Makoto Yonemaru

Comparison of the sensitivity and specificity of two whole blood interferon-gamma assays for M. tuberculosis infection

OBJECTIVES To compare the sensitivity and the specificity of the QuantiFERON-TB Gold (QFT-G) and QuantiFERON-TB Gold In Tube (QFT-GIT) diagnostic tests for Mycobacterium tuberculosis infection. METHODS One-hundred patients with culture and/or PCR confirmed M. tuberculosis infection and 168 volunteers with no risk factors for M. tuberculosis infection were tested to estimate sensitivity and specificity, respectively. RESULTS Analysis of data from the tuberculosis (TB) patients with valid results found the sensitivity of QFT-GIT (92.6%, 87/94) to be significantly higher than that for the QFT-G test (81.4%, 79/97; p=0.023). The specificity of both QFT-GIT and QFT-G was 98.8% (CI: 95.1%-99.8%) with 2 of the 160 low risk subjects with valid results for both tests being positive. Data analysis confirmed the manufacturers recommended test cut-off as being optimal, but identified higher sensitivity could be obtained by using a lower cut-off, with only a moderate decrease in specificity. CONCLUSIONS The QFT-GIT test had enhanced sensitivity for detection of M. tuberculosis infection over the QFT-G test, whilst maintaining equivalent high specificity. The logistic benefits of the QFT-GIT test format, as well as its higher sensitivity, should enable enhanced TB control.

Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia

A 31‐year‐old male was diagnosed as having chronic myelogenous leukaemia and has been treated with hydroxyurea and interferon‐α since February 1995. After 16 months, he complained of low‐grade fever and a cough. Bilateral hilar lymph node enlargement was detected on the chest X‐ray film and multiple subcutaneous erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid granuloma. Two months after the cessation of interferon therapy, the subcutaneous nodules and the hilar lymph node enlargement resolved. It is possible that continuous interferon administration can promote granuloma formation in sarcoidosis by activating T cells and macrophages.

Protective role of vascular endothelial growth factor in endotoxin-induced acute lung injury in mice.

BackgroundVascular endothelial growth factor (VEGF), a substance that stimulates new blood vessel formation, is an important survival factor for endothelial cells. Although overexpressed VEGF in the lung induces pulmonary edema with increased lung vascular permeability, the role of VEGF in the development of acute lung injury remains to be determined.MethodsTo evaluate the role of VEGF in the pathogenesis of acute lung injury, we first evaluated the effects of exogenous VEGF and VEGF blockade using monoclonal antibody on LPS-induced lung injury in mice. Using the lung specimens, we performed TUNEL staining to detect apoptotic cells and immunostaining to evaluate the expression of apoptosis-associated molecules, including caspase-3, Bax, apoptosis inducing factor (AIF), and cytochrome C. As a parameter of endothelial permeability, we measured the albumin transferred across human pulmonary artery endothelial cell (HPAEC) monolayers cultured on porous filters with various concentrations of VEGF. The effect of VEGF on apoptosis HPAECs was also examined by TUNEL staining and active caspase-3 immunoassay.ResultsExogenous VEGF significantly decreased LPS-induced extravascular albumin leakage and edema formation. Treatment with anti-VEGF antibody significantly enhanced lung edema formation and neutrophil emigration after intratracheal LPS administration, whereas extravascular albumin leakage was not significantly changed by VEGF blockade. In lung pathology, pretreatment with VEGF significantly decreased the numbers of TUNEL positive cells and those with positive immunostaining of the pro-apoptotic molecules examined. VEGF attenuated the increases in the permeability of the HPAEC monolayer and the apoptosis of HPAECs induced by TNF-α and LPS. In addition, VEGF significantly reduced the levels of TNF-α- and LPS-induced active caspase-3 in HPAEC lysates.ConclusionThese results suggest that VEGF suppresses the apoptosis induced by inflammatory stimuli and functions as a protective factor against acute lung injury.

Clinical evaluation of serum type IV collagen 7S in idiopathic pulmonary fibrosis

Abstract Type IV collagen is one of the major components of the basement membrane (BM). 7S domain (7S collagen) of type IV collagen is an N‐terminal peptide which is stable against protease and heat. We investigated serum concentration of 7S collagen in patients with idiopathic pulmonary fibrosis (IPF) and other pulmonary diseases. The aim of this study was to evaluate whether changes in the serum concentration of 7S collagen reflect the fibrotic process of IPF. We measured the concentration of serum 7S collagen with radioimmunoassay in patients with IPF, chronic pulmonary emphysema (CPE), sarcoidosis, infectious pulmonary diseases (IPD) and normal healthy controls. We also monitored 7S collagen during the clinical course in some patients with IPF and investigated the correlation between the serum 7S collagen, and lactate dehydrogenase (LDH) and erthrocyte sedimentation rate (ESR) in patients with IPF. Patients with IPF showed significantly higher serum concentration of 7S collagen than other pulmonary diseases and healthy controls. The serum concentration of 7S collagen significantly decreased in IPF patients who showed roentgenographic improvement after corticosteroid treatment. There was a correlation between the serum 7S collagen and LDH, and ESR. In conclusion, serum concentrations of 7S collagen increase in patients with IPE The measurement of 7S collagen is useful for the evaluation of fibrotic change in the lung.

Recurrence of Disseminated Mycobacterium avium Complex Disease in a Patient with Anti-Gamma Interferon Autoantibodies by Reinfection

ABSTRACT We report a case of recurrent disseminated Mycobacterium avium complex (DMAC) disease with anti-gamma interferon autoantibodies. To our knowledge, this is the first reported case caused by reinfection with a separate isolate of M. avium. DMAC disease activity was monitored using serum IgG antibody titers against lipid antigens extracted from a MAC strain.

Protein kinase inhibitor attenuates an increase in endothelial monolayer permeability induced by tumour necrosis factor-α

Abstract We questioned the mechanism of the increase in pulmonary endothelial permeability induced by tumour necrosis factor‐α (TNF‐α), a cytokine implicated in the pathogenesis of adult respiratory distress syndrome. As a measure of permeability, we determined the albumin transferred across cultured pulmonary endothelial monolayers prepared on a porous filter. The agents evaluated included protein kinase inhibitors H‐7 and H‐8, a calmodulin antagonist W‐7, and protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and SC‐9. H‐7, more potent in inhibiting PKC than H‐8, failed to attenuate the increase in permeability induced by TNF‐α. Neither PMA nor SC‐9 increased permeability. However, H‐8, which is a potent inhibitor of cyclic nucleotide‐dependent protein kinases, prevented the increase in permeability induced by TNF‐α. These results suggest that protein kinases other than PKC are involved in the signal transduction in endothelial permeability increase induced by TNF‐α. Calmodulin pathway may not be implicated in the increase in permeability induced by TNF‐α.

Screening of Helicobacter Pylori Infection in the Health Examination Detected by Urea Breath Test and Barium Meal Study

Screening of Helicobacter Pylori Infection in the Health Examination Detected by Urea Breath Test and Barium Meal Study: Fumihiro Yamasawa, et al. Marubeni Clinic

Attenuation of Septic-, Tumor Necrosis Factor-, and Interleukin-2-Induced Acute Lung Injury in Guinea Pigs by Pentoxifylline, Aminophylline, and HWA 138

AbstractIt has been demonstrated that cytokines play a central role in mediating host responses to endotoxemia. In this study, we examined and compared the effects of E. coli sepsis and the cytokines,