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1.
Nat Commun ; 12(1): 4377, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312382

RESUMO

The origin and dispersal of cultivated and wild mandarin and related citrus are poorly understood. Here, comparative genome analysis of 69 new east Asian genomes and other mainland Asian citrus reveals a previously unrecognized wild sexual species native to the Ryukyu Islands: C. ryukyuensis sp. nov. The taxonomic complexity of east Asian mandarins then collapses to a satisfying simplicity, accounting for tachibana, shiikuwasha, and other traditional Ryukyuan mandarin types as homoploid hybrid species formed by combining C. ryukyuensis with various mainland mandarins. These hybrid species reproduce clonally by apomictic seed, a trait shared with oranges, grapefruits, lemons and many cultivated mandarins. We trace the origin of apomixis alleles in citrus to mangshanyeju wild mandarins, which played a central role in citrus domestication via adaptive wild introgression. Our results provide a coherent biogeographic framework for understanding the diversity and domestication of mandarin-type citrus through speciation, admixture, and rapid diffusion of apomictic reproduction.


Assuntos
Apomixia/genética , Citrus/genética , Frutas/genética , Genoma de Planta/genética , Alelos , Citrus/classificação , Extremo Oriente , Frequência do Gene , Genética Populacional , Genótipo , Geografia , Haplótipos , Hibridização Genética , Filogenia , Especificidade da Espécie
2.
BMJ Open Respir Res ; 8(1)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34326155

RESUMO

BACKGROUND: Acute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs. METHODS: This study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse. RESULTS: Univariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality. CONCLUSIONS: A higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome. TRIAL REGISTRATION NUMBER: UMIN000014969.

3.
Commun Biol ; 4(1): 819, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188187

RESUMO

Bobtail and bottletail squid are small cephalopods with striking anti-predatory defensive mechanisms, bioluminescence, and complex morphology; that inhabit nektobenthic and pelagic environments around the world's oceans. Yet, the evolution and diversification of these animals remain unclear. Here, we used shallow genome sequencing of thirty-two bobtail and bottletail squids to estimate their evolutionary relationships and divergence time. Our phylogenetic analyses show that each of Sepiadariidae, Sepiolidae, and the three subfamilies of the Sepiolidae are monophyletic. We found that the ancestor of the Sepiolinae very likely possessed a bilobed light organ with bacteriogenic luminescence. Sepiolinae forms a sister group to Rossinae and Heteroteuthinae, and split into Indo-Pacific and Atlantic-Mediterranean lineages. The origin of these lineages coincides with the end of the Tethys Sea and the separation of these regions during the Eocene and the beginning of the Oligocene. We demonstrated that sepiolids radiated after the Late Cretaceous and that major biogeographic events might have shaped their distribution and speciation.


Assuntos
Decapodiformes/genética , Evolução Molecular , Filogenia , Animais , Decapodiformes/classificação , Luminescência
4.
Respir Investig ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33967014

RESUMO

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. If high-resolution computed tomography (HRCT) indicates the presence of PAP, a definitive diagnosis of PAP is established when consistent pathological findings are obtained. Herein, we retrospectively studied the yield and safety of bronchofiberscopy in the diagnosis of PAP. METHODS: One hundred and fifty consecutive patients with PAP were prospectively registered in the PAP cohort database of the National Hospital Organization Kinki-Chuo Chest Medical Center between January 1991 and December 2018. We examined 86 patients who underwent bronchofiberscopy with bronchoalveolar lavage (BAL) and transbronchial lung forceps biopsy (TBLB). RESULTS: The patients included 56 men and 30 women, with a median age of 57 years. All patients had autoimmune PAP, and the median level of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies was 42.8 µg/mL. The diagnostic yield was 90.7% (78/86) with BAL and 81.4% (70/86) with TBLB. The combination of BAL and TBLB increased the yield to 98.8%. Age, disease severity score, and frequency of traction bronchiectasis on HRCT were significantly different between the TBLB-positive and TBLB-negative groups. No patient developed serious complications due to bronchofiberscopy; TBLB-related complications included pneumothorax (3.5%) and minimal bleeding (7.0%). CONCLUSIONS: Bronchofiberscopy, in combination with BAL and TBLB, is an effective and safe method for the diagnosis of PAP, with a yield of 98.8%.

