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1.
Am J Respir Crit Care Med ; 207(8): 978-995, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36973004

RESUMO

Current American Thoracic Society (ATS) standards promote the use of race and ethnicity-specific reference equations for pulmonary function test (PFT) interpretation. There is rising concern that the use of race and ethnicity in PFT interpretation contributes to a false view of fixed differences between races and may mask the effects of differential exposures. This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation. The ATS convened a diverse group of clinicians and investigators for a workshop in 2021 to evaluate the use of race and ethnicity in PFT interpretation. Review of evidence published since then that challenges current practice and continued discussion concluded with a recommendation to replace race and ethnicity-specific equations with race-neutral average reference equations, which must be accompanied with a broader re-evaluation of how PFTs are used to make clinical, employment, and insurance decisions. There was also a call to engage key stakeholders not represented in this workshop and a statement of caution regarding the uncertain effects and potential harms of this change. Other recommendations include continued research and education to understand the impact of the change, to improve the evidence for the use of PFTs in general, and to identify modifiable risk factors for reduced pulmonary function.


Assuntos
Etnicidade , Sociedades , Humanos , Estados Unidos , Testes de Função Respiratória
2.
Mol Plant Microbe Interact ; 36(8): 489-501, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36892820

RESUMO

Fusarium head blight (FHB), caused by the hemibiotrophic fungus Fusarium graminearum, is one of the major threats to global wheat productivity. A wheat pore-forming toxin-like (PFT) protein was previously reported to underlie Fhb1, the most widely used quantitative trait locus in FHB breeding programs worldwide. In the present work, wheat PFT was ectopically expressed in the model dicot plant Arabidopsis. Heterologous expression of wheat PFT in Arabidopsis provided a broad-spectrum quantitative resistance to fungal pathogens including F. graminearum, Colletotrichum higginsianum, Sclerotinia sclerotiorum, and Botrytis cinerea. However, there was no resistance to bacterial or oomycete pathogens Pseudomonas syringae and Phytophthora capsici, respectively in the transgenic Arabidopsis plants. To explore the reason for the resistance response to, exclusively, the fungal pathogens, purified PFT protein was hybridized to a glycan microarray having 300 different types of carbohydrate monomers and oligomers. It was found that PFT specifically hybridized with chitin monomer, N-acetyl glucosamine (GlcNAc), which is present in fungal cell walls but not in bacteria or oomycete species. This exclusive recognition of chitin may be responsible for the specificity of PFT-mediated resistance to fungal pathogens. Transfer of the atypical quantitative resistance of wheat PFT to a dicot system highlights its potential utility in designing broad-spectrum resistance in diverse host plants. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Arabidopsis , Fusarium , Arabidopsis/genética , Arabidopsis/microbiologia , Triticum/genética , Triticum/microbiologia , Melhoramento Vegetal , Locos de Características Quantitativas , Fusarium/fisiologia , Plantas Geneticamente Modificadas , Doenças das Plantas/microbiologia , Resistência à Doença/genética
3.
Xenotransplantation ; 30(4): e12803, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37120823

