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Biomedical subjects

A Clermont

Publications and source records attributed to A Clermont.

At least 19 recordsLinked to original sources

Identification of immunorelevant genes from greater wax moth (Galleria mellonella) by a subtractive hybridization approach.

In this study we have analyzed bacterial lipopolysaccharide (LPS) induced genes in hemocytes of the Lepidopteran species Galleria mellonella using subtractive hybridization, followed by suppressive PCR. We have found genes that show homologies to molecules, such as gloverin, peptidoglycan recognition proteins and transferrin known to be involved in immunomodulation after bacterial infection in other species. In addition, a few molecules previously not described in the innate immune reactions were detected, such as a RNA binding molecule and tyrosine hydroxylase. Furthermore, the full-length cDNA of a LPS-induced molecule with six toxin-2-like domains is described to be a promising candidate to further elucidate the relationship between toxin- and defensin-like domains in arthropod host defense.

Amino Acid Sequence↗

Angiotensin AT(1) receptor stimulates heat shock protein 27 phosphorylation in vitro and in vivo.

The angiotensin type 1 receptor (AT(1)) exerts a variety of its signaling and cellular actions through its effects on protein phosphorylation. Phosphoproteomic analysis of angiotensin (Ang) II-stimulated aortic smooth muscle cells revealed that heat shock protein 27 (HSP27) represents a major protein phosphorylation target of the AT(1) signaling pathway. Stimulation of cells with Ang II resulted in 1.7-fold (P<0.05) and 5.5-fold (P<0.001) increases in HSP27 phosphoisoforms at pI 5.7 and pI 5.4, respectively. This was accompanied by a 54% (P<0.01) decrease in the nonphosphorylated HSP27 isoform, located at pI 6.4. Treatment of samples with alkaline phosphatase reversed this redistribution of HSP27 phosphoisoforms. Ang II-stimulated HSP27 phosphorylation was completely blocked by pretreatment of cells with the AT(1) antagonist CV11974. Phosphoamino acid analysis demonstrated that Ang II-induced phosphorylation of both HSP27 phosphoisoforms occurred exclusively on serine. Protein kinase C inhibition completely blocked phorbol ester-induced HSP27 phosphorylation but did not impair Ang II-stimulated phosphorylation of HSP27, suggesting that AT(1) increased HSP27 phosphorylation by a protein kinase C-independent pathway. Intrajugular infusion of Ang II in rats increased HSP27 in aorta by 1.7-fold (P<0.02), and this response was inhibited by CV11974. These results suggest that Ang II-induced HSP27 phosphorylation is a physiologically relevant AT(1) signaling event. Because serine phosphorylation of HSP27 blocks its ability to cap F-actin, Ang II/AT(1)-induced HSP27 phosphorylation may play a key role in actin filament remodeling required for smooth muscle cell migration and contraction.

Angiotensins↗

Cyclic stretch and hypertension induce retinal expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2: potential mechanisms for exacerbation of diabetic retinopathy by hypertension.

Systemic hypertension exacerbates diabetic retinopathy and other coexisting ocular disorders through mechanisms that remain largely unknown. Increased vascular permeability and intraocular neovascularization characterize these conditions and are complications primarily mediated by vascular endothelial growth factor (VEGF). Because systemic hypertension increases vascular stretch, we evaluated the expression of VEGF, VEGF-R2 (kinase insert domain-containing receptor [KDR]), and VEGF-R1 (fms-like tyrosine kinase [Flt]) in bovine retinal endothelial cells (BRECs) undergoing clinically relevant cyclic stretch and in spontaneously hypertensive rat (SHR) retina. A single exposure to 20% symmetric static stretch increased KDR mRNA expression 3.9 +/- 1.1-fold after 3 h (P = 0.002), with a gradual return to baseline within 9 h. In contrast, BRECs exposed to cardiac-profile cyclic stretch at 60 cpm continuously accumulated KDR mRNA in a transcriptionally mediated, time-dependent and stretch-magnitude-dependent manner. Exposure to 9% cyclic stretch increased KDR mRNA expression 8.7 +/- 2.9-fold (P = 0.011) after 9 h and KDR protein concentration 1.8 +/- 0.3-fold (P = 0.005) after 12 h. Stretched-induced VEGF responses were similar. Scatchard binding analysis demonstrated a 180 +/- 40% (P = 0.032) increase in high-affinity VEGF receptor number with no change in affinity. Cyclic stretch increased basal thymidine uptake 60 +/- 10% (P < 0.001) and VEGF-stimulated thymidine uptake by 2.6 +/- 0.2-fold (P = 0.005). VEGF-NAb reduced cyclic stretch-induced thymidine uptake by 65%. Stretched-induced KDR expression was not inhibited by AT1 receptor blockade using candesartan. Hypertension increased retinal KDR expression 67 +/- 42% (P < 0.05) in SHR rats compared with normotensive WKY control animals. When hypertension was reduced using captopril or candesartan, retinal KDR expression returned to baseline levels. VEGF reacted similarly, but Flt expression did not change. These data suggest a novel molecular mechanism that would account for the exacerbation of diabetic retinopathy by concomitant hypertension, and may partially explain the principal clinical manifestations of hypertensive retinopathy itself. Furthermore, these data imply that anti-VEGF therapies may prove therapeutically effective for hypertensive retinopathy and/or ameliorating the deleterious effects of coexistent hypertension on VEGF-associated disorders such as diabetic retinopathy.

