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Takami, Akiyoshi ; Asakura, Hidesaku ; Koshida, Kiyoshi ; Namiki, Mikio ; Nakao, Shinji ; 高見, 昭良 ; 朝倉, 英策 ; 越田, 潔 ; 並木, 幹夫 ; 中尾, 眞二
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金沢大学医薬保健研究域医学系<br />We report the cases of 3 patients with advanced renal cell carcinoma who underwent reduced-intensity
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allogeneic stem cell transplantation. In 2 partial responders, histologic analyses of metastases revealed prominent accumulation of CD8+ T cells and degenerative changes of clear cell carcinoma, suggestive of induction of tumor-specific cytotoxic T lymphocytes.
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Nakao, Shinji ; Ishiyama, Ken
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Embargo Period 12 months
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Ishiyama, Ken ; Yamazaki, Hirohito ; Senda, Yasuko ; Yamauchi, Hiromasa ; Nakao, Shinji
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金沢大学医薬保健研究域医学系 <br />東京都立大塚病院 血液内科（輸血科）<br />Leuconostoc is a Gram-positive coccus characterized by its resistance to
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glycopeptide antibiotics. Generally, this bacterium is susceptible to β-lactam antibiotics; however, here we present a leukemia patient who developed leuconostoc bacteremia during antimicrobial therapy with carbapenem. The appropriate choice of antibiotics at optimal doses enables leuconostoc infection to be overcome, even in compromised hosts. We report 3 cases of leuconostoc bacteremia: the leukemia case which was successfully treated, along with discussions of two other cases with malignancies. © 2010 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
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Yoshimoto, Akihiro ; Nakamura, Hiroyuki ; Fujimura, Masaki ; Nakao, Shinji
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金沢大学医薬保健研究域医学系<br />Objective: To evaluate severe community-acquired pneumonia (SCAP) patients in an intensive care unit
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(ICU) with regard to risk factors for mortality and to compare ICU patients with matched non-ICU patients to evaluate whether our judgement for ICU admission was appropriate or not. Materials and methods: During a 7-year period, all patients with CAP who were admitted to the ICU were examined. They underwent clinical and radiographic evaluations, and two commonly used severity of illness scores were also calculated using the Simplified Acute Physiological Score (SAPS) and the Acute Physiology and Chronic Health Evaluation (APACHE) II methods. To detect risk factors for ICU admission using existing guidelines, each study patient was matched with two patients hospitalized in a general medical ward. Results: Seventy-two patients were identified during the study period. Their mean age was 72.9 years, and 35 patients (48.6%) subsequently died. For the univariate analysis, there were significant differences with the pulse rate ≥130/min, blood urea nitrogen ≥30 mg/dl, multilobar shadow, SAPS ≥43, APACHE II ≥23, and the occurrence of septic shock between the survivors and those who died. For the multivariate analysis, septic shock (p=0.0005, odds ratio of 26.6) and blood urea nitrogen ≥30 mg/dl (p=0.037, odds ratio of 5.38) were associated with mortality. Regarding the characteristics of different clinical predictions for ICU admission, the revised American Thoracic Society criteria might have been the most accurate. Conclusion: Septic shock was associated with high mortality, which is a more accurate and higher predictor of mortality than was physical examination, laboratory or radiographic findings.
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Takato, Hazuki ; Yasui, Masahide ; Ichikawa, Yukari ; Fujimura, Masaki ; Nakao, Shinji ; Zen, Yoh ; Minato, Hiroshi
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金沢大学医薬保健研究域医学系<br />Recently, great attention has been drawn to IgG4-related diseases such as autoimmune pancreatitis (A
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IP) sclerosing sialadenitis, retroperitoneum fibrosis, sclerosing cholangitis. IgG4-related diseases are characterized by high serum IgG4 concentrations, sclerosing inflammation with numerous IgG4-positive plasma cells, and steroid sensitivity irrespective of their organs of origin. In this report, we describe a case of nonspecific interstitial pneumonia, in which possible involvement of IgG4 was suggested. The patient was 59-year-old man, who was found to have bilateral interstitial pneumonia. Laboratory tests revealed that he had antinuclear antibody and a high serum IgG4 concentration. Pathological examination of the video-assisted thoracic surgery biopsy taken from the right lower lobe showed interstitial thickening associated with lymphoplasmacytic infiltration containing many IgG4-positive plasma cells. He was effectively treated by corticosteroid. The present case had many clinical and clinicopathologic similarities to systemic IgG4-related autoimmune disease. There have been no descriptions on isolated interstitial pneumonia with IgG4-positive plasma cell infiltration. This case suggested that IgG4-related disorders could also occur in the lung, and interstitial pneumonia may be a pulmonary manifestation of systemic IgG4-related autoimmune disease © 2008 The Japanese Society of Internal Medicine.