5.
Respir Res ; 22(1): 115, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879137

RESUMO

BACKGROUND: Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP. METHODS: Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis. RESULTS: Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11-0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13-0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value. CONCLUSIONS: BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.

6.
Orphanet J Rare Dis ; 16(1): 115, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653382

RESUMO

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in immunoglobulin G production and are overproduced in various autoimmune disorders. We hypothesized that BAFF and/or APRIL levels would be elevated in serum and bronchoalveolar lavage fluid (BALF) and serum and BALF levels of BAFF and APRIL respond to the treatments (whole lung lavage (WLL) or inhalation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) in patients with APAP. SUBJECTS AND METHODS: BAFF and APRIL levels in serum and BALF from 110 patients with APAP were measured at baseline and during and after treatment, using an enzyme-linked immunosorbent assay kit. We enrolled 34 healthy volunteers as serum cytokine controls, and 13 disease controls for BALF. Associations of BAFF and APRIL levels with clinical measures were assessed to clarify their clinical roles. RESULTS: In patients with APAP, serum BAFF and APRIL levels were significantly increased relative to healthy volunteers (p < 0.0001 and p < 0.05, respectively), and BALF BAFF and APRIL levels were significantly increased versus disease controls (p < 0.0001 and p < 0.01, respectively). Serum BAFF levels (but not APRIL levels) were significantly correlated with Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, SP-A, and lactate dehydrogenase (p < 0.0001). There was no significant correlation between serum BAFF or APRIL levels and anti-GM-CSF autoantibody. BAFF and APRIL were negatively correlated with single-breath diffusion capacity for carbon monoxide (DLco) (p = 0.004) and forced vital capacity (p = 0.04), respectively. BAFF (but not APRIL) in BALF was negatively correlated with vital capacity (p = 0.04) and DLco (p = 0.006). There were significant correlations between disease severity and BAFF levels in serum (p = 0.04) and BALF (p = 0.007). Serum levels of anti-GM-CSF autoantibody, BAFF, and APRIL were not significantly affected by WLL or inhalation of recombinant human GM-CSF. CONCLUSIONS: BAFF and APRIL levels of sera and BALF in APAP were significantly increased compared with healthy volunteer and disease control, and the BAFF and APRIL pathway might have important specific roles in pathogenesis of APAP. Our data suggest a new perspective of future treatment for APAP.


Assuntos
Doenças Autoimunes , Proteinose Alveolar Pulmonar , Autoanticorpos , Linfócitos B , Ensaio de Imunoadsorção Enzimática , Humanos
7.
Intern Med ; 60(14): 2261-2268, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33518560

RESUMO

Dendriform pulmonary ossification (DPO) is a rare condition characterized by metaplastic bone formation in the lung parenchyma. It has been reported to be often associated with primary lung diseases, such as usual interstitial pneumonia (UIP) or chronic aspiration of gastric acid; however, its clinical features and pathophysiology remain unclear, especially in idiopathic cases. We herein report five DPO cases, including three with an idiopathic origin. In all cases of idiopathic DPO, the pathological and radiological examinations showed localized pulmonary lesions suggesting inflammation or hemorrhaging.


Assuntos
Fibrose Pulmonar Idiopática , Pneumopatias , Ossificação Heterotópica , Biópsia , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Ossificação Heterotópica/diagnóstico por imagem , Osteogênese
8.
J Thorac Dis ; 12(8): 4132-4147, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32944325

