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1.
Stem Cells ; 41(8): 809-820, 2023 08 16.
Article in English | MEDLINE | ID: mdl-37468433

ABSTRACT

Single-cell RNA sequencing is a valuable tool for dissecting cellular heterogeneity in complex systems. However, it is still challenging to estimate the proliferation and differentiation potentials of subpopulations within dormant tissue stem cells. Here, we established a new single-cell analysis method for profiling the organoid-forming capacity and differentiation potential of tissue stem cells to disclose stem cell subpopulations by integrating single-cell morphometrics, organoid-forming assay, and RNA sequencing, a method named scMORN. To explore lung epithelial stem cells, we initially developed feeder-free culture system, which could expand all major lung stem cells, including basal, club, and alveolar type 2 (AT2) cells, and found that club cells contained a subpopulation, which showed better survival rate and high proliferation capacity and could differentiate into alveolar cells. Using the scMORN method, we discovered a club cell subpopulation named Muc5b+ and large club (ML-club) cells that efficiently formed organoids than other club or AT2 cells in our feeder-free organoid culture and differentiated into alveolar cells in vitro. Single-cell transcriptome profiling and immunohistochemical analysis revealed that ML-club cells localized at the intrapulmonary proximal airway and distinct from known subpopulations of club cells such as BASCs. Furthermore, we identified CD14 as a cell surface antigen of ML-club cells and showed that purified CD14+ club cells engrafted into injured mouse lungs had better engraftment rate and expansion than other major lung stem cells, reflecting the observations in organoid culture systems. The scMORN method could be adapted to different stem cell tissues to discover useful stem-cell subpopulations.


Subject(s)
Lung , Transcriptome , Animals , Mice , Transcriptome/genetics , Stem Cells/metabolism , Organoids/metabolism , Gene Expression Profiling , Cell Differentiation
2.
Pathol Int ; 74(9): 538-545, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38994806

ABSTRACT

Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous syndrome associated with systemic complications that involve multiple organs, including the skin, central nervous system, eyes, and skeleton. LNSS is considered to be caused by mosaic RAS gene mutation. In this report, we present an autopsy case of LNSS in a Japanese boy. The affected neonate had hydrops fetalis and was born at 28 weeks and 4 days of gestation, weighing 2104 g. He had bilateral inverted eyelids, verrucous linear nevus separated along Blaschko's line, myocardial hypertrophy, and pharyngeal constriction, and underwent intensive treatment in NICU for arrhythmia, hydrocephalus, and respiratory distress. The hydrocephalus progressed gradually and he died at the age of 181 days, 12 days after a sudden cardiac arrest and recovery. KRAS G12D mutation was found in a skin biopsy specimen but not in blood cells, suggesting a postzygotic mosaicism. Autopsy revealed novel pathological findings related to LNSS, including intracranial lipomatous hamartoma and mesenteric lymphangioma, in addition to previously reported findings such as multicystic dysplastic kidney. There was the limited expression of mutated KRAS protein in kidneys.


Subject(s)
Autopsy , Mutation , Nevus, Sebaceous of Jadassohn , Proto-Oncogene Proteins p21(ras) , Humans , Male , Nevus, Sebaceous of Jadassohn/pathology , Nevus, Sebaceous of Jadassohn/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Infant, Newborn , Fatal Outcome
3.
Pathol Int ; 71(7): 453-462, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33819365

ABSTRACT

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients' antitumor immune response.


Subject(s)
Forkhead Transcription Factors/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Neoplasms, Glandular and Epithelial , Thymoma , Thymus Neoplasms , Adolescent , Adult , B-Lymphocytes/pathology , B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes/pathology , Cytodiagnosis , Diagnosis, Differential , Humans , Hyperplasia/pathology , Immunohistochemistry , Lymphocyte Count , Male , Middle Aged , Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/pathology , Thymoma/diagnosis , Thymoma/pathology , Thymus Neoplasms/diagnosis , Thymus Neoplasms/pathology , Tumor Microenvironment
4.
Respiration ; 100(1): 19-26, 2021.
Article in English | MEDLINE | ID: mdl-33401281

