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Showing papers by "Paris Descartes University published in 2002"


Journal ArticleDOI
TL;DR: In survivors of out-of-hospital cardiac arrest, hemodynamic instability requiring administration of vasoactive drugs is frequent and appears several hours after hospital admission, suggesting post-resuscitation myocardial dysfunction.

607 citations


Journal ArticleDOI
TL;DR: The potential uses of polysaccharides, the limits and the future developments in this field with these natural polymers are reviewed.

359 citations


Journal ArticleDOI
TL;DR: Patients with knee OA are characterized by an uncoupling of type II collagen synthesis and degradation which can be detected by assays for serum PIIANP and urinary CTX-II, and the combination of these two new markers could be useful for identifying patients at high risk for rapid progression of joint damage.
Abstract: Objective The hallmark of osteoarthritis (OA) is the loss of articular cartilage. This loss arises from an imbalance between cartilage synthesis and cartilage degradation over a variable period of time. The aims of this study were to investigate the rates of these processes in patients with knee OA using two new molecular markers and to investigate whether the combined use of these markers could predict the progression of joint damage evaluated by both radiography and arthroscopy of the joints during a period of 1 year. Methods Seventy-five patients with medial knee OA (51 women, 24 men; mean ± SD age 63 ± 8 years, mean ± SD disease duration 4.8 ± 5.2 years) were studied prospectively. At baseline, we measured serum levels of N-propeptide of type IIA procollagen (PIIANP) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) as markers of type II collagen synthesis and degradation, respectively. Joint space width (JSW) on radiography and medial chondropathy at arthroscopy (assessed using a 100-mm visual analog scale [VAS]) were measured in all patients at baseline and in 52 patients at 1 year. Progression of joint destruction was defined as a decrease of ≥0.5 mm in JSW on radiography and as increased chondropathy (an increase in the VAS score of >8.0 units) between the baseline and 1-year evaluations. Results At baseline, compared with 58 healthy age- and sex-matched controls, patients with knee OA had decreased serum levels of PIIANP (20 ng/ml versus 29 ng/ml; P < 0.001) and increased urinary excretion of CTX-II (618 ng/mmole creatinine [Cr] versus 367 ng/mmole Cr; P < 0.001). The highest discrimination between OA patients and controls was obtained by combining PIIANP and CTX-II in an uncoupling index (Z score CTX-II − Z score PIIANP), which yielded a mean Z score of 2.9 (P < 0.0001). Increased baseline values in the uncoupling index were associated with greater progression of joint damage evaluated either by changes in JSW (r = −0.46, P = 0.0016) or by VAS score (r = 0.36, P = 0.014). Patients with both low levels of PIIANP (less than or equal to the mean − 1 SD in controls) and high levels of CTX-II (greater than or equal to the mean + 1 SD in controls) had an 8-fold more rapid progression of joint damage than other patients (P = 0.012 and P < 0.0001 as assessed by radiography and arthroscopy, respectively) and had relative risks of progression of 2.9 (95% confidence interval [95% CI] 0.80–11.1) and 9.3 (95% CI 2.2–39) by radiography and arthroscopy, respectively. Conclusion Patients with knee OA are characterized by an uncoupling of type II collagen synthesis and degradation which can be detected by assays for serum PIIANP and urinary CTX-II. The combination of these two new markers could be useful for identifying knee OA patients at high risk for rapid progression of joint damage.

297 citations


Journal ArticleDOI
TL;DR: The aim of this study was to retrospectively assess the diagnostic value of this index in patients included in a randomized trial of interferon (IFN) using repeated measurements, two biopsies and hyaluronic acid as a comparative reference.
Abstract: A liver fibrosis index was recently prospectively validated in a cross-sectional study where patients infected by hepatitis C virus (HCV) had only one biopsy and no longitudinal follow-up. The aim of this study was to retrospectively assess the diagnostic value of this index in patients included in a randomized trial of interferon (IFN) using repeated measurements, two biopsies and hyaluronic acid as a comparative reference. One-hundred and sixty-five patients who had had two interpretable liver biopsies and at least one stored serum sample before IFN treatment were selected. Seventy-eight patients received 3 MU of IFN-alpha thrice weekly for 24 weeks and 87 followed a reinforced regimen for 48 weeks. A fibrosis index combining five biochemical markers (alpha2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase (GGT) and total bilirubin adjusted for gender and age) as well as hyaluronic acid was assessed on 461 samples available at baseline, at the end of treatment and at the end of follow-up (72 weeks). There was a significant decrease of the fibrosis index score among the 17 sustained virologic responders, from 0.33 +/- 0.06 (mean +/- SE) at baseline to 0.18 +/- 0.06 at 72 weeks in comparison with 92 nonresponders (from 0.41 +/- 0.03 at baseline to 0.44 +/- 0.03 at 72 weeks; P < 0.001) and in comparison with 56 relapsers (from 0.36 +/- 0.03 at baseline to 0.32 +/- 0.03 at 72 weeks; P=0.05). No significant differences were observed for hyaluronic acid.Hence, this fibrosis index could be used as a surrogate marker of the antifibrotic effect of treatments in patients with chronic hepatitis C.

