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1.
Mol Biol Cell ; 34(4): ar29, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36735498

RESUMO

The endoplasmic reticulum (ER) is a major cell compartment where protein synthesis, folding, and posttranslational modifications occur with assistance from a wide variety of chaperones and enzymes. Quality control systems selectively eliminate abnormal proteins that accumulate inside the ER due to cellular stresses. ER-phagy, that is, selective autophagy of the ER, is a mechanism that maintains or reestablishes cellular and ER-specific homeostasis through removal of abnormal proteins. However, how ER luminal proteins are recognized by the ER-phagy machinery remains unclear. Here, we applied the aggregation-prone protein, six-repeated islet amyloid polypeptide (6xIAPP), as a model ER-phagy substrate and found that cell cycle progression 1 (CCPG1), which is an ER-phagy receptor, efficiently mediates its degradation via ER-phagy. We also identified prolyl 3-hydroxylase family member 4 (P3H4) as an endogenous cargo of CCPG1-dependent ER-phagy. The ER luminal region of CCPG1 contains several highly conserved regions that we refer to as cargo-interacting regions (CIRs); these interact directly with specific luminal cargos for ER-phagy. Notably, 6xIAPP and P3H4 interact directly with different CIRs. These findings indicate that CCPG1 is a bispecific ER-phagy receptor for ER luminal proteins and the autophagosomal membrane that contributes to the efficient removal of aberrant ER-resident proteins through ER-phagy.


Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Proteínas de Transporte/metabolismo , Retículo Endoplasmático/metabolismo , Homeostase , Proteínas/metabolismo , Proteínas de Ciclo Celular/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-35940904

RESUMO

The endoplasmic reticulum (ER) is the largest organelle and has multiple roles in various cellular processes such as protein secretion, lipid synthesis, calcium storage, and organelle biogenesis. The quantity and quality of this organelle are controlled by the ubiquitin-proteasome system and autophagy (termed "ER-phagy"). ER-phagy is defined as the degradation of part of the ER by the vacuole or lysosomes, and there are at least two types of ER-phagy: macro-ER-phagy and micro-ER-phagy. In macro-ER-phagy, ER fragments are enclosed by autophagosomes, which is mediated by ER-phagy receptors. In micro-ER-phagy, a portion of the ER is engulfed directly by the vacuole or lysosomes. In these two pathways, some proteins in the ER lumen can be recognized selectively and subjected to ER-phagy. This review summarizes our current knowledge of ER-phagy, focusing on its membrane dynamics, molecular mechanisms, substrate specificity, and physiological significance.


Assuntos
Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/metabolismo , Autofagia/fisiologia , Proteínas de Transporte/metabolismo , Lisossomos/metabolismo
3.
EMBO Rep ; 23(6): e54801, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35417087

RESUMO

Selective autophagy cargos are recruited to autophagosomes primarily by interacting with autophagosomal ATG8 family proteins via the LC3-interacting region (LIR). The upstream sequence of most LIRs contains negatively charged residues such as Asp, Glu, and phosphorylated Ser and Thr. However, the significance of LIR phosphorylation (compared with having acidic amino acids) and the structural basis of phosphorylated LIR-ATG8 binding are not entirely understood. Here, we show that the serine residues upstream of the core LIR of the endoplasmic reticulum (ER)-phagy receptor TEX264 are phosphorylated by casein kinase 2, which is critical for its interaction with ATG8s, autophagosomal localization, and ER-phagy. Structural analysis shows that phosphorylation of these serine residues increases binding affinity by producing multiple hydrogen bonds with ATG8s that cannot be mimicked by acidic residues. This binding mode is different from those of other ER-phagy receptors that utilize a downstream helix, which is absent from TEX264, to increase affinity. These results suggest that phosphorylation of the LIR is critically important for strong LIR-ATG8 interactions, even in the absence of auxiliary interactions.


