RESUMEN
A 24-year-old man with cystic fibrosis underwent living-donor lobar lung transplantation (LDLLT) with grafts donated from his father, who had mild cirrhosis, and his uncle. The graft from his father failed, and retransplantation was required 44 h after LDLLT, using his sister's left lower lobe. The retransplantation was successful; 18 months postoperatively, the recipient and all three donors are doing well. The favorable outcome was achieved owing to the complete assessment of all potential donors in advance, and the appropriate decision to perform retransplantation in a timely manner. Whether this life-saving retransplant procedure for unexpected primary graft dysfunction after LDLLT can be justified requires further experience and a longer follow-up.
Asunto(s)
Fibrosis Quística/cirugía , Trasplante de Pulmón/métodos , Disfunción Primaria del Injerto/cirugía , Adulto , Humanos , Donadores Vivos , Masculino , Reoperación/métodosRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrosis and a poor prognosis. Alveolar epithelial cells (AECs) are considered to play important roles by releasing growth factors and matrix metalloproteinases (MMPs) and by being involved in epithelial mesenchymal transition in IPF. Doxycycline hydrochloride (DOXY), an inhibitor of MMPs, attenuates pulmonary fibrosis in models and in patients with IPF; however, the mechanism of this action remains obscure. OBJECTIVES: The present study investigated the effect of DOXY on growth factors and MMP production in AECs. METHODS: Bleomycin (BL)-induced murine pulmonary fibrosis was treated with DOXY and examined by pathological and immunohistochemical staining. The human alveolar epithelial cell line A549 was stimulated with transforming growth factor (TGF)-ß1 and incubated with DOXY, and then the expression of growth factors, MMPs, and collagen type I was evaluated at the mRNA and protein levels. We also evaluated the effects of DOXY on the TGF-ß1-induced Smad signaling pathway. RESULTS: DOXY reduced fibrosis scores and the production of collagen type I, connective tissue growth factor (CTGF), and TGF-ß1 in BL models. DOXY inhibited the mRNA expression of MMP-2, MPP-9, CTGF, and collagen type I as well as the production of MMP-2 and platelet-derived growth factor-AA protein induced in A549 cells by TGF-ß1 but not by Smad2 and Smad3 phosphorylation. We did not find a similar effect of DOXY in normal lung fibroblasts. CONCLUSIONS: Our results suggest that DOXY could be useful for attenuating pulmonary fibrosis through the inhibition of growth factors and MMP production in AECs.
Asunto(s)
Antibacterianos/farmacología , Doxiciclina/farmacología , Células Epiteliales/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Metaloproteinasas de la Matriz/efectos de los fármacos , Metaloproteinasas de la Matriz/metabolismo , Alveolos Pulmonares/citología , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Animales , Western Blotting , Línea Celular , Colágeno Tipo I/efectos de los fármacos , Colágeno Tipo I/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/efectos de los fármacos , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Pulmón/patología , Masculino , Metaloproteinasa 2 de la Matriz/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos ICR , Fosforilación , Factor de Crecimiento Derivado de Plaquetas/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Fibrosis Pulmonar/patología , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/fisiología , Proteínas Smad/fisiología , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
Cystic fibrosis (CF) is rare in Japan. We encountered a CF case with drug-resistant Pseudomonas aeruginosa infection and successfully performed lung transplant from living related donors. A combination of beta-lactams and aminoglycosides for drug-resistant P. aeruginosa infection was administered before lung transplantation. Intravenous colistin was also used immediately before and after transplant surgery. Gram staining of respiratory specimens was performed every day after surgery and it was useful in monitoring infection status. Strict monitoring of infections by the Gram staining and culture of respiratory specimens is considered to be effective in preventing lower respiratory infection in lung transplantation.
