scholarly journals Revisiting the Role of Leukocytes in Cystic Fibrosis

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3380
Author(s):  
Monica Averna ◽  
Paola Melotti ◽  
Claudio Sorio

Cystic fibrosis in characterized by pulmonary bacterial colonization and hyperinflammation. Lymphocytes, monocytes/macrophages, neutrophils, and dendritic cells of patients with CF express functional CFTR and are directly affected by altered CFTR expression/function, impairing their ability to resolve infections and inflammation. However, the mechanism behind and the contribution of leukocytes in the pathogenesis of CF are still poorly characterized. The recent clinical introduction of specific CFTR modulators added an important tool not only for the clinical management of the disease but also to the investigation of the pathophysiological mechanisms related to CFTR dysfunction and dysregulated immunity. These drugs treat the basic defect in cystic fibrosis (CF) by increasing CFTR function with improvement of lung function and quality of life, and may improve clinical outcomes also by correcting the dysregulated immune function that characterizes CF. Measure of CFTR function, protein expression profiling and several omics methods were used to identify molecular changes in freshly isolated leukocytes of CF patients, highlighting two roles of leukocytes in CF: one more generally related to the mechanism(s) causing immune dysregulation in CF and unresolved inflammation, and another more applicative role, which identifies in myeloid cells, an important tool predictive of the therapeutic response of CF patients. In this review we will summarize available data on CFTR expression and function in leukocyte populations and will discuss potential clinical applications based on available data.

2018 ◽  
Vol 399 (12) ◽  
pp. 1409-1419 ◽  
Author(s):  
Irene A. van Dijk ◽  
Enno C.I. Veerman ◽  
Eric A.J. Reits ◽  
Jan G.M. Bolscher ◽  
Jan Stap

Abstract Histatins are histidine-rich peptides present in the saliva of humans and higher primates and have been implicated in the protection of the oral cavity. Histatin 1 is one of the most abundant histatins and recent reports show that it has a stimulating effect on cellular adherence, thereby suggesting a role in maintaining the quality of the epithelial barrier and stimulating mesenchymal-to-epithelial transition. Here we summarize these findings and discuss them in the context of previous reports. The recent findings also provide new insights in the physiological functions of histatin 1, which are discussed here. Furthermore, we put forward a possible role of histatin 1 in various pathologies and its potential function in clinical applications.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ilaria Righi ◽  
Valentina Vaira ◽  
Letizia Corinna Morlacchi ◽  
Giorgio Alberto Croci ◽  
Valeria Rossetti ◽  
...  

Chronic lung allograft dysfunction (CLAD) is the main cause of poor survival and low quality of life of lung transplanted patients. Several studies have addressed the role of dendritic cells, macrophages, T cells, donor specific as well as anti-HLA antibodies, and interleukins in CLAD, but the expression and function of immune checkpoint molecules has not yet been analyzed, especially in the two CLAD subtypes: BOS (bronchiolitis obliterans syndrome) and RAS (restrictive allograft syndrome). To shed light on this topic, we conducted an observational study on eight consecutive grafts explanted from patients who received lung re-transplantation for CLAD. The expression of a panel of immune molecules (PD1/CD279, PDL1/CD274, CTLA4/CD152, CD4, CD8, hFoxp3, TIGIT, TOX, B-Cell-Specific Activator Protein) was analyzed by immunohistochemistry in these grafts and in six control lungs. Results showed that RAS compared to BOS grafts were characterized by 1) the inversion of the CD4/CD8 ratio; 2) a higher percentage of T lymphocytes expressing the PD-1, PD-L1, and CTLA4 checkpoint molecules; and 3) a significant reduction of exhausted PD-1-expressing T lymphocytes (PD-1pos/TOXpos) and of exhausted Treg (PD-1pos/FOXP3pos) T lymphocytes. Results herein, although being based on a limited number of cases, suggest a role for checkpoint molecules in the development of graft rejection and offer a possible immunological explanation for the worst prognosis of RAS. Our data, which will need to be validated in ampler cohorts of patients, raise the possibility that the evaluation of immune checkpoints during follow-up offers a prognostic advantage in monitoring the onset of rejection, and suggest that the use of compounds that modulate the function of checkpoint molecules could be evaluated in the management of chronic rejection in LTx patients.


PEDIATRICS ◽  
1982 ◽  
Vol 70 (5) ◽  
pp. 754-762 ◽  
Author(s):  
Robert L. Brent

Many forces have created the epidemic of negligence and malpractice litigation. One of the contributing factors to the rising rate of nonmeritorious litigation is the increasing number of unqualified and irresponsible expert witnesses. The high remuneration has attracted physican-scientists who are unaware of the proper role of an expert witness. They are frequently manipulated by the attorneys and function as partisans rather than scholars. The role of the expert witness should be taught in medical and graduate school. Testimony should be treated as a scholarly endeavor and experts should be encouraged to seek peer review of their opinions and not to testify secretly and in isolation. It is suggested that greater visibility of experts and their testimony (light of day phenomenon) should raise the quality of expert witness testimony and encourage more qualified experts to participate as expert witnesses, thus removing the stigmata usually associated with unqualified expert witnesses.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2594
Author(s):  
Yue Ruan ◽  
Tobias Böhmer ◽  
Subao Jiang ◽  
Adrian Gericke

The retina is a part of the central nervous system, a thin multilayer with neuronal lamination, responsible for detecting, preprocessing, and sending visual information to the brain. Many retinal diseases are characterized by hemodynamic perturbations and neurodegeneration leading to vision loss and reduced quality of life. Since catecholamines and respective bindings sites have been characterized in the retina, we systematically reviewed the literature with regard to retinal expression, distribution and function of alpha1 (α1)-, alpha2 (α2)-, and beta (β)-adrenoceptors (ARs). Moreover, we discuss the role of the individual adrenoceptors as targets for the treatment of retinal diseases.