232 citations


Journal ArticleDOI
TL;DR: The recent discovery of a novel H 4 receptor, which is expressed preferentially on immunocompetent cells, will have important consequences for the understanding of the regulatory functions of histamine during the immune response.

230 citations


Journal ArticleDOI
TL;DR: It was shown that mutation rates of strains vary considerably among different ecotypes, and Uropathogenic strains had the highest frequency of mutators, while strains from patients with bacteremia had the lowest mutation rates.
Abstract: By using a panel of 603 commensal and pathogenic Escherichia coli and Shigella isolates, we showed that mutation rates of strains vary considerably among different ecotypes. Uropathogenic strains had the highest frequency of mutators, while strains from patients with bacteremia had the lowest mutation rates. No correlation between the mutation rates and antibiotic resistance was observed among the studied strains.

179 citations


Journal ArticleDOI
TL;DR: HIV‐1 elicits a pro‐apoptotic signal transduction pathway relying on the sequential action of cyclin B–Cdk1, mTOR and p53, which prevents karyogamy, m TOR activation, p53S15 phosphorylation and apoptosis.
Abstract: Syncytia arising from the fusion of cells expressing the HIV‐1‐encoded Env gene with cells expressing the CD4/CXCR4 complex undergo apoptosis following the nuclear translocation of mammalian target of rapamycin (mTOR), mTOR‐mediated phosphorylation of p53 on Ser15 (p53 S15 ), p53‐dependent upregulation of Bax and activation of the mitochondrial death pathway. p53 S15 phosphorylation is only detected in syncytia in which nuclear fusion (karyogamy) has occurred. Karyogamy is secondary to a transient upregulation of cyclin B and a mitotic prophase‐like dismantling of the nuclear envelope. Inhibition of cyclin‐dependent kinase‐1 (Cdk1) prevents karyogamy, mTOR activation, p53 S15 phosphorylation and apoptosis. Neutralization of p53 fails to prevent karyogamy, yet suppresses apoptosis. Peripheral blood mononuclear cells from HIV‐1‐infected patients exhibit an increase in cyclin B and mTOR expression, correlating with p53 S15 phosphorylation and viral load. Cdk1 inhibition prevents the death of syncytia elicited by HIV‐1 infection of primary CD4 lymphoblasts. Thus, HIV‐1 elicits a pro‐apoptotic signal transduction pathway relying on the sequential action of cyclin B–Cdk1, mTOR and p53.

144 citations


Journal ArticleDOI
TL;DR: The results suggest that the sexual dimorphism of leptinemia in humans is mainly owing to the estrogen receptor-dependent stimulation of leptin expression in adipose tissue by estrogens and estrogen precursors in women.
Abstract: In the present study, we have explored, in vitro, the possibility that short exposure to androgens and estrogens for 24 h may directly influence leptin expression (ARNm and secretion) in sc adipose tissue from men and women. In men, only dihydrotestosterone at high concentration (100 nM) induced a reduction in leptin secretion and ob mRNA level. In women, 17β-estradiol (10–100 nM) increased ob mRNA expression (+180 to +500%) and leptin release (+75%). Moreover, in adipose tissue of women, the estrogen precursors testosterone (100 nM) and dehydroepiandrosterone (1 µM) also induced an increase in leptin secretion (+84 and +96%, respectively), an effect that was prevented by the aromatase inhibitor letrozole. Finally, the stimulatory effect of 17β-estradiol observed in women was antagonized by the antiestrogen ICI182780. Altogether, these results suggest that the sexual dimorphism of leptinemia in humans is mainly owing to the estrogen receptor-dependent stimulation of leptin expression in adipose tissue by estrogens and estrogen precursors in women.