RESUMO

Porcine cytomegalovirus (PCMV) is widely distributed in pigs and difficult to detect due to latency. PCMV infection of source pigs was associated with early graft failure after cardiac and renal xenotransplantation into nonhuman primates. Importantly, PCMV infection of the first genetically modified pig heart into a human may have contributed to the reduced survival of the patient. Sensitive and reliable assays for detection of latent PCMV infection are thus indispensable. Here, we report the development of five peptide-induced rabbit antisera specific for PCMV glycoprotein B (gB) and their validation for detection of PCMV in infected pig fallopian tube (PFT) cells by immunofluorescence and electron microscopy (EM). The anti-gB antibodies were also used for detection by Western blot analysis of PCMV purified from the supernatant of infected PFT cells. Sera of infected versus non-infected pigs have been compared. In parallel, PCMV viral load in blood samples of the animals was quantified by a novel highly sensitive nested-PCR and qPCR assay. A combination of four partly overlapping peptides from the gB C-terminus was used to establish a diagnostic ELISA for PCMV gB specific pig antibodies which is able to differentiate infected from non-infected animals and to quantify maternal antibodies in neonates. The combination of a highly sensitive nested PCR for direct virus detection with a sensitive peptide-based ELISA detecting anti-PCMV gB-antibodies, supplemented by Western blot analysis and/or immunohistochemistry for virus detection will reliably differentiate pigs with active infection, latently infected pigs, and non-infected pigs. It may significantly improve the virologic safety of xenotransplantation.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Feminino , Animais , Suínos , Humanos , Coelhos , Citomegalovirus/genética , Transplante Heterólogo , Infecções por Citomegalovirus/diagnóstico , Reação em Cadeia da Polimerase , Peptídeos
4.
Mol Microbiol ; 115(4): 508-525, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33089544

RESUMO

ß-barrel pore-forming toxins perforate cell membranes by forming oligomeric ß-barrel pores. The most crucial step is the membrane-insertion of the pore-forming motifs that create the transmembrane ß-barrel scaffold. Molecular mechanism that regulates structural reorganization of these pore-forming motifs during ß-barrel pore-formation still remains elusive. Using Vibrio cholerae cytolysin as an archetypical example of the ß-barrel pore-forming toxin, we show that a key tyrosine residue (Y321) in the hinge region of the pore-forming motif plays crucial role in this process. Mutation of Y321 abrogates oligomerization of the membrane-bound toxin protomers, and blocks subsequent steps of pore-formation. Our study suggests that the presence of Y321 in the hinge region of the pore-forming motif is crucial for the toxin molecule to sense membrane-binding, and to trigger essential structural rearrangements required for the subsequent oligomerization and pore-formation process. Such a regulatory mechanism of pore-formation by V. cholerae cytolysin has not been documented earlier in the structurally related ß-barrel pore-forming toxins.


Assuntos
Motivos de Aminoácidos , Perforina/química , Perforina/fisiologia , Tirosina/química , Vibrio cholerae/química , Vibrio cholerae/fisiologia , Proteínas de Bactérias/química , Proteínas de Bactérias/fisiologia , Linhagem Celular , Membrana Celular/metabolismo , Células Cultivadas , Citotoxinas/química , Citotoxinas/fisiologia , Humanos , Microscopia Eletrônica de Transmissão , Simulação de Dinâmica Molecular , Mutação , Perforina/ultraestrutura , Conformação Proteica , Multimerização Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Vibrio cholerae/ultraestrutura
5.
Sleep Breath ; 26(2): 725-732, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34328605

RESUMO

OBJECTIVE: To investigate the factors affecting compliance with positive airway pressure (PAP) therapy and establish the relationship between compliance and pulmonary function tests (PFT) in patients with OSA. MATERIAL AND METHODS: In this prospective study, patients with OSA using PAP devices were questioned about the complaints related to the device. Depression and anxiety scales along with PFT parameters were also assessed. RESULTS: Of 98 participants, 63% were men. The mean age was 52.0 ± 9.6 years. Sixty-seven percent of the patients were compliant with their devices. A significant difference was observed between the proportion of the participants compliant or non-compliant with the device, based on OSA severity (p < 0.05). Beck depression inventory (BDI) and Beck anxiety inventory (BAI) scores of the compliant patients were significantly lower than those of the non-compliant patients (p < 0.001, p = 0.044, respectively). No statistically significant difference was detected between the groups regarding individual pulmonary function tests (p > 0.05). The rates of nasal mask use, not having difficulty in tolerating CPAP, falling asleep, absence of abdominal distension, no facial sores, no air leakage, patients benefiting from the device, reduction in daytime sleepiness, and the belief that they are receiving appropriate therapy in participants compliant with the device were higher than those in non-compliant participants (p < 0.05). The rates of claustrophobia and discomfort due to pressure were significantly lower in patients compliant with the device than in the non-compliant patients (p < 0.05). CONCLUSION: While no relationship was detected between PFT parameters and PAP therapy compliance, significant factors affecting the device compliance were detected.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Apneia Obstrutiva do Sono , Adulto , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Prospectivos , Apneia Obstrutiva do Sono/terapia
6.
Allergol Immunopathol (Madr) ; 50(1): 80-84, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34935317

