scholarly journals Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis

2018 ◽  
Vol 51 (3) ◽  
pp. 1701910 ◽  
Author(s):  
A. Susanne Dittrich ◽  
Iris Kühbandner ◽  
Stefanie Gehrig ◽  
Verena Rickert-Zacharias ◽  
Matthew Twigg ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Forced Expiratory Volume ◽  
Healthy Controls ◽  
Elastase Activity ◽  
Residual Capacity ◽  
The Relationship

Neutrophil elastase (NE) is a key risk factor for severity of cystic fibrosis (CF) lung disease. Recent studies identified increased NE activity on the surface of airway neutrophils from CF-like mice and patients with CF. However, the role of surface-bound NE in CF lung disease remains unknown. We determined the relationship between surface-bound NE activity and severity of lung disease in CF.Surface-bound NE activity was measured on sputum neutrophils from 35 CF patients and eight healthy controls using novel lipidated Förster resonance energy transfer reporters and correlated with free NE activity, neutrophil counts, interleukin-8, myeloperoxidase and antiproteases in sputum supernatant, and with lung function parameters.Surface-bound NE activity was increased in CF compared to healthy controls (p<0.01) and correlated with free NE activity (p<0.05) and other inflammation markers (p<0.001). Surface-bound and free NE activity correlated with forced expiratory volume in 1 s % predicted (p<0.01 and p<0.05), but only surface-bound NE activity correlated with plethysmographic functional residual capacity % pred (p<0.01) in patients with CF.We demonstrate that surface-bound NE activity on airway neutrophils correlates with severity of lung disease in patients with CF. Our results suggest that surface-bound NE activity may play an important role in the pathogenesis and serve as novel biomarker in CF lung disease.

scholarly journals Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity

2018 ◽  
Vol 4 (2) ◽  
pp. 00068-2017 ◽  
Author(s):  
Shan F. Brunel ◽  
Janet A. Willment ◽  
Gordon D. Brown ◽  
Graham Devereux ◽  
Adilia Warris
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Disease Severity ◽  
Mononuclear Cells ◽  
Forced Expiratory Volume ◽  
Polymorphonuclear Cells ◽  
Healthy Controls ◽  
Transmembrane Conductance Regulator ◽  
Peripheral Blood Mononuclear

Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease.Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro. Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms.CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s) (p=0.014).CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity.

scholarly journals WS02.2 Role of soluble and membrane-associated neutrophil elastase activity in cystic fibrosis sputum

2017 ◽  
Vol 16 ◽  
pp. S3
Author(s):  
A.S. Dittrich ◽  
I. Kühbandner ◽  
S. Gehrig ◽  
V. Rickert-Zacharias ◽  
C.C. Taggart ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Neutrophil Elastase ◽  
Elastase Activity ◽  
Cystic Fibrosis Sputum

Probing the microscopic structural organization of neat ionic liquids (ILs) and ionic liquid-based gels through resonance energy transfer (RET) studies

2017 ◽  
Vol 19 (34) ◽  
pp. 23194-23203 ◽  
Author(s):  
Debashis Majhi ◽  
Moloy Sarkar
Keyword(s):  
Ionic Liquid ◽  
Energy Transfer ◽  
Ionic Liquids ◽  
Structural Organization ◽  
Rhodamine 6G ◽  
Resonance Energy Transfer ◽  
Resonance Energy

With the aim to understand the role of the ionic constituents of ionic liquids (ILs) in their structural organization, resonance energy transfer (RET) studies between ionic liquids (donor) and rhodamine 6G (acceptor) have been investigated.

scholarly journals Inflammation in the lungs of patients diagnosed with Cystic Fibrosis: Association with iron deficiency

SURG Journal ◽  
1969 ◽  
Vol 2 (1) ◽  
pp. 3-10
Author(s):  
Dawn Armstrong ◽  
Lindsay Robinson
Keyword(s):  
Cystic Fibrosis ◽  
Iron Deficiency ◽  
Inflammatory Cytokines ◽  
Wide Spectrum ◽  
Iron Status ◽  
Tissue Destruction ◽  
Hypoxic Conditions ◽  
Mediators Of Inflammation ◽  
The Relationship