Animals↗

Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor.

Prostacyclin-stimulating factor (PSF) acts on vascular endothelial cells to stimulate the synthesis of the vasodilatory molecule prostacyclin (PGI2). We have examined the expression, regulation, and hemodynamic bioactivity of PSF both in whole retina and in cultured cells derived from this tissue. PSF was expressed in all retinal cell types examined in vitro, but immunohistochemical analysis revealed PSF mainly associated with retinal vessels. PSF expression was constitutive in retinal pericytes (RPCs) but could be modulated in bovine retinal capillary endothelial cells (RECs) by cell confluency, hypoxia, serum starvation, high glucose concentrations, or inversely by soluble factors present in early vs. late retinopathy, such as TGF-beta, VEGF, or bFGF. In addition, RPC-conditioned media dramatically increased REC PGI2 production, a response inhibited by blocking PSF with a specific antisense oligodeoxynucleotide (ODN). In vivo, PGI2 increased retinal blood flow (RBF) in control and diabetic animals. Furthermore, the early drop in RBF during the initial weeks after inducing diabetes in rats, as well as the later increase in RBF, both correlated with levels of retinal PSF. RBF also responded to treatment with RPC-conditioned media, and this effect could be partially blocked using the antisense PSF ODN. We conclude that PSF expressed by ocular cells can induce PGI2, retinal vascular dilation, and increased retinal blood flow, and that alterations in retinal PSF expression may explain the biphasic changes in RBF observed in diabetes.

Animals↗

Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor.

Increased vascular permeability and excessive neovascularization are the hallmarks of endothelial dysfunction, which can lead to diabetic macular edema and proliferative diabetic retinopathy in the eye. Vascular endothelial growth factor (VEGF) is an important mediator of ocular neovascularization and a known vasopermeability factor in nonocular tissues. In these studies, we demonstrate that intravitreal injection of VEGF rapidly activates protein kinase C (PKC) in the retina at concentrations observed clinically, inducing membrane translocation of PKC isoforms alpha, betaII, and delta and >threefold increases in retinal vasopermeability in vivo. The effect of VEGF on retinal vascular permeability appears to be mediated predominantly by the beta-isoform of PKC with >95% inhibition of VEGF-induced permeability by intravitreal or oral administration of a PKC beta-isoform-selective inhibitor that did not inhibit histamine-mediated effects. These studies represent the first direct demonstration that VEGF can increase intraocular vascular permeability through activation of PKC in vivo and suggest that oral pharmacological therapies involving PKC beta-isoform-selective inhibitors may prove efficacious for the treatment of VEGF-associated ocular disorders such as diabetic retinopathy.

Animals↗

Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor.

The vascular complications of diabetes mellitus have been correlated with enhanced activation of protein kinase C (PKC). LY333531, a specific inhibitor of the beta isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC beta 1 and beta 2, with a half-maximal inhibitory constant of approximately 5 nM; this value was one-fiftieth of that for other PKC isoenzymes and one-thousandth of that for non-PKC kinases. When administered orally, LY333531 ameliorated the glomerular filtration rate, albumin excretion rate, and retinal circulation in diabetic rats in a dose-responsive manner, in parallel with its inhibition of PKC activities.

Administration, Oral↗

Efficacy of loratadine versus placebo in the prophylactic treatment of seasonal allergic rhinitis.

The efficacy of loratadine as prophylactic therapy for seasonal allergic rhinitis was evaluated in a randomized, double-blind, parallel group, placebo-controlled study. One hundred eighteen subjects received either loratadine, 10 mg once daily, or placebo for 6 weeks. Treatment was begun prior to the onset of grass pollen seasonal symptoms of allergic rhinitis. Total symptom-free days occurred more frequently in subjects receiving loratadine. More loratadine than placebo subjects (65% versus 49%) had no symptoms or mild rhinitis at the end of the study. In contrast, the differences between loratadine and placebo in symptom scores did not achieve significance. The incidence of sedation and anticholinergic effects were comparable between the groups. Prophylactic loratadine therapy was effective in suppressing symptoms of seasonal allergic rhinitis and providing patients with symptom-free days throughout the pollen season.

Adolescent↗

[Treatment of percutaneous angioplasty of restenoses of coarctation and stenosis of bioprostheses in children].

