae. 5. Molecular epidemiology of leprosy. 6. Searching for new anti leprosy drugs. 7. Developing vaccine. 8. In vitro cultivation. Other subjects as follows was proposed as prospective studies. 1. Mechanisms of relapse. 2. Establishing diagnostic tool of reaction and preventive measures. 3. Clarification of immunological mechanisms of anergy in LL case. The possibility of future collaboration between Korea and Japan to solve remaining problems in the clinical field was discussed and a course of action for collaboration was deliberated.
{"title":"[Collaboration between Korea and Japan for basic research on leprosy].","authors":"Masanori Matsuoka","doi":"10.5025/hansen.81.205","DOIUrl":"https://doi.org/10.5025/hansen.81.205","url":null,"abstract":"<p><p>New case detection in Japan has been markedly decreased and same trends have been also shown in Korea. Despite of unfavorable circumstances, research activities are still continuing and we have the accumulation of knowledge on leprosy both in Japan and Korea. Following basic studies for leprosy on going in Japan were reviewed. 1. Analysis of drug resistance mechanism and its application for clinical samples. 2. Establishment of early diagnostic technique. 3. Clarification of mechanisms of neuropathy. 4. Analysis of in vivo growth mechanisms of Mycobacterium leprae. 5. Molecular epidemiology of leprosy. 6. Searching for new anti leprosy drugs. 7. Developing vaccine. 8. In vitro cultivation. Other subjects as follows was proposed as prospective studies. 1. Mechanisms of relapse. 2. Establishing diagnostic tool of reaction and preventive measures. 3. Clarification of immunological mechanisms of anergy in LL case. The possibility of future collaboration between Korea and Japan to solve remaining problems in the clinical field was discussed and a course of action for collaboration was deliberated.</p>","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30934051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The epidemiological situation of leprosy is reported by the health division of each country to WHO. The reported data is collected by WHO and is immediately run on the Weekly Epidemiological Record. On this latest edition, data from the beginning of 2010 was reported. The Enhanced global strategy for further reducing the disease burden due to leprosy (plan period: 2011-2015) emphasizes reducing grade-2 disabilities among new cases. The burden of leprosy continues to decline globally as a result of sustained efforts carried out by national leprosy programmes along with continued support from both national and international partners. Improving the management of complications through the development of an effective referral service and increased community awareness about the disease will ensure that cases present for diagnosis at an early stage and will help reduce the disease burden further.
{"title":"[Present leprosy situation in the world in 2011].","authors":"Shuichi Mori, Sumana Barua, Koichi Suzuki, Norihisa Ishii, Rie Roselyne Yotsu","doi":"10.5025/hansen.81.145","DOIUrl":"https://doi.org/10.5025/hansen.81.145","url":null,"abstract":"<p><p>The epidemiological situation of leprosy is reported by the health division of each country to WHO. The reported data is collected by WHO and is immediately run on the Weekly Epidemiological Record. On this latest edition, data from the beginning of 2010 was reported. The Enhanced global strategy for further reducing the disease burden due to leprosy (plan period: 2011-2015) emphasizes reducing grade-2 disabilities among new cases. The burden of leprosy continues to decline globally as a result of sustained efforts carried out by national leprosy programmes along with continued support from both national and international partners. Improving the management of complications through the development of an effective referral service and increased community awareness about the disease will ensure that cases present for diagnosis at an early stage and will help reduce the disease burden further.</p>","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30618777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Pathology specimens suggest a history of Hansen's disease].","authors":"Hiroshi Tsutsumi","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30618241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Report on research approach to diabetic foot syndrome in Japan.","authors":"Eduard Herbst","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30618245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Ghana: the experience in the land highly endemic for Buruli ulcer].","authors":"Rie Yotsu","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":35918,"journal":{"name":"Japanese Journal of Leprosy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30618778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}