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Volume 73, Issue 9
Displaying 1-4 of 4 articles from this issue
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Kazue HIGUCHI, Nobuyuki HARADA, Takashi UCHIYAMA, Hiroshi FUJIWARA, Ch ...1998 Volume 73 Issue 9 Pages 531-543
Published: September 15, 1998
Released on J-STAGE: May 24, 2011
JOURNAL FREE ACCESSrotection of hosts against tuberculosis depends on expression of cellular immunity. To express cellular immunity, interleukin-12 (IL-12) has been shown to play an important role. Although Mycobacterium tuberculosis is known to induce IL-12 from macrophages (Mφs), the mechanism for the induction is still unclear.
To understand the mechanisms of IL-12 induction from Mφs by M. tuberculosis, the IL-12 inducing ability of substances derived from M. tuberculosis was investigated in vitro. Production of IL-12 in culture medium of Mφs was measured by ELISA system using specific antibodies. Live M. tuberculosis H37Rv induced slightly higher IL-12 production than live M. tuberculosis H37Ra upon stimulation of human or mouse alveolar macrophages (hAMφs or mAMφs). Heat-killed M. tuberculosis failed to induce IL-12 production of alveolar macrophages (AMφ). The responses of hAMφs and mAMφs to M. tuberculosis were remarkably different. mAMφs produced five times larger amount of IL-12, compared with that from hAMφs. Human peripheral blood mononuclear cells (PBMC) obtained by the density gradient centrifugation were also used for induction of IL-12production. Although production levels of IL-12 from PBMC stimulated with M. tuberculosis were below the detectable level, addition of interferon- γ (IFN-γA) or neutralizing antibody against IL-10 augmented the production of IL-12 from PBMC, suggesting that IFN- γ and IL-10 regulate the production of IL-12 from Mφ positively and negatively, respectively.
To characterize the physicochemical properties of IL-12-inducing molecules, M. tuberculosis H37Rv was disrupted by pressing with 1, 000 bar and centrifuged and separated into cytosol and cell wall fraction. The culture filtrate was also examined on IL-12-inducing activity. Among the three subjects examined, cytosol was found to induce the highest production of IL-12 from mAMφs 1 day after the stimulation. Addition of IFN- γ to the cytosol fraction markedly increased the production of IL-12 from mAMφs. The molecular weight of IL-12-inducing substance was shown to be more than 30kDa by fractionating with molecular filters. Treatment of 30kDa-fraction with IL-12-inducing activity by proteinase K completely abolished the activity. Furthermore, approximately 90% of IL-12-inducing activity of 30kDa-fraction was lost by proteinase K treatment even in the presence of IFN-γ. These results indicate that the major component of IL-12-inducing activity is a protein. The identification of this IL-12-inducing active substance may provide a new therapeutic tool for tuberculosis.View full abstractDownload PDF (1548K) -
Hidetoshi MINAMI1998 Volume 73 Issue 9 Pages 545-556
Published: September 15, 1998
Released on J-STAGE: May 24, 2011
JOURNAL FREE ACCESSMycobacterium avium complex (MAC) is one of the most important opportunistic pathogens co-infected with HIV (AIDS) and a typical intracellular parasitic bacteria similar to M. tuberculosis. It is also noticed that M. avium infection causes immunosuppression especially in the cellular immunity of host animals, and specific serotype-subspecies such as sero-2, -4 or-8 can be isolated frequently in human infection. Furthermore, the prognosis after infection differs by the serotypes and serotype-4 shows heavy infection in general, while serotype-16 shows rapid improvement. Therefore, we have been interested in the immunomodifying activity of surface glycopeptidolipid (GPL) antigen. However, to date, no information has been available on the virulence factor of MAC related directly with intracellular bactericidal activity. Recently, we have tested the effect of various GPLs purified form MAC complex on phagocytic processes of human peripheral blood monocytes (PBMC). We have used GPL-coated heat-killed staphylococcal cells to be phagocytosed by PBMC, and phagosome-lysosome (P-L) fusion was estimated by the acridine orange staining of fused vesicles including bacteria. It was revealed that the serotype-4, -12 and-7 GPLs showed strong phagocytosis promotion and marked inhibition of P-L fusion, while serotype-9, -13, -16 and-9 GPLs showed neither promotion of phagocytosis, nor inhibition of P-L fusion in phagocytic cells. Serotype-5, -7, -8and-1 0 GPLs showed stimulation of both phagocytosis and P-L fusion, concomitantly. These effects may be due to unknown interaction between specific carbohydrate chain of MAC and phagocytic cell membranes, and serotype-4, -12 and-17 GPLs may be one of the possible virulence factors in MAC.View full abstractDownload PDF (1942K) -
A CASE OF CUTANEOUS TUBERCULOSIS ASSOCIATED WITH STEROID THERAPY FOR MIXED CONNECTIVE TISSUE DISEASETakenori YAGI, Fumio YAMAGISHI, Fumio MIZUTANI, Yuka SASAKI, Masayoshi ...1998 Volume 73 Issue 9 Pages 557-562
Published: September 15, 1998
Released on J-STAGE: May 24, 2011
JOURNAL FREE ACCESSPatients receiving immunosuppressive therapy, such as adrenocorticosteroids, are high risk groups of tuberculosis. We report a case of cutaneous tuberculosis associated with steroid therapy for mixed connective tissue disease. A 63-year-old female was hospitalized after 6 months' treatment with prednisolone for connective tissue disease and bilat -eral abnormal shadows were revealed on her chest X-ray films. As her sputum smear was positive for acid-fast bacilli, the patient was transferred to our hospital for isolation and treatment. After three months' treatment with INH, RFP and EB, she complained the swelling of her left palm, left arm, and right leg, and skin puncture was performed. As smears of fluid aspirated from the swelling showed acid-fast bacilli, and fluid PCR tests showed positive for M. tuberculosis, she was diagnosed as cutaneous tuberculosis (scrofuloderma). In spite of administration of antituberculous agents, the swellingshowed little improvement.
Therefore, the dose of prednisolone was reduced and cutaneous lesions were resected by surgery. High risk of tuberculosis should be considered when a patient administered immunosuppressive drugs, such as adrenocorticosteroids.View full abstractDownload PDF (1838K) -
Satoshi KIMURA1998 Volume 73 Issue 9 Pages 563-571
Published: September 15, 1998
Released on J-STAGE: May 24, 2011
JOURNAL FREE ACCESSRecent advances in the chemotherapeutic agents against HIV enabled us to conduct combination therapies using two nucleoside reverse transcriptase inhibitors and a protease inhibitor. The three-drug combination chemotherapies have been shown to be very potent in inhibiting HIV replication; they markedly suppress plasma HIV-RNA levels, elevate CD 4 counts, reduce opportunistic infections and prolong survival of the patients. Early and hard treatment is now recommended.
Among opportunistic infections in patients with HIV infection/AIDS, most frequent are respiratory tract infections including Pneumocystis carinii pneumonia, bacterial pneumonia, pulmonary tuberculosis, CMV pneumonia and fungus infections. Sensitivity and specificity of PCR method to detect Pneumocystis carinii are much better than the conventional Grocott stain of sputa. Early diagnosis of tuberculosis and atypical mycobacteriosis became possible using PCR and other molecular technology. Multi-drug resistant tuberculosis is fortunately rare among Japanese HIV-positive patients. Early and correct diagnosis of opportunistic infections markedly improves the prognosis of the patients.View full abstractDownload PDF (1247K)
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