ABSTRACT

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare form of idiopathic interstitial pneumonia that is characterized by predominantly upper lobe pleural and subpleural lung parenchymal fibrosis. Pneumothorax is one of the major respiratory complications in PPFE patients; however, its clinical features are poorly understood. OBJECTIVE: We aimed to investigate the complication of pneumothorax in patients with idiopathic PPFE. METHODS: A retrospective multicenter study involving 89 patients who had been diagnosed with idiopathic PPFE was conducted. We investigated the cumulative incidence, clinical features, and risk factors of pneumothorax after the diagnosis of idiopathic PPFE. RESULTS: Pneumothorax developed in 53 patients (59.6%) with 120 events during the observation period (41.8 ± 35.0 months). The cumulative incidence of pneumothorax was 24.8, 44.9, and 53.9% at 1, 2, and 3 years, respectively. Most events of pneumothorax were asymptomatic (n = 85; 70.8%) and small in size (n = 92; 76.7%); 30 patients (56.6%) had recurrent pneumothorax. Chest drainage was required in 23 pneumothorax events (19.2%), and a persistent air leak was observed in 13 (56.5%). Patients with pneumothorax were predominantly male and frequently had pathological diagnoses of PPFE and prior history of pneumothorax and corticosteroid use; they also had significantly poorer survival than those without pneumothorax (log-rank test; p = 0.001). Multivariate analysis revealed that a higher residual volume/total lung capacity ratio was significantly associated with the development of pneumothorax after the diagnosis. CONCLUSION: Pneumothorax is often asymptomatic and recurrent in patients with idiopathic PPFE, leading to poor outcomes in some cases.


Subject(s)
Idiopathic Interstitial Pneumonias/complications , Idiopathic Pulmonary Fibrosis/complications , Lung , Pleura , Pneumothorax , Respiratory Function Tests , Aged , Asymptomatic Diseases/epidemiology , Asymptomatic Diseases/therapy , Female , Humans , Idiopathic Interstitial Pneumonias/diagnosis , Idiopathic Interstitial Pneumonias/physiopathology , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/physiopathology , Japan/epidemiology , Lung/diagnostic imaging , Lung/pathology , Male , Pleura/diagnostic imaging , Pleura/pathology , Pneumothorax/diagnosis , Pneumothorax/etiology , Pneumothorax/mortality , Pneumothorax/therapy , Residual Volume , Respiratory Function Tests/methods , Respiratory Function Tests/statistics & numerical data , Retrospective Studies , Severity of Illness Index , Survival Analysis , Thoracentesis/methods , Thoracentesis/statistics & numerical data , Tomography, X-Ray Computed/methods , Total Lung Capacity
5.
Lung ; 199(3): 289-298, 2021 06.
Article in English | MEDLINE | ID: mdl-33770226

ABSTRACT

PURPOSE: The differential diagnosis of interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF) versus other non-IPF ILDs, is important for selecting the appropriate treatment. This retrospective study aimed to explore the utility of gremlin-1 for the differential diagnosis. METHODS: Serum gremlin-1 concentrations were measured using an ELISA in 50 patients with IPF, 42 patients with non-IPF ILD, and 30 healthy controls. The baseline clinical data, including pulmonary functions, prognosis, and three serum biomarkers (Krebs von den Lungen-6 [KL6], surfactant protein-D [SP-D], and lactate dehydrogenase [LDH]), were obtained through a medical record review for analyzing their associations with serum gremlin-1 concentrations. To evaluate the origin of gremlin-1, we performed immunostaining on lung sections. RESULTS: Serum gremlin-1 concentrations were significantly higher in patients with IPF (mean concentration, 14.4 ng/mL), followed by those with non-IPF ILD (8.8 ng/mL) and healthy controls (1.6 ng/mL). The area under the curve for IPF versus non-IPF ILDs was 0.759 (95% confidence interval, 0.661-0.857), which was superior to that of KL6/SP-D/LDH. The sensitivity and specificity for gremlin-1 (cutoff, 10.4 ng/mL) was 72 and 69%, respectively. By contrast, serum gremlin-1 concentrations were not associated with the pulmonary functions nor the prognosis in all patients with ILDs. In immunostaining, the gremlin-1 was broadly upregulated in IPF lungs, particularly at myofibroblasts, bronchiolar/alveolar epithelium, and CD163-positive M2-like macrophages. CONCLUSIONS: Gremlin-1 may be a useful biomarker to improve the diagnostic accuracy for IPF compared to non-IPF ILDs, suggesting a role of this molecule in the pathogenesis of IPF.


