Multicolor flow cytometric analyses of CD4+ T cell responses to Mycobacterium tuberculosis-related latent antigens.

Although IFN-γ release assays (IGRAs) provide increased specificity over tuberculin skin tests, the early and sensitive detection of reactivation of latently infected Mycobacterium tuberculosis is required to control tuberculosis (TB). Recently, a multicolor flow cytometry has been developed to study CD4(+) T cell cytokine responses (IFN-γ/IL-2/TNF-α) to purified protein derivatives (PPD) and M. tuberculosis-specific antigens (ESAT-6/CFP-10) and provided useful information regarding anti-TB immunity.

[Evaluation of tuberculosis treatment including levofloxacin (LVFX) in cases who could not continue standard regimen].

Objective: The purpose of this study was to evaluate tuberculosis treatment including levofloxacin (LVFX) and to investigate the effectiveness of changing drug regimens at our hospital.

Subjects And Methods: A retrospective study was conducted on 331 patients with tuberculosis admitted to Tokyo National Hospital in 2005. Out of these 331 patients, LVFX was used in 48 (14.

[A case of tuberculous pleurisy developing contralateral effusion during anti-tuberculosis chemotherapy].

A 55-year-old woman was admitted to our hospital because of chest pain, fever, and right pleural effusion that was exudative and lymphocyte-dominant with a high level of adenosine deaminase (ADA). Since her blood QuantiFERON-TB 3G test (QFT) was positive, she was diagnosed with tuberculous pleurisy. After initiation of anti-tuberculosis chemotherapy with isoniazid, rifampicin, ethambutol, and pyrazinamide, her symptoms improved.

Reversion rates of QuantiFERON-TB Gold are related to pre-treatment IFN-gamma levels.

Objective: The quantitative interferon (IFN)-gamma in response to Mycobacterium tuberculosis-specific antigens declines in tuberculosis patients after starting treatment, however, in some cases remains high despite clinical improvements. Our aim was to evaluate clinical parameters associated with remaining QuantiFERON-TB Gold (QFT-G) positive after treatment.

Methods: A prospective cohort study of 101 culture-positive, positive QFT-G, HIV-uninfected patients with pulmonary tuberculosis.

[Six adult cases of respiratory complications caused by pandemic 2009 influenza A (H1N1) compared to seasonal influenza].

The first case in Japan of 2009 pandemic influenza A (H1N1) was reported in May, with pediatric hospitalization exceeding that of adults. We evaluated six adults hospitalized for 2009 H1N1 respiratory complications and compared the pandemic to seasonal influenza. Hospitalization was due to aggravated asthma in four of the six, two of whom had simultaneous pneumonia probably virus-caused, and two cases of bacterial pneumonia.

Stratified Threshold Values of QuantiFERON Assay for Diagnosing Tuberculosis Infection in Immunocompromised Populations.

Background. The detection of latent tuberculosis (TB) is essential for TB control, but T-cell assay might be influenced by degree of immunosuppression. The relationship between immunocompetence and interferon (IFN)-γ response in QuantiFERON-TB Gold (QFT) is uncertain, especially in HIV-negative populations.

[A case of cold abscess of the chest wall due to thoracic drainage for tuberculous pleuritis].

A 56-year-old man underwent thoracic drainage for two weeks for tuberculous pleuritis. He was put on antituberculosis chemotherapy with INH (400 mg), RFP (450 mg), and EB (750 mg). Two months later, he developed an elastic hard subcutaneous mass in the area of the previous thoracic drainage.

[Clinical investigation among elderly patients with tuberculosis].

Objectives: We discussed the factors which may confuse diagnosis and treatment of tuberculosis (TB) in elderly patients, in order to improve the situation.

Subjects And Methods: 414 patients who were hospitalized for active tuberculosis in Tokyo National Hospital were divided into three groups according to their ages (in years): less than 65, 65 to 74, and greater than 75. The three groups were compared in terms of performance status (PS), serum albumin level (whether over 3 g/dl or not), underlying diseases, symptoms at onset, sputum smear findings for acid-fast bacilli, presence or absence of cavitary lesion, regimen of treatment, adverse reaction to medications, and treatment outcome.

[Review of pulmonary Mycobacterium xenopi infection cases: 11 cases of our own and 18 other cases reported in Japan].

