Kekkaku(Tuberculosis)
Online ISSN : 1884-2410
Print ISSN : 0022-9776
ISSN-L : 0022-9776
Volume 54, Issue 9
Displaying 1-5 of 5 articles from this issue
  • Katsumoto UEDA
    1979 Volume 54 Issue 9 Pages 445-452
    Published: September 15, 1979
    Released on J-STAGE: May 24, 2011
    JOURNAL FREE ACCESS
    T-cell-mediated and non T-cell-mediated granuloma formation and antibacterial resistance were examined using nude mice infected with mycobacteria.
    Nude mice of BALB/c-background showed very low resistance to infections with a virulent and attenuated Mycobacterium bovis as well as to infection with M. avium in comparison with euthymic heterozygous littermate mice. This was evidenced by a shorter survival time, higher bacterial count and lesser number of granulomas in nude mice than in heterozygotes.
    A low level of antimycobacterial resistance, however, seems to be operative in the liver and lymphoreticular organs of nude mice. After the virulent M. bovis-infection, the reticuloendothelia organs fell to exudative-necrotic lesions later than the other organs. Growth of attenuated strain BCG was suppressed in the RES organs revealing plateau in contrast to progressive increase in the lung and kidney. Such antimycobacterial resistance was less pronounced in nude mice maintained under germ-free condition than flora-bearing nude mice suggesting floral organisms play a roleprobably via macrophage activity for the non T-cell-mediated resistance.
    Whether or not a T-cell independent immunological mechanism plays any role in the develop -ment of granulomas in nude mice after BCG infection or injection of killed organisms was pursued using nude mice rendered immunosuppressive against T independent antigen, Brucella abortus, by multiple injections of cyclophosphamide. The nude mice received such treatment still produced granulomas comparable in number and size to non-suppressed nude mice, and the fact indicates no participation of antibody-mediated mechanisms in the formation.
    The low level of resistance and granuloma formation of nude mice in mycobacterial infections could be recovered, although never reached to the level of the heterozygotes, by transplantation with the thymus or T-cell-containing lymphoid cell suspensions from heterozygotes. Transfusion of spleen cells from intact mice possessing major histocompatibility antigen of the same halotype as to recipient BCG-infected nude mice (H-2d) produced hepatic granulomas while spleen cells from H-2-incompatible ones lacked such activity, and it suggests an H-2restricetd cell-interaction is operative in the T-cell mediated granuloma formation. This kind of cell transfer method seems to provide a useful procedure to investigate cellular interactions undergoing granuloma formation
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  • Fumiyuki KUZE, Youngchol LEE, Nobuo MAEKAWA, Yasuhiro SUZUKI
    1979 Volume 54 Issue 9 Pages 453-460
    Published: September 15, 1979
    Released on J-STAGE: May 24, 2011
    JOURNAL FREE ACCESS
    The therapeutic effects of three combined antituberculous regimens were evaluated in vivo for conventional mice (dd white strain) infected intravenously with Mycobacterium intracellulare, TMC 1469 strain. The three regimens evaluated were SM·PAS·INH, KM·EB·INH and KM·RFP·TH·CS·EB, which were all administered to the animals in dosages roughly comparable with clinical use except INH. Successive viable units of bacilli in the right lungs as well as in the spleens of mice were counted on 1% Ogawa media using 10-fold dilution technique of the homogenized organs at one, three, six, nine and fifteen weeks after challenge of the bacilli, while the administration of the drugs was continued for eight weeks, in six days a week, starting one week after challenge. The histopathological findings were observed in gross pathology and in histologic sections of lung, liver, spleen and kidney as well.
    The control untreated mice retained ca.4-5×104 viable units of bacilli in 10mg of spleen during entire experimental period, while the viable units of bacilli in lung spontaneously regressed to roughly one fifth of the count at the end of the experiment, which was ca. 1.6×103 at the start of the treatment. In spleen, the treatments of all three regimens resulted in considerable decrease of viable unit of bacilli as the treatments went and the viable units of bacilli in 10mg of the organ were roughly one fifteenth in the regimen SM×PAS×INH, one tenth in KM×EB×INH and one hundredth in KM×RFP×TH×CS×EB, respectively of the count at the time immediately before treatment. In lung, the difference in the decreases of the viable units of bacilli was less among the three regimens in the range of one twentieth to one fortieth, though the counts went down more rapidly compared with the successive counts of the control untreated group of mice.
