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1.
Arthroplast Today ; 27: 101350, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38533423

RESUMO

Periprosthetic joint infection (PJI) can present challenges in diagnosis and treatment, particularly in the setting of atypical causative organisms such as fungi and mycobacteria. Herein, we present a case and provide a review of the diagnosis and treatment of an unusual PJI caused by bacillus Calmette-Guérin, administered during the treatment of bladder cancer 3 years prior to total knee arthroplasty and subsequent PJI. Although the patient's history of bladder cancer was known, neither his Bacillus Calmette-Guérin treatment nor its potential for distant site spread that could lead to PJI were appreciated, leading to a prolonged diagnostic evaluation and treatment course.

2.
Transplant Proc ; 55(8): 1981-1983, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37658010

RESUMO

Chylothorax is a rare complication after double lung transplantation. We report a case of a 55-year-old man with idiopathic pulmonary fibrosis. He underwent a double lung transplantation with venoarterial extracorporeal membrane support. The surgery was uncomplicated; however, his postoperative course was complicated with a refractory chylothorax that started postoperative day 4. Medical management could not control the chylothorax, including nil per os, total parenteral nutrition, and octreotide administration. After failed percutaneous embolization via lymphangiography and surgical ligation of the thoracic duct and pleurodesis via video-assisted thoracoscopic surgery, percutaneous needle disruption of the retroperitoneal lymph nodes was performed. After this procedure, the chylothorax resolved quickly. Percutaneous needle disruption of the retroperitoneal lymph node is safe and effective for refractory chylothorax. This technique can be one of the main modalities to manage chylothorax after lung transplantation.

3.
Chest ; 163(5): e201-e205, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37164583

RESUMO

Pulmonary arteriovenous malformations (PAVMs) are rare and most often identified in patients with hereditary hemorrhagic telangiectasia (HHT). We describe a patient with severe hypoxemia and orthodeoxia with imaging findings consistent with PAVMs. Resected lung pathologic findings confirmed the presence of numerous microscopic vascular abnormalities within the right lower lobe that was consistent with diffuse pulmonary arteriovenous shunts. Family history was negative for HHT but was positive for pulmonary arterial hypertension (PAH) in two second-degree relatives. A vascular malformation gene panel was negative for genes that commonly are associated with HHT but identified a pathogenic variant in the gene encoding bone morphogenetic protein receptor-2 (BMPR2 p.Cys123∗). Pathogenic variants in BMPR2 are a well-known cause of hereditary PAH; there have been several reports to date of patients with PAVMs and PAH. However, this is the first patient to be reported with a pathogenic variant in BMPR2 to have PAVMs in isolation.


Assuntos
Fístula Arteriovenosa , Malformações Arteriovenosas , Hipertensão Arterial Pulmonar , Veias Pulmonares , Telangiectasia Hemorrágica Hereditária , Humanos , Malformações Arteriovenosas/diagnóstico , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/cirurgia , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/genética , Pulmão , Fístula Arteriovenosa/complicações , Veias Pulmonares/cirurgia , Veias Pulmonares/anormalidades , Artéria Pulmonar/anormalidades , Hipertensão Pulmonar Primária Familiar/complicações , Hipertensão Arterial Pulmonar/complicações
4.
Physiol Rep ; 9(4): e14761, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33625796

