Masayuki Ando

Kumamoto University, Kumamoto, Kumamoto, Japan

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Publications (203)832.26 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: IntroductionIdiopathic pulmonary fibrosis (IPF) is a fatal disorder without specific treatments. Although the efficacy of intravenous immunoglobulin (IVIG) therapy for autoimmune diseases has been reported, that for IPF remains unknown.Objective To determine the efficacy and safety of IVIG for IPF.Methods In an exploratory, multicenter, nonrandomized, and prospective trial, patients with progressive IPF were enrolled. Patients were treated with IVIG for 5 consecutive days (5-day IVIG) or once-monthly for 5 consecutive months (5-month IVIG). Changes in the vital capacity (VC), diffusion capacity of the lung for carbon monoxide (DLCO), 6-minute walk test (6MWT), and high-resolution computed tomography (HRCT) findings were evaluated.ResultsTen patients with IPF were treated with IVIG: 6 were in 5-day IVIG and 4 were in 5-month IVIG group. In 5-day IVIG group, the treatment effects were temporal, and physiological and HRCT findings deteriorated in 3 of 6 patients. In 5-month IVIG group, changes in %VC, %DLCO, and walk-distance in 6MWT at 6 months were -0.9±5.3 %, 6.9±12.6 %, and 79±58 m (mean ± SD), respectively, and the treatment effects were long-lasting. The change in VC 6 months after starting IVIG was smaller than that 6-12 months after starting IVIG (after cessation of IVIG) (-0.02±0.15 vs. -0.33±0.14 L, p = 0.022). Ground glass opacities were diminished in 2 of 4 patients. Adverse events were mild and tolerable.Conclusion This preliminary study shows that once-monthly IVIG treatment may be effective and tolerable in patients with IPF.
    Full-text · Article · Feb 2015 · The Clinical Respiratory Journal
  • [Show abstract] [Hide abstract] ABSTRACT: Patients with familial amyloidotic polyneuropathy (FAP TTR Met 30) manifest clinical jindings, such as auto-nomic dysfunction, sensori-motor polyneuropathy, and visceral organ impairment with the progression of the disease. to clarih the clinical features of each patient and to determine the accurate clinical stages of FAt patients were given clinical scores and divided into 4 different groups by their clinical symptoms. Radar charts of the scores revealed that the shapes of the plotted scores between 2 different time examinations were similar until the bedridden stage of FAc suggesting that the clinical type of FAP had been determined at the onset of the disease and did not change as the disease progressed Retrospective stu4 revealed that most of the patients were near death when the total score became about 70. This evaluating method for FAP TTR Met30 may be useful in systematically evaluating the heterogeneity and the stage of each FAP patient, and also in elucidating the effect of therapies on the patients.
    No preview · Article · Jul 2009 · Amyloid
  • [Show abstract] [Hide abstract] ABSTRACT: 123I-MIBG (5 mCi) scintigraphy was applied and compared with power spectrum and coefficient of variance (CV) of the electrocardiographic R-R interval in 9 patients with familial amyloidotic polyneuropathy (FAP). Although a significant decrease of MIBG uptake was seen in all the patients examined, no change in either the ST or T wave in the electrocardiogram (ECG) nor any ultrasound echocardiography (UCG) abnormalities were recognized. Six of these patients under 201thallium (201TI) scintigraphy exhibited a normal pattern. The electrocardiographic R-R interval, was border-line in one patient and could not be calculated in 3 patients. In contrast, total absence of 123I-MIBG accumulation was recognized in 6 patients and in 3, a partial defect was found. These results suggest that MIBG scintigraphy may be a useful method for the diagnosis of dysautonomia in patients with FAP
    No preview · Article · Jul 2009 · Amyloid
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    [Show abstract] [Hide abstract] ABSTRACT: We examined the functional heterogeneity of eosinophils from an adult T-cell leukemia (ATL) patient with eosinophilia. A 63-year-old man was admitted to our hospital because of lymphadenopathy. The leukocyte count was 10 400 /mm 3, with 36.0% eosinophils and 3.0% abnormal lymphocytes. The diagnosis of ATL was based on the presence in serum of anti-human T-cell lymphotrophic virus-1 antibody and on histologic demonstration of ATL cells. The mononuclear cells spontaneously produced eosinophil-related cytokines (granulocyte–macrophage colony stimulating factor, 5600 pg/mL; interleukin (IL)-5, 375 pg/mL). Peripheral eosinophils were fractionated into normodense eosinophils (NE) and hypodense eosinophils (HE) by a Percoll density gradient method, and these cells were compared in terms of several heterogeneous functions. The NE were more chemotactically attracted to IL-5 than the HE. More apoptotic cells appeared among the NE than among the HE and this difference was correlated with the positive rate of Fas antigen on eosinophils. Survival of the HE was longer than that of the NE. Survival of the HE was prolonged by IL-5 stimulation, but survival of the NE was not. These data suggest that functionally heterogeneous eosinophils were present in this ATL patient with eosinophilia and that IL-5 enhanced this heterogeneity. The response of eosinophils to IL-5 may have contributed to the pathogenesis of eosinophilia in this patient.