107 citations


Journal ArticleDOI
TL;DR: Results emphasize the biological differences the coronal and radicular parts of the pulp, and the potential of bioactive molecules such as BMP 7 to provide an a alternative conventional endodontic treatments.

101 citations


Journal ArticleDOI
27 Mar 2002-Oncogene
TL;DR: In purified mitochondria, two ligands of ANT, bongkrekic acid and the protein vMIA from cytomegalovirus, failed to prevent MMP induced by BaxBH3 or Bcl2BH 3, which overcomes cytoprotection by B cl-2 and Bcl-XL.
Abstract: Peptides corresponding to the BH3 domains of Bax (BaxBH3) or Bcl-2 (Bcl2BH3) are potent inducers of apoptosis when fused to the Atennapedia plasma membrane translocation domain (Ant). BaxBH3Ant and Bcl2BH3Ant caused a mitochondrial membrane permeabilization (MMP) and apoptosis, via a mechanism that was not inhibited by overexpressed Bcl-2 or Bcl-XL, yet partially inhibited by cyclosporin A (CsA), an inhibitor of the mitochondrial permeability transition pore. When added to isolated mitochondria, BaxBH3 and Bcl2BH3 induced MMP, which was inhibited by CsA. However, Bcl-2 or Bcl-XL failed to inhibit MMP induced by BaxBH3 and Bc2BH3 in vitro, while they efficiently suppressed the induction of MMP by the Vpr protein (from human immunodeficiency virus-1), a ligand of the adenine nucleotide translocator (ANT). BaxBH3 but not Bcl2BH3 was found to interact with ANT, and only BaxBH3 (not Bcl2BH3) permeabilized ANT proteoliposomes and induced ANT to form non-specific channels in electrophysiological experiments. In contrast, both BaxBH3 and Bcl2BH3 were able to stimulate channel formation by recombinant Bax protein. Thus, BaxBH3 might induce MMP via an action on at least two targets, ANT and Bax-like proteins. In contrast, Bcl2BH3 would elicit MMP in an ANT-independent fashion. In purified mitochondria, two ligands of ANT, bongkrekic acid and the protein vMIA from cytomegalovirus, failed to prevent MMP induced by BaxBH3 or Bcl2BH3. In conclusion, BaxBH3 and Bcl2BH3 induce MMP and apoptosis through a mechanism which overcomes cytoprotection by Bcl-2 and Bcl-XL.

99 citations


Journal ArticleDOI
TL;DR: It is confirmed that CCND1 is an ER-responsive or ER-coactivator gene in breast cancer, and points to theCCND1 gene as a putative molecular marker predictive of hormone responsiveness in breast cancers.
Abstract: The CCND1 gene, a key cell-cycle regulator, is often altered in breast cancer, but the mechanisms underlying CCND1 dysregulation and the clinical significance of CCND1 status are unclear. We used real-time quantitative PCR and RT–PCR assays based on fluorescent TaqMan methodology to quantify CCND1 gene amplification and expression in a large series of breast tumours. CCND1 overexpression was observed in 44 (32.8%) of 134 breast tumour RNAs, ranging from 3.3 to 43.7 times the level in normal breast tissues, and correlated significantly with positive oestrogen receptor status (P=0.0003). CCND1 overexpression requires oestrogen receptor integrity and is exacerbated by amplification at 11q13 (the site of the CCND1 gene), owing to an additional gene dosage effect. Our results challenge CCND1 gene as the main 11q13 amplicon selector. The relapse-free survival time of patients with CCND1-amplified tumours was shorter than that of patients without CCND1 alterations, while that of patients with CCND1-unamplified-overexpressed tumours was longer (P=0.011). Only the good prognostic significance of CCND1-unamplified-overexpression status persisted in Cox multivariate regression analysis. This study confirms that CCND1 is an ER-responsive or ER-coactivator gene in breast cancer, and points to the CCND1 gene as a putative molecular marker predictive of hormone responsiveness in breast cancer. Moreover, CCND1 amplification status dichotomizes the CCND1-overexpressing tumors into two groups with opposite outcomes. British Journal of Cancer (2002) 86, 580–586. DOI: 10.1038/sj/bjc/6600109 www.bjcancer.com © 2002 Cancer Research UK