RESUMO

COVID-19 causes severe disease with poor outcomes. We tested the hypothesis that early SARS-CoV-2 viral infection disrupts innate immune responses. These changes may be important for understanding subsequent clinical outcomes. We obtained residual nasopharyngeal swab samples from individuals who requested COVID-19 testing for symptoms at drive-through COVID-19 clinical testing sites operated by the University of Utah. We applied multiplex immunoassays, real-time polymerase chain reaction assays and quantitative proteomics to 20 virus-positive and 20 virus-negative samples. ACE-2 transcripts increased with infection (OR =17.4, 95% CI [CI] =4.78-63.8) and increasing viral N1 protein transcript load (OR =1.16, CI =1.10-1.23). Transcripts for two interferons (IFN) were elevated, IFN-λ1 (OR =71, CI =7.07-713) and IFN-λ2 (OR =40.2, CI =3.86-419), and closely associated with viral N1 transcripts (OR =1.35, CI =1.23-1.49 and OR =1.33 CI =1.20-1.47, respectively). Only transcripts for IP-10 were increased among systemic inflammatory cytokines that we examined (OR =131, CI =1.01-2620). We found widespread discrepancies between transcription and translation. IFN proteins were unchanged or decreased in infected samples (IFN-γ OR =0.90 CI =0.33-0.79, IFN-λ2,3 OR =0.60 CI =0.48-0.74) suggesting viral-induced shut-off of host antiviral protein responses. However, proteins for IP-10 (OR =3.74 CI =2.07-6.77) and several interferon-stimulated genes (ISG) increased with viral load (BST-1 OR =25.1, CI =3.33-188; IFIT1 OR =19.5, CI =4.25-89.2; IFIT3 OR =245, CI =15-4020; MX-1 OR =3.33, CI =1.44-7.70). Older age was associated with substantial modifications of some effects. Ambulatory symptomatic patients had an innate immune response with SARS-CoV-2 infection characterized by elevated IFN, proinflammatory cytokine and ISG transcripts, but there is evidence of a viral-induced host shut-off of antiviral responses. Our findings may characterize the disrupted immune landscape common in patients with early disease.


Assuntos
COVID-19/imunologia , Imunidade Inata/imunologia , Doenças Nasofaríngeas/virologia , SARS-CoV-2/imunologia , Carga Viral/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/virologia , Criança , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Nasofaríngeas/imunologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/genética , Fatores Sexuais , Adulto Jovem
5.
medRxiv ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33173878

RESUMO

To examine innate immune responses in early SARS-CoV-2 infection that may change clinical outcomes, we compared nasopharyngeal swab data from 20 virus-positive and 20 virus-negative individuals. Multiple innate immune-related and ACE-2 transcripts increased with infection and were strongly associated with increasing viral load. We found widespread discrepancies between transcription and translation. Interferon proteins were unchanged or decreased in infected samples suggesting virally-induced shut-off of host anti-viral protein responses. However, IP-10 and several interferon-stimulated gene proteins increased with viral load. Older age was associated with modifications of some effects. Our findings may characterize the disrupted immune landscape of early disease.

8.
J Heart Lung Transplant ; 35(11): 1289-1294, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27381675

RESUMO

BACKGROUND: Prior coronary artery bypass grafting (CABG) has been a contraindication to lung transplantation (LTx) because of disease severity and technical considerations. Although patients increasingly are being referred for and receiving LTx, whether it should remain a contraindication is unknown. We sought to define the prevalence of LTx after CABG and determine the effect on outcomes. METHODS: The United Network for Organ Sharing Standard Transplant Analysis and Research data set was queried during the period 2004-2013 for adult LTx patients, as prior CABG became a mandatory reporting field in 2004. The primary end-points were 30-day and 1-, 3-, and 5-year survivals. RESULTS: The study cohort included 14,791 patients, of whom 292 patients had previously undergone CABG (single left, n = 68; single right, n = 181; bilateral, n = 43), representing 2% of all transplants. For the entire cohort, 30-day survival was 97%, and survival at 1, 3, and 5 years was 88%, 79%, and 74%. CABG was a predictor of mortality at all time points, with hazard ratios ranging from 1.97 (confidence interval, 1.23-3.16; p < 0.01) at 30 days to 1.38 (confidence interval, 1.12-1.69; p < 0.01) at 5 years. When stratified by type of transplant, CABG strongly predicted mortality at all time points for patients receiving bilateral, but not single, transplants. CONCLUSIONS: Although LTx after CABG is uncommon, it is increasingly performed in the current era. Single right LTx is the most common procedure performed in patients with prior CABG. CABG before LTx is an independent predictor of mortality at all time points and is driven by increased mortality in patients receiving bilateral LTx.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Doença da Artéria Coronariana/complicações , Seguimentos , Humanos , Pneumopatias/complicações , Guias de Prática Clínica como Assunto , Reoperação , Resultado do Tratamento
9.
Chest ; 145(2): 231-236, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24135949