    Preview · Article · Jun 2008 · Allergology International
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    [Show abstract] [Hide abstract] ABSTRACT: Nitric oxide (NO) and its derivatives can directly cause DNA damage and mutation in vitro and may play a role in the multistage carcinogenic process. It has been reported that NO induces mutation in the p53 tumor suppressor gene; we therefore analyzed the relationship between NO synthase 9 activity and p53 gene status in early-stage lung adenocarcinoma. Surgical samples were classified into two categories: 14 lung adenocarcinomas with high NOS activity (>25 pmol/min/g tissue, category A), and 16 with low NOS activity (<25 pmol/min/g tissue, category B). A yeast functional assay for p53 mutations disclosed a red colony that corresponded to a mutation in the p53 gene in 8 cases (57.1%) in category A and 3 cases (18.8%) in category B, the frequency being significantly higher in the former (P<0.05). A p53 DNA sequence analysis revealed that 5 of the 8 p53 mutation-positive samples in category A had a G:C-to-T:A transversion, which is reported to be a major target of NO. The mechanism of carcinogenesis of adenocarcinoma is not fully understood, but these results suggest that an excess of endogenously formed NO may induce a p53 gene mutation containing mainly G:C-to-T:A transversion in the early stage of lung adenocarcinoma. Our results suggest that NO has potential mutagenic and carcinogenic activity, and may play important roles in human lung adenocarcinoma.
    Full-text · Article · Aug 2005 · Cancer Science
  • [Show abstract] [Hide abstract] ABSTRACT: Only limited information exists concerning the clinical and pathological features of chronic hypersensitivity pneumonitis (HP) in Japan and elsewhere. We present data on clinicopathological features of chronic HP obtained through a Japanese nationwide survey. We studied the clinical and pathological findings in 10 patients with chronic HP who underwent surgical lung biopsy or postmortem examination. There were three types of clinical course: six of the 10 patients had persistent symptoms followed by repeated acute episodes; two showed a subacute onset with persistent symptoms; and two exhibited an insidious onset. Five patients made no attempt to avoid antigen exposure and they all had progressive disease. Pathological findings indicated that lesions were mainly centrilobular with or without epithelioid cell granulomas in specimens obtained during the acute or subacute stage. In contrast, most patients in the chronic stage predominantly showed interstitial fibrosis with a usual interstitial pneumonia pattern. The pathological findings of chronic HP depend on the stage of the disease at tissue sampling.
    No preview · Article · Jan 2003 · Respirology
  • [Show abstract] [Hide abstract] ABSTRACT: Interleukin-3 (IL-3) is one of the cytokines of significance for the regulation of hematopoiesis and inflammation. Recently, we established IL-3-dependent Ba/F3 pro-B cells ectopically expressing RON tyrosine kinase, a receptor for macrophage-stimulating protein (MSP), and showed that MSP stimulation specifically promoted cell morphological changes through tyrosine phosphorylation of the IL-3 common beta-chain receptor subunit (betac) by activated RON kinase without activation of JAK2 tyrosine kinase. Here we investigate the IL-3 signaling pathway leading to morphological changes through tyrosine phosphorylation of betac. Treatment of RON-expressing cells with PD98059 or U0126, inhibitors of mitogen-activated protein kinase kinase activity, blocked both IL-3- and MSP-induced morphological changes. Upon stimulation with IL-3 or MSP, extracellular-regulated kinase (ERK) and F-actin were redistributed in uropod-like structures. ERK and F-actin were colocalized within uropod-like structures, and a majority of F-actin were localized around the peripheries of accumulated ERK. Tyrosine phosphorylation of ERK was detected after stimulation with IL-3 or MSP, whereas treatment with U0126 specifically inhibited IL-3- or MSP-induced ERK phosphorylation but not tyrosine phosphorylation of betac. These results suggest that the activation and localization of ERK to uropod-like structures play a role in IL-3-induced morphological changes.