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Watanabe, Kazuyoshi ; Fujimura, Masaki ; Kasahara, Kazuo ; Yasui, Masahide ; Myou, Shigeharu ; Kita, Toshiyuki ; Watanabe, Akira ; Nakao, Shinji
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金沢大学医薬保健研究域医学系<br />A 21-year-old woman presented with acute progressive dyspnea. Chest computed tomography (CT) reveale
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d diffuse bilateral infiltrates. Based on the results of transbronchial lung biopsy (TBLB) and bronchoalveolar lavage fluid (BALF) and her clinical course, she was diagnosed as having acute eosinophilic pneumonia. We suspected that the disease was related to smoking because she had started smoking ten days before the onset of symptoms. Therefore, a cigarette-smoking challenge test was done with the patient's informed consent. After the challenge, eosinophilic pneumonia was documented by BALF and TBLB findings, which were similar to those detected on admission, without significant radiographic findings.
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Kita, Toshiyuki ; Fujimura, Masaki ; Sone, Takashi ; Inuzuka, Kanako ; Myou, Shigeharu ; Nakao, Shinji
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金沢大学医薬保健研究域医学系<br />Background and Objective: The purpose of this study was to evaluate the relationship between the wal
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l structure assessed by using endobronchial ultrasonography (EBUS) and bronchial hyperresponsiveness in patients with asthma. Methods: Twenty-four patients with stable asthma and 11 individuals without asthma were studied. EBUS was performed with a radial 20-MHz ultrasonic probe inserted into the intermediate bronchus undergoing flexible bronchoscopy to assess the airway wall structure. The percentage of airway wall thickness {WT%; defined as [(ideal outer diameter-ideal luminal diameter)/ideal outer diameter] × 100} was determined by EBUS. We measured bronchial hyperresponsiveness to methacholine [the provocative concentration of methacholine causing a decrease of 20% or more in forced expiratory volume in 1 s (PC20)]. Results: Percentage wall thickness measured by EBUS was significantly greater in patients with asthma than that in subjects without asthma (P < 0.01). The evaluation of the laminar structure using EBUS indicated that the thickness of the second layer in patients with asthma was greater than that in subjects without asthma (P < 0.05). PC20 was negatively correlated with the thickness of the second layer (r=0.52, P < 0.01) but was not significantly correlated with other layers in patients with asthma. Conclusions: The evaluation of the bronchial mural structure using EBUS might be advantageous for assessing the relationship between airway wall remodeling and bronchial hyperresponsiveness. © 2010 Lippincott Williams & Wilkins.
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Katagiri, Takamasa ; Shiobara, Shintaro ; Nakao, Shinji ; Wakano, Miki ; Muranaka, Eriko ; Kuba, Nahoko ; Furukawa, Tatsuo ; Tsukada, Junichi ; Takeda, Hiroko ; Aizawa, Yoshifusa ; Harada, Mine
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金沢大学大学院医学系研究科<br />We determined the alleles of five polymorphic molecules including HA-1 and four adhesion molecules fo
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r 106 patients transplanted with HLA-identical stem cell grafts and investigated the association of mismatches as correlates of relapse and graft-versus-host disease (GVHD). All 106 recipients underwent stem cell transplantation (SCT) after myeloablative conditioning between 1985 and 2002. Risk status of disease at SCT was standard (n = 63) and high (n = 42). After SCT, 36, 49 and 33 developed acute GVHD, chronic GVHD and relapsed, respectively. Our patients relapsed at rates of 16.7 and 38.6% with one or more and without incompatibilities (P = 0.013). The relapse rates of patients with CD62L, CD31 codon 563, CD31 codon 125, HA-1 and CD49b incompatibilities were 5.9, 11.8, 15.4, 16.0 and 33.3%, respectively. The frequency of acute GVHD did not differ regardless of incompatibilities. In standard-risk group, the accumulated relapse rates of 19 and 44 patients with and without minor histocompatibility antigen incompatibility were 22% and unexpectedly 66%, respectively (P = 0.02). The probability of 12-year survival was 88% in the former and 66% in the latter patients (P = 0.03). Our data suggest that incompatibility of CD62L, CD31 codon 563 and CD31 codon 125 contributes to a graft-versus-leukemia effect rather than to GVHD, resulting in prolonged survival after HLA-identical SCT.