RESUMO

Background: We previously reported that high-resolution computed tomography (HRCT) patterns and certain serum marker levels can predict survival in patients with acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) and in those with idiopathic interstitial pneumonias (IIPs). The utility of serum marker changes before and during AE has not been previously evaluated. This study aimed to clarify whether changes in serum marker levels could improve the prognostic significance of HRCT patterns in patients with AE-IIPs. Methods: Seventy-seven patients (60 males, 17 females) with AE-IIP diagnosed between 2004 and 2016 and whose serum Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D levels were measured before and at the onset of AE were enrolled in this study. The HRCT pattern of each patient was classified as diffuse, multifocal, or peripheral. We examined the prognostic significance of the HRCT pattern, increased serum marker levels, and a combination of these parameters using Cox proportional hazard regression analysis. Results: Fifty-three patients had IPF and 24 had non-IPF IIP. A serum KL-6 level that was increased compared with the level in the stable state (ΔKL-6/ST-KL-6: ≤0.211) was a significantly poor prognostic factor in patients with a multifocal pattern. Multivariate Cox analysis identified long-term oxygen therapy, a partial oxygen tension/fraction of inspired oxygen ratio ≤200 Torr, and an elevated SP-D level during a stable state to be significantly poor prognostic factors in all patients. A diffuse HRCT pattern was not a significant prognostic factor in an AE-IIP in multivariate analysis after adjustment; however, a multifocal pattern accompanying a ΔKL-6/ST-KL-6 ≤0.211 or a diffuse pattern was a significantly poor prognostic factor than a peripheral pattern or a multifocal pattern with ΔKL-6/ST-KL-6 >0.211. Conclusions: Combining the HRCT pattern and the ΔKL-6/ST-KL-6 value can improve our ability to predict the survival of AE-IIP patients.

9.
Orphanet J Rare Dis ; 15(1): 272, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993757

RESUMO

BACKGROUND: Anti-granulocyte-macrophage colony-stimulating factor autoantibody (GMAb) has been recognized as a diagnostic biomarker for autoimmune pulmonary alveolar proteinosis (aPAP). The aims of this study were to know the incidence of increased level of serum GMAb in granulomatous lung diseases (sarcoidosis and hypersensitivity pneumonitis [HP]) and to clarify the role of GMAb. Consecutive individuals diagnosed with sarcoidosis (n = 92) and HP (n = 45) at National Hospital Organization Kinki-Chuo Chest Medical Center were retrospectively analyzed. We measured serum GMAb levels at the diagnosis. Cut-off values of GMAb discriminating aPAP (n = 110) from healthy controls (n = 31) were determined by receiver operating characteristic (ROC) curve analysis. We compared the clinical features of sarcoidosis and HP patients with GMAb levels above the cut-off value ("Elevated-GMAb") with those of patients whose GMAb levels below the cut-off value ("Low-GMAb"). Radiological and pathological findings in elevated-GMAb patients were re-evaluated to elucidate the role of GMAb in granulomatous lung diseases. RESULTS: Analysis of ROC indicated a sensitivity and specificity of 100% at GMAb level of 3.33 µg/mL for discriminating aPAP from healthy controls (area under curve = 1.000, p < 0.0001). The percentages of elevated-GMAb sarcoidosis and HP patients were 5.4% (n = 5) and 11.1% (n = 5), respectively. The number of comorbid sarcoidosis and HP patients with aPAP was two and one, respectively. Elevated-GMAb sarcoidosis patients presented with significantly higher serum levels of Krebs von den Lungen (KL)-6, surfactant protein-D (SP-D), lactate dehydrogenase, and the requirement of systemic corticosteroid therapy. Elevated-GMAb HP patients demonstrated older age, higher serum KL-6, SP-D, carcinoembryonic antigen, and cytokeratin fragment 21-1 levels, and a higher percentage of lymphocytes in bronchoalveolar lavage than low-GMAb patients. A subset of patients presented with radiological and pathological findings characteristic of aPAP. CONCLUSIONS: We demonstrated the percentage of elevated-GMAb sarcoidosis and HP patients who presented with several features suggestive of aPAP. Elevated-GMAb sarcoidosis and HP patients without definitive aPAP diagnosis may have subclinical or early-stage aPAP and may not necessarily indicate false positives. Upon diagnosis of sarcoidosis or HP, measurement of GMAb may be useful in detecting possible comorbidity of subclinical or early-onset aPAP.