Asunto(s)
Fibrosis Quística/diagnóstico , Trasplante de Pulmón , Infecciones por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/aislamiento & purificación , Resistencia betalactámica , Aminoglicósidos/uso terapéutico , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Farmacorresistencia Bacteriana , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/etiología , Adulto Joven , beta-Lactamas/uso terapéuticoRESUMEN
A 70-year-old woman with a history of sinobronchial syndrome was admitted to the hospital because of a cough, sputum, and abnormal chest shadow. She was diagnosed with pulmonary mucosa-associated lymphoid tissue lymphoma (p-MALToma) based on results of a pathologic examination and the gene rearrangements in the Ig heavy chain on Southern blot hybridization. Although p-MALToma did not regress with conventional therapy, it was reduced after long-term treatment with clarithromycin (CAM) (200 mg/d). A 57-year-old woman with a history of Sjögren syndrome and lymphocytic interstitial pneumonia had a mass lesion in the left lower lung field. CT image-guided biopsy established a diagnosis of p-MALToma. The p-MALToma regressed with long-term treatment with CAM (200 mg/d), whereas Helicobacter pylori (HP) eradication therapy was not effective in concurrent atrophic gastritis with HP. It is suggested that CAM, a macrolide antibiotic, may be effective in some patients with p-MALToma.
Asunto(s)
Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Mucosa Respiratoria , Anciano , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Linfoma de Células B de la Zona Marginal/complicaciones , Linfoma de Células B de la Zona Marginal/diagnóstico , Persona de Mediana EdadRESUMEN
A 73-year-old woman who had been diagnosed with systemic sclerosis was admitted for further examination of bilateral hilar lymphadenopathy. Sarcoidosis was confirmed based on elevated serum levels of angiotensin-converting enzyme, a high proportion of lymphocytes and a high CD4/CD8 ratio in bronchoalveolar lavage fluid, abnormal (67)Gallium uptake in the mediastinum and noncaseating granulomas in skin biopsy specimens. In addition, high levels of antimitochondrial M2 antibodies and alkaline phosphatase indicated primary biliary cirrhosis (PBC). Here we describe a rare triplex of sarcoidosis, SSc and PBC. Although the etiology of this complex remains unknown, these three diseases might share some pathogenesis.
Asunto(s)
Cirrosis Hepática Biliar/diagnóstico , Sarcoidosis/diagnóstico , Esclerodermia Sistémica/diagnóstico , Anciano , Femenino , Humanos , Cirrosis Hepática Biliar/complicaciones , Sarcoidosis/complicaciones , Esclerodermia Sistémica/complicacionesRESUMEN
alpha-Defensins, antimicrobial peptides produced mainly by neutrophils, have been reported to be associated with a wide variety of lung diseases, including idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and diffuse panbronchiolitis (DPB). In each disease, alpha-defensins are located in different areas, such as around the alveolar septa in IPF and around the airways in CF and DPB, suggesting that alpha-defensins play different roles. Meanwhile, growth factors are known to contribute to IPF, CF, and DPB. alpha-Defensins are known to induce interleukin (IL)-8 in airway epithelial cells, but the effects of alpha-defensins on the release of growth factors from various components in the lung have not been sufficiently investigated. In the present study, the in vitro effects of human neutrophil peptide (HNP)-1 (a subtype of alpha-defensin) on the expressions of IL-8 and growth factors in lung fibroblasts, bronchial epithelial cells, and alveolar epithelial cells were examined. HNP-1 mainly enhanced the expression of IL-8 in epithelial cells, whereas it enhanced transforming growth factor-beta and vascular endothelial growth factor expressions in lung fibroblasts. These results suggest that alpha-defensins play different roles in the pathogenesis of IPF, CF, and DPB according to the location in the lung where the alpha-defensins are mainly produced.