Assuntos
Caseína Quinase II , Proteínas Associadas aos Microtúbulos , Autofagia , Família da Proteína 8 Relacionada à Autofagia/química , Proteínas de Transporte/metabolismo , Caseína Quinase II/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Fosforilação , Serina/metabolismo
4.
Nat Commun ; 12(1): 3292, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078910

RESUMO

Autophagy regulates primary cilia formation, but the underlying mechanism is not fully understood. In this study, we identify NIMA-related kinase 9 (NEK9) as a GABARAPs-interacting protein and find that NEK9 and its LC3-interacting region (LIR) are required for primary cilia formation. Mutation in the LIR of NEK9 in mice also impairs in vivo cilia formation in the kidneys. Mechanistically, NEK9 interacts with MYH9 (also known as myosin IIA), which has been implicated in inhibiting ciliogenesis through stabilization of the actin network. MYH9 accumulates in NEK9 LIR mutant cells and mice, and depletion of MYH9 restores ciliogenesis in NEK9 LIR mutant cells. These results suggest that NEK9 regulates ciliogenesis by acting as an autophagy adaptor for MYH9. Given that the LIR in NEK9 is conserved only in land vertebrates, the acquisition of the autophagic regulation of the NEK9-MYH9 axis in ciliogenesis may have possible adaptive implications for terrestrial life.


Assuntos
Autofagia/genética , Cílios/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Cadeias Pesadas de Miosina/genética , Quinases Relacionadas a NIMA/genética , Sequência de Aminoácidos , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Linhagem Celular , Cílios/genética , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Rim/citologia , Rim/metabolismo , Fígado/citologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Quinases Relacionadas a NIMA/deficiência , Ligação Proteica , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais
5.
Autophagy ; 17(4): 1046-1048, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33629888

RESUMO

Phase-separated droplets with liquid-like properties can be degraded by macroautophagy/autophagy, but the mechanism underlying this degradation is poorly understood. We have recently derived a physical model to investigate the interaction between autophagic membranes and such droplets, uncovering that intrinsic wetting interactions underlie droplet-membrane contacts. We found that the competition between droplet surface tension and the increasing tendency of growing membrane sheets to bend determines whether a droplet is completely engulfed or isolated in a piecemeal fashion, a process we term fluidophagy. Intriguingly, we found that another critical parameter of droplet-membrane interactions, the spontaneous curvature of the membrane, determines whether the droplet is degraded by autophagy or - counterintuitively - serves as a platform from which autophagic membranes expand into the cytosol. We also discovered that the interaction of membrane-associated LC3 with the LC3-interacting region (LIR) found in the autophagic cargo receptor protein SQSTM1/p62 and many other autophagy-related proteins influences the preferred bending directionality of forming autophagosomes in living cells. Our study provides a physical account of how droplet-membrane wetting underpins the structure and fate of forming autophagosomes.


Assuntos
Autofagossomos , Autofagia , Citosol , Macroautofagia , Proteínas Associadas aos Microtúbulos
6.
Nature ; 591(7848): 142-146, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33473217

RESUMO

Compartmentalization of cellular material in droplet-like structures is a hallmark of liquid-liquid phase separation1,2, but the mechanisms of droplet removal are poorly understood. Evidence suggests that droplets can be degraded by autophagy3,4, a highly conserved degradation system in which membrane sheets bend to isolate portions of the cytoplasm within double-membrane autophagosomes5-7. Here we examine how autophagosomes sequester droplets that contain the protein p62 (also known as SQSTM1) in living cells, and demonstrate that double-membrane, autophagosome-like vesicles form at the surface of protein-free droplets in vitro through partial wetting. A minimal physical model shows that droplet surface tension supports the formation of membrane sheets. The model also predicts that bending sheets either divide droplets for piecemeal sequestration or sequester entire droplets. We find that autophagosomal sequestration is robust to variations in the droplet-sheet adhesion strength. However, the two sides of partially wetted sheets are exposed to different environments, which can determine the bending direction of autophagosomal sheets. Our discovery of this interplay between the material properties of droplets and membrane sheets enables us to elucidate the mechanisms that underpin droplet autophagy, or 'fluidophagy'. Furthermore, we uncover a switching mechanism that allows droplets to act as liquid assembly platforms for cytosol-degrading autophagosomes8 or as specific autophagy substrates9-11. We propose that droplet-mediated autophagy represents a previously undescribed class of processes that are driven by elastocapillarity, highlighting the importance of wetting in cytosolic organization.