RESUMO

BACKGROUND: Inborn errors of immunity (IEIs) are a group of congenital diseases caused by genetic defects in the development and function of the immune system. The involvement of the respiratory tract is one of the most common presentations in IEIs. METHODS: Overall, 117 patients with diagnosed IEIs were followed-up within 8 years at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD). Demographic, clinical, and laboratory data were collected in a questionnaire. Pulmonary function test (PFT), chest X-ray (CXR), and high-resolution computed tomography (HRCT) scans were obtained where applicable. RESULTS: Our study population consisted of 48 (41%) patients with predominantly antibody deficiencies (PADs), 39 (32%) patients with congenital defects of phagocytes, 14 (11.9%) patients with combined immunodeficiency (CID), and 16 (14%) patients with Mendelian susceptibility to mycobacterial diseases (MSMD). . Recurrent pneumonia was the most common manifestation, while productive cough appeared to be the most common symptom in almost all diseases. PFT showed an obstructive pattern in patients with PAD, a restrictive pattern in patients with CID, and a mixed pattern in patients with CGD. HRCT findings were consistent with bronchiectasis in most PAD patients, whereas consolidation and mediastinal lesions were more common in the other groups. CONCLUSIONS: Pulmonary manifestations vary among different groups of IEIs. The screening for lung complications should be performed regularly to reveal respiratory pathologies in early stages and follow-up on already existing abnormalities.


Assuntos
Bronquiectasia , Pneumopatias , Bronquiectasia/epidemiologia , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/epidemiologia , Testes de Função Respiratória
7.
J Digit Imaging ; 35(2): 115-126, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35018538

RESUMO

Advanced bronchoscopic lung volume reduction treatment (BLVR) is now a routine care option for treating patients with severe emphysema. Patterns of low attenuation clusters indicating emphysema and functional small airway disease (fSAD) on paired CT, which may provide additional insights to the target selection of the segmental or subsegmental lobe of the treatments, require further investigation. The low attenuation clusters (LACS) were segmented to identify the scalar and spatial distribution of the lung destructions, in terms of 10 fractions scales of low attenuation density (LAD) located in upper lobes and lower lobes. The LACs of functional small airway disease (fSAD) were delineated by applying the technique of parametric response map (PRM) on the co-registered CT image data. Both emphysematous LACs of inspiratory CT and fSAD LACs on expiratory CT were used to derive the coefficients of the predictive model for estimating the airflow limitation. The voxel-wise severity is then predicted using the regional LACs on the co-registered CT to indicate the functional localization, namely, the bullous parametric response map (BPRM). A total of 100 subjects, 88 patients with mild to very severe COPD and 12 control participants with normal lung functions (FEV1/FVC % > 70%), were evaluated. Pearson's correlations between FEV1/FVC% and LAV%HU-950 of severe emphysema are - 0.55 comparing to - 0.67 and - 0.62 of LAV%HU-856 of air-trapping and LAV%fSAD respectively. Pearson's correlation between FEV1/FVC% and FEV1/FVC% predicted by the proposed model using LAD% of HU-950 and fSAD on BPRM is 0.82 (p < 0.01). The result of the Bullous Parametric Response Map (BPRM) is capable of identifying the less functional area of the lung, where the BLVR treatment is aimed at removing from a hyperinflated area of emphysematous regions.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Volume Expiratório Forçado/fisiologia , Humanos , Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem
8.
Qatar Med J ; 2022(2): 26, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909393

