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73 巻, 2 号
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佐藤 勝昌, 清水 利朗, 赤木 竜也, 冨岡 治明1998 年 73 巻 2 号 p. 47-52
発行日: 1998/02/15
公開日: 2011/05/24
ジャーナル フリーThe MycoDotTM is a new diagnostic kit for tuberculosis which was devised by DynaGen Inc., USA. The MycoDot test is based on the detection of anti-mycobacterial antibodies in the serum samples of patients by employing plastic combs coated with lipoarabinomannan (LAM) antigen which is a highly immunogenic lipopolysaccharide presenting in the cell wall of all species of mycobacteria. It has been reported that healthy infected and BCGvaccinated individuals do not react to the MycoDot test, while a positive reaction occurs in patients with active tuberculosis or atypical mycobacteriosis with good sensitivity and specificity. In this study, we evaluated the efficacy of MycoDot test for the detection of anti-LAM antibodies in sera of mice infected with Mycobacterium tuberculosis or M.avium complex (MAC). By using the MycoDot test, anti-LAM antibodies were positive in 2 out of 4 mice infected with M.tuberculosis 2 weeks before, while all of M.intracellulare-infected mice were negative at the same phase of infection. On the other hand, anti-mycobacterial (MB) antibodies were detected in the serum samples of mice infected with M.intracellulare as well as M.tuberculosis by home-made ELISA testing using whole cells of test mycobacteria as antigen. In the next experiment, mice were infected with M.avium. All the serum samples of mice obtained at 13 weeks after infection were negative for anti-LAM antibodies in MycoDot test, whereas they reacted positively to anti-MB antibodies in ELISA test. These results indicate that the MycoDot test is capable of detecting M.tuberculosis infection but not MAC infection induced in mice.抄録全体を表示PDF形式でダウンロード (814K) -
(1) 経気道感染モデルと尾静脈感染モデルを用いた短期治療効果の検討土井 教生1998 年 73 巻 2 号 p. 53-64
発行日: 1998/02/15
公開日: 2011/05/24
ジャーナル フリーObjectives: This study aims to compare in vivo activity of benzoxazinorifamycin KRM-1648 (KRM) with those of rifampicin (RFP) and rifabutin (RBT) against experimental murine tuberculosis.
Study design: Mice were infected with Mycobacterium tuberculosis or M. bovis by the intratracheal (IT) or intravenous (IV) routes, and treated for 10 days with various doses of each drug starting from the 8th or 11th day after the TB-infection.
Results: (A) A rapid test for in vivo evaluation of three rifamycins was conducted by examining the survival days of treated mice infected with 106 cfu of M. bovis Ravenel. Mice treated with KRM exhibited 2.1-3.7 times longer survival times, in comparison with those treated with RFP or RBT. (B) In the IT-model of M. bovis Ravenel infection, three rifamycin derivatives gave “distinctive dose-response curves” in the correlation of dose sizes with the mean survival times or “log10 CFU/lungs reductions”. (C) In M. tuberculosis Kurono infection models, the ranking of the anti-TB activity of the three rifamycins in each organ was as follows: IT-and IV-lungs: KRM>RFP=RBT, IV-spleen: KRM≈≈RBT>RFP, IV-liver: KRM≈RBT>RFP. (D) Based on the results of“log10CFU reductions”in different organs in M. tuberculosis Kurono infection models, “characteristic in vivo activity patterns of each rifamycin” were obtained. (E) The therapeutic efficacy of KRM in lungs was greater than in spleen and liver with any dose. In contrast, RBT exhibited more remarkable in vivo activity in the spleen and liver than in lungs.