Assuntos
Autofagossomos/metabolismo , Autofagia , Compartimento Celular , Citosol/metabolismo , Molhabilidade , Adesividade , Autofagossomos/química , Linhagem Celular , Citosol/química , Humanos , Membranas Intracelulares/química , Membranas Intracelulares/metabolismo , Proteína Sequestossoma-1/metabolismo , Tensão Superficial
7.
Cell Rep ; 33(10): 108477, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33296658

RESUMO

Autophagy is an intracellular degradation system, but its physiological functions in vertebrates are not yet fully understood. Here, we show that autophagy is required for inflation of air-filled organs: zebrafish swim bladder and mouse lung. In wild-type zebrafish swim bladder and mouse lung type II pulmonary epithelial cells, autophagosomes are formed and frequently fuse with lamellar bodies. The lamellar body is a lysosome-related organelle that stores a phospholipid-containing surfactant complex that lines the air-liquid interface and reduces surface tension. We find that autophagy is critical for maturation of the lamellar body. Accordingly, atg-deficient zebrafish fail to maintain their position in the water, and type-II-pneumocyte-specific Fip200-deficient mice show neonatal lethality with respiratory failure. Autophagy suppression does not affect synthesis of the surfactant phospholipid, suggesting that autophagy supplies lipids and membranes to lamellar bodies. These results demonstrate an evolutionarily conserved role of autophagy in lamellar body maturation.


Assuntos
Sacos Aéreos/metabolismo , Autofagia/fisiologia , Pulmão/metabolismo , Sacos Aéreos/patologia , Células Epiteliais Alveolares/metabolismo , Animais , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/fisiologia , Células Epiteliais/metabolismo , Feminino , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Organelas/metabolismo , Surfactantes Pulmonares/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
8.
Trends Cell Biol ; 30(5): 384-398, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32302550

RESUMO

The endoplasmic reticulum (ER) is the largest organelle in cells and has fundamental functions, such as folding, processing, and trafficking of proteins, cellular metabolism, and ion storage. To maintain its function, it is turned over constitutively, and even more actively under certain stress conditions. Quality control of the ER is mediated primarily by two pathways: the ubiquitin-proteasome system and autophagy (termed 'ER-phagy'). The identification of ER-phagy adaptor molecules has shed light on the mechanisms and physiological significance of ER-phagy. Here, we describe recent findings on various types of ER-phagy and present unanswered questions related to their mechanism and regulation.


Assuntos
Autofagia , Retículo Endoplasmático/metabolismo , Animais , Humanos , Modelos Biológicos , Complexo de Endopeptidases do Proteassoma/metabolismo , Agregados Proteicos , Dobramento de Proteína , Ubiquitina/metabolismo
9.
Intern Med ; 58(18): 2605-2613, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31178482

RESUMO

Objective Rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody potentially presents with a fatal clinical course and requires early intensive treatment. Recently, perilobular opacity was reported to pathologically correspond to the acute phase of diffuse alveolar damage in RP-ILD with anti-MDA5 antibody. We aimed to investigate whether or not perilobular opacity was a common radiological finding in RP-ILD patients with anti-MDA5 antibody. Methods We conducted a retrospective review of the medical records of eight consecutive patients with RP-ILD with anti-MDA5 antibody. The clinical features and radiological findings of follow-up computed tomography (CT) during the course of their disease were evaluated. Results Among eight RP-ILD patients with anti-MDA-5 antibody, six showed perilobular opacity in the lower lobes, and the remaining two had only consolidation on high-resolution CT. Of note, the perilobular opacity in all six patients thickened and progressed to consolidation with a loss of lung volume in a short period. Despite intensive treatment, 6 patients (75%) died within 100 days after the first visit. Notably, the two patients with consolidation presented with a very rapid clinical course and died in 13 days each. In the two survivors, the perilobular opacity and consolidation recovered with improvement in the loss of lung volume. Conclusion Rapidly progressive perilobular opacity that thickens and progresses to consolidation is characteristic of RP-ILD with anti-MDA5 antibody. Chest physicians should immediately check the status of anti-MDA-5 antibody in order to initiate early aggressive therapy in RP-ILD patients with rapidly progressive perilobular opacity.