Subject(s)
Gene Expression Regulation , Idiopathic Pulmonary Fibrosis/diagnosis , Intercellular Signaling Peptides and Proteins/genetics , Lung Diseases, Interstitial/diagnosis , Lung/diagnostic imaging , RNA, Messenger/genetics , Aged , Animals , Biomarkers/blood , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Idiopathic Pulmonary Fibrosis/blood , Idiopathic Pulmonary Fibrosis/genetics , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/biosynthesis , Intercellular Signaling Peptides and Proteins/blood , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/genetics , Male , Mice , Middle Aged , Prognosis , Retrospective Studies
6.
BMC Pulm Med ; 20(1): 21, 2020 Jan 21.
Article in English | MEDLINE | ID: mdl-31964365

ABSTRACT

BACKGROUND: Lung fibrosis is a serious life-threatening condition whose manifestation varies according to the localization and characteristics of fibroblasts, which are considered heterogeneous. Therefore, to better understand the pathology and improve diagnosis and treatment of this disease, it is necessary to elucidate the nature of this heterogeneity and identify markers for the accurate classification of human lung fibroblast subtypes. METHODS: We characterized distinct mouse lung fibroblast subpopulations isolated by fluorescence-activated cell sorting (FACS) and performed microarray analysis to identify molecular markers that could be useful for human lung fibroblast classification. Based on the expression of these markers, we evaluated the fibroblast-like cell subtype localization in normal human lung samples and lung samples from patients with idiopathic pulmonary fibrosis (IPF). RESULTS: Mouse lung fibroblasts were classified into Sca-1high fibroblasts and Sca-1low fibroblasts by in vitro biological analyses. Through microarray analysis, we demonstrated CD248 and integrin alpha-8 (ITGA8) as cell surface markers for Sca-1high fibroblasts and Sca-1low fibroblasts, respectively. In mouse lungs, Sca-1high fibroblasts and Sca-1low fibroblasts were localized in the collagen fiber-rich connective tissue and elastic fiber-rich connective tissue, respectively. In normal human lungs and IPF lungs, two corresponding major fibroblast-like cell subtypes were identified: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. CONCLUSION: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells were localized in an almost exclusive manner in human lung specimens. This human lung fibroblast classification using two cell surface markers may be helpful for further detailed investigations of the functions of lung fibroblast subtypes, which can provide new insights into lung development and the pathological processes underlying fibrotic lung diseases.


Subject(s)
Antigens, CD/metabolism , Antigens, Neoplasm/metabolism , Fibroblasts/metabolism , Idiopathic Pulmonary Fibrosis/pathology , Integrin alpha Chains/metabolism , Lung/cytology , Aged , Animals , Antigens, Ly/metabolism , Connective Tissue/pathology , Connective Tissue Cells , Elastic Tissue , Fibroblasts/classification , Flow Cytometry , Humans , In Vitro Techniques , Male , Membrane Proteins/metabolism , Mice , Middle Aged , Tissue Array Analysis
7.
Mod Rheumatol ; 30(2): 350-357, 2020 Mar.
Article in English | MEDLINE | ID: mdl-30924376

ABSTRACT

Objectives: Using a murine model of systemic Kawasaki disease (KD)-like vasculitis induced by Candida albicans cell-wall-derived mannan · ß-glucan · protein complexes, the objective was to elucidate the relationships of ß-glucan receptor dectin-1 (D1) and α-mannan receptor dectin-2 (D2) to the onset of that vasculitis.Methods: The incidence and histological severity of vasculitis were compared among mice lacking the genes for D1 or D2 (i.e. D1-/- and D2-/-) and wild-type (WT) mice.Results: The incidences of vasculitis in the three animal groups were 100% (18/18) in the WT group, 100% (18/18) in the D1-/- group, and 0% (0/18) in the D2-/- group. In the WT and D1-/- mice, severe inflammatory cell infiltration, consisting mainly of neutrophils and macrophages, was seen in the aortic root and the coronary arteries. On the other hand, in the D2-/- mice, not even mild vascular lesions such as endoarteritis were seen.Conclusion: Recognition of α-mannan by D2 played an important role in the onset of vasculitis in the studied murine model.