Journal ArticleDOI
TL;DR: Docking models support the proposal that the stabilization of a closed state represents a key step in agonist activation of mGluRs.
Abstract: Several potent and group selective agonists of metabotropic glutamate receptors (mGluRs) have been docked at mGlu1,2,4R binding sites in the closed conformation of the bilobate extracellular domain. Quisqualic acid and (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) were selected for mGlu1R, dicarboxycyclopropylglycine (DCG-IV), LY354740, (S)-4-carboxyphenylglycine (4CPG) for mGlu2R, and (S)-2-amino-4-phosphonobutyric acid (AP4), 1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I), (S)-4-phosphonophenylglycine (PPG) for mGlu4R. The models show a conserved binding pattern for the glycine moiety (α-amino and α-acidic functions) and group specific bindings for the distal acidic function. The best agonists allow optimized interaction with both lobes of the binding domain. Interlobe connections around the ligand are also described and participate in stabilizing the closed form of the amino-terminal domain. Altogether, the docking models support the proposal that the stabilization of a closed state represents a key...

Journal ArticleDOI
TL;DR: It appears that Vpr induces apoptosis through a caspase-independent mitochondrial pathway, and HIV-1-Env, which causes MMP through an indirect pathway, exhibit additive (but not synergic) cytotoxic effects.
Abstract: Previous biochemical studies suggested that HIV-1-encoded Vpr may kill cells through an effect on the adenine nucleotide translocase (ANT), thereby causing mitochondrial membrane permeabilization (MMP). Here, we show that Vpr fails to activate caspases in conditions in which it induces cell killing. The knock-out of essential caspase-activators (Apaf-1 or caspase-9) or the knock-out of a mitochondrial caspase-independent death effector (AIF) does not abolish Vpr-mediated killing. In contrast, the cytotoxic effects of Vpr are reduced by transfection-enforced overexpression of two MMP-inhibitors, namely the endogenous protein Bcl-2 or the cytomegalovirus-encoded ANT-targeted protein vMIA. Vpr, which can elicit MMP through a direct effect on mitochondria, and HIV-1-Env, which causes MMP through an indirect pathway, exhibit additive (but not synergic) cytotoxic effects. In conclusion, it appears that Vpr induces apoptosis through a caspase-independent mitochondrial pathway.

Journal ArticleDOI
24 Oct 2002-Oncogene
TL;DR: It is suggested that IBC tumours constitute a distinct subset with a specific pathogenesis, and the importance of TP53 and ERBB2 in the response to treatments, have important therapeutic implications for the clinical management of IBC patients.
Abstract: Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. We studied the biological characteristics of these tumours by comparing the overexpression of oncogenes ERBB2, MYC, CCND1 and RHOC and TP53 gene mutation rates in IBC with those found in locally advanced and not otherwise specified breast cancers. The prevalence of the TP53 mutation was much higher in IBC than in the two other types of cancer (57% vs 30). Unexpectedly, however, in IBC tumours, histological grade was independent of TP53 status. In addition, ERBB2 overexpression was twice as frequent in inflammatory as in non-inflammatory tumours, whereas the frequencies of MYC, CCND1 and RHOC overexpression did not vary significantly among the three types of breast cancer. These findings suggest that IBC tumours constitute a distinct subset with a specific pathogenesis. Given the importance of TP53 and ERBB2 in the response to treatments, our observations have important therapeutic implications for the clinical management of IBC patients.