Assuntos
Autoanticorpos/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais , Adulto , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
Mol Cell ; 74(5): 909-921.e6, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31006538

RESUMO

Certain proteins and organelles can be selectively degraded by autophagy. Typical substrates and receptors of selective autophagy have LC3-interacting regions (LIRs) that bind to autophagosomal LC3 and GABARAP family proteins. Here, we performed a differential interactome screen using wild-type LC3B and a LIR recognition-deficient mutant and identified TEX264 as a receptor for autophagic degradation of the endoplasmic reticulum (ER-phagy). TEX264 is an ER protein with a single transmembrane domain and a LIR motif. TEX264 interacts with LC3 and GABARAP family proteins more efficiently and is expressed more ubiquitously than previously known ER-phagy receptors. ER-phagy is profoundly blocked by deletion of TEX264 alone and almost completely by additional deletion of FAM134B and CCPG1. A long intrinsically disordered region of TEX264 is required for its ER-phagy receptor function to bridge the gap between the ER and autophagosomal membranes independently of its amino acid sequence. These results suggest that TEX264 is a major ER-phagy receptor.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Autofagia/genética , Retículo Endoplasmático/genética , Proteínas Intrinsicamente Desordenadas/genética , Sequência de Aminoácidos/genética , Proteínas Relacionadas à Autofagia/química , Proteínas de Ciclo Celular/genética , Retículo Endoplasmático/química , Estresse do Retículo Endoplasmático/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Intrinsicamente Desordenadas/química , Proteínas de Membrana , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Neoplasias/genética , Proteólise
11.
Respirology ; 23(1): 55-59, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28980363

RESUMO

BACKGROUND AND OBJECTIVE: Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc. METHODS: We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital. RESULTS: Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc. CONCLUSION: Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis.


Assuntos
Doenças Pulmonares Intersticiais/complicações , Pleurodese/efeitos adversos , Síndrome do Desconforto Respiratório/etiologia , Talco/efeitos adversos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Picibanil/uso terapêutico , Derrame Pleural/complicações , Derrame Pleural/tratamento farmacológico , Pleurodese/métodos , Pneumotórax/complicações , Pneumotórax/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
13.
Respir Care ; 61(12): 1664-1670, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27899541

RESUMO

BACKGROUND: Pneumothorax is one of the most important complications after bronchoscopy. This study was conducted to determine the risk factors for post-bronchoscopy pneumothorax. METHODS: We retrospectively reviewed the medical records of 23 consecutive subjects who were diagnosed with iatrogenic pneumothorax after bronchoscopy between August 2010 and February 2014. Forty-six control subjects who did not develop pneumothorax after bronchoscopy were randomly selected. The factors affecting the occurrence of pneumothorax were determined by univariate and multivariate analyses. RESULTS: Among 991 patients who underwent bronchoscopy during the study period, 23 (2.3%) developed pneumothorax after bronchoscopy. Among these 23 subjects, 13 (57%) required chest tube drainage. Compared with the control group (46 randomly selected from 968 subjects who did not develop pneumothorax), the group that developed pneumothorax had a preponderance of women and had more target lesions located in the subpleural area (odds ratio [OR] 7.8, 95% CI 0.9-64), especially those that were close to the interlobular pleura (OR 5.1, 95% CI 1.6-16.1) and the left lung (OR 3.2, 95% CI 1.1-9.5). Multivariate analysis revealed that a subinterlobular pleural location of a lesion was a risk factor for pneumothorax (OR 4.8, 95% CI 1.1-20.4). CONCLUSIONS: Pneumothorax occurred significantly more frequently when bronchoscopy was performed for subinterlobular pleural lesions. Close attention and care should be taken during bronchoscopy, especially when target lesions are abutting the interlobular pleura.