Subject(s)
Lectins, C-Type/metabolism , Mannans/pharmacology , Mucocutaneous Lymph Node Syndrome/metabolism , Vasculitis/metabolism , Animals , Aorta/metabolism , Aorta/pathology , Candida albicans/chemistry , Coronary Vessels/metabolism , Coronary Vessels/pathology , Lectins, C-Type/genetics , Macrophages/metabolism , Mannans/toxicity , Mice , Mucocutaneous Lymph Node Syndrome/etiology , Mucocutaneous Lymph Node Syndrome/pathology , Vasculitis/etiology , Vasculitis/pathology
8.
Eur Respir J ; 53(5)2019 05.
Article in English | MEDLINE | ID: mdl-30880283

ABSTRACT

Multidisciplinary discussion (MDD) requiring close communication between specialists (clinicians, radiologists and pathologists) is the gold standard for the diagnosis of idiopathic interstitial pneumonias (IIPs). However, MDD by specialists is not always feasible because they are often separated by time and location. An online database would facilitate data sharing and MDD. Our aims were to develop a nationwide cloud-based integrated database containing clinical, radiological and pathological data of patients with IIPs along with a web-based MDD system, and to validate the diagnostic utility of web-based MDD in IIPs.Clinical data, high-resolution computed tomography images and lung biopsy slides from patients with IIPs were digitised and uploaded to separate servers to develop a cloud-based integrated database. Web-based MDD was performed using the database and video-conferencing to reach a diagnosis.Clinical, radiological and pathological data of 524 patients in 39 institutions were collected, uploaded and incorporated into the cloud-based integrated database. Subsequently, web-based MDDs with a pulmonologist, radiologist and pathologist using the database and video-conferencing were successfully performed for the 465 cases with adequate data. Overall, the web-based MDD changed the institutional diagnosis in 219 cases (47%). Notably, the MDD diagnosis yielded better prognostic separation among the IIPs than did the institutional diagnosis.This is the first study of developing a nationwide cloud-based integrated database containing clinical, radiological and pathological data for web-based MDD in patients with IIPs. The database and the web-based MDD system that we built made MDD more feasible in practice, potentially increasing accurate diagnosis of IIPs.


Subject(s)
Cloud Computing , Data Management/organization & administration , Idiopathic Interstitial Pneumonias/diagnosis , Interdisciplinary Communication , Aged , Biopsy , Databases, Factual , Diagnosis, Differential , Female , Humans , Idiopathic Interstitial Pneumonias/mortality , Japan/epidemiology , Male , Middle Aged , Pathologists , Practice Patterns, Physicians' , Pulmonologists , Radiologists , Survival Analysis , Tomography, X-Ray Computed
10.
Chron Respir Dis ; 16: 1479972318809476, 2019.
Article in English | MEDLINE | ID: mdl-30380910

ABSTRACT

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a devastating condition that frequently occurs in the advanced stage of IPF. However, the clinical features in AE of connective tissue disease-associated interstitial pneumonia (AE-CTD-IP) have not been well-established. The aim of this study was to clarify the clinical features of AE-CTD-IP and to compare them with those of AE-IPF. Fifteen AE-CTD-IP patients and 48 AE-IPF patients who were diagnosed and treated at our hospital were retrospectively studied. Compared with AE-IPF patients, AE-CTD-IP patients had a significantly higher %FVC (median, 94.8 vs. 56.3%; p < 0.001) and a lower extent of honeycombing on HRCT ( p = 0.020) within 1 year before AE. At AE, AE-CTD-IP patients showed higher white blood cell counts (12.0 vs. 9.9 × 103/µL; p = 0.023), higher CRP (10.2 vs. 6.7 mg/dL; p = 0.027), and longer period from admission to the beginning of AE treatment (4 vs. 1 days; p = 0.003) than AE-IPF patients. In addition, patients with AE-CTD-IP had poor prognosis as in those with AE-IPF (log-rank; p = 0.171). In conclusion, AE-CTD-IP occurred even in the early stage of IP and had more inflammatory status than in AE-IPF.


Subject(s)
Connective Tissue Diseases/complications , Disease Management , Idiopathic Pulmonary Fibrosis/diagnosis , Lung Diseases, Interstitial/diagnosis , Tomography, X-Ray Computed/methods , Aged , Aged, 80 and over , Biopsy , Connective Tissue Diseases/diagnosis , Diagnosis, Differential , Disease Progression , Female , Forced Expiratory Volume/physiology , Humans , Idiopathic Pulmonary Fibrosis/physiopathology , Idiopathic Pulmonary Fibrosis/therapy , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/therapy , Male , Middle Aged , Prognosis , Recurrence , Retrospective Studies
11.
Histopathology ; 72(7): 1209-1215, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29468722