RESUMO

BACKGROUND: Prior to pulmonary function testing (PFT), local and international recommendations advise pre-procedural screening. Pulmonary function tests generate aerosol droplets containing millions of viruses, significantly increasing the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission not only to the individuals in and around the PFT office, but also to subsequent patients who undergo the test later in the same room. METHODS: This clinical audit was carried out to establish the rate of positive pre-procedural SARS-CoV-2 PCR testing before a PFT. The data were obtained over a 6-week period from our ATS accredited pulmonary function laboratory at the Hamad General Hospital, Qatar (December 01, 2021, to January 10, 2022). The PFT laboratory was closed from January 10, 2022, till the date of this report (January 27, 2022) owing to an increase in COVID cases in the community in Qatar during the fourth wave. RESULTS: All the patients scheduled for PFT were asymptomatic of COVID-19. A total of 331 individuals were scheduled for PFT, and 221 PFTs were performed. There were 109 no-shows for both the PCR and the PFT. Between weeks 1 and 4, all the pre-procedural SARS-CoV-2 PCR tests were negative. The weekly average number of COVID-19 cases in Qatar increased from 157 per 100,000 population in week 1 to 2,918 in week 6.2 There was a similar trend in the pre-procedural SARS-CoV-2 PCR tests that increased and resulted in identifying 9 cases with positive SARS-CoV-2 PCR test over weeks 5 and 6 (Figure 1). CONCLUSION: As the number of documented positive SARS-CoV-2 PCR tests in the community grew, so did the pre-procedural COVID-19 PCR positivity and the number of no-shows. The large number of no-shows may indicate greater worry or concern about contracting COVID-19 when visiting the hospital amid peak community cases. Our findings further call into question the utility of routinely performing pre-procedural PCR screening in asymptomatic cases when the prevalence of COVID-19 is low in the local population. Perhaps, it is time to consider replacing this with on-the-spot quick antigen testing for more effective use of resources.

9.
Ann Bot ; 127(3): 381-395, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33038222

RESUMO

BACKGROUND AND AIMS: Fine-scale spatial patterns of the seedlings of co-occurring species reveal the relative success of reproduction and dispersal and may help interpret coexistence patterns of adult plants. To understand whether postfire community dynamics are controlled by mathematical, biological or environmental factors, we documented seedling-adult (putative parent) distances for a range of co-occurring species. We hypothesized that nearest-seedling-to-adult distances should be a function of the distance between the closest conspecific seedlings, closest inter-adult distances and seedling-to-parent ratios, and also that these should scale up in a consistent way from all individuals, to within and between species and finally between functional types (FTs). METHODS: We assessed seedling-adult, seedling-seedling and adult-adult distances for 19 co-occurring shrub species 10 months after fire in a species-rich shrubland in south-western Australia. Species were categorized into 2 × 2 FTs: those that are killed by fire [non-(re)sprouters] vs. those that survive (resprouters) in nine taxonomically matched pairs, and those that disperse their seeds prefire (geosporous) vs. those that disperse their seeds postfire (serotinous). KEY RESULTS: For the total data set and means for all species, seedling-adult distance was essentially a mathematical phenomenon, and correlated positively with seedling-seedling distance and adult-adult distance, and inversely with seedlings per adult. Among the four FTs, seedling-adult distance was shortest for geosporous non-sprouters and widest for serotinous resprouters. Why adults that produce few seedlings (resprouters) should be further away from them defies a simple mathematical or biological explanation at present. Ecologically, however, it is adaptive: the closest seedling was usually under the (now incinerated) parent crown of non-sprouters whereas those of resprouters were on average four times further away. CONCLUSIONS: Our study highlights the value of recognizing four reproductive syndromes within fire-prone vegetation, and shows how these are characterized by marked differences in their seedling-adult spatial relations that serve to enhance biodiversity of the community.