Asunto(s)
Fibrosis Quística/metabolismo , Fibrosis Pulmonar Idiopática/metabolismo , Interleucina-8/metabolismo , Pulmón/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factores de Crecimiento Endotelial Vascular/metabolismo , alfa-Defensinas/fisiología , Bronquiolitis/metabolismo , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Infecciones por Haemophilus/metabolismo , Humanos , Interleucina-8/análisis , Pulmón/efectos de los fármacos , Factor de Crecimiento Transformador beta/análisis , Factores de Crecimiento Endotelial Vascular/análisis , alfa-Defensinas/farmacologíaRESUMEN
A 51-year-old man was admitted to our hospital with cough, hemosputum, dyspnea and chest pain. Chest high-resolution computed tomography (HRCT) revealed diffuse ground-glass opacities in both lungs with peripheral predominance. Bronchoalveolar lavage fluid was fresh-bloody and analysis indicated an increase in the eosinophil proportion. Benzbromarone-induced lymphocyte stimulation test was positive. Therefore, the patient was diagnosed as having drug-induced eosinophilic pneumonia with pulmonary alveolar hemorrhage caused by benzbromarone. After discontinuation of benzbromarone and administration of corticosteroids, chest HRCT images and respiratory manifestation improved. Here, we report this rare case of benzbromarone-induced eosinophilic pneumonia with pulmonary alveolar hemorrhage.
Asunto(s)
Benzbromarona/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/diagnóstico , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/diagnóstico , Eosinofilia Pulmonar/inducido químicamente , Eosinofilia Pulmonar/diagnóstico , Benzbromarona/uso terapéutico , Líquido del Lavado Bronquioalveolar , Gota/tratamiento farmacológico , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Uricosúricos/efectos adversos , Uricosúricos/uso terapéuticoRESUMEN
BACKGROUND: The histopathologic pattern is currently the most important prognostic marker for idiopathic interstitial pneumonia (IIP). However, more highly sensitive markers are now required. Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and it has been demonstrated that HSP47 expression is significantly higher in the lung specimens of idiopathic UIP than in UIP associated with collagen vascular diseases (CVD). However, its expression in nonspecific interstitial pneumonia (NSIP), the other common pathological pattern of IIP, has not been well investigated. Therefore, the association between lung fibroblast HSP47 expression and prognosis in fibrotic NSIP was evaluated. METHODS: Surgical lung biopsy specimens of 63 patients [idiopathic fibrotic NSIP=19, fibrotic NSIP associated with CVD=9, idiopathic UIP=26, and UIP associated with CVD=9] were reviewed, and a score for lung fibroblast HSP47 expression was assigned. These patients' clinical features and survival were also analyzed. RESULTS: There was no significant difference in HSP47 expression between idiopathic fibrotic NSIP and fibrotic NSIP associated with CVD. The idiopathic fibrotic NSIP patients with higher HSP47 expression levels in their lung specimens had a poorer prognosis than patients with lower HSP47 expression levels. CONCLUSIONS: The present results suggest that lung fibroblast HSP47 expression may be a useful new prognostic marker for idiopathic fibrotic nonspecific interstitial pneumonia.
Asunto(s)
Fibroblastos/patología , Proteínas del Choque Térmico HSP47/metabolismo , Enfermedades Pulmonares Intersticiales/patología , Pulmón/patología , Fibrosis Pulmonar/patología , Anciano , Femenino , Humanos , Inmunohistoquímica , Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/mortalidad , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Idiopathic interstitial pneumonias (IIPs) comprises a group of diffuse parenchymal lung diseases of unknown etiology with varying degrees of inflammation and fibrosis including cryptogenic organizing pneumonia (COP), idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). Tenascin-C is an extracellular matrix molecule that is expressed during wound healing in various tissues. The present study was aimed to investigate the role of tenascin-C in the pathogenesis of IIPs. METHODS: We used enzyme-linked immunosorbent assays to measure levels of tenascin-C in serum and bronchoalveolar lavage fluid (BALF) from 17 patients with IPF, 12 with NSIP, 15 with COP and from 23 healthy individuals. RESULTS: Serum levels of tenascin-C were significantly elevated in patients with COP compared with those in all other participants, whereas those in patients with IPF and NSIP were not significantly elevated compared with healthy individuals. The levels of tenascin-C in BALF from patients with COP and NSIP were significantly higher than those of healthy individuals. In addition, serum tenascin-C was significantly correlated with levels of serum C-reactive protein, which is a serum acute phase protein. CONCLUSION: Systemic inflammation in the lung with IIPs might be associated with tenascin-C. These results suggest that tenascin-C is responsible for the pathogenesis of IIPs especially via inflammation, and that it might serve as a serum marker of COP.
