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Inoue Y.,Shimada Municipal Hospital
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society | Year: 2010

A 73-year-old man was admitted with high fever and right chest pain. Chest X-ray showed a rapidly growing mass shadow in the right lower lung field. The patient had been in remission for malignant lymphoma and had developed interstitial pneumonia and diabetes mellitus following 1 year of corticosteroid therapy. His illness was diagnosed as invasive aspergillosis because of a high level of beta-D-glucan and cultured Aspergillus fumigatus in the sputum. He was treated with a combination of micafungin and itraconazole. However, because these agents did not improve his clinical condition, transbronchial lung biopsy was performed. Histologically, Mucor hyphae were detected in these specimens. Micafungin and itraconazole were stopped and infusion of liposomal amphotericin B was initiated. Because his condition worsened, a right lower lobectomy was performed. Rhizopus Oryzae was detected in the lung tissue. We report a case of pulmonary mucormycosis in which mixed infection with A. fumigatus was suspected. Pulmonary mucormycosis is a life-threatening infection in which it is rare that an antemortem diagnosis is established and organisms are isolated. We believe diagnostic tests should be performed aggressively, even when pulmonary aspergillosis is suspected.

Saheki T.,Tokushima Bunri University | Inoue K.,Tokushima Bunri University | Tushima A.,Tokushima Bunri University | Mutoh K.,Shimada Municipal Hospital | Kobayashi K.,Kagoshima University
Molecular Genetics and Metabolism | Year: 2010

In this paper, we describe the historical aspects of citrin and citrin deficiency, characteristic food preference and food aversion of citrin-deficient subjects, and carbohydrate toxicity in relation to ureogenesis and issues of the conventional treatment procedures for hyperammonemia in citrin deficiency, leading to current treatment concepts for citrin deficiency. We also emphasize the importance of a citrin deficiency mouse model in elucidating the pathophysiology and developing novel therapeutics based on the pathophysiology, such as sodium pyruvate. © 2010 Elsevier Inc. All rights reserved.

Fujiyama T.,Hamamatsu University School of Medicine | Ito T.,Hamamatsu University School of Medicine | Ogawa N.,Hamamatsu University School of Medicine | Suda T.,Hamamatsu University School of Medicine | And 2 more authors.
Clinical and Experimental Immunology | Year: 2014

Dermatomyositis (DM) and polymyositis (PM) are collectively termed autoimmune myopathy. To investigate the difference between muscle- and skin-infiltrating T cells and to address their role for myopathy, we characterized T cells that were directly expanded from the tissues. Enrolled into this study were 25 patients with DM and three patients with PM. Muscle and skin biopsied specimens were immersed in cRPMI medium supplemented with interleukin (IL)-2 and anti-CD3/CD28 antibody-conjugated microbeads. The expanded cells were subjected to flow cytometry to examine their phenotypes. We analysed the cytokine concentration in the culture supernatants from the expanded T cells and the frequencies of cytokine-bearing cells by intracellular staining. There was non-biased in-vitro expansion of tissue-infiltrating CD4+ and CD8+ T cells from the muscle and skin specimens. The majority of expanded T cells were chemokine receptor (CCR) type 7-CD45RO+ effecter memory cells with various T cell receptor (TCR) Vβs. The skin-derived but not muscle-derived T cells expressed cutaneous lymphocyte antigen (CLA) and CCR10 and secreted large amounts of IL-17A, suggesting that T helper type 17 (Th17) cells may have a crucial role in the development of skin lesions. Notably, the frequency of IL-4-producing chemokine (C-X-C motif) receptor (CXCR)4+ Th2 cells was significantly higher in the muscle-derived cells and correlated inversely with the serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels. stromal-derived factor (SDF)-1/CXCL12, a ligand for CXCR4, was expressed at a high level in the vascular endothelial cells between muscular fasciculi. Our study suggests that T cell populations in the muscle and skin are different, and the Th2 cell infiltrate in the muscle is associated with the low severity of myositis in DM. © 2014 British Society for Immunology.

