Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease

2006 ◽  
Vol 291 (5) ◽  
pp. L1005-L1017 ◽  
Author(s):  
Irving C. Allen ◽  
Amy J. Pace ◽  
Leigh A. Jania ◽  
Julie G. Ledford ◽  
Anne M. Latour ◽  
...  
Keyword(s):  
Lung Disease ◽  
Disease Risk ◽  
Transmembrane Protein ◽  
Cholinergic Receptor ◽  
Human Lung Tissue ◽  
Allergic Lung Disease ◽  
Asthma Susceptibility ◽  
Before And After ◽  
And Function ◽  
Deficient Mice

A genetic contribution to asthma susceptibility is well recognized, and linkage studies have identified a large number of genes associated with asthma pathogenesis. Recently, a locus encoding a seven-transmembrane protein was shown to be associated with asthma in founder populations. The expression of the protein GPRA (G protein-coupled receptor for asthma susceptibility) in human airway epithelia and smooth muscle, and its increased expression in a mouse model of asthma, suggested that a gain-of-function mutation in this gene increased the disease risk. However, we report here that the development of allergic lung disease in GPRA-deficient mice is unaltered. A possible explanation for this finding became apparent upon reexamination of the expression of this gene. In contrast to initial studies, our analyses failed to detect expression of GPRA in human lung tissue or in mice with allergic lung disease. We identify a single parameter that distinguishes GPRA-deficient and wild-type mice. Whereas the change in airway resistance in response to methacholine was identical in control and GPRA-deficient mice, the mutant animals showed an attenuated response to thromboxane, a cholinergic receptor-dependent bronchoconstricting agent. Together, our studies fail to support a direct contribution of GPRA to asthma pathogenesis. However, our data suggest that GPRA may contribute to the asthmatic phenotype by altering the activity of other pathways, such as neurally mediated mechanisms, that contribute to disease. This interpretation is supported by high levels of GPRA expression in the brain and its recent identification as the neuropeptide S receptor.

scholarly journals FHL2 (SLIM3) Is Not Essential for Cardiac Development and Function

2000 ◽  
Vol 20 (20) ◽  
pp. 7460-7462 ◽  
Author(s):  
Po-Hsien Chu ◽  
Wendy M. Bardwell ◽  
Yusu Gu ◽  
John Ross ◽  
Ju Chen
Keyword(s):  
Cellular Differentiation ◽  
Cardiac Development ◽  
Cardiovascular Development ◽  
Vertebrate Development ◽  
Lim Domain ◽  
Aortic Constriction ◽  
Before And After ◽  
And Function ◽  
Deficient Mice ◽  
Normal Cardiac Function

ABSTRACT LIM domain-containing proteins play critical roles in vertebrate development and cellular differentiation. Recently, four members of the four and one-half LIM protein (FHL) family have been identified and cloned. One of these, FHL2, is expressed in a restricted manner in the cardiovascular system throughout development into adulthood, suggesting that FHL2 may play an important role in cardiovascular development and function. Here we describe the generation and analysis of mice carrying a null mutation of the FHL2 gene.FHL2-deficient mice are viable and maintain normal cardiac function both before and after acute mechanical stress induced by aortic constriction. These data suggest that FHL2 is not essential for cardiac development and function.

EFEITOS DO DEEP RUNNING SOBRE A AMPLITUDE DE MOVIMENTO E A CAPACIDADE FUNCIONAL DOS MEMBROS SUPERIORES DE MULHERES MASTECTOMIZADAS: RELATO DE CASOS

2019 ◽  
pp. 121-131
Keyword(s):  
Range Of Motion ◽  
Upper Limb ◽  
Functional Capacity ◽  
External Rotation ◽  
Treatment Protocol ◽  
Range Of Movement ◽  
Flexion Extension ◽  
Before And After ◽  
In The Beginning ◽  
And Function