Assuntos
Alveolite Alérgica Extrínseca , Proteinose Alveolar Pulmonar , Sarcoidose , Idoso , Autoanticorpos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Estudos Retrospectivos
10.
Respir Med ; 171: 106078, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917352

RESUMO

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare interstitial lung disease characterized by unique radiological and pathological findings. However, pathological evaluations are available only in a limited number of patients. Therefore, several clinical diagnostic criteria have been proposed. Nevertheless, the applicability of these criteria has not yet been validated. Moreover, the clinical course of iPPFE and its prognosis have not yet been completely elucidated. METHODS: The present study assessed previously proposed clinical diagnostic criteria by comparing the clinical features between pathologically diagnosed iPPFE (p-iPPFE) and clinically diagnosed iPPFE (c-iPPFE). Subsequently, the clinical features of iPPFE were characterized and compared with those of idiopathic pulmonary fibrosis (IPF, n = 323). RESULTS: Clinical characteristics of c-iPPFE (n = 27) and p-iPPFE (n = 35) were similar. No significant difference was observed in terms of prognosis between c-iPPFE and p-iPPFE. The number of patients with iPPFE (both c-iPPFE and p-iPPFE) who developed lung cancer was significantly lower than that of patients with IPF. However, acute exacerbation (AE) showed similar incidence in patients with iPPFE and IPF. Survival of patients with iPPFE was significantly worse than that of patients with IPF (5-year survival rate: 38.5% vs. 63.5%, p < 0.0001), and the most common cause of death was chronic respiratory failure (73.8%), followed by AE (14.3%). Male gender was the only poor prognostic factor of iPPFE. CONCLUSION: The present study demonstrated efficiency of clinical diagnosis and also revealed clinically important characteristics of iPPFE that should be considered for management of iPPFE.


Assuntos
Pneumonias Intersticiais Idiopáticas , Fibrose Pulmonar Idiopática , Idoso , Causas de Morte , Doença Crônica , Progressão da Doença , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Pneumonias Intersticiais Idiopáticas/mortalidade , Pneumonias Intersticiais Idiopáticas/patologia , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Respiratória , Estudos Retrospectivos , Fatores Sexuais , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
11.
Intern Med ; 59(20): 2539-2546, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32611952

RESUMO

Autoimmune pulmonary alveolar proteinosis (APAP) is caused by macrophage dysfunction due to anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody. We experienced 2 cases of APAP complicated with sarcoidosis in a 42-year-old woman and a 51-year-old man (age at the sarcoidosis diagnosis). APAP preceded sarcoidosis in the woman, and both diseases were diagnosed simultaneously in the man. Sarcoidosis lesions were observed in the lung, skin, and eyes, and the pathological findings of APAP were not marked at the diagnosis of sarcoidosis in either case. Low-grade positive serum anti-GM-CSF autoantibody was suspected to be correlated with the occurrence of sarcoidosis and resolution of APAP.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/complicações , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Proteinose Alveolar Pulmonar/complicações , Proteinose Alveolar Pulmonar/imunologia , Sarcoidose/etiologia , Adulto , Doenças Autoimunes/sangue , Doenças Autoimunes/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteinose Alveolar Pulmonar/sangue , Proteinose Alveolar Pulmonar/diagnóstico , Sarcoidose/fisiopatologia
12.
BMJ Open Respir Res ; 7(1)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32423894

RESUMO

BACKGROUND: Acute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP. METHODS: In this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP. RESULTS: We developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0). CONCLUSIONS: Treatment with rhTM might improve survival in AE-IIP cases with poor prognoses.Trial registration numberUMIN000014969, date: 28 August 2014.