Objective: To investigate clinical features of patients with pulmonary Mycobacterium xenopi infection treated at our hospital.

Subjects And Methods: We diagnosed 11 cases of M. xenopi infection at Tokyo National Hospital between 2000 and 2008 and recorded the drug susceptibility, patient characteristics, radiographic findings, treatments given and clinical courses.

Impact of peripheral lymphocyte count on the sensitivity of 2 IFN-gamma release assays, QFT-G and ELISPOT, in patients with pulmonary tuberculosis.

Objective: This study evaluated the effect of peripheral lymphocyte count on 2 interferon-gamma release assays [QuantiFERON TB-Gold (QFT-G) and enzyme-linked immunospot (ELISPOT)] and their sensitivity in patients with pulmonary tuberculosis, including HIV-negative immunocompromised patients.

Patients And Methods: Two hundred thirty patients with microbiologically confirmed active pulmonary tuberculosis were subjected to the tests. Lymphocyte counts were analyzed simultaneously.

[Two cases of tuberculosis after treatment of rheumatoid arthritis with infliximab].

We report two cases of tuberculosis (TB) after treatment with infliximab (IFX) for rheumatoid arthritis (RA). The first case, a 69-year-old woman with RA, developed miliary TB with acute respiratory distress syndrome 21 months after initiation of IFX therapy. Sputum samples revealed smears and cultures positive for Mycobacterium tuberculosis and also positive polymerase chain reaction for TB (PCR-TB); in addition urine samples were smear-negative and culture-positive for TB.

The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.

Objective: This study assessed the diagnostic rate of pulmonary tuberculosis (PTB) using fiberoptic bronchoscopy (FBS) in patients with suspected PTB, and negative pre-bronchoscopy smear and polymerase-chain reaction (PCR) in sputum.

Patients And Methods: We retrospectively reviewed 201 culture-positive PTB patients that underwent FBS because both smear and PCR results in sputum were negative. The positive rates of smear for acid fast bacilli, PCR for Mycobacterium tuberculosis, the presence of granuloma in transbronchial biopsy (TBB), and culture of M.

[Interferon-gamma release assay in cerebrospinal fluid of a patient with tuberculous meningitis: a case report].

Interferon-gamma release assay (IGRA) using specific tuberculous antigens is a rapid, specific and sensitive method for the detection of tuberculous infection, and usually done in peripheral blood sample. We examined IGRA in cerebrospinal fluid (CSF) in a patient strongly suspected of having tuberculous meningitis. A 53-year old woman had a month history of headache and fever with meningeal sign.

[Usefulness of bronchofiberscopy for the diagnosis of pulmonary non-tuberculous mycobacteriosis--an analysis mainly on pulmonary M. avium complex disease].

Objectives: The aim of this study was to evaluate the usefulness of bronchofiberscopy (BFS) in the diagnosis of pulmonary non-tuberculous mycobacteriosis (PNTM).

Materials And Methods: Among 909 PNTM patients admitted to our hospital during the period from 1995 to 2006, BFS was performed for the diagnosis of PNTM in 107 patients (12%) who had either a negative sputum-smear for acid-fast bacilli (AFB) (n = 100) or from whom it had been impossible to collect sputum (n =7). For these 107 cases, we retrospectively compared and analyzed the findings from specimens obtained by BFS, such as smears, cultures, polymerase-chain reaction (PCR), and transbronchial lung biopsy (TBLB), with clinical, radiological, and sputum examination disease, was also seen in the positive ratios of other nontuberculous mycobacteriosis cases.

[Evolution of IGRA researches].

The progress of genomic analysis in mycobacterium including M. tuberculosis (Mtb) allowed us to find Mtb-specific antigens, ESAT-6 and CFP-10, which induce strong interferon-gamma (IFN-gamma) from sensitized T cells. Shortly after discovery of these antigens, diagnostic tests for tuberculosis (TB) infection were developed using these antigens.

[Drug-induced hepatotoxicity caused by anti-tuberculosis drugs in tuberculosis patients complicated with chronic hepatitis].

Objectives: To investigate retrospectively the incidence of drug-induced hepatitis (DIH) caused by antituberculosis drugs including isoniazid (INH), rifampicin (RFP), with and without pyrazinamide (PZA), and to evaluate risk factors for DIH in tuberculosis patients complicated with chronic hepatitis (CH).

