Search results for "4b"
showing 10 items of 72 documents
Selective Inhibition of Phosphodiesterases 4A, B, C and D Isoforms in Chronic Respiratory Diseases: Current and Future Evidences
2016
Chronic respiratory diseases affect millions of people every day. According to the World Health Organization estimates, ~235 million people suffer from asthma, ~64 million suffer from chronic obstructive pulmonary disease (COPD), and millions more suffer from allergic rhinitis around the world. In recent last years, the first phosphodiesterase 4 (PDE4) inhibitor, roflumilast, was approved as a treatment to reduce the risk of exacerbations in stable and severe COPD associated with chronic bronchitis and a history of exacerbations. PDE4 exists as four subtypes (A, B, C, and D) each with a capacity to degrade cAMP, a second messenger involved in inflammatory responses. PDE4 inhibitors inhibit …
Heterozygous Variants in KDM4B Lead to Global Developmental Delay and Neuroanatomical Defects
2020
International audience; KDM4B is a lysine-specific demethylase with a preferential activity on H3K9 tri/di-methylation (H3K9me3/2)-modified histones. H3K9 tri/di-demethylation is an important epigenetic mechanism responsible for silencing of gene expression in animal development and cancer. However, the role of KDM4B on human development is still poorly characterized. Through international data sharing, we gathered a cohort of nine individuals with mono-allelic de novo or inherited variants in KDM4B. All individuals presented with dysmorphic features and global developmental delay (GDD) with language and motor skills most affected. Three individuals had a history of seizures, and four had a…
Tissue factor prothrombotic activity is regulated by integrin-arf6 trafficking
2017
Objective— Coagulation initiation by tissue factor (TF) is regulated by cellular inhibitors, cell surface availability of procoagulant phosphatidylserine, and thiol-disulfide exchange. How these mechanisms contribute to keeping TF in a noncoagulant state and to generating prothrombotic TF remain incompletely understood. Approach and Results— Here, we study the activation of TF in primary macrophages by a combination of pharmacological, genetic, and biochemical approaches. We demonstrate that primed macrophages effectively control TF cell surface activity by receptor internalization. After cell injury, ATP signals through the purinergic receptor P2rx7 induce release of TF + microvesicles. T…
Infinitesimal deformations of double covers of smooth algebraic varieties
2003
The goal of this paper is to give a method to compute the space of infinitesimal deformations of a double cover of a smooth algebraic variety. The space of all infinitesimal deformations has a representation as a direct sum of two subspaces. One is isomorphic to the space of simultaneous deformations of the branch locus and the base of the double covering. The second summand is the subspace of deformations of the double covering which induce trivial deformations of the branch divisor. The main result of the paper is a description of the effect of imposing singularities in the branch locus. As a special case we study deformations of Calabi--Yau threefolds which are non--singular models of do…
Three solutions for a two-point boundary value problem with the prescribed mean curvature equation
2015
The existence of at least three classical solutions for a parametric ordinary Dirichlet problem involving the mean curvature operator are established. In particular, a variational approach is proposed and the main results are obtained simply requiring the sublinearity at zero of the considered nonlinearity.
Exact Fourier expansion in cylindrical coordinates for the three-dimensional Helmholtz Green function
2009
A new method is presented for Fourier decomposition of the Helmholtz Green Function in cylindrical coordinates, which is equivalent to obtaining the solution of the Helmholtz equation for a general ring source. The Fourier coefficients of the Helmholtz Green function are split into their half advanced+half retarded and half advanced-half retarded components. Closed form solutions are given for these components in terms of a Horn function and a Kampe de Feriet function, respectively. The systems of partial differential equations associated with these two-dimensional hypergeometric functions are used to construct a fourth-order ordinary differential equation which both components satisfy. A s…
β-Adrenoceptor stimulation up-regulates phosphodiesterase 4 activity and reduces prostaglandin E 2 -inhibitory effects in human neutrophils
2000
Human neutrophils were treated for 4 h with a combination of salbutamol (1 µM), a β2-adrenoceptor agonist, and rolipram (30 µM), a selective phosphodiesterase 4 inhibitor, to investigate whether this treatment produces up-regulation of phosphodiesterase activity with functional consequences. Anion-exchange chromatography coupled with the use of selective activators and inhibitors demonstrated that a phosphodiesterase activity with characteristics of the isoenzyme type 4 was increased in drug-treated cells. Kinetic analysis showed a ~1.5-fold increase in V max without alteration of K m values. The augmented phosphodiesterase activity in drug-treated cells was abolished by actinomycin D. Cycl…
C4BQ0: a genetic marker of familial HCV-related liver cirrhosis
2004
Source Department of Medicine and Pneumology, V Cervello Hospital, Via Trabucco 180, 90146 Palermo, Italy. lindpas@yahoo.it Abstract BACKGROUND AND METHODS: Host may have a role in the evolution of chronic HCV liver disease. We performed two cross-sectional prospective studies to evaluate the prevalence of cirrhosis in first degree relatives of patients with cirrhosis and the role of two major histocompatibility complex class III alleles BF and C4 versus HCV as risk factors for familial clustering. FINDINGS: Ninety-three (18.6%) of 500 patients with cirrhosis had at least one cirrhotic first degree relative as compared to 13 (2.6%) of 500 controls, (OR 7.38; CI 4.21-12.9). C4BQ0 was signifi…
Immunonephelometric determination of the C4b-binding protein.
1993
A fully mechanised immunonephelometric method for the rapid and specific determination of C4b-binding protein (C4b-BP) in citrated plasma is described. The method utilizes commercially available rabbit antiserum against human C4b-BP and a nephelometer analyser. A single determination can be performed within 6 min, requiring 80 microliters sample volume. The measuring range is about 10 to 200% of normal C4b-BP. Precision is characterized by intraassay coefficients of variation between 1.5% and 2.8%, and interassay coefficients of variation between 4.0% and 4.6% for the same C4b-BP concentrations. The nephelometry of C4b-BP was correlated with electroimmunodiffusion (Laurell technique; r = 0.…
Singular solutions to a quasilinear ODE
2005
In this paper, we prove the existence of infinitely many radial solutions having a singular behaviour at the origin for a superlinear problem of the form $-\Delta_pu=|u|^{\delta-1}u$ in $B(0,1)\setminus\{0\}\subset\mathbb R^N$,\, $u=0$ for $|x|=1$, where $N>p>1$ and $\delta>p-1$. Solutions are characterized by their nodal properties. The case $\delta+1 <\frac{Np}{N-p}$ is treated. The study of the singularity is based on some energy considerations and takes into account the classification of the behaviour of the possible solutions available in the literature. By following a shooting approach, we are able to deduce the main multiplicity result from some estimates on the rotation numbers asso…