Journal ArticleDOI
TL;DR: It is found that human endothelial cells typically expressed large amounts of a pancreatic‐type RNase that is related to, if not identical to, human pancreatic RNase, and suggests that it is endowed with non‐digestive functions and involved in vascular homeostasis.
Abstract: Pyrimidine-specific ribonucleases are a superfamily of structurally related enzymes with distinct catalytic and biological properties. We used a combination of enzymatic and non-enzymatic assays to investigate the release of such enzymes by isolated cells in serum-free and serum-containing media. We found that human endothelial cells typically expressed large amounts of a pancreatic-type RNase that is related to, if not identical to, human pancreatic RNase. This enzyme exhibits pyrimidine-specific catalytic activity, with a marked preference for poly(C) substrate over poly(U) substrate. It was potently inhibited by placental RNase inhibitor, the selective pancreatic-type RNase inhibitor Inhibit-Ace, and a polyclonal antibody against human pancreatic RNase. The enzyme isolated from medium conditioned by immortalized umbilical vein endothelial cells (EA.hy926) possesses an amino-terminal sequence identical to that of pancreatic RNase, and shows molecular heterogeneity (molecular weights 18,000-26,000) due to different degrees of N-glycosylation. Endothelial cells from arteries, veins, and capillaries secreted up to 100 ng of this RNase daily per million cells, whereas levels were low or undetectable in media conditioned by other cell types examined. The corresponding messenger RNA was detected by RT-PCR in most cell types tested so far, and level of its expression was in keeping with the amounts of protein. The selective strong release of pancreatic-type RNase by endothelial cells suggests that it is endowed with non-digestive functions and involved in vascular homeostasis.

Journal ArticleDOI
TL;DR: Clinical outcome, histological and immunohistochemical features of chronic GVHD with intestinal involvement, and the apoptotic process could be related to cytotoxic T lymphocytes are reported on.
Abstract: Graft-versus-host disease (GVHD) can be acute or chronic. The pathogenesis of chronic GVHD is unclear. Chronic GVHD affects mainly skin, liver and digestive tract. Intestinal involvement is uncommon and histological features are poorly described. We report here the clinical, histological and immunohistochemical features of chronic GVHD with intestinal involvement. Intestinal biopsies from children with chronic GVHD (n=17) were compared to control children (n=21: 10 non-transplant cases, four non-GVHD transplant cases, seven acute GVHD). We evaluated clinical outcome, histological features and characterized immunohistochemically the immune cells involved locally. Chronic GVHD with intestinal involvement was usually multisystemic (88.2%) and preceded by acute GVHD in 88.2% of cases. The outcome was severe with complete recovery in only 58.8% of cases, and death related to chronic GVHD in 17.6% of cases. Histological features were characterized by (1) villous atrophy and (2) glandular lesions, mainly apoptotic with variable intensity and (3) lamina propria infiltrate with cytotoxic T lymphocytes (CD3+, CD8+, TiA1+, granzyme B-) which were significantly (P<0.001) increased compared to non-GVHD transplant and non-transplant controls. Therefore in chronic intestinal GVHD, the apoptotic process could be related to cytotoxic T lymphocytes.

Journal ArticleDOI
TL;DR: Evaluation of the SDD of the symptomatic outcome or process variables is a starting point to determine the minimum clinically important difference, permitting the presentation of results of clinical studies on an individual basis.
Abstract: Objective To evaluate the smallest detectable difference (SDD) of symptomatic outcome or process variables in ankylosing spondylitis (AS) patients from various countries. Methods Thirty consecutive AS patients with axial involvement were recruited from 1 center in each of 4 countries (Spain, Morocco, France, The Netherlands), for a total of 120 patients. Fourteen variables were studied in 6 domains: pain (3 variables), stiffness (1 variable), function (2 variables), spinal mobility (3 variables), patient global assessment (4 variables), and the domain of enthesiopathy (1 variable). All patients were evaluated twice within a 1-week period during which no clinical or therapeutic change occurred. Intracenter reliability was evaluated using the intraclass correlation coefficient (ICC). The SDD was determined using the Bland-Altman method. Results Of the 14 variables evaluated in the 120 patients (82% males, 42 ± 12 years old, with a mean disease duration of 17 ± 13 years), only the SDD for the variable occiput-to-wall distance showed statistically significant difference among centers. For the entire group, the SDD, expressed as percentage of the range of the variable, varied from 10% (Mander enthesis index) to 39% (spinal pain at night last week). The intraobserver reliability was good (ICC > 0.80) except for the variables morning stiffness and modified Schober test (ICCs of 0.76 and 0.60, respectively). Conclusion This study suggests that the evaluation of AS patients is homogenous and reliable in different centers of different European and North African countries. Evaluation of the SDD of the symptomatic outcome or process variables is a starting point to determine the minimum clinically important difference, permitting the presentation of results of clinical studies on an individual basis.