    No preview · Article · Dec 2002 · Immunology Letters
  • [Show abstract] [Hide abstract] ABSTRACT: To characterize thin-section computed tomographic (CT) findings of pathologic subgroups of nonspecific interstitial pneumonia (NIP) in a sizeable number of patients. The study included 55 cases of pathologically proven NIP. The 55 cases were categorized histologically into four grades: grade 1, interstitial inflammation without fibrosis (n = 6); grade 2, interstitial inflammation predominating over fibrosis (n = 16); grade 3, fibrosis predominating over inflammation (n = 5); and grade 4, fibrosis only (n = 28). Two independent observers evaluated the presence, extent, and distribution of various CT findings. Thin-section CT findings and histologic grades were compared by using the Spearman rank correlation coefficient. Observer agreement was assessed. Areas with ground-glass attenuation and architectural distortion were present in all 55 patients. Traction bronchiectasis and intralobular reticular opacities were seen in 52 and 48 patients, respectively. The extent of traction bronchiectasis (r = 0.68; P <.001) and intralobular reticular opacities (r = 0.35; P <.05) correlated with the histologic grade. Honeycombing was seen in 12 (43%) of 28 patients with grade 4 NIP and in three (11%) of the remaining 27 patients (chi(2) test, P <.001). There was good agreement between the observers for the presence (kappa = 0.7-1.0) and extent (Spearman rank correlation; r = 0.87-0.98; P <.001) of various abnormalities. The extent of traction bronchiectasis and intralobular reticulation at thin-section CT correlates with increased fibrosis in NIP. Honeycombing is seen almost exclusively in patients with fibrotic NIP.
    No preview · Article · Nov 2002 · Radiology
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    [Show abstract] [Hide abstract] ABSTRACT: We report a novel localized amyloidosis associated with lactoferrin. To elucidate the precursor protein of corneal amyloidosis associated with trichiasis, we analyzed amyloid deposits from three patients by histopathology and biochemistry. Amyloid deposits showed immunoreactivity, confirmed by electron microscopy, for only anti-human lactoferrin antibody. Electrophoresis of amyloid fibrils revealed lactoferrin with and without sugar chains; N-terminal sequence analysis revealed full-length lactoferrin and a truncated tripeptide of N-terminal amino acids, Gly-Arg-Arg. Carboxymethylated wild-type lactoferrin formed amyloid fibrils in vitro. Lactoferrin gene analysis in the three patients revealed a Glu561Asp mutation in all of the patients and a compound heterozygote of Ala11Thr and Glu561Asp mutations in one patient. A heterozygotic Glu561Asp mutation appeared in 44.8% of healthy Japanese volunteers, suggesting that the mutation may not be an essential mutation for amyloid formation (p = 0.104). Results thus suggest that lactoferrin is this precursor protein.