2021 ◽  
Author(s):  
Parameet Kumar ◽  
Dharmendra Kumar Soni ◽  
Chaitali Sen ◽  
Mads B Larsen ◽  
Krystyna Mazan-Mamczarz ◽  
...  

Abstract Cystic Fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.


2021 ◽  
Vol 1 (2) ◽  
pp. 289-300
Author(s):  
Sandy Surya ◽  
Ahmad Zainuri ◽  
Sayid Habiburrahman

Discipline culture is a reflection of the quality of educational institutions. The low level of discipline is the main problem of every educational institution. The role of leadership is very much needed in overcoming this problem. This paper aims to describe the leadership role of madrasah principals in improving the disciplinary culture of students at MAS Patra Mandiri Plaju Palembang. This research uses a qualitative approach with a descriptive analytic study method. Data were collected using interview techniques, observation and documentation study. The results of this study indicate that the headmaster of MAS Patra Mandiri Plaju Palembang has played its role and function in improving the disciplinary culture of students in a fairly good category. This is supported by 2 factors, namely (1) the role models of madrasah principals in complying with school regulations; and (2) socialization of school discipline rules and sanctions for violations. The obstacles faced by madrasah principals are (1) there are still some teachers who do not exemplify student attitudes; and (2) there are still students who are not "deterred" to be given disciplinary violations.


2012 ◽  
Vol 50 (4) ◽  
pp. 360-369
Author(s):  
K.I. Macdonald ◽  
A. Gipsman ◽  
A. Magit ◽  
M. Fandino ◽  
E. Massoud ◽  
...  

Introduction: The role of endoscopic sinus surgery (ESS) in patients with cystic fibrosis (CF) is not clearly defined. Objective: TO perform a systematic review of subjective and objective outcomes of ESS in CF. Methods: A systematic review was performed using the keywords 'sinusitis,' 'sinus surgery,' 'nasal polyps' and 'cystic fibrosis.' The quality of papers was assessed using the NICE scoring scale. Outcomes included safety, subjective symptoms, objective endoscopy scores, days spent in hospital, courses of antibiotics, and pulmonary function tests (PFTs). Results: Nineteen studies involving 586 patients were included in the review. There were four prospective cohort trials, and three were rated as good quality. There were no major complications attributable to ESS. There was consistent evidence in four cohort studies of improved sinonasal symptoms, including nasal obstruction, facial pain, headaches, rhinorrhea and olfaction. Three studies reported conflicting results in post-operative endoscopy scores. Three studies showed a decrease in days spent in hospital, and two showed a significant decrease in courses of intravenous antibiotics. A recent study, however, did not show a difference in either days spent in hospital or courses of antibiotics. Pulmonary function tests were not improved by ESS in six cohort trials, and one small study found significant improvement. A meta-analysis of FEV1 scores confirmed no significant difference. Conclusion: THE most consistent findings of this review were that ESS in patients with CF is safe, produces symptomatic benefit, and does not consistently improve PFTs. There were more conflicting results with regards to endoscopy scores, days spent in hospital, and courses of intravenous antibiotics. Future prospective studies, utilizing validated quality of life, symptom and endoscopy scales, are needed to further elucidate the role of ESS in the management of chronic rhinosinusitis in CF patients.


1995 ◽  
Vol 85 (7) ◽  
pp. 394-402 ◽  
Author(s):  
MA McReynolds

The sequelae of human immunodeficiency virus (HIV) disease include a host of devastating conditions involving the lower extremity. These include rheumatologic dysfunction, Kaposi's sarcoma, peripheral neuropathies, and skin ulcers. Pain, weakness, and loss of range of motion caused by these conditions can lead to changes in gait pattern, loss of mobility and function, and limited quality of life. The role of the rehabilitation specialist in the care and treatment of HIV disease as it affects the lower extremity, and the treatment strategies, precautions, and suggestions will be discussed.


2007 ◽  
Vol 11 (1) ◽  
pp. 25-29
Author(s):  
Krisna Yetti

AbstrakContinuous Ambulatory Peritoneal Dialysis (CAPD) merupakan salah satu terapi pengganti pada Penyakit Ginjal Tahap Akhir (PGTA). Empat area yang menjadi tanggung jawab perawat CAPD adalah predialisis, rawat inap, sebelum dan selama pelatihan CAPD, serta pada saat pasien di rumah. Merujuk pada empat peran perawat, yaitu sebagai praktisi, pengelola, peneliti, dan pendidik, maka peran perawat CAPD mempunya peran dan fungsi yang berbeda pula pada masing-masing area ini. Tujuan utama peran dan fungsi perawat di setiap area ini adalah agar layanan keperawatan yang diterima oleh pasien menjadi prima. Pada artikel ini dibahas peran perawat sebagai praktisi dan pengelola pelayanan keperawatan. Sedangkan dua peran lagi yaitu pendidik dan peneliti tidak dibahas. AbstractContinuous Ambulatory Peritoneal Dialysis (CAPD) is one of replacement therapy of End Stage Renal Disease (ESRD). CAPD nurse takes the responsibility in four areas. Those are pre-dialysis stage, during hospitalization, before and during peritoneal dialysis training, and patient at home. Refer to the roles of the nurses, as a care provider, manager, educator and researcher, CAPD nurse has a comprehensible role and function. This comprehensible role and function is also applied in this each area in order to get the better quality of life of the CAPD patients. In this article the role of care provider and manager are discussed. However, the other two, educator and researcher roles are not discussed.


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