Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Virus-induced respiratory disease accounts for the majority of hospitalizations of young children during the winter months. The major viral causes of lower respiratory tract disease in infants and children are respiratory syncytial virus (RSV), rhinovirus, metapneumovirus (hMPV), parainfluenza virus 3 (PIV-3), and influenza. The primary antiviral mechanism involves the activation of cytotoxic T cells and the clearance of virus-infected epithelial cells, and Toll-like receptors that recognize microbial molecular patterns are thought to initiate and orchestrate the immune response. Here, we review the role of Toll-like receptors in modulating the immune response to respiratory viral disease, including the role of maturation of the TLR system in early life.
Curr Mol Med 2009 Jun
PMID:The role of toll pathways in viral respiratory disease during early childhood. 1960 4

Pulmonary hypertension (PH) is a commonly recognized complication of chronic respiratory disease. Enhanced vasoconstriction, pulmonary vascular remodeling, and in situ thrombosis contribute to the increased pulmonary vascular resistance observed in PH associated with hypoxic lung disease. The tissue factor pathway regulates fibrin deposition in response to acute and chronic vascular injury. We hypothesized that inhibition of the tissue factor pathway would result in attenuation of pathophysiologic parameters typically associated with hypoxia-induced PH. We tested this hypothesis using a chronic hypoxia-induced murine model of PH using mice that overexpress tissue factor pathway inhibitor (TFPI) via the smooth muscle-specific promoter SM22 (TFPI(SM22)). TFPI(SM22) mice have increased pulmonary TFPI expression compared with wild-type (WT) mice. In WT mice, exposure to chronic hypoxia (28 d at 10% O(2)) resulted in increased systolic right ventricular and mean pulmonary arterial pressures, changes that were significantly reduced in TFPI(SM22) mice. Chronic hypoxia also resulted in significant pulmonary vascular muscularization in WT mice, which was significantly reduced in TFPI(SM22) mice. Given the pleiotropic effects of TFPI, autocrine and paracrine mechanisms for these hemodynamic effects were considered. TFPI(SM22) mice had less pulmonary fibrin deposition than WT mice at 3 days after exposure to hypoxia, which is consistent with the antithrombotic effects of TFPI. Additionally, TFPI(SM22) mice had a significant reduction in the number of proliferating (proliferating cell nuclear antigen positive) pulmonary vascular smooth muscle cells compared with WT mice, which is consistent with in vitro findings. These findings demonstrate that overexpression of TFPI results in improved hemodynamic performance and reduced pulmonary vascular remodeling in a murine model of hypoxia-induced PH. This improvement is in part due to the autocrine and paracrine effects of TFPI overexpression.
Am J Respir Cell Mol Biol 2010 Jul
PMID:Tissue factor pathway inhibitor overexpression inhibits hypoxia-induced pulmonary hypertension. 1964 71

Respiratory diseases are a major cause of mortality and morbidity worldwide. Current treatments offer no prospect of cure or disease reversal. Transplantation of pulmonary progenitor cells derived from human embryonic stem cells (hESCs) may provide a novel approach to regenerate endogenous lung cells destroyed by injury and disease. Here, we examine the therapeutic potential of alveolar type II epithelial cells derived from hESCs (hES-ATIICs) in a mouse model of acute lung injury. When transplanted into lungs of mice subjected to bleomycin (BLM)-induced acute lung injury, hES-ATIICs behaved as normal primary ATIICs, differentiating into cells expressing phenotypic markers of alveolar type I epithelial cells. Without experiencing tumorigenic side effects, lung injury was abrogated in mice transplanted with hES-ATIICs, demonstrated by recovery of body weight and arterial blood oxygen saturation, decreased collagen deposition, and increased survival. Therefore, transplantation of hES-ATIICs shows promise as an effective therapeutic to treat acute lung injury.
Mol Ther 2010 Mar
PMID:Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice. 2019 63