Journal ArticleDOI
TL;DR: This study was designed to map in Alzheimer's disease patients the correlations between resting-state brain glucose utilization measured by PET and the number of intrusions obtained by means of a specially designed episodic memory test separately in free recall and in cued recall.

Journal ArticleDOI
TL;DR: In this paper, the authors outline the way in which the individual constructs a cognitive and behavioral relationship with the environment at three different levels: housing, the residential neighborhood, and the city as a whole.
Abstract: Based on the results of three field research studies in Paris, this article outlines the way in which the individual constructs a cognitive and behavioral relationship with the environment at three different levels: housing, the residential neighborhood, and the city as a whole. Identity and environmental identification generating social cohesion and satisfaction is, according to the City-Identity-Sustainability model, an important condition for ecological behavior to occur. The appropriation or nonappropriation of a particular environmental context is analyzed in light of the differentiation of the relation to the dwelling, the immediate neighborhood, and the city and described in terms of modalities of interpersonal relationships, affective investment, satisfaction, and self-expression through residential history and place identity. The characteristics of modern urban life (mobility, transitional situations, and the denaturalization of the urban context) contribute to alter the individual’s relations to...

Journal ArticleDOI
06 Dec 2002-AIDS
TL;DR: The results suggest that HIV does not replicate and does not integrate its genome infat tissue in patients with fat redistribution abnormalities, and determination of concentration in adipocyte lysates suggests that PI may diffuse in fat tissue with the same pattern of distribution for all structurally related components tested.
Abstract: Objective: To determine HIV and antiretroviral drug distribution in plasma and fat tissue of HIV-infected patients with lipodystrophy. Methods: Twenty-three consecutive HIV-infected patients (median age, 43 years; male: female ratio, 18 : 5; median CD4 cell count, 419 X 10 6 /l) undergoing Coleman's lipostructure were enrolled prospectively in this study. HIV-1 RNA and plasma concentration of antiretroviral drugs were determined blindly in plasma and adipocyte lysate samples. HIV-1 proviral DNA was detected by nested PCR in fresh frozen adipocytes. Results: Mean plasma HIV-1 RNA was significantly higher than that in adipocyte lysate samples (this was below the limit of detection in all patients tested). HIV-1 proviral DNA was positive in two out of 18 adipocyte samples with a level between 2 and 5 copies; the distribution seemed to be specific and comparable within each therapeutic class - protease inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTI). NNRTI concentrations in adipocyte lysates were approximately 100-fold higher than those of PI. Efavirenz may accumulate in fat tissue as a function of treatment duration. Conclusion: Our results suggest that HIV does not replicate and does not integrate its genome in fat tissue in patients with fat redistribution abnormalities. In patients with effective nadir plasma concentrations of PI and NNRTI, determination of concentration in adipocyte lysates suggests that PI may diffuse in fat tissue with the same pattern of distribution for all structurally related components tested. NNRTI present a high affinity for fat tissue and may accumulate in this compartment.

Journal ArticleDOI
TL;DR: The amount of elastic fibers from lesional and healthy skin areas of five patients with anetoderma was determined by automated image analysis and it is proposed that these metalloproteinases also participate in the degradation of Elastic fibers in anetodermic skin.
Abstract: The amount of elastic fibers from lesional and healthy skin areas of five patients with anetoderma was determined by automated image analysis. Dermal elastic fibers were almost completely absent in anetodermic skin and preelastic fibers were undetectable or extremely rare. Organ cultures were performed using explants from affected and unaffected skin areas of the same patient. We identified and quantified proteases in the culture media of explants: MMP-1 (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MMP-3 (stromelysin 1), MMP-7 (matrilysin 1), and tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2. The data were compared with those of two healthy donors. For the five samples of anetodermic skin, MMP-1 levels were significantly higher compared with the uninvolved cultures and the two healthy samples. A significant increase of TIMP-1 expression was also observed in the affected cultures. We demonstrated a significant increase in the production of gelatinase A in lesional skin when compared with nonlesional skin and healthy donor samples. We found no significant production of TIMP-2 in the five samples of anetodermic skin compared with the samples from the two healthy donors. There was a significant decrease in TIMP-2 expression in the five nonlesional samples compared with the control samples. These data are in favor of an altered balance in anetodermic patients between MMP-2 and TIMP-2. Levels of MMP-9, MMP-3, and MMP-7 were significantly higher in the culture-conditioned media of the anetodermic skin samples than the nonlesional skin cultures. Because MMP-3, MMP-7, MMP-9 are known to degrade elastin, and MMP-3 can activate the latent forms of MMP-7 and MMP-9, we propose that these metalloproteinases also participate in the degradation of elastic fibers in anetodermic skin.