Assuntos
Incêndios , Plântula , Plantas , Sementes , Austrália do Sul , Austrália Ocidental
10.
Phytopathology ; 111(12): 2309-2316, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34058858

RESUMO

Fusarium head blight (FHB), mainly caused by Fusarium graminearum, has become one of the most serious diseases that damage wheat. The TaPFT (pore-forming toxin-like) and TaHRC (histidine-rich calcium-binding protein) genes at the quantitative trait locus Fhb1 were identified to confer resistance to FHB in the wheat cultivar Sumai 3. In this study, a wheat ricin B-like lectin gene (designated TaRBL) that interacted with TaPFT was isolated by a yeast two-hybrid screen of a wheat cDNA library. A yeast two-hybrid and bimolecular fluorescence complementation study further verified that TaRBL interacted with TaPFT but not with TaHRC. Gene expression studies showed that upon F. graminearum infection, TaRBL expression was upregulated in resistant cultivars but downregulated in susceptible cultivars. Furthermore, knockdown of TaRBL expression by barley stripe mosaic virus-induced gene silencing significantly reduced the resistance of wheat to FHB in both the resistant cultivar Sumai 3 and the susceptible cultivar Jimai 22. Thus, we conclude that TaRBL encodes a ricin B-like lectin protein that interacts with TaPFT and is involved in resistance to FHB in wheat.


Assuntos
Fusarium , Ricina , Resistência à Doença/genética , Doenças das Plantas , Locos de Características Quantitativas , Triticum/genética
11.
BMC Pulm Med ; 21(1): 324, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663275

RESUMO

BACKGROUND: Cardiopulmonary exercise testing (CPET) and pulmonary function testing (PFT) are noninvasive methods to evaluate the respiratory and circulatory systems. This research aims to evaluate and monitor chronic thromboembolic pulmonary hypertension (CTEPH) noninvasively and effectively by these two methods. Moreover, the research assesses the predictive value of CPET and PFT parameters for severe CTEPH. METHODS: We used data from 86 patients with CTEPH (55 for test set, and 31 for validation set) at the Shanghai Pulmonary Hospital Affiliated to Tongji University. The clinical, PFT and CPET data of CTEPH patients of different severity classified according to pulmonary artery pressure (PAP) (mm Hg) were collected and compared. Logistic regression analysis was performed to appraise the predictive value of each PFT and CPET parameter for severe CTEPH. The performance of CPET parameters for predicting severe CTEPH was determined by receiver operating characteristic (ROC) curves and calibration curves. RESULTS: Data showed that minute ventilation at anaerobic threshold (VE @ AT) (L/min) and oxygen uptake at peak (VO2 @ peak) (mL/kg/min) were independent predictors for severe CTEPH classified according to PAP (mm Hg). Additionally, the efficacy of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) in identifying severe CTEPH was found to be moderate with the area under ROC curve (AUC) of 0.769 and 0.740, respectively. Furthermore, the combination of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) had a moderate utility value in identifying severe CTEPH with the AUC of 0.843. CONCLUSION: Our research suggests that CPET and PFT can noninvasively and effectively evaluate, monitor and predict the severity of CTEPH.


Assuntos
Teste de Esforço/métodos , Hipertensão Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico , Testes de Função Respiratória/métodos , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/fisiopatologia , Estudos Retrospectivos
12.
BMC Pulm Med ; 21(1): 241, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273962

RESUMO

INTRODUCTION: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. METHOD: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). RESULTS: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. CONCLUSION: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.


Assuntos
COVID-19/fisiopatologia , Pneumonia Viral/fisiopatologia , Idoso , Gasometria , COVID-19/complicações , Monóxido de Carbono , Dispneia/virologia , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Capacidade de Difusão Pulmonar , Volume Residual , SARS-CoV-2 , Índice de Gravidade de Doença , Teste de Caminhada
13.
Differentiation ; 114: 58-66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32771207