Asunto(s)
Neumonía en Organización Criptogénica/sangre , Tenascina/sangre , Adulto , Anciano , Biomarcadores/sangre , Líquido del Lavado Bronquioalveolar/química , Neumonía en Organización Criptogénica/etiología , Neumonía en Organización Criptogénica/patología , Femenino , Humanos , Neumonías Intersticiales Idiopáticas/sangre , Neumonías Intersticiales Idiopáticas/etiología , Neumonías Intersticiales Idiopáticas/patología , Mediadores de Inflamación/sangre , Mediadores de Inflamación/fisiología , Masculino , Persona de Mediana Edad , Tenascina/biosíntesisRESUMEN
OBJECTIVES: Mucus hypersecretion is a prominent feature in patients with chronic respiratory tract infections such as cystic fibrosis and diffuse panbronchiolitis, and the clinical effectiveness of macrolide antibiotics has been reported in these patients. Because human neutrophil peptide-1 (HNP-1), an antimicrobial peptide in neutrophils, exists in high concentrations in the airway fluid of these patients, we examined the direct effect of HNP-1 on MUC5AC mucin production using NCI-H292 cells. The effects of macrolide antibiotics on the response were also examined. METHODS: MUC5AC synthesis was assayed using RT-PCR and ELISA. Phosphorylation of ERK1/2 was determined by western blotting. RESULTS: Stimulation with HNP-1 or lipopolysaccharide (LPS) derived from Pseudomonas aeruginosa increases the production of MUC5AC mRNA and protein, and an additive effect was found upon co-stimulation with both HNP-1 and LPS. Azithromycin and clarithromycin had inhibitory effects on overproduction of MUC5AC induced by HNP-1 or LPS stimulation. Telithromycin also had an inhibitory effect on MUC5AC production induced by LPS, but not on production by HNP-1. Phosphorylation of ERK1/2 was induced by HNP-1 or LPS stimulation, and azithromycin, clarithromycin and telithromycin had inhibitory effects on ERK1/2 phosphorylation induced by LPS, but not by HNP-1. CONCLUSIONS: These findings suggest that neutrophil-derived defensins as bacterial components contribute to excessive mucus production in patients with respiratory tract infections, and that macrolide and ketolide antibiotics directly inhibit these actions by interfering with intracellular signal transduction. However, the mechanism of telithromycin inhibition of MUC5AC synthesis may differ from the response induced by azithromycin and clarithromycin.
Asunto(s)
Antibacterianos/metabolismo , Azitromicina/metabolismo , Claritromicina/metabolismo , Cetólidos/metabolismo , Lipopolisacáridos/metabolismo , Mucina 5AC/biosíntesis , alfa-Defensinas/metabolismo , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Humanos , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Mucina 5AC/genética , Fosforilación , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
A 65-year-old man had been admitted with exertional dyspnea 2 years previously. Reticular shadows in bilateral lower lung fields were detected on chest roentogenogram and observed the natural course. The clinical symptoms and radiological findings progressed one month later and then he was admitted to our hospital to be examined for diagnosis and treatment. Video-assisted thoracoscopic surgery (VATS) was performed and chronic hypersensitivity pneumonitis was diagnosed. At five days after the surgery, dyspnea and radiological findings deteriorated and we diagnosed acute exacerbation of chronic hypersensitivity pneumonitis. He was treated immediately with steroid pulse therapy, immunosuppressant and polymyxin B-immobilized fiber column-direct hemoperfusion, which relieved his clinical symptoms and radiological findings. Although this is a very rare case, we have to consider the possibility of acute exacerbation of chronic hypersensitivity pneumonitis after VATS, as we do in idiopathic pulmonary fibrosis.