Chronic obstructive pulmonary disease is a multifactorial respiratory disorder. Members of the cytochrome P450 family catalyze the oxidative metabolism of exogenous chemicals and activate their substrates into reactive intermediates that may initiate lung injury. The aim of this study was to learn interethnic variation in frequency distribution patterns of CYP1B1 and CYP2F1 genes polymorphic markers and to analyse its association withchronic obstructive pulmonary disease. The polymorphic markers Leu432Val(CYP1B1) and c.14_15insC(CYP2F1) were studied at chronic obstructive pulmonary disease patients (Russian (N=169), Tatar (N=137)) and cases of healthy individuals (Russian (N=191), Tatar (N=198) and Bashkir (N=78)), residents of Bashkortostan by PCR-RFLP method. It was shown that the CYP2F1 gene genotype frequency distribution patterns differed between three ethnic groups (chi2 = 21.29, df=4, P = 0.0001), because of high frequency of c.14_15insC/c.14_15insC genotype in Tatars (6.38%). On the other hand, high frequency (39.74%) of normal/ c.14_15insC genotype was appeared in Bashkirs. Association analysis of CYP2F1 geneinsertion variant with chronic obstructive pulmonary disease have shown high frequency (87.5%) of normal allele in Tatars patients with very severe stage and manifestation of chronic obstructive pulmonary disease after 55 years (chi2 = 3.964, df=1, P = 0.046; OR = = 2.268). It was shown that allele and genotype frequency distribution of Leu432ValCYP1B1 gene not differed between Russian, Tatar and Bashkir ethnic groups. We did not find any association of Leu432Val CYP1B1 gene with chronic obstructive pulmonary disease.
Mol Biol (Mosk)
PMID:[The CYP1B1 and CYP2F1 genes polymorphisms frequency in three ethnic groups of Bashkortostan and chronic obstructive pulmonary disease patients]. 2019 57

Maternal smoking during pregnancy increases the risk of respiratory disease in offspring, but surprisingly little is known about the underlying mechanisms. Nicotinic acetylcholine receptors (nAChRs) expressed in bronchial epithelial cells (BECs) mediate the effects of nicotine on lung development and function. Recently, BECs were also shown to express a GABAergic paracrine loop that was implicated in mucus overproduction in asthma. We therefore investigated the interactions between cholinergic and GABAergic signaling in rhesus macaque BECs, and found that nicotine upregulated GABA signaling in BECs through the sequential activation of BEC nAChR and GABA receptors. The incubation of primary cultures of rhesus BECs increased concentrations of GAD, GABA(A) receptors, and mucin mRNA. The nicotine-induced increase in glutamatic acid decarboxylase (GAD) and GABA(A) receptor mRNA resulted in increased GABA-induced currents and increased expression of mucin. The ability of nicotine to increase mucin expression was blocked by nicotinic and GABA(A) antagonists. These results implicate GABA signaling as a middleman in nicotine's effects on mucus overproduction. Similar effects of nicotine on GABA signaling and the expression of mucin were seen in vivo after chronic exposure of rhesus monkeys to nicotine. These data provide a new mechanism linking smoking with the increased mucin seen in asthma and chronic obstructive pulmonary disorder, and suggest a new paradigm of communication between non-neuronal transmitter systems in BECs. The existence of neural-like transmitter interactions in BECs suggests that some drugs active in the central nervous system may possess previously unexpected utility in respiratory diseases.
Am J Respir Cell Mol Biol 2011 Feb
PMID:Prenatal nicotine exposure increases GABA signaling and mucin expression in airway epithelium. 2044 51

Outbreaks of viral respiratory disease in institutions may be associated with high morbidity and mortality, depending upon the viral etiology and the age and immune status of the affected patients. Control of outbreaks may include isolation and/or cohorting, and prophylaxis or treatment with specific antiviral agents may be indicated, all dependent upon the specific cause of the outbreak. Conventional methods of viral diagnosis detect only a limited number of the viruses that are known to cause outbreaks. The availability of sensitive and specific molecular assays has facilitated rapid diagnosis of a wider range of viruses from respiratory outbreaks. Molecular methods have distinct advantages over conventional methods, including the ability to rapidly develop assays for emerging viruses and new variants of existing viruses. In addition, molecular testing allows rapid detection of resistance to antiviral agents or mutations leading to increased virulence. However, high-throughput molecular testing requires batch processes that may compromise the ability to respond quickly to urgent testing demands.
Mol Diagn Ther 2010 Oct 01
PMID:Molecular diagnostic assays for detection of viral respiratory pathogens in institutional outbreaks. 2105 94