ABSTRACT

Pathological differential diagnoses of pleuroparenchymal fibroelastosis (PPFE) include usual interstitial pneumonia (UIP) and pulmonary apical cap (PAC); however, there are no specific immunostaining makers to distinguish between these diseases. We performed immunohistochemistry using several pleural mesothelial cell-related markers, including cytokeratin-5/6, CAM5.2, WT-1, calretinin, desmin and podoplanin, for PPFE (n = 4), UIP (n = 10) and PAC (n = 3) lung sections. Among the examined markers, in PPFE and PAC lungs podoplanin commonly showed positivity for spindle cells both in thickened pleura and subpleural fibroelastosis lesions; these cells were also stained with α-smooth muscle actin, a marker of myofibroblasts. However, even in elastic fibre-rich cases, UIP lungs did not show such podoplanin-positive myofibroblasts in pleura/subpleura and fibroblastic foci. These findings were also verified using immunofluorescence. By contrast, immunohistochemically as well as morphologically, the difference between PPFE and PAC was not apparent. The presence of podoplanin-positive myofibroblasts could be a pathological hallmark of PPFE, suggesting a pathogenic process distinct from UIP but common to PAC.


Subject(s)
Idiopathic Pulmonary Fibrosis/diagnosis , Lung Diseases, Interstitial/diagnosis , Myofibroblasts/metabolism , Aged , Databases, Factual , Diagnosis, Differential , Elastic Tissue/pathology , Female , Humans , Idiopathic Pulmonary Fibrosis/metabolism , Idiopathic Pulmonary Fibrosis/pathology , Lung Diseases, Interstitial/metabolism , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Myofibroblasts/pathology , Pleura/pathology
12.
Clin Sci (Lond) ; 132(14): 1565-1580, 2018 07 31.
Article in English | MEDLINE | ID: mdl-30006483

ABSTRACT

Although differentiation of lung fibroblasts into α-smooth muscle actin (αSMA)-positive myofibroblasts is important in the progression of idiopathic pulmonary fibrosis (IPF), few biomarkers reflecting the fibrotic process have been discovered. We performed microarray analyses between FACS-sorted steady-state fibroblasts (lineage (CD45, TER-119, CD324, CD31, LYVE-1, and CD146)-negative and PDGFRα-positive cells) from untreated mouse lungs and myofibroblasts (lineage-negative, Sca-1-negative, and CD49e-positive cells) from bleomycin-treated mouse lungs. Amongst several genes up-regulated in the FACS-sorted myofibroblasts, we focussed on Ltbp2, the gene encoding latent transforming growth factor-ß (TGF-ß) binding protein-2 (LTBP2), because of the signal similarity to Acta2, which encodes αSMA, in the clustering analysis. The up-regulation was reproduced at the mRNA and protein levels in human lung myofibroblasts induced by TGF-ß1. LTBP2 staining in IPF lungs was broadly positive in the fibrotic interstitium, mainly as an extracellular matrix (ECM) protein; however, some of the αSMA-positive myofibroblasts were also stained. Serum LTBP2 concentrations, evaluated using ELISA, in IPF patients were significantly higher than those in healthy volunteers (mean: 21.4 compared with 12.4 ng/ml) and showed a negative correlation with % predicted forced vital capacity (r = -0.369). The Cox hazard model demonstrated that serum LTBP2 could predict the prognosis of IPF patients (hazard ratio for death by respiratory events: 1.040, 95% confidence interval: 1.026-1.054), which was validated using the bootstrap method with 1000-fold replication. LTBP2 is a potential prognostic blood biomarker that may reflect the level of differentiation of lung fibroblasts into myofibroblasts in IPF.


Subject(s)
Biomarkers/metabolism , Idiopathic Pulmonary Fibrosis/genetics , Latent TGF-beta Binding Proteins/genetics , Lung/metabolism , Myofibroblasts/metabolism , Aged , Animals , Bleomycin/pharmacology , Cells, Cultured , Female , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression Profiling/methods , Humans , Idiopathic Pulmonary Fibrosis/blood , Idiopathic Pulmonary Fibrosis/metabolism , Latent TGF-beta Binding Proteins/blood , Latent TGF-beta Binding Proteins/metabolism , Lung/cytology , Male , Mice, Inbred C57BL , Middle Aged , Myofibroblasts/cytology , Myofibroblasts/drug effects , Transforming Growth Factor beta1/pharmacology
13.
Respirology ; 23(5): 519-525, 2018 May.
Article in English | MEDLINE | ID: mdl-29130562