    Minimal or moderate therapeutic efficacy was obtained at least in the regimen of KM×RFP×TH×CS×EB, however ca. 8×102 viable units and ca. 7×103 viable units of bacilli still remained in lung and spleen, respectively, at the time of discontinuation of the treatments. Moreover, the gradual increase of the bacilli after the discontinuation of the treatment observed in the final period of the experiment suggested that even the five-drug regimen of KM×RFP×TH×CS×EB was not potentenough to manage M. intracellulare infection.
    The main histopathologic findings of the organs of mice infected with TMC 1469 strain were thickening of alveolar septa, peribronchial cell infiltration, microglanuloma in lungs and both mononuclear cell aggregates and multiple minute granulomas in liver and spleen. No significant differences were noticed among the untreated and three treated groups.
    Mycobacterium intracellulare, TMC 1469 strain, used in this study was one of the strains which were kindly provided by the U.S.-Japan Cooperative Medical Science Program-NIAID in 1975. The brochure which was simultaneously provided by NIH described the colony morphology of the strain as smooth, pyramidal, thick center, transparent entire edge. The colony morphology which was again observed by us at the time immediately after the challenge to mice confirmed thin transparent colony in 15.8% and the remaining colonies showed thick opaque dome-shaped type.
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  • 2. Animal Experiments
    Mareichi TOYOHARA
    1979 Volume 54 Issue 9 Pages 461-465
    Published: September 15, 1979
    Released on J-STAGE: May 24, 2011
    JOURNAL FREE ACCESS
    Antibacterial activity in vitro of EVM for atypical mycobacteria was already reported. In this report antibacterial activity in vivo was studied using mice.
    Two strains of Miura and Brownell were chosen from M. kansasii and two strains of Yamawaki and Battey 100616 from M. intracellulare.
    Two strains of M. kansasii were sensitive to 5μg/ml of EVM in Dubos liquid media. Strain Yamawaki of M. intracellulare was resistant incompletely to 20μg/ml, and Strain Battey 100616 was sensitive to 5μg/ml.
    CF1 mice were employed for M. kansasii, Balb/c and nu/nu mice were used for M. intracellulare.
    Each mouse was injected 4mg or 8mg of EVM subcutaneously for four weeks from one week after the intravenous challenge by atypical mycobacteria.All mice were killed one week after stopping treatment by EVM, and macroscopic changes and viable units in lungs and spleens were examined.
    Results are shown in Tables 1, 2, 3, 4 and 5. Virulence of Strain Miura was rather strong to mice. Bacilli in lungs and spleens multiplied in untreated mice, but decreased remarkably by the daily subcutaneous injection of 4 mg of EVM.
    Virulence of Strain Brownell was not so strong. EVM was effective also for the infection of Strain Brownell.
    Virulence of both strains of M. intracellulare was generally weak for Balb/c mice, but Strain Yamawaki multiplied in nu/nu mice.
    Bacilli in organs of the infected nude mice with Strain Yamawaki decreased remarkably especially in lung and also swelling of spleens was improved by treatment of 8 mg EVM for four weeks. It was thought from this result that the effect of EVM to Strain Yamawaki was not always parallel between in vitro and in vivo.
    Battey strain of M. intracellulare did not multiply even in nude mice, but the decrease of bacilli was faster by EVM treatment than without treatment.
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  • 6-9 Month Short-course Chemotherapy
    Kazuo YAMAMOTO, Harumi AIZAWA, Ikunoshin INOUE, Meiichi SASAOKA, Takas ...