Assuntos
Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Fármacos do Sistema Respiratório/uso terapêutico , Trombomodulina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Respir Investig ; 58(2): 91-101, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31882370

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease often accompanied by skeletal muscle wasting. We investigated whether skeletal muscle mass and muscle attenuation on computed tomography (CT) are predictors of mortality in IPF patients, using a nationwide cloud-based database and web-based multidisciplinary discussion (MDD) system. METHODS: IPF patients diagnosed using MDD from April 2009 to March 2014 were included. We analyzed the cross-sectional area (CSA) of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA), muscle attenuation of the ESM (ESMMA), and PM (PMMA) on single-slice axial CT. Survival probability was assessed using the Kaplan-Meier method and compared by the log-rank test. Multivariate Cox proportional hazards models were used to evaluate the relationship among the ESMCSA, PMCSA, ESMMA, PMMA, clinical parameters, and prognosis. RESULTS: A total of 199 IPF patients were enrolled. Seventy-four patients died during the study period and the most frequent cause was acute exacerbation (13.1%). The group with the lowest quartile of ESMCSA had significantly worse survival than other groups (P = 0.009). Survival rates of the groups with the lowest quartile of PMCSA, lower ESMMA, and lower PMMA did not differ from those of other groups. According to multivariate analysis, ESMCSA < lower quartile was significantly associated with all-cause mortality (hazards ratio, 1.96; P = 0.030), whereas, ESMMA < median, PMCSA < lower quartile, and PMMA < median were not. CONCLUSIONS: Low ESMCSA on CT images may be a strong risk factor for all-cause mortality in IPF patients based on MDD diagnosis.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Músculo Esquelético/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Humanos , Comunicação Interdisciplinar , Japão , Estudos Retrospectivos
14.
Commun Biol ; 2: 465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31840110

RESUMO

Bobtail squid are emerging models for host-microbe interactions, behavior, and development, yet their species diversity and distribution remain poorly characterized. Here, we combine mitochondrial and transcriptome sequences with morphological analysis to describe three species of bobtail squid (Sepiolidae: Sepiolinae) from the Ryukyu archipelago, and compare them with related taxa. One Ryukyuan type was previously unknown, and is described here as Euprymna brenneri sp. nov. Another Ryukyuan type is morphologically indistinguishable from Sepiola parva Sasaki, 1913. Molecular analyses, however, place this taxon within the genus Euprymna Steenstrup, 1887, and additional morphological investigation led to formal rediagnosis of Euprymna and reassignment of this species as Euprymna parva comb. nov. While no adults from the third Ryukyuan type were found, sequences from hatchlings suggest a close relationship with E. pardalota Reid, 2011, known from Australia and East Timor. The broadly sampled transcriptomes reported here provide a foundation for future phylogenetic and comparative studies.


Assuntos
Decapodiformes/anatomia & histologia , Decapodiformes/genética , Animais , Decapodiformes/classificação , Perfilação da Expressão Gênica , Ilhas , Tipagem Molecular , Fenótipo , Filogenia
15.
PLoS One ; 14(2): e0212776, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30818375

RESUMO

BACKGROUND: In lymphangioleiomyomatosis (LAM), tuberous sclerosis gene mutations activate the mechanistic target of the rapamycin pathway, resulting in vascular endothelial growth factor-D (VEGF-D) overproduction. While the utility of serum VEGF-D testing for the diagnosis of LAM is outlined in ATS/JRS LAM Guidelines, the assay has not been fully validated for Asian populations. Our aims were to validate serum VEGF-D testing in Japan, by directly comparing measurements in Japan and the U.S., determining the diagnostic cut-off for serum VEGF-D levels among the Japanese women with typical thin walled cystic change on CT, and determining the performance of VEGF-D as a prognostic biomarker. SUBJECTS AND METHODS: We determined serum VEGF-D levels from 108 LAM patients, 14 disease controls, and 51 healthy volunteers from the Japanese population. Measurements of 61 LAM patients were compared to those from the principal VEGF-D laboratory in the U.S at Cincinnati Children's Hospital Medical Center. We correlated baseline serum VEGF-D levels with baseline and longitudinal clinical data to determine how pregnancy, sirolimus or gonadotrophin-releasing hormone (GnRH) agonists influence serum VEGF-D levels. RESULTS: Serum VEGF-D measurements in Japan and the U.S. were very similar. Baseline serum VEGF-D levels effectively distinguished LAM from other diseases and healthy volunteers at a cut-off level of 645 pg/ml and were diagnostically specific at 800 pg/ml, consistent with the recommendations of the ATS/JRS LAM Guidelines. Baseline serum VEGF-D correlated negatively with the DLco baseline % predicted and with the annual decrease in DLco % predicted. There was no significant association between baseline serum VEGF-D level and the outcomes of death or transplant. Serum VEGF-D levels markedly decreased during treatment with sirolimus, but not with GnRH analogues. Serum VEGF-D levels of most LAM patients did not increase over time, and neither pregnancy nor menopause significantly modulated serum VEGF-D levels. CONCLUSIONS: Serum VEGF-D is a useful diagnostic and therapeutic biomarker for LAM. Satisfactory precision and international inter-laboratory agreement of the clinical assay support VEGF-D recommendations in the ATS/JRS LAM Guidelines for the Japanese population.