Cystic Fibrosis (CF) is characterized by a wide spectrum of phenotypic characteristics such as; deep coughing, increased mucous production, and weight loss. However, only recently was the role of inflammation on the etiology of the disease recognized. CF is characterized as a cyclic progression of infective exacerbations and stable periods initiated by the presence of Pseudomonas Aeruginosa (PA). An increase in inflammatory cytokines/mediators and a decrease in anti-inflammatory cytokines contribute to the net inflammation and overall tissue destruction of the lungs. PA is associated with the low iron status that is seen in 60-75% of the CF population, through the presence of iron sequestering siderophores which distract iron from the tissues. Iron deficiency (ID) initiates further symptoms such as; fatigue, tachycardia, weakness, brittle nails etc, in addition to those caused by CF. The colonization of PA may be the cause or a result of increased iron (ferritin) concentrations in the lungs, but independent of the original relationship, results in a decreased iron status. Iron is used by PA under hypoxic conditions such as in the fibrosis lung, as a source of energy. Studies on the relationship between CF and ID contribute a variety of possible causes although currently no direct connection has been discovered. At this stage, further studies in this area are needed. This review will primarily focus on the affects of CF on iron status in humans, and secondarily examine the effect of mediators of inflammation in respects to ID.

scholarly journals The chemokine CCL18 characterises Pseudomonas infections in cystic fibrosis lung disease

2014 ◽  
Vol 44 (6) ◽  
pp. 1608-1615 ◽  
Author(s):  
Andreas Hector ◽  
Carolin Kröner ◽  
Melanie Carevic ◽  
Martina Bakele ◽  
Nikolaus Rieber ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Gene Expression Analysis ◽  
Ex Vivo ◽  
Healthy Controls ◽  
Protein Levels ◽  
Cystic Fibrosis Lung Disease ◽  
Potential Biomarker ◽  
Infection And Inflammation ◽  
Airway Cells

Cystic fibrosis (CF) lung disease is characterised by chronic Pseudomonas aeruginosa infection and leukocyte infiltration. Chemokines recruit leukocytes to sites of infection. Gene expression analysis identified the chemokine CCL18 as upregulated in CF leukocytes. We hypothesised that CCL18 characterises infection and inflammation in patients with CF lung disease.Therefore, we quantified CCL18 protein levels in the serum and airway fluids of CF patients and healthy controls, and studied CCL18 protein production by airway cells ex vivo.These studies demonstrated that CCL18 levels were increased in the serum and airway fluids from CF patients compared with healthy controls. Within CF patients, CCL18 levels were increased in P. aeruginosa-infected CF patients. CCL18 levels in the airways, but not in serum, correlated with severity of pulmonary obstruction in CF. Airway cells isolated from P. aeruginosa-infected CF patients produced significantly higher amounts of CCL18 protein compared with airway cells from CF patients without P. aeruginosa infection or healthy controls.Collectively, these studies show that CCL18 levels characterise chronic P. aeruginosa infection and pulmonary obstruction in patients with CF. CCL18 may, thus, serve as a potential biomarker and therapeutic target in CF lung disease.

Computed tomography study of pineal calcification in schizophrenia

1999 ◽  
Vol 14 (3) ◽  
pp. 163-166 ◽  
Author(s):  
G Bersani ◽  
A Garavini ◽  
I Taddei ◽  
G Tanfani ◽  
M Nordio ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Pineal Gland ◽  
Potential Role ◽  
Ct Scans ◽  
Entire Group ◽  
Positive Symptoms ◽  
Healthy Controls ◽  
Mean Size ◽  
The Relationship

SummaryComputed tomography studies concerning pineal calcification (PC) in schizophrenia have been conducted mainly by one author who correlated this calcification with several aspects of the illness. On the basis of these findings the aim of the present study was to analyze size and incidence of pineal gland calcification by CT in schizophrenics and healthy controls, and to verify the relationship between pineal calcification and age, and the possible correlation with psychopathologic variables. Pineal calcification was measured on CT scans of 87 schizophrenics and 46 controls divided into seven age subgroups of five years each. No significant differences in PC incidence and mean size between patients and controls were observed as far as the entire group was considered. PC size correlated with age both in schizophrenics and controls. We found a higher incidence of PC in schizophrenics in the age subgroup of 21–25 years, and a negative correlation with positive symptoms of schizophrenia in the overall group. These findings could suggest a premature calcific process in schizophrenics and a probable association with `non-paranoid' aspects of the illness. Nevertheless the potential role of this process possibly related to some aspects of the altered neurodevelopment in schizophrenia is still unclear.