RESUMO

BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is a rare disease of capillary proliferation of unknown cause and with a high mortality. Families with multiple affected individuals with PCH suggest a heritable cause although the genetic etiology remains unknown. METHODS: We used exome sequencing to identify a candidate gene for PCH in a family with two affected brothers. We then screened 11 unrelated patients with familial (n = 1) or sporadic (n = 10) PCH for mutations. RESULTS: Using exome sequencing, we identified compound mutations in eukaryotic translation initiation factor 2 α kinase 4 (EIF2AK4) (formerly known as GCN2) in both affected brothers. Both parents and an unaffected sister were heterozygous carriers. In addition, we identified two EIF2AK4 mutations in each of two of 10 unrelated individuals with sporadic PCH. EIF2AK4 belongs to a family of kinases that regulate angiogenesis in response to cellular stress. CONCLUSIONS: Mutations in EIF2AK4 are likely to cause autosomal-recessive PCH in familial and some nonfamilial cases.


Assuntos
Pneumopatias/genética , Mutação/genética , Neovascularização Patológica/genética , Proteínas Serina-Treonina Quinases/genética , Doenças Vasculares/genética , Adolescente , Adulto , Capilares/patologia , Exoma/genética , Feminino , Heterozigoto , Humanos , Pneumopatias/patologia , Pneumopatias/cirurgia , Transplante de Pulmão , Masculino , Neovascularização Patológica/patologia , Neovascularização Patológica/cirurgia , Pais , Linhagem , Irmãos , Doenças Vasculares/patologia , Doenças Vasculares/cirurgia
12.
Am J Physiol Lung Cell Mol Physiol ; 296(3): L489-99, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19036873

RESUMO

Persistent hypoxia can cause pulmonary arterial hypertension that may be associated with significant remodeling of the pulmonary arteries, including smooth muscle cell proliferation and hypertrophy. We previously demonstrated that the NADPH oxidase homolog NOX4 mediates human pulmonary artery smooth muscle cell (HPASMC) proliferation by transforming growth factor-beta1 (TGF-beta1). We now show that hypoxia increases HPASMC proliferation in vitro, accompanied by increased reactive oxygen species generation and NOX4 gene expression, and is inhibited by antioxidants, the flavoenzyme inhibitor diphenyleneiodonium (DPI), and NOX4 gene silencing. HPASMC proliferation and NOX4 expression are also observed when media from hypoxic HPASMC are added to HPASMC grown in normoxic conditions, suggesting autocrine stimulation. TGF-beta1 and insulin-like growth factor binding protein-3 (IGFBP-3) are both increased in the media of hypoxic HPASMC, and increased IGFBP-3 gene expression is noted in hypoxic HPASMC. Treatment with anti-TGF-beta1 antibody attenuates NOX4 and IGFBP-3 gene expression, accumulation of IGFBP-3 protein in media, and proliferation. Inhibition of IGFBP-3 expression with small interfering RNA (siRNA) decreases NOX4 gene expression and hypoxic proliferation. Conversely, NOX4 silencing does not decrease hypoxic IGFBP-3 gene expression or secreted protein. Smad inhibition does not but the phosphatidylinositol 3-kinase (PI3K) signaling pathway inhibitor LY-294002 does inhibit NOX4 and IGFBP-3 gene expression, IGFBP-3 secretion, and cellular proliferation resulting from hypoxia. Immunoblots from hypoxic HPASMC reveal increased TGF-beta1-mediated phosphorylation of the serine/threonine kinase (Akt), consistent with hypoxia-induced activation of PI3K/Akt signaling pathways to promote proliferation. We conclude that hypoxic HPASMC produce TGF-beta1 that acts in an autocrine fashion to induce IGFBP-3 through PI3K/Akt. IGFBP-3 increases NOX4 gene expression, resulting in HPASMC proliferation. These observations add to our understanding hypoxic pulmonary vascular remodeling.