Materials: One hundred and seven tuberculosis patients with CH (M/F= 96/11, mean age +/- SE, 60.8 +/- 1.

Diagnosis of active tuberculous serositis by antigen-specific interferon-gamma response of cavity fluid cells.

Background: To develop a more accurate methodology for diagnosing active tuberculous pleurisy, as well as peritonitis and pericardits of tuberculous origin, we established an antigen-specific interferon gamma (IFN-gamma)-based assay that uses cavity fluid specimens.

Methods: Over a 19-month period, 155 consecutive, nonselected patients with any cavity effusion were evaluated. Study subjects were 28 patients with bacteriologically confirmed active tuberculous serositis and 47 patients with definitive nontuberculous etiology.

[Features of bronchial tuberculosis--an analysis of 103 cases].

Objectives: The aim of this study is to clarify the features of bronchial tuberculosis.

Materials And Methods: We analyzed the clinicopathological data from 103 out of 4467 (2.3%) cases of culture positive tuberculosis admitted to the National Hospital Organization Tokyo National Hospital in the period from 1993 to 2004 in which bronchial tuberculosis was confirmed by bronchofiberscopy.

[Usefulness of a whole blood interferon gamma assay (QuantiFERON-TB-2G) for detecting tuberculosis infection in HIV-infected persons].

Background: New blood test (QuantiFERON-TB-2G: QFT-2G), based on detection of IFN-gamma released by T cells in response to M. tuberculosis specific antigens, has the high sensitivity and specificity for diagnosis of tuberculosis. However, it is essential to evaluate this T cell-based approach in individuals with HIV-associated impairment in T cell immunity.

[Bone and joint tuberculosis concurrent with tuberculosis of other organs].

Objectives: To study the characteristics of bone or joint tuberculosis (TB) accompanied by TB in other organs (especially the lung), and to study patients' and doctors' delay in detecting bone or joint TB.

Subjects And Methods: A retrospective study was conducted on 33 patients with bone or joint TB concurrent with TB of other organs, especially the lung, who were admitted to our hospital between 1981 and 2005. The patients were divided into the following three groups according to the organ of concurrent TB : (1) miliary TB group (N = 10), (2) pulmonary TB group (N = 19), and (3) other TB site group (N = 4).

[Coexisting lung cancer and active pulmonary mycobacteriosis].

We reviewed 72 patients with coexisting lung cancer and pulmonary mycobacteriosis, and discuss the features and transition of these coexistent cases. There were 56 pulmonary tuberculosis (PTB) cases and 16 non-tuberculous mycobacteriosis (PNTM) cases, 62 men and 10 women, with a mean age of 69 years. In 43 cases, both diseases were concurrently detected, lung cancer was first detected in 19 cases, and mycobacteriosis was first detected in 10 cases.

Instruction of naive CD4+ T-cell fate to T-bet expression and T helper 1 development: roles of T-cell receptor-mediated signals.

Using T-cell receptor (TCR) transgenic mice, we demonstrate that TCR stimulation of naive CD4(+) T cells induces transient T-bet expression, interleukin (IL)-12 receptor beta2 up-regulation, and GATA-3 down-regulation, which leads to T helper (Th)1 differentiation even when the cells are stimulated with peptide-loaded I-A(b)-transfected Chinese hamster ovary cells in the absence of interferon-gamma (IFN-gamma) and IL-12. Sustained IFN-gamma and IL-12 stimulation augments naive T-cell differentiation into Th1 cells. Intriguingly, a significant Th1 response is observed even when T-bet(-/-) naive CD4(+) T cells are stimulated through TCR in the absence of IFN-gamma or IL-12.

Augmented induction of CD8+ cytotoxic T-cell response and antitumour resistance by T helper type 1-inducing peptide.

The effector CD8(+) T cells recognize major histocompatibility complex (MHC) class I binding altered self-peptides expressed in tumour cells. Although the requirement for CD4(+) T helper type 1 (Th1) cells in regulating CD8(+) T cells has been documented, their target epitopes and functional impact in antitumour responses remain unclear. We examined whether a potent immunogenic peptide of Mycobacterium tuberculosis eliciting Th1 immunity contributes to the generation of CD8(+) T cells and to protective antitumour immune responses to unrelated tumour-specific antigens.