Introduction: Breast cancer is the most common type of cancer among women in Brazil and in the worl. The surgical treatment procedure may cause severe morbidity in the upper limb homolateral to surgery, including the reduction of the range of motion, with consequent impairment of function. A physiotherapeutic approach has an important role in the recover range of motion and the functionality of these women, guaranteeing the occupational, domestestic, familiar and conjugated activities, and, in this way, also improving the quality of life. Objectives: To analyse chances in the shoulder's range of motion and the functional capacity of the upper limbs, promoted by the deep running procedure in women with late postoperative mastectomy. Methods: All the patients were submitted to an evaluation in the beginning and end of the treatment, including: goniometry of flexion, extension, abduction, adduction, internal and external rotation of the shoulder joint; and function capacity analysis in activities that involve the upper members by DASH questionnaire. The treatment protocol includes twelve sessions of deep running, realized twice a week, in deep pool, for 20-minute during six weeks. Results: Were submitted to treatment a total of 4 patients. Despite the improvement in the numerical values, statistically significant differences were not found on the range of movements and in the functional capacity of upper members before and after the deep running sessions in post-mastectomy women. Conclusion: Deep running had effects on the numerical values of range of movement and upper limb functionality in women in the late postoperative period of the mastectomy procedure, but without statistically significant differences.

scholarly journals Are Three Weeks of Oral Anticoagulation Sufficient for Safe Cardioversion in Atrial Fibrillation?

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 554
Author(s):  
Stefan Naydenov ◽  
Nikolay Runev ◽  
Emil Manov
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Oral Anticoagulation ◽  
Left Atrial ◽  
Left Atrial Volume ◽  
Open Label ◽  
Before And After ◽  
Individualized Approach ◽  
Baseline Factors ◽  
And Function

Background and Objectives: Patients with atrial fibrillation (AF), lasting >48 h, considered for cardioversion, are recommended ≥3 weeks of oral anticoagulation before sinus rhythm restoration because of high risk of development of left atrial thrombosis (LAT) and stroke. However, the optimal duration of anticoagulation in the presence of overt LAT is unknown. Materials and Methods: An open-label study aimed to investigate the prevalence of spontaneous echo contrast (SEC) and LAT before and after 3 weeks of direct oral anticoagulant (DOAC) treatment. We included 51 consecutive patients (50.9% males), mean age 69.3 ± 7.4 years with paroxysmal/unknown duration of AF, considered for cardioversion, who agreed to have transesophageal echocardiography at enrollment and 3 weeks later. Results: At baseline SEC was present in 26 (50.9%) and LAT in 10 (19.6%) of 51 patients. After 3 weeks on DOAC, SEC persisted in 12 (25.0%) and LAT in 7 (14.5%) of 48 patients, p < 0.05 vs. baseline. Factors, associated most strongly with persistence of SEC/LAT, were left atrial appendage (LAA) emptying velocity <20 cm/s (OR = 2.82), LAA lobes >2 (OR = 1.84), and indexed left atrial volume ≥34 mL/m2 (OR = 1.37). Conclusions: In our study the incidence of SEC/LAT, particularly in AF with unknown duration, was not as low as we expected. The prevalence of SEC/LAT seemed to be dependent on factors not routinely evaluated in AF patients planned for cardioversion (indexed LA volume, LAA morphology and number of lobules, LAA emptying velocity, etc.). Our data suggested an individualized approach for DOAC duration in AF patients before an attempt for restoration of sinus rhythm is made, taking into consideration the LAA morphology and function.

scholarly journals Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

2021 ◽  
Vol 22 (5) ◽  
pp. 2732
Author(s):  
Nadine Reichhart ◽  
Vladimir M. Milenkovic ◽  
Christian H. Wetzel ◽  
Olaf Strauß
Keyword(s):  
Transmembrane Protein ◽  
Functional Characterization ◽  
Missense Mutations ◽  
Mutant Proteins ◽  
Functional Consequences ◽  
New Perspective ◽  
The Stability ◽  
Dynamics Simulations ◽  
And Function

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.

scholarly journals Regulation of M3 Muscarinic Receptor Expression and Function by Transmembrane Protein 147

2010 ◽  
Vol 79 (2) ◽  
pp. 251-261 ◽  
Author(s):  
Erica Rosemond ◽  
Mario Rossi ◽  
Sara M. McMillin ◽  
Marco Scarselli ◽  
Julie G. Donaldson ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Transmembrane Protein ◽  
Receptor Expression ◽  
And Function ◽  
M3 Muscarinic Receptor

scholarly journals Surfactant Composition and Function in a Primate Model of Infant Chronic Lung Disease: Effects of Inhaled Nitric Oxide

2006 ◽  
Vol 59 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Philip L Ballard ◽  
Linda W Gonzales ◽  
Rodolfo I Godinez ◽  
Marye H Godinez ◽  
Rashmin C Savani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Inhaled Nitric Oxide ◽  
Primate Model ◽  
Surfactant Composition ◽  
And Function