Assuntos
Pneumopatias/diagnóstico , Linfangioleiomiomatose/diagnóstico , Fator D de Crescimento do Endotélio Vascular/sangue , Adulto , Grupo com Ancestrais do Continente Asiático , Biomarcadores , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Voluntários Saudáveis , Humanos , Japão , Estudos Longitudinais , Pneumopatias/sangue , Pneumopatias/tratamento farmacológico , Linfangioleiomiomatose/sangue , Linfangioleiomiomatose/tratamento farmacológico , Menopausa/sangue , Pessoa de Meia-Idade , Gravidez/sangue , Complicações Neoplásicas na Gravidez/sangue , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Sirolimo/uso terapêutico , Resultado do Tratamento
16.
Respirology ; 24(7): 658-666, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30835911

RESUMO

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) or other idiopathic interstitial pneumonias (IIP) is a poor prognostic event despite conventional therapy with corticosteroids and/or immunosuppressants. We aimed to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhTM) for AE-IIP. METHODS: For this prospective single-arm open-label multicentre cohort study, we retrospectively registered 61 cases of AE-IIP treated with conventional therapy between 2011 and 2013 (control arm), and prospectively enrolled 39 cases of AE-IIP treated with conventional therapy and rhTM (380 U/kg/day for 6 days) between 2014 and 2016 (rhTM arm). To reduce potential confounding in treatment comparisons, an adjusted mortality analysis for 90-day survival was conducted with weighted Cox proportional hazards regression models using inverse probability of treatment weighting. Weights were derived from propensity scores estimated using a multivariable logistic regression analysis including potential confounders. RESULTS: The 90-day survival rates of AE-IIP patients treated with/without rhTM were 66.7% (26/39) and 47.5% (29/61), respectively. After adjusting for imbalances, rhTM therapy was significantly associated with reduced mortality (adjusted hazard ratio (HR): 0.453; 95% CI: 0.237-0.864; P = 0.0163). The frequencies of adverse events with/without rhTM were 17.9% (7/39) and 19.7% (12/61), which were similar in both arms (P = 1.0). Two bleeding-related adverse events occurred in the rhTM arm. CONCLUSION: Safety and efficacy were observed for rhTM treatment of AE-IIP. A future randomized controlled trial is required to draw final conclusions.


Assuntos
Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Pontuação de Propensão , Trombomodulina/uso terapêutico , Idoso , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/diagnóstico , Pneumonias Intersticiais Idiopáticas/mortalidade , Japão/epidemiologia , Masculino , Prognóstico , Estudos Prospectivos , Proteínas Recombinantes , Taxa de Sobrevida/tendências , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Eur Respir J ; 53(5)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30880283

RESUMO

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.


Assuntos
Computação em Nuvem , Gerenciamento de Dados/organização & administração , Pneumonias Intersticiais Idiopáticas/diagnóstico , Comunicação Interdisciplinar , Idoso , Biópsia , Bases de Dados Factuais , Diagnóstico Diferencial , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/mortalidade , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Patologistas , Padrões de Prática Médica , Pneumologistas , Radiologistas , Análise de Sobrevida , Tomografia Computadorizada por Raios X
18.
Intern Med ; 58(4): 569-574, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30333386