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| 9.
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Okumura, Hirokazu ; Yamaguchi, Masaki ; Kotani, Takeharu ; Sugimori, Naomi ; Sugimori, Chiharu ; Ozaki, Jun ; Kondo, Yukio ; Yamazaki, Hirohito ; Chuhjo, Tatsuya ; Takami, Akiyoshi ; Ueda, Mikio ; Ohtake, Shigeki ; Nakao, Shinji
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金沢大学大学院医学系研究科機能再生学<br />Human leukocyte antigen (HLA)-mismatched stem cell transplantation from non-inherited maternal a
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ntigen (NIMA)-complementary donors is known to produce stable engraftment without inducing severe graft-versus-host disease (GVHD). We treated two patients with acute myeloid leukemia (AML) and one patient with severe aplastic anemia (SAA) with HLA-mismatched stem cell transplantation (SCT) from NIMA-complementary donors (NIMA-mismatched SCT). The presence of donor and recipient-derived blood cells in the peripheral blood of recipient (donor microchimerism) and donor was documented respectively by amplifying NIMA-derived DNA in two of the three patients. Graft rejection occurred in the SAA patient who was conditioned with a fludarabine-based regimen. Grade III and grade IV acute GVHD developed in patients with AML on day 8 and day 11 respectively, and became a direct cause of death in one patient. The findings suggest that intensive conditioning and immunosuppression after stem cell transplantation are needed in NIMA-mismatched SCT even if donor and recipient microchimerisms is detectable in the donor and recipient before SCT. © 2007 The Authors.
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| 10.
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Hara, Johsuke ; Fujimura, Masaki ; Myou, Shigeharu ; Oribe, Yoshitaka ; Furusho, Shiho ; Kita, Toshiyuki ; Katayama, Nobuyuki ; Abo, Miki ; Ohkura, Noriyuki ; Herai, Yoriko ; Hori, Akihiro ; Ishiura, Yoshihisa ; Nobata, Kouichi ; Ogawa, Haruhiko ; Yasui, Masahide ; Kasahara, Kazuo ; Nakao, Shinji
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金沢大学大学院医学系研究科機能再生学<br />Background Late asthmatic response is observed following antigen challenge in actively, but not
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passively, sensitized guinea pigs. Although cough reflex sensitivity is increased after antigen challenge in actively sensitized guinea pigs, it is unknown whether the antigen-induced increase in cough reflex sensitivity develops in passively sensitized animals. The aim of this study was to compare the cough reflex sensitivity to inhaled capsaicin after an inhaled antigen challenge between actively and passively sensitized guinea pigs. Methods Measurement of number of coughs elicited by increasing concentrations of capsaicin (10-6 and 10-4 M) and bronchial responsiveness to ascending concentrations of methacholine, and analysis of bronchoalveolar lavage fluid (BALF) were separately performed 24 h after an antigen challenge in actively and passively sensitized guinea pigs. Results Percentage of eosinophils in BALF and bronchial responsiveness to methacholine were increased 24 h after the antigen challenge in both actively and passively sensitized animals compared with saline-challenged actively and passively sensitized animals, respectively. Absolute number of eosinophils in BALF from actively sensitized and antigen-challenged guinea pigs was significantly greater than that from passively sensitized and antigen-challenged animals. Cough response to capsaicin and concentration of substance P in BALF were increased 24 h after the antigen challenge in actively sensitized guinea pigs, but not in passively sensitized guinea pigs. Bronchial responsiveness, cough reflex sensitivity and substance P concentration and total cells in BALF were increased in actively sensitized and saline challenged guinea pigs compared with passively sensitized and saline challenged animals. Conclusion The results suggest that active sensitization per se increases cough reflex sensitivity accompanied by increased inflammatory cells and substance P level in BALF, and antigen challenge further increases them, while simple IgE- and/or IgG-mediated allergic reaction per se or the low intensity of eosinophil infiltration in the airway itself may not affect cough reflex sensitivity in guinea pigs.
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