Assuntos
Hipóxia Celular/fisiologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/biossíntese , Miócitos de Músculo Liso/metabolismo , NADPH Oxidases/metabolismo , Artéria Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/biossíntese , Comunicação Autócrina , Hipóxia Celular/genética , Proliferação de Células , Células Cultivadas , Expressão Gênica , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Modelos Biológicos , Miócitos de Músculo Liso/citologia , NADPH Oxidase 4 , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artéria Pulmonar/citologia , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
13.
Transplantation ; 86(5): 636-7, 2008 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18791441

RESUMO

Pediatric lung transplantation for cystic fibrosis has uncertain survival effects. Three retrospective studies disagree on survival benefit. The US Lung Allocation Score has changed patient selection for lung transplantation but confounds the analysis of survival outcomes. A prospective trial is needed to resolve clinical equipoise and explore quality-of-life effects.


Assuntos
Fibrose Cística/cirurgia , Criança , Sobrevivência de Enxerto , Humanos , Transplante de Pulmão , Seleção de Pacientes , Resultado do Tratamento
15.
N Engl J Med ; 359(5)2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-27559197

RESUMO

BACKGROUND: The effects of lung transplantation on the survival and quality of life in children with cystic fibrosis are uncertain. METHODS: We used data from the U.S. Cystic Fibrosis Foundation Patient Registry and from the Organ Procurement and Transplantation Network to identify children with cystic fibrosis who were on the waiting list for lung transplantation during the period from 1992 through 2002. We performed proportional-hazards survival modeling, using multiple clinically relevant covariates that were available before the children were on the waiting list and the interactions of these covariates with lung transplantation as a time-dependent covariate. The data were insufficient in quality and quantity for a retrospective quality-of-life analysis. RESULTS: A total of 248 of the 514 children on the waiting list underwent lung transplantation in the United States during the period from 1992 through 2002. Proportional-hazards modeling identified four variables besides transplantation that were associated with changes in survival. Burkholderia cepacia infection was associated with a trend toward decreased survival, regardless of whether the patient underwent transplantation. A diagnosis of diabetes before the patient was placed on the waiting list decreased survival while the patient was on the waiting list but did not decrease survival after transplantation, whereas older age did not affect waiting-list survival but decreased post-transplantation survival. Staphylococcus aureus infection increased waiting-list survival but decreased post-transplantation survival. Using age, diabetes status, and S. aureus infection status as covariates, we estimated the effect of transplantation on survival for each patient group, expressed as a hazard factor of less than 1 for a benefit and more than 1 for a risk of harm. Five patients had a significant estimated benefit, 283 patients had a significant risk of harm, 102 patients had an insignificant benefit, and 124 patients had an insignificant risk of harm associated with lung transplantation. CONCLUSIONS: Our analyses estimated clearly improved survival for only 5 of 514 patients on the waiting list for lung transplantation. Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis. A prospective, randomized trial is needed to clarify whether and when patients derive a survival and quality-of-life benefit from lung transplantation.

