Comparison of Pulmonary Involvement Between Patients Expressing Anti-PL-7 and Anti-Jo-1 Antibodies

Anti-PL-7 is an anti-tRNA synthetase antibody, and interstitial lung disease (ILD) is the most frequent complication of anti-PL-7-associated antisynthetase syndrome. However, the features of ILD have not been fully elucidated. The present study retrospectively compares 7 and 15 patients who were positive for anti-PL-7 and anti-Jo-1 antibodies, respectively. The features of ILD did not significantly differ between the two groups, but the ratio of lymphocytes in bronchoalveolar lavage fluid was higher in the Jo-1 than in the PL-7 group. High-resolution computed tomography revealed nonspecific interstitial pneumonia in all patients in the PL-7 group and organizing pneumonia in four of the 15 patients in the Jo-1 group. These findings suggest that pulmonary complications slightly differ between patients expressing anti-PL-7 and anti-Jo-1 antibodies. Further studies are required to clarify the features of ILD associated with PL-7

Myelodysplastic Syndromes in Atomic Bomb Survivors in Nagasaki: A Preliminary Analysis

Myelodysplastic syndromes (MDS) are a heterogenous hematological group characterized by an ineffective hematopoiesis resulting in a variety of cytopenias, morphological abnormalities of blood cells, chromosomal aberrations, and an increases risk of transformation into acute myeloid leukemia. Despite of its nature of close relation to leukemia, MDS has been not well investigated in atomic bomb (A-bomb) survivors. We conducted a retrospective cohort study with over 80,000 A-bomb survivors in Nagasaki to assess the incidence of MDS and its relation with A-bomb exposure status. In a preliminary analysis, we confirmed 162 MDS cases during 1980 to 2004. The median age at diagnosis was 71 years old. The incidence rate was higher in men than women, and an inverse relationship was observed between incidence of MDS and the distance from the hypocenter. We suggest that A-bomb radiation may affect the occurrence of MDS in A-bomb survivors even more than 50 years passed after the explosion. Further detail analyses are necessary to confirm these results

Bronchiolitis in a Patient with Ulcerative Colitis Treated with Erythromycin

A 47-year-old man was referred to our hospital with an abnormal shadow on a chest X-ray. He had a history of untreated chronic sinusitis and suspected ulcerative colitis (UC). Chest CT revealed a diffuse centrilobular granular shadow, while laboratory tests demonstrated an increased proportion of neutrophils; however, no microorganisms were detected in bronchoalveolar lavage fluid. Therefore, sinobronchial syndrome or small airway disease associated with UC was diagnosed, and the patient was treated with long-term erythromycin therapy. Small airway disease associated with UC is usually treated with steroids. Our experience shows that airway involvement in patients with inflammatory bowel disease can be treated with macrolides

A Japanese Patient with Lofgren’s Syndrome with an HLA-DR12 Allele and Review of Literature on Japanese Patients

Sarcoidosis is a granulomatous disorder of unknown etiology, with several clinical manifestations. Lofgren’s syndrome is an acute type of sarcoidosis, characterized by the triad of arthritis, erythema nodosum, and bilateral hilar lymphadenopathy (BHL), which spontaneously resolve within about 2 years. Lofgren’s syndrome is common among young white women from Nordic countries and Ireland, but it is very rare in Japan. Because the incidence of Lofgren’s syndrome varies according to race, most studies on Lofgren’s syndrome, including HLA typing, have been reported in Western countries. Indeed, HLA-DR3 has been reported to be associated with Lofgren’s syndrome in Western countries, although the association between HLA typing and Japanese Lofgren’s syndrome remains unclear. Here we present a Japanese patient with Lofgren’s syndrome. A 34-year-old female patient was hospitalized with arthritis and erythema nodosum. Chest computed tomography revealed mediastinal and BHL. Endobronchial ultrasound-guided transbronchial needle aspiration showed non-caseating epithelioid cell granulomas. Lofgren’s syndrome was thus diagnosed. Her ankle arthralgia and bilateral ankle swelling recovered without steroid treatment within two months, and the BHL almost completely diminished one year after admission. Her HLA genotype contains DR12. We also reviewed the literature on 11 Japanese patients with Lofgren’s syndrome, showing that HLA-DR12 is present in fve out of nine patients (55.6%). The relevant data were unavailable in the remaining three patients. Importantly, only 5.4% of registered donors in the Japan Marrow Donor Program are positive for this allele. We suggest the potential link between HLA-DR12 and the pathogenesis of Lofgren’s syndrome in Japanese patients

An Autopsy Case of Hermansky-Pudlak Syndrome: A Case Report and Review of the Literature on Treatment

Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder, the most common complication of which influencing the prognosis is pulmonary fibrosis. In the present report, we describe an autopsy case of a Japanese woman with HPS. The patient was diagnosed at 50 years of age based on the presence of oculocutane-ous albinism, hemorrhagic diathesis, ceroid-lipofuscin accumulation and pulmonary fibrosis. Although systemic steroids, immunosuppressants and pirfenidone were administered for pulmonary involvement, she died from respiratory failure two years later. Obtaining an early diagnosis and taking into consideration the need for lung transplantation is necessary in order to improve the prognosis of HPS. We herein report this very rare Japanese case of HPS with a review of the treatment approaches for HPS complicated with pulmonary fibrosis

ヘリコバクター・ピロリVacAの肺内同定とその呼吸器系細胞への作用

Objective: Prior reports suggested that infection with Helicobacter pylori was associated with respiratory diseases; pathogenetic mechanisms however, were not defined. We tested the hypothesis that VacA, an exotoxin of H. pylori, a gastric pathogen, was aspirated into the lung and could stimulate secretion of inflammatory cytokines by lung epithelial cells. Methods: The presence of VacA was determined by immunohistochemistry in surgical lung biopsy tissue samples from 72 patients with interstitial pneumonia. The effects of VacA on A549 human alveolar epithelial adenocarcinoma cells and normal human bronchial epithelial cells were determined. After incubation with VacA, the secretions of cytokines were measured by Multiplex LuminexR Assays. Results: VacA was detected with anti-VacA antibodies in bronchial epithelial cells and alveolar epithelialcells from 10 of 72 patients with interstitial pneumonia. VacA was more prevalent in lungs of patients with collagen vascular disease-associated interstitial pneumonia than in those of patients with idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia and cryptogenic organizing pneumonia. Incubation of A549 cells and normal human bronchial epithelial cells with VacA for 24 h was cytotoxic, andresulted in vacuolation. VacA induced interleukin-8 production by A549 cells and normal human bronchial epithelial cells and interleukin-6 production by A549 cells. Based on multiplex screening,interleukin-8 and interleukin-6 were the primary secretory products induced by VacA.Conclusions: H. pylori VacA is present in human lung and can induce interleukin-8 and interleukin-6 production by human lung cells. VacA could have a role in the pathogenesis of respiratory diseases byits cytotoxic effects and by inducing the secretion of interleukin-8 and interleukin-6 by targeted airway epithelial cells.長崎大学学位論文 学位記番号:博(医歯薬)甲第792号 学位授与年月日:平成27年8月5日Nagasaki University (長崎大学)課程博