Journal ArticleDOI
TL;DR: After decreasing at low ionic strength, lysozyme solubility increases with high concentration of polyvalent cations, probably due to co-ion binding and therefore the concomitant increase of the net charge of the protein-salt complex.
Abstract: The influence of salt nature and concentration on tetragonal lysozyme chloride crystal solubility is presented for a set of mono-, di- and trivalent cations (Cs+, Rb+, Mn2+, Co2+ and Yb3+). The results show that cations have as strong an effect on protein solubility as anions and that they present their own particular effects as co-ions. Indeed, after decreasing at low ionic strength, lysozyme solubility increases with high concentration of polyvalent cations, probably due to co-ion binding and therefore the concomitant increase of the net charge of the protein-salt complex. These new results are discussed in order to progress in the understanding of the crystallisation process at the atomic level.

Journal Article
TL;DR: Data suggest a benefit of anti-TNFalpha therapy on BMD in patients with Spondylarthropathy treated with infliximab, may be through an uncoupling effect on bone cells.
Abstract: Osteoporosis is frequently associated with Ankylosing Spondylitis (AS). Bone mineral density (BMD) decreased predominantly in patients with active disease. Moreover, conventional therapy, i.e. NSAID seems to have no influence in the bone loss. It has been suggested that local or systemic inflammatory cytokine release might be implicated in bone loss. Monoclonal antibody to TNFalpha in patients with AS demonstrated significant clinical response with significant reduction in the acute-phase reactants ESR and CRP. We evaluated the changes in bone mineral density (BMD) in patients with Spondylarthropathy (SpA) treated with infliximab (a human/mouse neutralising chimeric monoclonal antibody). We included 29 patients. In 6 months, there was a statistically significant increase in BMD both at the spine and total hip. There was an increase in osteocalcin between baseline and week 6. These data suggest a benefit of anti-TNFalpha therapy on BMD in patients with SpA, may be through an uncoupling effect on bone cells.

Proceedings ArticleDOI
TL;DR: The test methodology and the results used to evaluate dummy ability to discriminate both restraint types and dummy measurement ability to be representative of thoracic injury risk for all restraint types are presented.
Abstract: Load-limiting belt restraints have been present in French cars since 1995. An accident study showed the greater effectiveness in thorax injury prevention using a 4 kN load limiter belt with an airbag than using a 6 kN load limiter belt without airbag. The criteria for thoracic tolerance used in regulatory testing is the sternal deflection for all restraint types, belt and/or airbag restraint. This criterion does not assess the effectiveness of the restraint 4 kN load limiter belt with airbag observed in accidentology. To improve the understanding of thoracic tolerance, frontal sled crashes were performed using the Hybrid III and THOR dummies and PMHS. The sled configuration and the deceleration law correspond to those observed in the accident study. Restraint conditions evaluated are the 6 kN load-limiting belt and the 4 kN load-limiting belt with an airbag. Loads between the occupant and the sled environment were recorded. Various measurements (including thoracic deflections and head, thorax and pelvis accelerations and angular velocities on the dummies) characterize the dummy and PMHS behavior. PMHS anthropometry and injuries were noted. This study presents the test methodology and the results used to evaluate dummy ability to discriminate both restraint types and dummy measurement ability to be representative of thoracic injury risk for all restraint types. The injury results of the PMHS tests showed the same tendency as the accident study. Some of the criteria proposed in the literature did not show a better protection of the 4 kN load limiter belt with airbag restraint, in particular thoracic deflection maxima for both dummies. The four thoracic deflections measured on the THOR and Hybrid III dummies may allow more accurate analysis of the loading pattern and therefore of injury risk.