The authors discuss the percutaneous balloon dilatation procedure and the results obtained in 10 children (age range: 2.5-13 years) over a 2 year period (April 1986-April 1988). Six cases of coarctation restenosis were observed and good clinical and hemodynamic results were noted in 2 cases, while in 4 cases the procedure was not totally successful. For the 4 cases of stenosis of bioprosthetic valves in right ventricular-to-pulmonary arterial conduits, good results were obtained with a significant reduction of the trans-stenotic gradient from 50 to 23 mmHg. While long-term effectiveness of the procedure is still uncertain, those encouraging preliminary results suggest that this procedure could be considered as an alternative treatment for coarctation restenosis and stenosis of bioprosthetic valves in right ventricular to pulmonary artery conduits.

Adolescent↗

[Treatment of congenital pulmonary valve stenosis by percutaneous valvuloplasty].

The purpose of this study was to evaluate the efficacy technique and follow-up results of balloon valvuloplasty for congenital valvular pulmonary stenosis. Percutaneous dilatation was performed in 48 patients aged 0.5 to 21 years (m = 7.5 yrs) from two pediatric cardiology centers (Lyon and Montreal). The right ventricular peak systolic pressure ranged from 42 to 180 mmHg (m = 93) before dilatation and fell from 24 to 105 mmHg (m = 48) immediately after dilatation. The pulmonary valvular peak systolic pressure gradient ranged from 22 to 156 mmHg (m = 73) and fell to 4 to 70 mmHg (m = 27) after the procedure (P less than 0.001). Follow-up continuous doppler data was available from 33 patients at 1 to 37 months (m = 9.2 months) after dilatation. The maximal instantaneous gradient from right ventricle pulmonary artery ranged from 0 to 74 mmHg (m = 27).

Adolescent↗

[The concept of critical arterial stenosis: value of a model of measures obtained by an angiographic method and the Doppler technic before and after transluminal angioplasty of the iliac arteries].

INTRODUCTION: Numerous studies in the literature have proven the fact that a critical size appears during the stenosis evolution. The work presented is a non invasive approach of this value, with correlation to the invasive results. The study was realized on a homogeneous group of 23 arteriopathic patients, selected for iliac artery angioplasty procedure. MATERIAL AND METHODS: Patients selection: twenty-three patients including 24 angioplasty procedures have been selected on a 21 month time study. Invasive data: two measurements are realized during angioplasty: trans-stenotic pressure gradient before and after angioplasty. stenosis calibration: both diameter and section have been calculated on radiological films. Non invasive data: a standard Doppler test is performed on lower limbs. Two parameters are compared with the invasive data: the ascending time of velocity curve at the common femoral level. the systolic pressure index (peripheral pressure/radial pressure). RESULTS: 1) Critical stenosis--invasive techniques (fig. 1): trans-stenotic pressure gradient versus stenotic measurements shaw an hyperbolic correlation. The critical stenotic level is found to be 60% in diameter and 80% in section. 2) Critical stenosis--non invasive techniques: stenotic measurements compared to ascending time (fig. 2) as well as pressure index at rest (fig. 3) shaw the same type of curve. The critical stenotic level is found to be the same than with invasive techniques. DISCUSSION: Some discordant results open the discussion about angioplasty as a "gold standard", specially with a geometrical analysis. Bad precision in non regular stenosis. Hemodynamic consequences of turbulent stenosis are not evaluated. Clinical interest of critical stenotic notion is underlined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Digital arteriography of the lower limbs by sequential, automatic table translation. Feasibility. Preliminary results].

Digital subtraction angiography (DSA) as a method of evaluating lower limb arteries required examination of one limb at a time up to now. Moreover repeated injections of contrast material were necessary. This problem was mainly due to the relative small image intensifier field available and to the difficulty of repositioning the patient between mask and image acquisition. The authors report the preliminary results obtained with 24 patients studied on angiographic unit equipped with: A DSA system (DG 300-CGR) using 512 X 512 matrix size, an angiographic table (Angix M 200) allowing an automatic sequential translation, a removable image intensifier using a 16 inch field below the table. Thus, all those characteristics allow DSA of lower limb arteries. Only one injection of contrast material (Ioxaglate: 80 ml at 8-10 ml/second) was used per procedure. This, usually, allows good quality examination of lower limb arteries.

Angiography↗

Embolization of the systemic arteries of the lung.

Embolization of the systemic arteries of the lung (described by Remy and colleagues in 1973) is now a useful method for the treatment of hemoptysis or hemorrhagic lesions of the lung prior to surgical treatment, or for local treatment of hemoptysis when surgery is contraindicated or unnecessary. The technique is based on the anatomy of the different divisions of the systemic circulation (bronchial and extrabronchial), which for various physiologic reasons may develop hypervascularization. The results, complications, and contraindications of systemic embolization have previously been described and the technique is now commonly practiced.

Embolization, Therapeutic↗