RESUMO

Osteoclasts are terminally multinucleated cells that are regulated by nuclear factor-activated T cells c1 (NFATc1), and are responsible for bone resorption while the tartrate resistant acid phosphatase (TRAP) enzymes releases into bone resorption lacunae. Furthermore, tumor suppressor p53 is a negative regulator during osteoclastogenesis. Osteoprotegerin (OPG) inhibits osteoclastogenesis and bone resorption by activating autophagy, however, whether p53 is involved in OPG-mediated inhibition of osteoclastogenesis remains unclear. In the current study, OPG could enhance the expression of p53 and tuberin sclerosis complex 2 (TSC2). Moreover, the expression of p53 is regulated by autophagy during OPG-mediated inhibition of osteoclastogenesis. Inhibition of p53 by treated with pifithrin-α (PFTα) causing augments of osteoclastogenesis and bone resorption, also reversed OPG-mediated inhibition of osteoclastogenesis by reducing the expression of TSC2. In addition, knockdown of TSC2 using siRNA could rescue OPG-mediated inhibition of osteoclastogenesis by reducing autophagy, which is manifested by the decrease of the expression of Beclin1 and the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase beta 1 (S6K1, also known as p70S6K). Collectively, p53 plays a critical role during OPG-mediated inhibition of osteoclastogenesis via regulating the TSC2-induced autophagy in vitro.


Assuntos
Fatores de Transcrição NFATC/genética , Osteogênese/genética , Osteoprotegerina/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína Supressora de Tumor p53/genética , Autofagia/genética , Benzotiazóis/farmacologia , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Osteoclastos/citologia , Osteoclastos/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Serina-Treonina Quinases TOR/genética , Tolueno/análogos & derivados , Tolueno/farmacologia , Proteína 2 do Complexo Esclerose Tuberosa/antagonistas & inibidores , Proteína Supressora de Tumor p53/antagonistas & inibidores
14.
J Membr Biol ; 253(5): 469-478, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32955633

RESUMO

Pore-forming proteins/toxins (PFPs/PFTs) are the distinct class of membrane-damaging proteins. They act by forming oligomeric pores in the plasma membranes. PFTs and PFPs from diverse organisms share a common mechanism of action, in which the designated pore-forming motifs of the membrane-bound protein molecules insert into the membrane lipid bilayer to create the water-filled pores. One common characteristic of these pore-forming motifs is that they are amphipathic in nature. In general, the hydrophobic sidechains of the pore-forming motifs face toward the hydrophobic core of the membranes, while the hydrophilic residues create the lining of the water-filled pore lumen. Interestingly, pore-forming motifs of the distinct subclass of PFPs/PFTs share very little sequence similarity with each other. Therefore, the common guiding principle that governs the sequence-to-structure paradigm in the mechanism of action of these PFPs/PFTs still remains an enigma. In this article, we discuss this notion using the examples of diverse groups of membrane-damaging PFPs/PFTs.


Assuntos
Sequência de Aminoácidos , Variação Genética , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/genética , Toxinas Biológicas/química , Toxinas Biológicas/genética , Animais , Membrana Celular/química , Membrana Celular/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Relação Estrutura-Atividade , Toxinas Biológicas/metabolismo
15.
Planta ; 250(5): 1449-1460, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31309322