The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis

1995 ◽  
Vol 20 (2) ◽  
pp. 63-70 ◽  
Author(s):  
K. Balough ◽  
M. McCubbin ◽  
M. Weinberger ◽  
W. Smits ◽  
R. Ahrens ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Early Stages ◽  
Infection And Inflammation ◽  
The Relationship

scholarly journals Dynamic remodeling of scaffold interactions in dendritic spines controls synaptic excitability

2012 ◽  
Vol 198 (2) ◽  
pp. 251-263 ◽  
Author(s):  
Enora Moutin ◽  
Fabrice Raynaud ◽  
Jonathan Roger ◽  
Emilie Pellegrino ◽  
Vincent Homburger ◽  
...  
Keyword(s):  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Membrane Receptors ◽  
Physical Interaction ◽  
Scaffolding Proteins ◽  
Cellular Functions ◽  
Electrophysiological Recordings ◽  
Living Neurons ◽  
Activity Dependent

Scaffolding proteins interact with membrane receptors to control signaling pathways and cellular functions. However, the dynamics and specific roles of interactions between different components of scaffold complexes are poorly understood because of the dearth of methods available to monitor binding interactions. Using a unique combination of single-cell bioluminescence resonance energy transfer imaging in living neurons and electrophysiological recordings, in this paper, we depict the role of glutamate receptor scaffold complex remodeling in space and time to control synaptic transmission. Despite a broad colocalization of the proteins in neurons, we show that spine-confined assembly/disassembly of this scaffold complex, physiologically triggered by sustained activation of synaptic NMDA (N-methyl-d-aspartate) receptors, induces physical association between ionotropic (NMDA) and metabotropic (mGlu5a) synaptic glutamate receptors. This physical interaction results in an mGlu5a receptor–mediated inhibition of NMDA currents, providing an activity-dependent negative feedback loop on NMDA receptor activity. Such protein scaffold remodeling represents a form of homeostatic control of synaptic excitability.

scholarly journals Regulatory γ1 subunits defy symmetry in functional modulation of BK channels

2018 ◽  
Vol 115 (40) ◽  
pp. 9923-9928 ◽  
Author(s):  
Vivian Gonzalez-Perez ◽  
Manu Ben Johny ◽  
Xiao-Ming Xia ◽  
Christopher J. Lingle
Keyword(s):  
Single Channel ◽  
Regulatory Protein ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Bk Channels ◽  
Bk Channel ◽  
Single Type ◽  
Regulatory Subunits ◽  
And Function

Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory regulatory proteins can also critically define the precise functional role of such channels. For instance, the pore-forming subunit of the large conductance voltage and calcium-activated potassium (BK, Slo1, or KCa1.1) channels encoded by a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional diversity arises from two families of regulatory subunits, β and γ, which help define the range of voltages over which BK channels in a given cell are activated, thereby defining physiological roles. A BK channel can contain zero to four β subunits per channel, with each β subunit incrementally influencing channel gating behavior, consistent with symmetry expectations. In contrast, a γ1 subunit (or single type of γ1 subunit complex) produces a functionally all-or-none effect, but the underlying stoichiometry of γ1 assembly and function remains unknown. Here we utilize two distinct and independent methods, a Forster resonance energy transfer-based optical approach and a functional reporter in single-channel recordings, to reveal that a BK channel can contain up to four γ1 subunits, but a single γ1 subunit suffices to induce the full gating shift. This requires that the asymmetric association of a single regulatory protein can act in a highly concerted fashion to allosterically influence conformational equilibria in an otherwise symmetric K+channel.

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