With the introduction of fiberoptic bronchoscopy and the ability to carry out bronchoscopic biopsy and broncho-alveolar lavage (BAL) in patients and control subjects, characterisation of inflammation in airways diseases such as asthma and chronic obstructive respiratory disease (COPD) has been possible. This has allowed emphasis to be placed on the role of inflammation in diseases such as asthma (1) and COPD (2). Bronchoscopy, being an invasive procedure, carries an associated morbidity (3,4). Although bronchoscopy is carried out in patients with moderate or even severe airflow limitation for clinical indications, it is not ethically justified to carry out research bronchoscopies on such patients, as it is essential to pursue research procedures carrying the minimum risk to volunteer subjects. Thus BAL, for the purposes of research in airways diseases, is limited to patients with mild airflow obstruction, thus requiring extrapolation of findings to a more heterogeneous group of patients. As a consequence of its invasive nature, the number of times the procedure can be repeated is limited so that it may be difficult to study the kinetics of the inflammatory response. In addition, it may be difficult to recruit volunteers for studies that necessitate bronchoscopy.
Methods Mol Med 2001
PMID:Induced sputum : whole sample. 2133 92

Oxidative stress is implicated in the pathogenesis and progression of asthma (1,2), chronic obstructive respiratory disease (COPD) (3), and cystic fibrosis (4). Reactive oxygen species (ROS) are unstable compounds with unpaired electrons, capable of initiating oxidation. Several of the inflammatory cells which participate in the inflammatory response, such as macrophages, neutrophils, and eosinophils release increased amounts of ROS (1,5) exceeding the already reduced tissue antioxidant defences of asthmatic and COPD patients (2).
Methods Mol Med 2001
PMID:Measurement of exhaled hydrocarbons. 2133 94

During the Phase I/II assessment of new therapies with the potential to suppress eosinophil and neutrophil inflammation, there is a need to assess the peripheral blood pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the drug. This has relevance in respiratory disease since drugs that target eosinophillic inflammation are in development for asthma; whereas neutrophil-directed therapies are being introduced for treatment of chronic obstructive airways disease (COPD). Pharmacokinetic evaluation is required to determine the concentration of drug substance (and possibly metabolites) in peripheral blood at intervals following single or repeated dosing. Pharmacodynamic assessment is also required since many drug substances have a duration of action which is prolonged beyond the time when drug substance is detectable in the blood (see Fig. 1). Fig. 1. Whole blood pharmacodynamics. In preclinical studies, animal or human blood is treated with test agents. In clinical studies, human subjects are treated with drug and blood removed for analysis. GAFS, gated autofluorescence forward scatter; PK, pharmacokinetics; PD, pharmacoldynamics.
Methods Mol Med 2001
PMID:Measurement of granulocyte pharmacodynamics in whole blood by flow cytometry. 2133 12

MicroRNAs are a class of small noncoding RNA molecules that play a pivotal role in the regulation of gene expression at the posttranscriptional level. Most large double-stranded DNA viruses, mainly the herpesvirus family, are known to express miRNAs. Viral miRNAs can regulate both viral- and cellular transcripts. By eliminating cloning steps for large number of Sanger sequencing reactions, recent development of massively parallel next-generation sequencing methods has accelerated identification of small RNA species expressed from viruses, prokaryotes, and eukaryotes. The miRNAs expressed from infectious laryngotracheitis virus (ILTV), which is an alphaherpesvirus belonging to the herpesviridae family and which causes an acute respiratory disorder in chicken, were identified by small RNA enrichment and the 454 FLX sequencing method.
Methods Mol Biol 2011
PMID:Identification of virus encoding microRNAs using 454 FLX sequencing platform. 2143 64


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