ABSTRACT

BACKGROUND AND OBJECTIVE: Pneumothorax is a co-morbidity in patients with idiopathic pulmonary fibrosis (IPF). However, its incidence, risk factors and prognostic significance in IPF remain unclear. The aim of this study was to clarify the incidence and prognostic significance of pneumothorax in patients with IPF, and to further investigate the risk factors for its onset. METHODS: Eighty-four consecutive patients with IPF based on the consensus guideline were included in this study. We retrospectively reviewed the medical records, pulmonary function tests and chest high-resolution computed tomography images, and determined the incidence of pneumothorax. The prognostic significance of pneumothorax was evaluated using the Cox proportional hazards model analysis with time-dependent covariates. We also assessed the cumulative incidence and the risk factors for pneumothorax. RESULTS: Of the 84 patients, 17 (20.2%) developed pneumothorax. The cumulative incidence of pneumothorax was 8.5%, 12.5% and 17.7% at 1, 2 and 3 years, respectively. Univariate analysis demonstrated that pneumothorax was significantly related to poor prognosis (hazards ratio, 2.99; P = 0.002). Multivariate analysis, adjusting for sex, age and forced vital capacity (% predicted), revealed that pneumothorax was an independent predictor of poor outcome in IPF (hazards ratio, 2.85; P = 0.006). Lower BMI and the presence of extensive reticular abnormalities were significantly associated with developing pneumothorax. CONCLUSION: These results confirm that patients with IPF often develop pneumothorax during their clinical course and that the onset of pneumothorax predicts a poor outcome.


Subject(s)
Idiopathic Pulmonary Fibrosis/epidemiology , Pneumothorax/epidemiology , Aged , Aged, 80 and over , Body Mass Index , Comorbidity , Female , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/physiopathology , Incidence , Male , Middle Aged , Pneumothorax/diagnostic imaging , Pneumothorax/physiopathology , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Time Factors , Tomography, X-Ray Computed
14.
BMC Pulm Med ; 16(1): 168, 2016 12 01.
Article in English | MEDLINE | ID: mdl-27903248

ABSTRACT

BACKGROUND: Anti-glycyl-tRNA synthetase (anti-EJ) antibody is occasionally positive in patients with interstitial lung disease (ILD). We aimed to define the clinical, radiological and pathological features of patients with anti-EJ antibody-positive ILD (EJ-ILD). METHODS: We retrospectively analyzed the medical records of 12 consecutive patients with EJ-ILD who underwent surgical lung biopsy. RESULTS: The median follow-up time was 74 months (range, 17-115 months). The median age was 62 years (range, 47-75 years). Seven of 12 patients were female. Eight patients presented with acute onset. Six patients eventually developed polymyositis/dermatomyositis. On high-resolution computed tomography, consolidation and volume loss were predominantly observed in the middle or lower lung zone. Nine patients presented pathologically nonspecific interstitial pneumonia with organizing pneumonia, alveolar epithelial injury and prominent interstitial cellular infiltrations whereas the other three patients were diagnosed with unclassifiable interstitial pneumonia. Although all patients but one improved with the initial immunosuppressive therapy, five patients relapsed. When ILD relapsed, four of the five patients were treated with corticosteroid monotherapy. Four of the six patients without relapse have been continuously treated with combination therapy of corticosteroid and immunosuppressant. CONCLUSIONS: Patients with EJ-ILD often had acute onset of ILD with lower lung-predominant shadows and pathologically nonspecific interstitial pneumonia or unclassifiable interstitial pneumonia with acute inflammatory findings. Although the disease responded well to the initial treatment, relapse was frequent. Because of the diversity of the clinical courses, combination therapy of corticosteroid and immunosuppressant should be on the list of options to prevent relapse of EJ-ILD.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Autoantibodies/blood , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/pathology , Aged , Biopsy , Dermatomyositis/etiology , Female , Glycine-tRNA Ligase/immunology , Humans , Immunosuppressive Agents/therapeutic use , Japan , Lung/pathology , Lung Diseases, Interstitial/diagnostic imaging , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
15.
Kekkaku ; 91(2): 59-63, 2016 Feb.
Article in Japanese | MEDLINE | ID: mdl-27263227