    Full-text · Article · Jul 2002 · Laboratory Investigation
  • [Show abstract] [Hide abstract] ABSTRACT: This study compared high-resolution computed tomography (CT) findings between 10 survivors and 21 nonsurvivors of acute interstitial pneumonia and evaluated whether the CT findings were predictive of patients' response to treatment. The survivor and nonsurvivor groups with pathologically or clinically diagnosed acute interstitial pneumonia were similar in age, sex, disease duration, and lung injury score. Retrospective, subjective evaluations of the CT scans were conducted by two independent observers without knowledge of patient outcomes. CT findings were graded on a one to six scale corresponding to consecutive pathologic phases as follows: areas of (1) normal attenuation, (2) ground-glass attenuation, (3) consolidation, (4) ground-glass attenuation associated with traction bronchiolectasis or bronchiectasis, (5) consolidation associated with traction bronchiolectasis or bronchiectasis, and (6) honeycombing. An overall score was obtained by quantifying the extent of each abnormality in three lung zones in each lung. The extent of ground-glass attenuation or consolidation associated with traction bronchiolectasis or bronchiectasis was less in survivors than nonsurvivors (p = 0.004 and p = 0.009, respectively). Architectural distortion was less frequent, and ground-glass attenuation or consolidation without traction bronchiolectasis or bronchiectasis was more extensive in survivors than in nonsurvivors (p = 0.007, p = 0.002, and p = 0.029, respectively). Overall CT scores of survivors were significantly lower than those of nonsurvivors (p = 0.0003). A CT score of less than 245 had an 80% positive and a 90% negative predictive value for survival. There was good interobserver agreement in the assessment of the CT findings (Kappa 0.75). The results indicate that CT assessment is potentially helpful in predicting patient prognosis in acute interstitial pneumonia regardless of the degree of physiologic abnormality.
    No preview · Article · Jul 2002 · American Journal of Respiratory and Critical Care Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Here, we report a case of systemic lupus erythematosus (SLE) complicated by cytomegalovirus (CMV)-induced hemophagocytic syndrome (HPS) and colitis. A 44-year-old woman with SLE was treated with corticosteroid and cyclophosphamide for lupus nephritis. Although her lupus nephritis improved, fever, progressive pancytopenia and intestinal bleeding were observed. A bone marrow aspiration showed an increase in mature histiocytes with hemophagocytosis. In addition, a colonoscopy showed hemorrhagic colitis with ulcer and the biopsy specimen from the colon revealed typical CMV cells with CMV inclusions confirmed by immunohistochemistry. Furthermore, a large number of CMV antigen-positive leukocytes was detected, suggesting an active CMV infection. CMV infection is serious in compromised hosts. Therefore clinicians should be aware of the clinical settings in which this infection can arise and the target organs potentially affected in order to initiate the appropriate intervention.
    No preview · Article · Mar 2002 · Internal Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Ubiquitin ligases define the substrate specificity of protein ubiquitination and subsequent proteosomal degradation. The catalytic sequence was first characterized in the C terminus of E6-associated protein (E6AP) and referred to as the HECT (homologous to E6AP C terminus) domain. The human homologue of the regulator of cell proliferation hyperplastic discs in Drosophila, designated hHYD, is a HECT-domain ubiquitin ligase. Here we show that hHYD provides a ubiquitin system for a cellular response to DNA damage. A yeast two-hybrid screen showed that DNA topoisomerase IIbeta-binding protein 1 (TopBP1) interacted with hHYD. Endogenous hHYD bound the BRCA1 C-terminus domains of TopBP1 that are highlighted in DNA damage checkpoint proteins and cell cycle regulators. Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks. These results demonstrated that hHYD coordinated TopBP1 in the DNA damage response.
    Full-text · Article · Mar 2002 · Journal of Biological Chemistry
  • [Show abstract] [Hide abstract] ABSTRACT: Here, we report two rare female cases of Sjögren's syndrome with multiple bullae, involving a 66- and a 51-year-old. Neither had any obvious pulmonary complaint. Chest radiographs and high-resolution CT (HRCT) scans showed interstitial linear and nodular opacities and multiple bullae. In the first case spirometry indicated an obstructive change judged by FEV1.0 and V50/V25. In both cases, histologic examination of the lung revealed thickening of alveolar septa and interstitial mononuclear cell infiltration. In the first case the bullae decreased in size with corticosteroid treatment. Airway narrowing due to peribronchiolar mononuclear cell infiltration causes a check-valve mechanism, which may lead to bullae formation. Although a rare occurrence, it is important to recognize that cystic or bullous lung disease can accompany Sjögren's syndrome.
    No preview · Article · Mar 2002 · Internal Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.