Assuntos
Broncoscopia/efeitos adversos , Doenças Pleurais/cirurgia , Pneumotórax/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia/métodos , Estudos de Casos e Controles , Tubos Torácicos/efeitos adversos , Drenagem/efeitos adversos , Drenagem/métodos , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pleura/patologia , Pleura/cirurgia , Doenças Pleurais/patologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
14.
J Thorac Dis ; 8(9): 2646-2650, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27747019

RESUMO

We report the case of a 55-year-old man with stage IV lung adenocarcinoma who received carboplatin-paclitaxel-bevacizumab chemotherapy as second-line therapy. After four cycles of chemotherapy, he experienced syncope with a decrease in blood pressure. Electrocardiography (ECG) revealed atrial fibrillation. Cardiac ultrasonography showed a markedly reduced ejection fraction (45%), with moderate decrease in comparison to that before chemotherapy (66%). Bisoprolol fumarate was initiated, and the conversion to sinus rhythm was detected by ECG 4 days after the syncope. At that time, no improvement in the ejection fraction was detected. Bevacizumab-associated cardiotoxicity was suspected, and bevacizumab maintenance therapy was discontinued, although the chemotherapy achieved a stable disease status based on the Response Evaluation Criteria in Solid Tumors. Two months after bevacizumab cessation, the ejection fraction improved to pretreatment level (62%). To the best of our knowledge, this is the first report on cardiogenic syncope due to left ventricular dysfunction that is most consistent with bevacizumab-associated cardiotoxicity in non-small cell lung cancer (NSCLC). Our results indicate that bevacizumab could lead to cardiotoxicity in patients with NSCLC and suggest the importance of the follow-up cardiac ultrasonography.

15.
Respiration ; 92(5): 348-355, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27705974

RESUMO

Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis that often involves the lung. However, interstitial pneumonia (IP) is rarely seen in GPA patients. We herein report 3 cases of IP associated with GPA diagnosed by surgical lung biopsy. High-resolution CT showed uniform subpleural reticular opacity with traction bronchiectasis. Biopsies from all 3 patients revealed neutrophilic capillaritis, microabscesses with giant cells, and coexisting histological findings of usual IP pattern or fibrosing nonspecific IP pattern. All 3 patients had elevated levels of serum myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), but not proteinase 3-ANCA. We diagnosed GPA and treated with corticosteroid and cyclophosphamide. Follow-up CT showed improvement of the lesions in all patients. Surgical lung biopsy specimens which revealed GPA enabled us to conduct the most suitable therapy. This report indicates the importance of surgical lung biopsy for differentiating idiopathic IPs from GPA-associated IP and suggests a relationship between MPO-ANCA and IP in GPA.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Granulomatose com Poliangiite/imunologia , Doenças Pulmonares Intersticiais/imunologia , Pulmão/patologia , Peroxidase/imunologia , Corticosteroides/uso terapêutico , Idoso , Biópsia , Ciclofosfamida/uso terapêutico , Feminino , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/patologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
16.
Intern Med ; 55(16): 2241-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27523002

RESUMO

We herein present the first case of rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody evaluated by surgical lung biopsy (SLB). High-resolution CT scan revealed perilobular opacities, which rapidly became thicker and formed consolidation, resulting in remarkable loss of lung volume. Specimens taken from SLB revealed membranous organization with alveolar occlusion, dilation of alveolar ducts, and sacs with collapsed alveoli, which are typical features of diffuse alveolar damage (DAD). Rapidly progressive perilobular opacities may be characteristic of RP-ILD with anti-MDA5 antibody and DAD.