ABSTRACT

An 86-year-old woman with severe dementia had been treated with oral prednisolone at 2 mg/day for autoimmune bullous dermatosis for several years. One year ago, she referred to our hospital due to an ulcerative skin lesion over the right tibial tuberosity. The lesion was treated by an iodine-containing ointment, but did not heal. Subsequently, a new skin lesion appeared in the right popliteal fossa. One month ago, the patient had increased sputum production that was accompanied by fever, anorexia, and dyspnea; consequently, she visited our department. Chest computed tomography revealed diffuse micronodules with ground-glass attenuation. Acid-fast bacteria staining of the sputum was positive and the polymerase chain reaction detected Mycobacterium tuberculosis. In addition, the bacilli were also found in the skin lesions of the right limb. Therefore, a diagnosis of cutaneous, and miliary tuberculosis was made. Although the anti-tuberculous combination chemotherapy consisting of isoniazid, rifampicin, and ethambutol was immediately initiated, her condition did not improve. She died on day 19 of hospitalization. Drug susceptibility testing revealed no resistance to all the three drugs; hence, it was concluded that the time-delay in diagnosis of cutaneous tuberculosis lead to the progression to miliary tuberculosis and subsequent death.


Subject(s)
Tuberculosis, Cutaneous/complications , Tuberculosis, Miliary/etiology , Aged, 80 and over , Antitubercular Agents/administration & dosage , Diagnosis, Differential , Drug Therapy, Combination , Ethambutol/administration & dosage , Fatal Outcome , Female , Humans , Isoniazid/administration & dosage , Mycobacterium tuberculosis/isolation & purification , Rifampin/administration & dosage , Tomography, X-Ray Computed , Tuberculosis, Cutaneous/diagnosis , Tuberculosis, Cutaneous/microbiology , Tuberculosis, Miliary/diagnosis , Tuberculosis, Miliary/microbiology
17.
J Infect Chemother ; 21(9): 691-4, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26025682

ABSTRACT

Mycobacterium chelonae frequently involves the skin, and the disseminated form can be observed in immunocompromised patients. In contrast, rhinosinusitis caused by the bacterium is a rare manifestation, which occurs independently of immune status. We report here a rare case of M. chelonae infection presenting as both disseminated cutaneous infection and rhinosinusitis in an immunocompromised patient. He had received systemic corticosteroids for 11 months due to cryptogenic organizing pneumonia. Before admission, he sustained injuries to his left arm and hand; those injuries succumbed to an infection that would subsequently spread to his other limbs, face, and even nasal cavities. This valuable case suggests that disseminated cutaneous infection by M. chelonae could spread to other organs.


Subject(s)
Maxillary Sinusitis/microbiology , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium chelonae , Rhinitis/microbiology , Skin Diseases, Bacterial/microbiology , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Fatal Outcome , Humans , Immunocompromised Host , Male , Mycobacterium Infections, Nontuberculous/drug therapy
20.
Pathol Int ; 64(11): 581-4, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25349101

ABSTRACT

Fetal gut-like adenocarcinoma is a rare carcinoma, previously reported in the stomach, which features clear cytoplasm cell papillotubular carcinoma and morphology similar to the fetal gut epithelium. SALL4, a novel marker for progenitor-type tumors, has shown high expression in fetal gut-like adenocarcinoma, which may represent oncofetal protein expression and fetal differentiation. Herein, we report the first case of fetal gut-like adenocarcinoma of the duodenum. An 81-year-old man was admitted on account of jaundice. A deeply ulcerating duodenal tumor formed a 4 cm periampullar mass. Pancreatoduodenectomy with lymphadenectomy was performed. Funicular and solid growth of clear cytoplasmic cells that resembled the fetal gut epithelium formed a poorly differentiated adenocarcinoma. Lymph node metastasis was present. Immunohistochemistry analysis showed diffuse nuclear positivity for SALL4. For postoperative therapy, S-1 was administered. The patient is alive with no recurrence, 83 months postoperatively. This case may contribute to further elucidate the disease entity of SALL4 positive, fetal-type carcinomas.


Subject(s)
Adenocarcinoma/metabolism , Duodenal Neoplasms/metabolism , Neoplasm Recurrence, Local/metabolism , Stomach Neoplasms/metabolism , Transcription Factors/metabolism , Aged, 80 and over , Duodenal Neoplasms/pathology , Humans , Immunohistochemistry/methods , Lymphatic Metastasis , Male , Neoplasm Recurrence, Local/pathology , Stomach Neoplasms/pathology
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