    Full-text · Article · Feb 2002 · Journal of Clinical Microbiology
  • [Show abstract] [Hide abstract] ABSTRACT: To investigate whether tachykinins are released in the airways by stimulating the esophagus, airway plasma extravasation induced by intraesophageal hydrochloric acid (HCl) in the presence or absence of the neutral endopeptidase (NEP) inhibitor phosphoramidon and the neurokinin-1-receptor antagonist FK888 was studied in anesthetized guinea pigs. Airway plasma extravasation also was studied in the presence of the NEP inhibitor in guinea pigs pretreated with capsaicin or bilateral vagotomy. Propranolol and atropine were used in all animals to block adrenergic and cholinergic nerve effects. Airway plasma leakage was evaluated by measuring extravasated Evans blue dye. One normal HCl infusion into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation induced by HCl infusion into the esophagus in the trachea and main bronchi, and FK888 significantly inhibited extravasation in a dose-related manner. In capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilaterally vagotomized animals. These results suggest that locally acting substances are released by intraesophageal HCl stimulation that cause airway plasma extravasation. These substances are generated through activation of neural pathways, including some that traffic through the vagus nerves that link the esophagus or airways.
    No preview · Article · Dec 2001 · The American Journal of Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: To evaluate the correlation between the degree of basement membrane (BM) preservation and clinicopathological characteristics in the replacement-growth type (lepidic growth type) of small peripheral adenocarcinomas of the lung, the BM components of 72 surgically resected replacement-growth type adenocarcinomas of the lung, 2 cm or less in diameter, were evaluated immunohistochemically by using a monoclonal antibody to Type IV collagen and polyclonal antibodies to 7S collagen and laminin. The tumors were classified into the following three distinctive histological types according to the condition of the elastic framework: Type I, bronchioloalveolar carcinoma without fibrotic foci; Type II, sclerosing bronchioloalveolar carcinoma without elastic framework destruction; and Type III, sclerosing bronchioloalveolar carcinoma with elastic framework destruction. The BM was well preserved in the area of bronchioloalveolar spread along fully expanded alveoli in all tumor types; however, BM preservation was significantly lost in the areas of collapsed alveoli in Type III tumors. There were no BM component staining reactions in the scarred regions of Type III tumors. In addition, lymph node metastasis was significantly greater in Type III tumors and BM-destroyed tumors. We concluded that the BM was largely destroyed by tumor cell invasion in the scarred region of Type III adenocarcinomas. Type III tumors had discontinuous BMs in the area of collapsed alveoli, indicating that this BM-destructive pattern must be the first step in tumor invasion. Type I and II tumors were concluded to be noninvasive adenocarcinomas, because their BM components were well preserved and they had a good outcome.Keywords: Adenocarcinoma, Basement membrane, Bronchioloalveolar carcinoma, Early invasion, Laminin, Lung cancer, Type IV collagen
    Preview · Article · Nov 2001 · Modern Pathology
  • [Show abstract] [Hide abstract] ABSTRACT: The antigen KL-6, a mucin-like high-molecular-weight glycoprotein, is expressed on type-2 pneumocytes and bronchiolar epithelial cells. Serum levels of KL-6 have been shown to correlate well with the activities of several different kinds of interstitial pneumonia. The purpose of this study was to assess the usefulness of monitoring serum KL-6 levels in patients who had received thoracic radiotherapy (TRT). In particular, the usefulness of such a protocol for the early diagnosis of severe radiation pneumonitis (RP) and the evaluation of its progress and severity was examined. Serum KL-6 levels were retrospectively monitored in 16 patients with lung cancer who had received TRT with or without chemotherapy. Eight of these patients had developed severe RP and eight had developed localized (within the irradiated field) RP. Serum KL-6 levels were measured using a modified sandwich-type enzyme-linked immunosorbent assay. In patients who developed severe RP, serum KL-6 levels showed a consistent tendency to increase after the clinical diagnosis of RP. In four patients, serum KL-6 levels even began to rise before a clinical diagnosis of severe RP had been made. In the patients with localized RP, on the other hand, the serum levels did not show any tendency to increase during or after TRT. Moreover, patients whose serum KL-6 levels rose more than 1.5 times higher than their pre-treatment serum KL-6 level, had a large chance of developing severe RP that was unresponsive to steroid hormones and resulted in death. Serum KL-6 levels, therefore, should be useful indicators for the early diagnosis of severe RP and for estimating its progress and severity in patients treated with TRT.