RESUMO

MAIN CONCLUSION: Despite AtJ3 and AtJ2 sharing a high protein-sequence identity and both being substrates of protein farnesyltransferase (PFT), AtJ3 but not AtJ2 mediates in Arabidopsis the heat-dependent phenotypes derived from farnesylation modification. Arabidopsis HEAT-INTOERANT 5 (HIT5)/ENHANCED RESPONSE TO ABA 1 (ERA1) encodes the ß-subunit of the protein farnesyltransferase (PFT), and the hit5/era1 mutant is better able to tolerate heat-shock stress than the wild type. Given that Arabidopsis AtJ2 (J2) and AtJ3 (J3) are heat-shock protein 40 (HSP40) homologs, sharing 90% protein-sequence identity, and each contains a CaaX box for farnesylation; atj2 (j2) and atj3 (j3) mutants were subjected to heat-shock treatment. Results showed that j3 but not j2 manifested the heat-shock tolerant phenotype. In addition, transgenic j3 plants that expressed a CaaX- abolishing J3C417S construct maintained the same capacity to tolerate heat shock as j3. The basal transcript levels of HEAT-SHOCK PROTEIN 101 (HSP101) in hit5/era1 and j3 were higher than those in the wild type. Although the capacities of j3/hsp101 and hit5/hsp101 double mutants to tolerate heat-shock stress declined compared to those of j3 and hit5/era1, they were still greater than that of the wild type. These results show that a lack of farnesylated J3 contributes to the heat-dependent phenotypes of hit5/era1, in part by the modulation of HSP101 activity, and also indicates that (a) mediator(s) other than J3 is (are) involved in the PFT-regulated heat-stress response. In addition, because HSP40s are known to function in dimer formation, bimolecular fluorescence complementation experiments were performed, and results show that J3 could dimerize regardless of farnesylation. In sum, in this study, a specific PFT substrate was identified, and its roles in the farnesylation-regulated heat-stress responses were clarified, which could be of use in future agricultural applications.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas de Choque Térmico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico/genética , Resposta ao Choque Térmico , Fenótipo , Plantas Geneticamente Modificadas , Prenilação de Proteína
16.
BMC Pulm Med ; 19(1): 148, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409407

RESUMO

BACKGROUND: Oxygen toxicity is one potential side effect of hyperbaric oxygen therapy (HBOT). Previous small studies showed mild reductions in pulmonary functions reflecting reductions in small airway conductance after repetitive hyperbaric oxygen sessions. However, there are no updated data with well performed pulmonary tests that address the pulmonary effect of the currently used HBOT protocols. The aim of this study was to evaluate the effect of HBOT on pulmonary functions of patients receiving the currently used HBOT protocol. METHODS: Prospective analysis included patients, 18 years or older, scheduled for 60 daily HBOT sessions between 2016 and 2018. Each session was 90 min of 100% oxygen at 2 ATA with 5 min air breaks every 20 min, 5 days per week. Pulmonary functions, measured at baseline and after HBOT, included forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and peak expiratory flow rate (PEF). RESULTS: The mean age was 60.36 ± 15.43 and 62.5% (55/88) were males. Most of the patients (83/88, 94.3%) did not have any pulmonary disease prior to inclusion and 30.7% (27/88) had a history of smoking. Compared to baseline values, at the completion of 60 HBOT sessions, there were no significant changes in FEV1 (0.163), FEV1/FVC ratio (0.953) and FEF25-75% (0.423). There was a statistically significant increase though not clinically relevant increase in FVC (0.1 ± 0.38 l) and PEF (0.5 ± 1.4 l) with a 0.014 and 0.001 respectively. CONCLUSION: Regarding pulmonary functions, repeated hyperbaric oxygen exposure based on the currently used HBOT protocol is safe. Surprisingly, there was a modest non clinically significant though statistically significant improvement in PEF and FVC in the current cohort of patients who were without chronic lung diseases. TRIAL REGISTRATION: Clinicaltrials.gov, trial ID: NCT03754985 , (Nov 2018) Retrospectively registered.


Assuntos
Oxigenoterapia Hiperbárica , Pulmão/fisiologia , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório , Estudos Prospectivos , Capacidade Vital
17.
Pol J Radiol ; 84: e381-e388, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31969954