Journal ArticleDOI
TL;DR: This work uses a Brownian snake, which has values which are trajectories of standard Poisson process stopped at some random finite lifetime with Brownian evolution, to construct a self-similar fragmentation as introduced by Bertoin.
Abstract: Our main object that we call the Poisson snake is a Brownian snake as introduced by Le Gall. This process has values which are trajectories of standard Poisson process stopped at some random finite lifetime with Brownian evolution. We use this Poisson snake to construct a self-similar fragmentation as introduced by Bertoin. A similar representation was given by Aldous and Pitman using the Continuum Random Tree. Whereas their proofs used approximation by discrete models, our representation allows continuous time arguments.

Journal ArticleDOI
TL;DR: The limits of haptic orientation deficit observed in patients with left visuo-spatial neglect (VSN) in the fronto-parallel plane are addressed and no specific pattern was observed in the haptic production of different orientations in these subjects as compared to the two other groups.
Abstract: This study addresses the limits of haptic orientation deficit observed in patients with left visuo-spatial neglect (VSN) in the fronto-parallel plane. We concentrated on two aspects of the haptic perception of vertical, horizontal and oblique orientations: first, the global level of performances compared with normal subjects and, second, the occurrence of the oblique effect (i.e. lower performances in oblique orientations than in vertical-horizontal orientations). Subjects were asked to position a rod, presented in the fronto-parallel plane, to one of four orientations: vertical, horizontal, left 45 degrees oblique and right 45 degrees oblique. First, we found a haptic orientation deficit in neglect patients: The precision was lower in the neglect patients than in the normal (young adults and seniors) subjects. Second, we observed in both neglect patients and control subjects the occurrence of a similar haptic oblique effect and there were no differences between the results in the left and right hemispaces. Taken together, this means that, in spite of the global haptic orientation production deficit observed in VSN patients, no specific pattern was observed in the haptic production of different orientations in these subjects as compared to the two other groups. The haptic orientation deficit of neglect patients seems to affect in the same way all values and spatial positions of orientations.

Journal ArticleDOI
01 Jan 2002-Bone
TL;DR: Results show that histamine inhibition by an H(2) receptor antagonist partially prevents the consequences of castration on cancellous bone, possibly by an action on osteoclast differentiation in this model of osteopenia.

Journal ArticleDOI
TL;DR: It is argued that it is the specific properties of the language, such as rhythm, that could explain the differences between the results observed for the two languages and a model where prefixed and suffixed words are decomposed at different stages during their identification process is proposed.

Journal ArticleDOI
TL;DR: The present data support the notion that at least some forms of extinction (and perhaps neglect) are contingent on relative sensory/perceptual impairments and that they reflect more or less drastic forms of criterion/decision shifts.
Abstract: Previous detection performances obtained in a multi-varied contrast environment showed that observers tend to report significantly less the occurrence of the relatively lower contrast targets and significantly more the occurrence of the higher contrast ones than in conditions where each of these stimuli was tested in isolation (Gorea & Sagi, 2000). This criterion shift phenomenon is a form of contrast-dependent extinction in normal observers. To add more ground to the analogy between this type of “natural” extinction and the stroke-related one, we present a series of experiments where identical targets are displayed (1) at the same eccentricity but in opposite hemifields (along both the horizontal and vertical meridians), (2) at different eccentricities, and (3) where different spatial frequency targets of equal contrasts are displayed at the same eccentricity. Hemifield, eccentricity, and spatial frequency manipulations were intended to entail sensitivity differences for identical contrast stimuli. Some ...

Journal ArticleDOI
TL;DR: Recognition of the concept of the spondyloarthropathy is of great importance not only for research purposes but also in daily practice because such recognition permits earlier diagnosis, facilitates patients' education and monitoring, and has prognostic implications.
Abstract: The concept of spondyloarthropathy was recognized first by clinicians based on the aggregation of several diseases occurring either sequentially in the same patient or simultaneously in a family. This concept was thereafter confirmed by the higher prevalence of the HLA-B27 antigen, not only in the group of patients suffering from an axial involvement of ankylosing spondylitis but also in other diseases belonging to the concept of spondyloarthropathy, i.e. psoriatic arthritis, reactive arthritis, inflammatory-bowel-disease-related arthritis and/or other clinical manifestations such as acute anterior uveitis. Recognition of the concept of the spondyloarthropathy is of great importance not only for research purposes but also in daily practice because such recognition has at least a threefold effect: (a) it permits earlier diagnosis, (b) it facilitates patients' education and monitoring, and (c) it has prognostic implications