Asunto(s)
Alveolitis Alérgica Extrínseca/cirugía , Biopsia/efectos adversos , Cirugía Torácica Asistida por Video/efectos adversos , Enfermedad Aguda , Anciano , Alveolitis Alérgica Extrínseca/diagnóstico , Alveolitis Alérgica Extrínseca/patología , Alveolitis Alérgica Extrínseca/terapia , Enfermedad Crónica , Hemoperfusión , Humanos , Inmunosupresores/uso terapéutico , Masculino , Metilprednisolona/administración & dosificación , Polimixina B/uso terapéutico , Quimioterapia por Pulso , Resultado del TratamientoRESUMEN
Animals and plants express endogenous peptide antibiotics called defensins. Defensins show broad-spectrum antimicrobial activity, even against bacteria that have resistance to conventional antibiotics, which has made them viable candidates for new antibiotics. However, human defensins have failed to reach the market because of their cytotoxic effects and non-antimicrobial bioactivities. Plectasin is a defensin that has shown promise but has not had its potentially negative effects clarified. To address this issue, we examined plectasin's cytotoxicity in human cells using an AlamarBlue reduction assay, its interleukin (IL)-8-inducing capacity using real-time PCR and ELISA, and measured its MIC against bacteria. We confirmed that plectasin has specific antibacterial activity against Streptococcus pneumoniae. Plectasin showed no cytotoxicity to A549 cells, normal human bronchial epithelial cells, or lung fibroblasts, and it did not induce IL-8 transcription or production in A549 cells. Our results suggest that plectasin could be an inoffensive alternative antibiotic for clinical application.
Asunto(s)
Antibacterianos/farmacología , Defensinas/farmacología , Péptidos/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Bronquios/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Humanos , Interleucina-8/biosíntesis , Pruebas de Sensibilidad Microbiana , Biosíntesis de Proteínas/efectos de los fármacos , ARN Mensajero/biosíntesisRESUMEN
Multicentric reticulohistiocytosis (MR) is an uncommon disease characterized by joint and cutaneous manifestations. The diagnosis must be confirmed by histological evidence of typical histiocytes and multinucleated giant cells. Many conditions, including malignancy, have been described in association with MR. We herein report a female case of MR in whom partial improvement was obtained by steroid and low-dose methotrexate treatments. However, ovarian cancer was found and therefore a surgical resection and chemotherapy were performed. These treatments resulted in the complete resolution of the skin and joint symptoms. These findings support the close linkage between MR and malignancy and the efficacy of cytotoxic drugs for the treatment of MR.
Asunto(s)
Histiocitosis de Células no Langerhans/diagnóstico , Neoplasias Ováricas/diagnóstico , Antígenos CD/biosíntesis , Antígenos de Diferenciación Mielomonocítica/biosíntesis , Femenino , Células Gigantes/metabolismo , Histiocitosis de Células no Langerhans/complicaciones , Histiocitosis de Células no Langerhans/diagnóstico por imagen , Humanos , Inmunohistoquímica/métodos , Metotrexato/farmacología , Persona de Mediana Edad , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico por imagen , Ovario/patología , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/diagnóstico , Piel/patología , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
A 15-year-old girl was admitted to our hospital because of polydipsia, polyuria, bilateral hilar lymphadenopathy and uveitis. A diagnosis of sarcoidosis with central diabetes insipidus was made by radiological, serological, bronchoalveolar lavage examinations, fluid restriction test and vasopression test. Prednisolone therapy improved all of her clinical findings except diabetes insipidus. So she had to continue intranasal 1-desamino-8-arginine vasopressin (DDAVP) therapy. In addition, we reviewed the clinical features of 27 patients of sarcoidosis with diabetes insipidus reported in Japan. They included 12 patients in young men and 21 patients having uveitis. These patients showed low frequency of lung complications in comparison with sarcoidosis without diabetes insipidus. Steroid therapy improved the symptoms of diabetes insipidus in only 3 patients, and all these 3 patients started steroid therapy within 1 month after the onset. Therefore we think that early diagnosis and treatment are important. Though central neurosarcoidosis was generally considered to have poor prognosis, there were only 3 patients who had recurrence by steroid tapering.