RESUMO

PURPOSE: The aim of the study was to evaluate the role of high-resolution computed tomography (HRCT) in the prediction of presence and severity of chronic obstructive pulmonary disease (COPD), based on the pulmonary function test (PFT), to correlate the various quantitative and qualitative indices of COPD in HRCT with PFT values, and to derive at the threshold values for various quantitative HRCT indices of COPD. MATERIAL AND METHODS: A one-year retrospective and prospective evaluation of the HRCTs of 90 cases and 38 controls was performed. Quantitative and qualitative parameters of COPD were assessed in HRCT and were correlated with PFT. RESULTS: Among the qualitative parameters, significant correlation with spirometry was found with the qualitative scoring for emphysema and presence and inhomogeneous attenuation. Among the quantitative indices, anterior junction line length, thoracic cage ratio at both aortic arch and inferior pulmonary vein level, thoracic cross-sectional area/[height]² at the aortic arch were found to have good correlation with spirometry. There was significant strong correlation of anterior junction line length and tracheal index with residual volume/total lung capacity (RV/TLC). The threshold values of chest X-ray and HRCT quantitative parameters were calculated and were found to be lower than those of the western population. CONCLUSION: HRCT has a definite role in the diagnosis of COPD and can be used to predict the severity of emphysema.

18.
Br J Nutr ; 120(10): 1159-1170, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30205856

RESUMO

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (P race difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (P race difference=0·56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.


Assuntos
Envelhecimento , Cardiopatias/genética , Coração/fisiologia , Pneumopatias/genética , Pulmão/fisiologia , Testes de Função Respiratória , Vitamina D/sangue , Adulto , Idoso , População Negra , Estudos Transversais , Feminino , Volume Expiratório Forçado , Genoma Humano , Cardiopatias/prevenção & controle , Humanos , Pneumopatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Estudos Prospectivos , Análise de Regressão , Fumar , Capacidade Vital , Vitamina D/análogos & derivados , População Branca
19.
Curr Allergy Asthma Rep ; 18(1): 3, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29380068

RESUMO

PURPOSE OF REVIEW: Chronic respiratory diseases affecting adults and children are widely prevalent, so lung function testing is imperative for diagnosis and management. Spirometry is the traditional standard measure of lung function; however, certain groups of patients are unable to provide accurate and reproducible exhalation maneuvers. Consequently, the impedance oscillometry system (IOS) has been developed as an effort, independent technique to assess airway function in children and the elderly. To better understand this emerging modality, the following review will compare IOS with spirometry, examine the function of the device, provide interpretation strategies, and discuss the evidence supporting its use in adults and children with chronic lung disease. RECENT FINDINGS: In a population of symptomatic adults with suspected COPD, impedance oscillometry resistance measurements correlate with FEV1 and lung resistance increases with the severity of airflow limitation. In patients with asthma, IOS is a sensitive measure of airway hyperresponsiveness and bronchodilator response. Impedance oscillometry is evolving as an alternative measure to assess lung function pediatric and adult populations.


Assuntos
Impedância Elétrica/uso terapêutico , Oscilometria/métodos , Doença Pulmonar Obstrutiva Crônica/terapia , Testes de Função Respiratória/métodos , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
20.
Br J Haematol ; 177(3): 388-394, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28340285

RESUMO

The six-minute walk test (6MWT) has been widely used as an objective evaluation of functional exercise capacity and response to medical intervention in cardiopulmonary diseases. However, little is known about the 6MWT in evaluating patients with AL amyloidosis. We performed a retrospective study of 120 adults with systemic AL amyloidosis (60 with cardiac involvement and 60 without cardiac involvement) who had their initial evaluation at the Amyloidosis Center between 2013 and 2015 and had undergone 6MWT as a measure of functional exercise capacity. Forty-seven patients with cardiac involvement and 41 patients without cardiac involvement were included in the final analysis. The six-minute walk distances (6MWD) were 368 ± 105 m and 420 ± 116 m (mean ± SD), respectively (P = 0·03). Among AL amyloidosis patients with cardiac involvement, the 6MWD was associated with New York Heart Association class (P < 0·001), B-type natriuretic peptide (P = 0·003) and overall survival (hazard ratio 0·381, 95% confidence interval 0·215-0·676, P = 0·001). In conclusion, the 6MWT is a valuable tool in assessing functional exercise capacity in patients with AL amyloidosis.


Assuntos
Amiloidose/fisiopatologia , Cardiomiopatias/fisiopatologia , Teste de Caminhada/métodos , Idoso , Tolerância ao Exercício/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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