RESUMO

A 34-year-old woman experiencing shortness of breath was referred to our hospital. The patient was diagnosed with sporadic lymphangioleiomyomatosis based on the observation of bilateral diffuse multiple thin-walled cysts on computed tomography of the chest, chylous effusion, elevated serum vascular endothelial growth factor-D levels and transbronchial biopsy findings. This patient was a hepatitis B virus (HBV) carrier. Treatment with 1 mg daily of sirolimus was started after HBV DNA was brought below the cut-off level using entecavir. Sirolimus was effective, as the chylous effusion resolved completely and the dyspnea improved. The sirolimus dosage was increased to 2 mg daily without causing HBV reactivation.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/fisiopatologia , Linfangioleiomiomatose/tratamento farmacológico , Sirolimo/uso terapêutico , Adulto , Feminino , Guanina/uso terapêutico , Humanos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Orphanet J Rare Dis ; 13(1): 182, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-30342527

RESUMO

BACKGROUND: Lymphangioleiomyomatosis (LAM) and connective tissue diseases (CTDs) occur more frequently among women than men. We investigated the frequency of comorbid CTD and positive serum autoantibody findings in patients with LAM. METHODS: A total of 152 patients with LAM were prospectively and consecutively registered in the National Hospital Organization Kinki-Chuo Chest Medical Centre cohort. The clinical data were retrospectively analysed, and patients were categorised into the following three groups: a CTD group, a non-CTD-autoantibody-positive group, and a non-CTD-autoantibody-negative group. RESULTS: All patients were women. We identified five patients with comorbid CTDs (3.3%): Sjögren's syndrome (SjS) (n = 3), systemic lupus erythematosus (n = 1), and rheumatoid arthritis (n = 1). One patient with SjS was also diagnosed with antiphospholipid antibody syndrome. The positive rate for anti nuclear antibody was 31.5% and 6.9% at dilution of 1:40 or higher, and those of 1:160 or higher, respectively.  It tended to be lower in patients with LAM than in healthy women. The positive rate for anti-SS-A and anti-SS-B antibody was 7.9% and 1.8%, respectively. No significant differences in age, type of LAM, smoking status, serum vascular endothelial growth factor D level, respiratory function, treatment, or prognosis were observed among the three groups. CONCLUSIONS: Comorbid CTDs, especially SjS, in LAM patients should be considered.


Assuntos
Autoanticorpos , Comorbidade , Doenças do Tecido Conjuntivo/complicações , Linfangioleiomiomatose/complicações , Adulto , Estudos de Coortes , Doenças do Tecido Conjuntivo/imunologia , Feminino , Humanos , Linfangioleiomiomatose/imunologia , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Respirology ; 23(3): 331-338, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28960664

RESUMO

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease that occurs in women of childbearing age. LAM can be diagnosed on a clinical basis in patients with typical high-resolution computed tomography (HRCT) patterns and at least one other corroborating disease feature, such as chylothorax, angiomyolipoma, tuberous sclerosis complex or elevated serum vascular endothelial growth factor (VEGF)-D. However, patients who do not meet these criteria require tissue confirmation for a definitive diagnosis, and the utility of methods that are less invasive than surgical lung biopsy, such as transbronchial lung biopsy (TBLB), are not well studied. We retrospectively studied the efficacy and safety of TBLB for the diagnosis of LAM. METHODS: From January 1991 to August 2015, 131 consecutive LAM patients were prospectively registered in our study, and a TBLB was conducted for 24 patients. We retrospectively studied the yield and safety of TBLB in this cohort. RESULTS: All 24 patients were women; the median age was 42 years. HRCT showed multiple round thin-walled cysts diffusely scattered throughout the lungs. The median level of serum VEGF-D was 2109 pg/mL. Characteristic pathological findings for LAM were identified in 17 patients (70.8%) by two expert pathologists. The %predicted value for diffusing capacity of carbon monoxide was significantly lower in the 17 TBLB-positive LAM patients compared to the seven TBLB-negative LAM patients (P = 0.046). There were no serious adverse events such as pneumothorax or uncontrollable bleeding due to TBLB. CONCLUSION: TBLB is a safe and effective method for the pathological diagnosis of LAM.


Assuntos
Biópsia/métodos , Broncoscopia/métodos , Neoplasias Pulmonares/diagnóstico , Linfangioleiomiomatose/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
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