728 research outputs found
A selective cyclic integrin antagonist blocks the integrin receptors α(v)β(3 )and α(v)β(5 )and inhibits retinal pigment epithelium cell attachment, migration and invasion
BACKGROUND: Proliferative vitreoretinopathy (PVR) is a leading cause of blindness after failed retinal reattachment surgery. PVR is characterized by the proliferation, migration and contraction of retinal pigmented epithelial cells (RPE), and these cellular responses are influenced by the expression and function of integrin receptors. The effect of a cyclic integrin antagonist containing the amino acid sequence Arg-Gly-Asp-D-Phe-Val (RGDfV), specific for the integrin receptors α(v)β(3 )and α(v)β(5), was investigated on basic fibroblast growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), and serum induced human RPE proliferation, migration, invasion and attachment to the extracellular matrix. Furthermore, the effects of bFGF and PDGF-BB regulated expression of integrins α(v)β(3 )and α(v)β(5 )on RPE cells was examined. METHODS: The effect of a cyclic integrin antagonist and a control peptide (0.01 μg/ml to 300 μg/ml) was investigated on serum or cytokine (bFGF or PDGF-BB pretreatment) induced human fetal RPE cell proliferation by H(3)-thymidine uptake. The effect of the cyclic integrin antagonist on RPE cell attachment onto different extracellular matrices (laminin, collagen IV, fibronectin), RPE cell invasion stimulated by PDGF-BB or serum, and migration stimulated by PDGF-BB, vascular endothelial growth factor (VEGF) or serum was explored. PDGF-BB and bFGF modulation of the integrin receptors α(v)β(3 )and α(v)β(5 )was evaluated by flow cytometry. RESULTS: The integrin antagonist did not inhibit DNA synthesis stimulated by serum, bFGF, or PDGF-BB treatment. RPE attachment onto fibronectin was inhibited in a concentration range of 1–10 μg/ml (p < 0.05). Attachment of the RPE cells onto collagen IV and laminin was inhibited in a range of 3–10 μg/ml (p < 0.05). Serum and PDGF-BB stimulated migration was inhibited by the cyclic integrin antagonist in a concentration range of 1–10 μg/ml (p < 0.05). Furthermore, the cyclic integrin antagonist inhibited PDGF-BB stimulated RPE cell invasion through fibronectin (3μg/ml: 66% inhibition, p < 0.001). In each of these experiments, the control peptides had no significant effects. PDGF-BB and bFGF pretreatment of RPE cells increased the expression of integrin receptors α(v)β(3 )(bFGF: 1.9 fold, PDGF-BB: 2.3 fold) and α(v)β(5 )(bFGF: 2.9 fold, PDGF-BB: 1.5 fold). CONCLUSION: A selective inhibition of the integrin receptors α(v)β(3 )and α(v)β(5 )through a cyclic integrin antagonist is able to inhibit RPE cell attachment, migration and invasion. Since these steps are of importance for the progression of PVR, a cyclic integrin antagonist should be further evaluated for the treatment of this disease
Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population
<p>Abstract</p> <p>Background</p> <p>Crohn's disease (CD) and ulcerative colitis (UC), the two main types of inflammatory bowel disease (IBD), are multifactorial conditions of unknown etiology. The objective of this study is to examine the combined gene-environment interactions influencing IBD susceptibility in a well-defined Caucasian cohort in rural mid-America.</p> <p>Methods</p> <p>Patients were diagnosed to have CD or UC using conventional radiologic, endoscopic, and/or histopathologic findings. Histological diagnosis was made by a single specialist gastrointestinal pathologist with a particular interest in IBD. Information regarding cigarette smoke exposure was obtained by administration of the Behavioral Risk Factor Surveillance System Survey (BRFSS) to all patients. Genomic DNA was extracted from peripheral blood leukocytes, and polymerase chain reaction (PCR) amplification and genotyping were performed for 11 Single Nucleotide Polymorphisms (SNP) in <it>NOD2</it>, <it>IL23r</it>, <it>OCTN1 </it>genes along with <it>IGR</it>.</p> <p>Results</p> <p>Our cohort consists of 1196 patients: 435 controls, 485 CD patients, and 276 UC patients. Only patients with genotype data for at least 7 of 11 SNPs were included in our data analysis. The control groups for all 11 SNPs were in Hardy-Weinberg Equilibrium. In genotype-association SNP analysis, all <it>NOD2 </it>SNPs (rs5743293, rs2066844, rs2066845) and the <it>IL23r </it>SNP (rs11465804) showed a significant association to IBD (<it>p </it>< 0.03). A multiple gene-interaction analysis showed an association between <it>NOD2 </it>and <it>IL23r </it>with UC (<it>p </it>= 0.04). There were no associations between any <it>OCTN1 </it>and <it>IGR </it>SNPs and IBD in this cohort. A multivariable logistic regression analysis showed that female gender, "current" or "former" smoking status, family history of IBD, and <it>NOD2 </it>SNP minor alleles were associated with CD.</p> <p>Conclusion</p> <p>IBD remains to be challenging to properly diagnose, characterize, and treat. Our study proposes a combined genetic, phenotypic, and environmental approach in an attempt to better understand IBD. Previously demonstrated associations between OCTN1 and IGR and IBD were not confirmed.</p
Photoproduction of phi(1020) mesons on the proton at large momentum transfer
The cross section for meson photoproduction on the proton has been
measured for the first time up to a four-momentum transfer -t = 4 GeV^2, using
the CLAS detector at the Thomas Jefferson National Accelerator Facility. At low
four-momentum transfer, the differential cross section is well described by
Pomeron exchange. At large four-momentum transfer, above -t = 1.8 GeV^2, the
data support a model where the Pomeron is resolved into its simplest component,
two gluons, which may couple to any quark in the proton and in the .Comment: 5 pages; 7 figure
Dependence of Quadrupole Strength in the Transition
Models of baryon structure predict a small quadrupole deformation of the
nucleon due to residual tensor forces between quarks or distortions from the
pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through
the dependence of the magnetic (), electric (), and
scalar () multipoles in the
transition. We report new experimental values for the ratios
and over the range = 0.4-1.8 GeV, extracted from
precision data using a truncated multipole expansion.