Conclusion: The prominent in vivo activity of KRM may allow small dose for effective therapy;1/3 dose or less in comparison with those of RFP or RBT, or intermittent therapy of tuberculosis.抄録全体を表示PDF形式でダウンロード (2055K) -
結核菌菌体成分の免疫活性を中心に東 市郎1998 年 73 巻 2 号 p. 65-70
発行日: 1998/02/15
公開日: 2011/05/24
ジャーナル フリーIn 1954, Dr. Yuichi Yamamura and his coassociates, National Sanatorium Toneyama Hospital, has reported the formation of experimental tuberculous cavity in rabbits. This work was a milestone of the researches in the field of cellular immunology. In 1960, I have started my scientific carrier in Kyushu University Medical School as the post-graduate student under the guidance of Prof. Yamamura. Since then, I have worked on the field of biochemical and immunological properties of tubercle bacilli. The arabinose mycolate, polysaccharides, cell-wall skeleton (CWS) and trehalose dimycolate (TDM) were purified from tubercle bacilli and their Chemical structures and biological activities were investigated in detail in our laboratory.
In 1971, we have reported that adjuvant active principle of tubercle bacilli was a CWS fraction, and the details of chemical structure and adjuvantity of mycobacterial CWS were investigated in our research group. The application of BCG-CWS to cancer immunotherapy was also studied. In 1974, Prof. E. Lederer and his coworkers, University of Paris, have reported that N-acetyl muramyl-L-alanyl-D-isoglutamine (MDP) was the minimum adjuvant-active structure of bacterial cell wall. We have synthesized several hundreds of MDP derivatives and selected, MDP-Lys (L18), romurtide, as the candidate of cytokine inducer for the clinical application. Romurtide is applied in cancer patients for the recovery of the number and functions of monocytes, neutrophils and platelets. These results suggest that the tubercle bacilli, especially, CWS and related synthetic MDP derivatives, are effective for the potentiation of host resistance against infectious diseases and cancer.抄録全体を表示PDF形式でダウンロード (1050K) -
1.感染における生体防御機構冨岡 治明, 佐藤 勝昌, 清水 利朗, 赤木 竜也1998 年 73 巻 2 号 p. 71-92
発行日: 1998/02/15
公開日: 2011/05/24
ジャーナル フリーIn order to know profiles of the antimicrobial action of some microbicidal effector molecules against Mycobacterium avium complex (MAC) and M. tuberculosis (MTB), profiles of collaborating effects among reactive nitrogen intermediates (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) were studied. RNI and FFA exerted synergistic effects in killing MAC and MTB, while the combination of ROI (H2O2-mediated halogenation system) with FFA conversely caused antagonism. The combination of RNI with ROI displayed additive effects in killing MTB, whereas the same combination showed antagonistic effects against MAC. Murine peritoneal macrophages (Mφs) produced and/or released these three antimicrobial effectors in the order ROI, FFA, and RNI in response to cellular stimulation induced by their contact with MAC or MTB organisms. These findings indicate that the collaborating effect of RNI with FFA is crucial for Mφ-mediated intracellular killing of MAC and MTB. Secondly, we examined the modes of bacterial growth of MAC and MTB in murine peritoneal Mφs and A-549 type II alveolar epithelial cell line. The growth rate of these organisms was much larger in A-549 cells than in Mφs. In addition, the growth rate of high-vilulence MAC (N-260 strain) was significantly larger than that of low-virulence MAC (N-444 strain), when they were residing in Mφs or A-549 cells. Although a high-virulence MTB (strain Kurono) also showed much more rapid growth in Mφs than did low-virulence MTB (strain H37Ra), such a phenomenon was not observed for their intracellular growth in A-549 cells. MTB exhibited strong cytotoxic effects against Mφs but not against A-549 cells when resided in these cells. On the other hand, MAC organisms did not cause cytotoxicity even in Mφs. Although MAC and MTB infections caused significant increase in RNI production by Ms but not by A-549 cells, there was no significant relationship between the degree of Mφ RNI production by a given mycobacterial organism and its virulence. These findings indicate some important roles of type II alveolar epithelial cells as a target cell for primary invasion and transient growth of mycobacterial organsisms in the host lungs.抄録全体を表示PDF形式でダウンロード (2860K) -
日本結核病学会予防委員会1998 年 73 巻 2 号 p. 95-99
発行日: 1998/02/15
公開日: 2011/05/24
ジャーナル フリーPDF形式でダウンロード (831K)
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