NKR-P1B Receptor Expression and Function in the Different Innate Lymphoid Cells of the Lung

2021 ◽  
Author(s):  
Lucas Vajko
Keyword(s):  
Nk Cell ◽  
Γδ T Cells ◽  
Bronchial Epithelium ◽  
Lung Parenchyma ◽  
Recognition System ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Receptor Expression ◽  
And Function ◽  
Deficient Mice

Group 2 innate lymphoid cells (ILC2) are the majority of ILCs in murine lungs at steady state. ILC2s are the main producer of type-2-cytokines, IL-4, IL-5, IL-9, IL-13, and amphiregulin, playing key roles in lung tissue homeostasis, airway responses to pathogens and allergens, and in cancer-related defenses. ILC functions are regulated by cell surface receptors. NKR-P1B is an inhibitory receptor, which recognizes C-type lectin-related protein (Clr-b) as its ligand. NKR-P1B is expressed on subsets of natural killer cells, ILC2, ILC3, γδ T cells, macrophages and dendritic cells in a tissue-specific manner and regulates NK cell and ILC3 functions in the gut. Expression and function of NKR-P1B in the lung ILC populations is unexplored. Moreover, Clr-b, the ligand for NKR-P1B, is expressed in the bronchial epithelium, endothelial cells and in lung parenchyma, but its role in immune regulation in the lung is unknown. We hypothesize that ILC2s in the lung express NKR-P1B, and their function is regulated by the NKR-P1B:Clr-b recognition system. Using wild-type (WT) and NKR-P1B-deficient mice, we study the expression of NKR-P1B on lung ILC2, and the function of NKR-P1B:Clr-b recognition system in ILC2 development and function. We compare the phenotype, frequency, numbers and cytokine production by ILC2s upon stimulation between WT and NKR-P1B-deficient mice using antibody staining and flow cytometry analysis. This study will reveal the role of NKR-P1B as a model system for its human homolog, NKR-P1A, in the regulation of ILC development and function, advancing our understanding of how immune responses in the lung are regulated.

Abstract 17266: Right Atrial Volumes Changes in Tetralogy of Fallot

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Ashish Patel ◽  
Divya Shakti ◽  
Chad Blackshear
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Tetralogy Of Fallot ◽  
Surgical Repair ◽  
Left Ventricular ◽  
Right Atrial ◽  
Before And After ◽  
Ventricular Diastolic Dysfunction ◽  
And Function ◽  
Averaged Model

Introduction & Hypothesis: There is limited information on right atrial (RA) function in the congenital heart defects. RA volume and function may give insight into the right ventricle (RV) diastolic function. We sought to assess RA function in tetralogy of Fallot (TOF) patients prior to and after complete surgical repair. Methods: Infants with TOF prior to complete repair were included for retrospective chart review and offline analysis of 2-dimensional echocardiograms (echo) before and after surgical repair. RA phasic volumes and stroke volumes were calculated. All volumes were indexed to body surface area. Results: There were 40 infants with TOF (45% females), of which 70% had pulmonary stenosis, 30% pulmonary atresia. Roughly 85% and 60% had 3, or more, echo available pre- and postoperatively. Table 1 (attached) shows the patient characteristics and phasic RA volumes. The indexed RA phasic volumes were in normal range in initial echo prior to surgery. We used normal index RA phasic volumes published by European Society of Echocardiography. There was the increasing trend of indexed RA phasic volume on follow up echo immediately before TOF repair. These phasic volumes continued to remain elevated after complete surgical repair (Table 1). Trends in RA stroke volumes for all available echos before and after surgery were modeled using a population-averaged model with an exchangeable within-panel correlation structure (Figure 2), showing no statistically significant difference after surgery. But there was statistical significance noted in RA ejection fraction. Please see attached image for statistical analysis and results of the study. Conclusions: The indexed RA phasic volumes in children with TOF are normal initially and increases before TOF repair and it continued to increase after TOF repair. The increase RA phasic volumes suggest RV diastolic dysfunction similar to the findings of LA phasic volumes and left ventricular diastolic dysfunction. Our findings indicate slow worsening RV diastolic function in patients with TOF after surgical repair. RA volume and function can be the novel marker to diagnose and monitor right ventricular diastolic dysfunction.

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