16.
Indian J Crit Care Med ; 12(4): 145-52, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19742269

RESUMO

BACKGROUND: Herpes simplex-1 virus (HSV-1) reactivation in the respiratory tract is common in intensive care unit (ICU) patients. However, susceptible ICU populations are poorly defined. Clinical recognition of HSV infection of the respiratory tract is difficult and the impact of such reactivation is not understood. MATERIALS AND METHODS: A retrospective analysis of HSV-1 positive patients encountered over a 5-year period at a multispecialty ICU was carried out. HSV-1 was identified in respiratory secretions using a qualitative polymerase chain reaction (PCR) technique. Patient charts were reviewed for clinical features that would typify HSV-1 respiratory involvement, and the morbidity and mortality risks found with HSV-1 respiratory involvement. RESULTS: A review of 48 HSV-1 positive ICU patients showed that patients reactivating HSV in the respiratory tract fell into one of the three categories: (1) septic elderly patients with and without ARDS, (2) immunosuppressed patients, especially those receiving high-dose steroids, and (3) post-thoracotomy patients. Abnormalities suggestive of HSV-1 reactivation in the respiratory tract included, haemorrhagic or excessive respiratory secretions, concomitant orofacial herpes (42%), and bronchoscopic abnormalities (hemorrhagic ulcers and mucosal friability) (83%). Twenty eight percent of the HSV-1 infected patients experienced postextubation stridor. HSV-1 reactivation was associated with extended ventilator stays, significant mortality (42%), and ventilator-associated pneumonias (52%). CONCLUSIONS: Identification of susceptible populations and definition of clinical features of HSV-1 related respiratory disease can enable diagnosis of HSV-1 infection in ICU patients. Although detection by a PCR technique can rapidly diagnose HSV-1 reactivation, prospective studies are required to clarify HSV disease versus mere shedding, and understand the impact of HSV-1 reactivation in hospitalized patients.

17.
N Engl J Med ; 357(21): 2143-52, 2007 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-18032764

RESUMO

BACKGROUND: The effects of lung transplantation on the survival and quality of life in children with cystic fibrosis are uncertain. METHODS: We used data from the U.S. Cystic Fibrosis Foundation Patient Registry and from the Organ Procurement and Transplantation Network to identify children with cystic fibrosis who were on the waiting list for lung transplantation during the period from 1992 through 2002. We performed proportional-hazards survival modeling, using multiple clinically relevant covariates that were available before the children were on the waiting list and the interactions of these covariates with lung transplantation as a time-dependent covariate. The data were insufficient in quality and quantity for a retrospective quality-of-life analysis. RESULTS: A total of 248 of the 514 children on the waiting list underwent lung transplantation in the United States during the period from 1992 through 2002. Proportional-hazards modeling identified four variables besides transplantation that were associated with changes in survival. Burkholderia cepacia infection was associated with a trend toward decreased survival, regardless of whether the patient underwent transplantation [corrected]. A diagnosis of diabetes before the patient was placed on the waiting list decreased survival while the patient was on the waiting list but did not decrease survival after transplantation, whereas older age did not affect waiting-list survival but decreased post-transplantation survival. Staphylococcus aureus infection increased waiting-list survival but decreased post-transplantation survival. Using age, diabetes status, and S. aureus infection status as covariates, we estimated the effect of transplantation on survival for each patient group, expressed as a hazard factor of less than 1 for a benefit and more than 1 for a risk of harm. Five patients had a significant estimated benefit, 283 patients had a significant risk of harm, 102 patients had an insignificant benefit, and 124 patients had an insignificant risk of harm associated with lung transplantation [corrected]. CONCLUSIONS: Our analyses estimated clearly improved survival for only 5 of 514 patients on the waiting list for lung transplantation. Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis. A prospective, randomized trial is needed to clarify whether and when patients derive a survival and quality-of-life benefit from lung transplantation.