    No preview · Article · Nov 2001 · Lung Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: We describe a 74-year-old patient with dyspnoea and tachypnoea induced by chlorpromadinone acetate, a synthetic progesterone used to treat prostatic hyperplasia. The dyspnoea, tachypnoea and hypocapnia improved after discontinuing the chlorpromadinone acetate. It is important to recognize that synthetic progesterones can cause dyspnoea and hyperventilation.
    No preview · Article · Oct 2001 · Respirology
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    [Show abstract] [Hide abstract] ABSTRACT: We previously reported an epitope presenting vector, pCI, a derivative of a human invariant chain (Ii) expression vector, in which the class II associated invariant chain peptide (CLIP, Ii p89-101) could be substituted with antigenic peptides. In the current study, we used this vector to develop a new expression cloning system to identify CD4+ T cell epitopes. We inserted double-stranded oligo DNAs of randomized sequences into this vector and prepared an epitope-presenting library which loads randomized 13-mer peptides onto HLA class II molecules coexpressed in COS-7 cells. Utilizing this library, we isolated a cross-reactive epitope recognized by a glutamic acid decarboxylase (GAD) 65-autoreactive T cell clone established from a patient with insulin-dependent diabetes mellitus. Although the newly identified epitope (PVQLSNQWHVVGATF) was far different from the original epitope, GAD65 p116-128 (NILLQYVVKSFDR), it did have the capacity to stimulate the T cell clone comparable to that of the original GAD epitope. Our system may be applicable not only for identifying of cross-reactive epitopes for CD4+ T cells of known specificity, but also for detection of epitopes stimulatory for CD4+ T cells the epitopes of which are unknown.
    Full-text · Article · Jul 2001 · Biochemical and Biophysical Research Communications
  • [Show abstract] [Hide abstract] ABSTRACT: The inflammatory process in granulomatous disorders such as sarcoidosis is mainly the consequence of delayed hypersensitivity induced by causative antigens. Propionibacterial DNA was isolated recently by PCR from human sarcoidosis tissue. Hence, we developed a model using sensitized rabbits for T cell-mediated pulmonary granulomatosis induced by Propionibacterium acnes (P. acnes) and investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of the granuloma formation in vivo. Intravenous injection of P. acnes into sensitized rabbits induced massive pulmonary granulomas on day 3. Maximum levels of MCP-1 in sera and bronchoalveolar lavage fluid (BALF) were detected on day 1 and preceded recruitment of monocyte/macrophages and T cells. In BALF, monocyte chemotaxis peaked 1 day after P. acnes challenge, and T cell chemotaxis peaked 3 days after P. acnes challenge. Anti-MCP-1 IgG inhibited monocyte chemotaxis by 80.2% and T cell chemotaxis by 35.7%. Phenotypic analysis of migrating T cells revealed that activated and memory T cells (CD26(+)/CD45RO(+)) but not naive cells were preferentially attracted to BALF. Administration of MCP-1 antiserum in vivo inhibited the development of granulomas in both size 59.9% reduction and number 28.6% reduction, the number of infiltrating leukocytes in BALF, and the expression of adhesion molecules on leukocytes in peripheral blood and BALF. Our data indicate that MCP-1 plays important roles in granuloma formation by attracting and activating specific types of cells in this model. Furthermore, results suggest that the rabbit model resembles human angiocentric granulomatosis and would be useful for investigating the immunopathogenesis of human pulmonary granulomatosis.
    No preview · Article · May 2001 · Microscopy Research and Technique

Publication Stats

5k Citations
832.26 Total Impact Points


  • 1986-2009
    • Kumamoto University
      • • School of Medicine
      • • Department of Medical Biochemistry
      Kumamoto, Kumamoto, Japan
  • 1999
    • University of British Columbia - Vancouver
      • Department of Radiology
      Vancouver, British Columbia, Canada
  • 1996-1999
    • Umeå University
      • Department of Medical Biochemistry and Biophysics
      Umeå, Vaesterbotten, Sweden
  • 1994
    • National Cancer Institute (USA)
      • Laboratory of Tumor Immunology and Biology
      베서스다, Maryland, United States