Assuntos
Autoanticorpos/sangue , Óxidos N-Cíclicos/sangue , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Alvéolos Pulmonares , Biomarcadores/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
17.
Kekkaku ; 91(5): 495-502, 2016 May.
Artigo em Japonês | MEDLINE | ID: mdl-28661590

RESUMO

The proportion of the elderly in patients with pulmonary tuberculosis is increasing, and failure to complete the standard treatment regimen is not uncommon in these patients. We examined the compliance rate and prob- lems of the standard regimen in the late elderly pulmonary tuberculosis patients. [Methods] We reviewed the medical records of late elderly patients with pulmonary tuberculosis aged 75 or above who were smear-positive and treated in Kanagawa Cardiovascular and Respiratory Center between January 2011 and December 2014. Our retrospective study examined patient characteris- tics, imaging findings, laboratory results, and outcomes. The compliance rate of standard regimen during the hospitaliza- tion period was calculated. We compared the discontinua- tion rate and the incidence of adverse drug reactions by body weight equivalent doses of anti-tuberculosis drugs. [Results] A total of 298 patients were included in this study, and 76% of those patients were aged 80 or above. Anti-tuberculosis therapy was not able to be initiated for 3 patients (1%), and treatment other than standard regimen was inevitably introduced at initiation in 21 patients. The remaining 274 patients (92%) were administered the stan- dard regimen. Among them, at least one medication was subsequently discontinued for 85 patients (29%), and the medication was changed due to drug resistance in 6 patients . (2%). The remaining 183 patients (61%) complied with the standard regimen during hospitalization. In the comparison by body weight equivalent dose, significantly more patients discontinued their medication in the group using ethambutol with a higher standard dose per weight (37% vs. 21%, p=0.02). [Conclusion] Nearly 40% of the late elderly patients could not comply with the standard regimen. We may need to be more careful when calculating ethambutol equivalent dose.


Assuntos
Antituberculosos/uso terapêutico , Cooperação do Paciente , Tuberculose Pulmonar/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/administração & dosagem , Etambutol/administração & dosagem , Etambutol/uso terapêutico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
18.
Lung Cancer ; 90(3): 610-3, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26452431

RESUMO

We herein report a case of a 46-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged stage IV lung adenocarcinoma who received the ALK inhibitor crizotinib as second-line therapy. On the 47th day following crizotinib initiation, a chest computed tomography scan revealed ground-glass opacities with a clinical manifestation of desaturation, although a partial response to treatment was detected. The diagnosis of crizotinib-induced interstitial lung disease (ILD) was confirmed, and crizotinib was discontinued, followed by the initiation of corticosteroid therapy. After improvement of ILD with corticosteroid therapy, alectinib was administered as salvage therapy, resulting in tumor shrinkage without any recurrence of ILD. To the best of our knowledge, this is the first report of successful alectinib treatment following crizotinib-induced ILD. Our results indicate that alectinib could be a promising alternative treatment option in patients with crizotinib-induced ILD.


Assuntos
Antineoplásicos/efeitos adversos , Carbazóis/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Crizotinibe , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Radiografia Torácica , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Intern Med ; 54(16): 2035-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26278298

RESUMO

We herein present a case of pulmonary aluminosis diagnosed with in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis. The diagnosis of pulmonary aluminosis was supported by the occupational exposure to aluminum, ground glass opacity and ill-defined centrilobular nodular opacities seen in high resolution CT, and respiratory bronchioles accompanied by pigmented dust by histological examination by in-air micro-PIXE analysis of the lung tissues. The possibility of developing this rare condition should not be underestimated in workers at high-risk jobs. This is an important report showing the usefulness of an in-air micro-PIXE analysis for the early diagnosis of aluminosis.


Assuntos
Alumínio/efeitos adversos , Bronquite/etiologia , Exposição por Inalação/efeitos adversos , Pulmão/patologia , Exposição Ocupacional/efeitos adversos , Pneumoconiose/diagnóstico , Espectrometria por Raios X , Idoso , Bronquite/patologia , Desenho de Equipamento , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pneumoconiose/patologia , Radiografia , Espectrometria por Raios X/instrumentação , Indenização aos Trabalhadores
20.
PLoS One ; 10(4): e0123584, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25901797

RESUMO

BACKGROUND: Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear. OBJECTIVE: The relation between various infections and adult asthma exacerbations was investigated in clinical practice. METHODS: The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis. RESULTS: Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients. CONCLUSION: Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation.


Assuntos
Asma/microbiologia , Asma/virologia , Infecções Bacterianas/complicações , Viroses/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/complicações , Asma/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/microbiologia , Nasofaringe/virologia , Pneumonia/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia
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