Assuntos
Fibrose Cística/mortalidade , Fibrose Cística/cirurgia , Transplante de Pulmão/mortalidade , Adolescente , Fatores Etários , Infecções por Burkholderia/complicações , Burkholderia cepacia , Criança , Fibrose Cística/complicações , Feminino , Volume Expiratório Forçado , Rejeição de Enxerto/mortalidade , Humanos , Estimativa de Kaplan-Meier , Transplante de Pulmão/efeitos adversos , Masculino , Modelos de Riscos Proporcionais , Qualidade de Vida , Sistema de Registros , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/complicações , Staphylococcus aureus , Análise de Sobrevida , Resultado do Tratamento , Listas de Espera
18.
Curr Opin Pulm Med ; 12(6): 459-63, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17053498

RESUMO

PURPOSE OF REVIEW: To examine recent publications on lung transplantation for cystic fibrosis for changes in surgical techniques, selection criteria of patients, and impact on quality of life. RECENT FINDINGS: Recent evidence focuses on cystic fibrosis patient subsets enabling better decisions about listing for lung transplantation as a therapeutic option. There is information about Burkholderia cepacia infection, ventilator dependence, young age, and arthropathy. In the US, the United Network for Organ Sharing has addressed perceived inequities in organ distribution by allocating organs by illness severity rather than time on the waiting list. A Lung Allocation Score ranks severity for patients 12 years of age and older for transplantation based on variables including lung function, oxygen and ventilatory needs, diabetes, weight and physical performance. Some recently studied important variables that influence survival in cystic fibrosis and after lung transplantation, including airway infections, pancreatic exocrine function and acute exacerbations, are not included in the Lung Allocation Score. Few publications have examined quality of life after transplantation, and a definitive work has yet to appear. SUMMARY: New information has refined decision-making about lung transplantation for patients with cystic fibrosis. We examine recent findings and make recommendations for patients, families and medical providers.


Assuntos
Fibrose Cística/cirurgia , Transplante de Pulmão , Fibrose Cística/fisiopatologia , Humanos , Seleção de Pacientes , Período Pós-Operatório , Qualidade de Vida , Alocação de Recursos , Obtenção de Tecidos e Órgãos
19.
Am J Physiol Lung Cell Mol Physiol ; 290(4): L661-L673, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16227320

RESUMO

Transforming growth factor-beta1 (TGF-beta1) is abundantly expressed in pulmonary hypertension, but its effect on the pulmonary circulation remains unsettled. We studied the consequences of TGF-beta1 stimulation on freshly isolated human pulmonary artery smooth muscle cells (HPASMC). TGF-beta1 initially promoted differentiation, with upregulated expression of smooth muscle contractile proteins. TGF-beta1 also induced expression of Nox4, the only NAD(P)H oxidase membrane homolog found in HPASMC, through a signaling pathway involving Smad 2/3 but not mitogen-activated protein (MAP) kinases. TGF-beta1 likewise increased production of reactive oxygen species (ROS), an effect significantly reduced by the NAD(P)H oxidase flavoprotein inhibitor diphenylene iodonium (DPI) and by Nox4 siRNAs. In the absence of TGF-beta1, Nox4 was present in freshly cultured cells but progressively lost with each passage in culture, paralleling a decrease in ROS production by HPASMC over time. At a later time point (72 h), TGF-beta1 promoted HPASMC proliferation in a manner partially inhibited by Nox4 small interfering RNA and dominant negative Smad 2/3, indicating that TGF-beta1 stimulates HPASMC growth in part by a redox-dependent mechanism mediated through induction of Nox4. HPASMC activation of the MAP kinases ERK1/2 was reduced by the NAD(P)H oxidase inhibitors DPI and 4-(2-aminoethyl)benzenesulfonyl fluoride, suggesting that TGF-beta1 may facilitate proliferation by upregulating Nox4 and ROS production, with transient oxidative inactivation of phosphatases and augmentation of growth signaling cascades. These findings suggest that Nox4 is the relevant Nox homolog in HPASMC. This is the first observation that TGF-beta1 regulates Nox4, with important implications for mechanisms of pulmonary vascular remodeling.


Assuntos
Miócitos de Músculo Liso/citologia , NADPH Oxidases/metabolismo , Artéria Pulmonar/citologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas Contráteis/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NADPH Oxidase 4 , Artéria Pulmonar/metabolismo , Transdução de Sinais/fisiologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1
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