Results are best described by recent unitary models in which the pion cloud
plays a dominant role.Comment: 5 pages, 5 figures, 1 table. To be published in Phys. Rev. Lett.
(References, figures and table updated, minor changes.
Measurement of the Polarized Structure Function for in the Resonance Region
The polarized longitudinal-transverse structure function
has been measured using the reaction in the
resonance region at and 0.65 GeV. No previous
data exist for this reaction channel. The kinematically
complete experiment was performed at Jefferson Lab with the CEBAF Large
Acceptance Spectrometer (CLAS) using longitudinally polarized electrons at an
energy of 1.515 GeV. A partial wave analysis of the data shows generally better
agreement with recent phenomenological models of pion electroproduction
compared to the previously measured channel. A fit to both
and channels using a unitary isobar model suggests the unitarized
Born terms provide a consistent description of the non-resonant background. The
-channel pion pole term is important in the channel through a
rescattering correction, which could be model-dependent.Comment: 6 pages, LaTex, 5 eps figures: Submitted to PRC/Brief Reports v2:
Updated referenc
Deeply virtual and exclusive electroproduction of omega mesons
The exclusive omega electroproduction off the proton was studied in a large
kinematical domain above the nucleon resonance region and for the highest
possible photon virtuality (Q2) with the 5.75 GeV beam at CEBAF and the CLAS
spectrometer. Cross sections were measured up to large values of the
four-momentum transfer (-t < 2.7 GeV2) to the proton. The contributions of the
interference terms sigma_TT and sigma_TL to the cross sections, as well as an
analysis of the omega spin density matrix, indicate that helicity is not
conserved in this process. The t-channel pi0 exchange, or more generally the
exchange of the associated Regge trajectory, seems to dominate the reaction
gamma* p -> omega p, even for Q2 as large as 5 GeV2. Contributions of handbag
diagrams, related to Generalized Parton Distributions in the nucleon, are
therefore difficult to extract for this process. Remarkably, the high-t
behaviour of the cross sections is nearly Q2-independent, which may be
interpreted as a coupling of the photon to a point-like object in this
kinematical limit.Comment: 15 pages,19 figure
Q^2 Dependence of the S_{11}(1535) Photocoupling and Evidence for a P-wave resonance in eta electroproduction
New cross sections for the reaction are reported for total
center of mass energy =1.5--2.3 GeV and invariant squared momentum transfer
=0.13--3.3 GeV. This large kinematic range allows extraction of new
information about response functions, photocouplings, and coupling
strengths of baryon resonances. A sharp structure is seen at 1.7 GeV.
The shape of the differential cross section is indicative of the presence of a
-wave resonance that persists to high . Improved values are derived for
the photon coupling amplitude for the (1535) resonance. The new data
greatly expands the range covered and an interpretation of all data with
a consistent parameterization is provided.Comment: 31 pages, 9 figure
Measurement of Inclusive Spin Structure Functions of the Deuteron
We report the results of a new measurement of spin structure functions of the
deuteron in the region of moderate momentum transfer ( = 0.27 -- 1.3
(GeV/c)) and final hadronic state mass in the nucleon resonance region (
= 1.08 -- 2.0 GeV). We scattered a 2.5 GeV polarized continuous electron beam
at Jefferson Lab off a dynamically polarized cryogenic solid state target
(ND) and detected the scattered electrons with the CEBAF Large
Acceptance Spectrometer (CLAS). From our data, we extract the longitudinal
double spin asymmetry and the spin structure function . Our
data are generally in reasonable agreement with existing data from SLAC where
they overlap, and they represent a substantial improvement in statistical
precision. We compare our results with expectations for resonance asymmetries
and extrapolated deep inelastic scaling results. Finally, we evaluate the first
moment of the structure function and study its approach to both the
deep inelastic limit at large and to the Gerasimov-Drell-Hearn sum rule
at the real photon limit (). We find that the first moment varies
rapidly in the range of our experiment and crosses zero at between
0.5 and 0.8 (GeV/c), indicating the importance of the resonance at
these momentum transfers.Comment: 13 pages, 8 figures, ReVTeX 4, final version as accepted by Phys.
Rev.
- …