    1979 Volume 54 Issue 9 Pages 467-472
    Published: September 15, 1979
    Released on J-STAGE: May 24, 2011
    JOURNAL FREE ACCESS
    As our results of 12 month short-course chemotherapy were good, studies on 6-9 month short-course chemotherapy have been started for newly diagnosed smear-positive cavitary tuberculosis patients since 1976.
    During initial 3 months SM, INH and RFP are administered daily (Table 1). At the end of the third month, the next regimen is determined according to the results of a culture taken at the end of the first month. If this culture is positive, SM twice weekly with INH and RFP daily is given for 3 months, which is then followed by INH and PAS for 3 months and chemotherapy is terminated (regimen I). When the culture is negative, the regimen is changed to INH and RFP for the next 3 months. At this time, 6 months after starting chemotherapy, the regimen is changed accord ing to the presence or absence of cavities. In cases with cavities, INH and PAS is administered for 3 months (regimen II), and for non-cavity cases chemotherapy is either terminated at this point or INH alone for another 3 months (regimen III). If side effects to SM or PAS appear, EB is used in place of SM or PAS.
    Among 255 cases, 70 were dropped out during 6-9 month treatment period (Table 2).
    In 185 cases administered SM·INH·RFP, the negative conversion of sputum by culture was seen in 84% at the second month and in all cases at the fourth month (Fig. 1). Moderate to marked improvement of radiographic findings was seen in 76% when the therapy was completed (Table 4). Among 185 cases, there 52 were dropped out during the follow-up period (Table 5).
    In 133 cases who were followed up for more than 6 months after the completion of the therapy, a further radiographic improvement was seen in 20% of cases after stopping chemotherapy (Table 7). This fact shows that when chemotherapy is carried out with a regimen containing the bactericidal drugs such as INH and RFP, there is no need to continue chemotherapy to the radiographic therapeutic target point.
    Only 2 cases (1.5%) showed radiographic and bacteriological relapses at 8th month after stopping chemotherapy (Table 7).
    Six to nine month short-course chemotherapy for newly diagnosed pulmonary tuberculosis patients with SM·INH·RFP showed excellent results.
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  • Kazuro TWAT, Chieko KINO, Shouich TSUCHIYA, Renpei KITA, Tsugiko KINOS ...
    1979 Volume 54 Issue 9 Pages 473-478
    Published: September 15, 1979
    Released on J-STAGE: May 24, 2011
    JOURNAL FREE ACCESS
    It has been noticed that the worsening of the X-ray shadows of tuberculous lung lesions, appearance of pleural effusion or enlargement of lymphnode tuberculosis were observed during the first to third month of anti-tuberculosis chemotherapy. The frequency was estimated to be 1 to 4% under SM treatment, whereas 8 to 14% during RFP administration. The reason why the most effective drug, RFP, provoke such worsening of the X-ray shadow more frequently, remains to be elucidated.
    In this paper, a histological study on such a case was reported. A 32 years old female was treated by INH and RFP daily since the discovery of the infiltrative shadow in the left lung, though no tubercle bacilli was detected in sputum. X-ray film taken 3 months later, revealed appearance of new shadows around the original shadow, and the left upper lobe lobectomy was carried out considering the possibility of lung cancer. Histological examination of the resected lung showed a small, fibrotic walled cavity which contain few caseous necrosis in the narrow lumen, where a few acid-fast rods were found. Around this preceeding lesion, there was a newly formed caseous pneumonia of sublobular size, and aspirated caseous mass in the healthy alveolar spaces, showing that the aspiration pneumonia was probably the main feature of aggravation.
    The other remarkable finding was the interstitial spread of the tuberculous change along the alveolar walls, interlobular septum or bronchial walls, where many epithelioid cell granulomas and/or lymphocytic infiltration were seen in conglomerulated or beaded form. Peribronchial inflammation and fibrosis resulted in bronchioloectasis and accumulation of necrotic mass in the lumens. The interstitial extension of the lesion could be based upon the some immunological changes during RFP treatment, as tuberculin reaction and lymphocyte blast transformation by PHA were known to reduce during the 1st to 2nd month of RFP treatment.
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