Ito T.,Hamamatsu University School of Medicine | Hashizume H.,Shimada Municipal Hospital | Shimauchi T.,Hamamatsu University School of Medicine | Funakoshi A.,Hamamatsu University School of Medicine | And 4 more authors.
Journal of Dermatological Science | Year: 2013

Background: Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease. T lymphocytes densely surround lesional hair bulbs, which is histologically referred to as " swarm of bees" However, pathomechanisms of " swarm of bees" are still uncertain. Objective: We investigated the pathological mechanisms of " swarm of bees" , focusing on T-cell chemotaxis so that inhibition of chemotaxis may be strong candidate of novel treatments for AA. Methods: We investigate the expression of chemokine receptors on T cells obtained from peripheral blood mononuclear cells (PBMCs) and skin infiltrating cells in AA patients. In addition, real-time chemotaxis assay was also demonstrated. Results: In PBMCs, the frequency of CXCR3+CD4+ T cells (Th1) was significantly higher in acute-phase AA than in chronic-phase AA or healthy control, while CXCR3+CD8+ T cells (Tc1) were significantly increased in chronic-phase AA. In the skin lesions of acute-phase AA, CXCR3+CD4+ and CXCR3+CD8+ T cells infiltrated in the juxta-follicular area. In chronic-phase AA, CXCR3+CD8+ T cells dominated the infiltrate around hair bulbs, possibly contributing to the prolonged state of hair loss. Lymphocytes obtained from a lesional skin of acute-phase AA contained CXCR3+CD4+ and CXCR3+CD8+ T cells at higher percentages than those of PBMCs, suggesting preferential emigration from the blood. Immunohistochemical and real-time RT-PCR studies demonstrated that hair follicles of acute-phase AA expressed a high level of Th1-associated chemokine CXCL10. By chemotaxis assay, freshly isolated PBMCs from acute-phase AA patients had a strong velocity of chemotaxis toward CXCL10 with increased expression of F-actin. Conclusions: These results suggest that the increased production of CXCL10 from hair follicles induces preferential infiltrates of highly chemoattracted Th1 and Tc1 cells in the acute phase of AA, and Tc1 infiltration remains prolonged in the chronic phase. © 2012 Japanese Society for Investigative Dermatology.

Taniguchi T.,Kyoto University | Morimoto T.,Hyogo College of Medicine | Shiomi H.,Kyoto University | Ando K.,Kokura Memorial Hospital | And 32 more authors.
Journal of the American College of Cardiology | Year: 2015

Background Current guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS). Objectives The study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS. Methods We used data from a large multicenter registry enrolling 3,815 consecutive patients with severe AS (peak aortic jet velocity >4.0 m/s, or mean aortic pressure gradient >40 mm Hg, or aortic valve area <1.0 cm2) between January 2003 and December 2011. Among 1,808 asymptomatic patients, the initial AVR and conservative strategies were chosen in 291 patients, and 1,517 patients, respectively. Median follow-up was 1,361 days with 90% follow-up rate at 2 years. The propensity score-matched cohort of 582 patients (n = 291 in each group) was developed as the main analysis set for the current report. Results Baseline characteristics of the propensity score-matched cohort were largely comparable, except for the slightly younger age and the greater AS severity in the initial AVR group. In the conservative group, AVR was performed in 41% of patients during follow-up. The cumulative 5-year incidences of all-cause death and heart failure hospitalization were significantly lower in the initial AVR group than in the conservative group (15.4% vs. 26.4%, p = 0.009; 3.8% vs. 19.9%, p < 0.001, respectively). Conclusions The long-term outcome of asymptomatic patients with severe AS was dismal when managed conservatively in this real-world analysis and might be substantially improved by an initial AVR strategy. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140) © 2015 American College of Cardiology Foundation.

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