Browsing
     by title


0-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

or enter first few letters:   
OK
Full Text
See detailNovel Strategies towards aminophosphonic derivatives by [4+2] cycloadditions
Monbaliu, Jean-Christophe ULg

Doctoral thesis (2008)

Aminophosphonic and related compounds were almost unknown 50 years ago, but today the literature data have considerably increased. Their negligible mammalian toxicity and their similarity with aminoacids ... [more ▼]

Aminophosphonic and related compounds were almost unknown 50 years ago, but today the literature data have considerably increased. Their negligible mammalian toxicity and their similarity with aminoacids confer on these compounds a top place as potential candidates for drugs. The discovery of numerous natural aminophosphonic derivatives endowed with biological properties useful to both medicinal and agricultural fields enhanced the infatuation for synthetic analogs and homologs. Intensive work has been performed towards alpha-aminophosphonic compounds, the direct analogs of natural alpha-aminoacids, disclosing versatile strategies, compatible both with molecular diversity and asymmetric synthesis. Less synthetic effort was devoted to the synthesis of higher homologs. Recent developments of the Diels-Alder reaction offer an asymmetric and convergent entry to various six-membered highly functionalizable key intermediates, compatible with molecular variety. As it is, the Diels-Alder (D-A) reaction should provide an original and versatile entry to beta-, gamma- and delta-aminophosphonic compounds, a challenging research area. As a direct consequence of the strategy, one of the two D-A partners (diene or dienophile) will act as vehicle for the phosphonate moiety. By contrast to its common use for the stabilization of alpha-negative charges, its implication in D-A reactions remains scarce. Indeed, the phosphonate moiety is not an efficient substituent susceptible to activate the D-A reaction; its use requires compensation by the activation of the other partner or by specific activation. Both synthetic organic and computational chemistry will furnish information to propose a fine understanding of the key D-A steps, in view to optimize the achievement of the corresponding cycloadducts. These cycloadducts will be considered as synth-/chirons for the synthesis of aminophosphonic compounds. [less ▲]

Detailed reference viewed: 6 (0 ULg)
See detailA novel strategy for the dispersion, selective deposition and decoration of carbon nanotubes
Detrembleur, Christophe ULg; Lou, Xudong; Stoffelbach, François et al

Poster (2005, May 11)

Detailed reference viewed: 12 (1 ULg)
Full Text
Peer Reviewed
See detailA novel strategy of transcription regulation by intragenic nucleosome ordering.
Palmeira, Leonor ULg; Vaillant, Cédric; Chevereau, Guillaume et al

in Genome Research (2009)

Numerous studies of chromatin structure showed that nucleosome free regions (NFRs) located at 5' gene ends contribute to transcription initiation regulation. Here, we determine the role of intragenic ... [more ▼]

Numerous studies of chromatin structure showed that nucleosome free regions (NFRs) located at 5' gene ends contribute to transcription initiation regulation. Here, we determine the role of intragenic chromatin structure on gene expression regulation. We show that, along Saccharomyces cerevisiae genes, nucleosomes are highly organized following two types of architecture that depend only on the distance between the NFRs located at the 5' and 3' gene ends. In the first type, this distance constrains in vivo the positioning of n nucleosomes regularly organized in a "crystal-like" array. In the second type, this distance is such that the corresponding genes can accommodate either n or (n + 1) nucleosomes, thereby displaying two possible crystal-like arrays of n weakly compacted or n + 1 highly compacted nucleosomes. This adaptability confers "bi-stable" properties to chromatin and is a key to its dynamics. Compared to crystal-like genes, bi-stable genes present higher transcriptional plasticity, higher sensitivity to chromatin regulators, higher H3 turnover rate, and lower H2A.Z enrichment. The results strongly suggest that transcription elongation is facilitated by higher chromatin compaction. The data allow us to propose a new paradigm of transcriptional control mediated by the stability and the level of compaction of the intragenic chromatin architecture and open new ways for investigating eukaryotic gene expression regulation. [less ▲]

Detailed reference viewed: 59 (27 ULg)
Full Text
Peer Reviewed
See detailA Novel Strategy to Translate the Biomechanical Rupture Risk of Abdominal Aortic Aneurysms to their Equivalent Diameter Risk: Method and Retrospective Validation.
Gasser, T. C.; Nchimi, A.; Swedenborg, J. et al

in European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery (2014)

OBJECTIVE: To translate the individual abdominal aortic aneurysm (AAA) patient's biomechanical rupture risk profile to risk-equivalent diameters, and to retrospectively test their predictability in ... [more ▼]

OBJECTIVE: To translate the individual abdominal aortic aneurysm (AAA) patient's biomechanical rupture risk profile to risk-equivalent diameters, and to retrospectively test their predictability in ruptured and non-ruptured aneurysms. METHODS: Biomechanical parameters of ruptured and non-ruptured AAAs were retrospectively evaluated in a multicenter study. General patient data and high resolution computer tomography angiography (CTA) images from 203 non-ruptured and 40 ruptured aneurysmal infrarenal aortas. Three-dimensional AAA geometries were semi-automatically derived from CTA images. Finite element (FE) models were used to predict peak wall stress (PWS) and peak wall rupture index (PWRI) according to the individual anatomy, gender, blood pressure, intra-luminal thrombus (ILT) morphology, and relative aneurysm expansion. Average PWS diameter and PWRI diameter responses were evaluated, which allowed for the PWS equivalent and PWRI equivalent diameters for any individual aneurysm to be defined. RESULTS: PWS increased linearly and PWRI exponentially with respect to maximum AAA diameter. A size-adjusted analysis showed that PWS equivalent and PWRI equivalent diameters were increased by 7.5 mm (p = .013) and 14.0 mm (p < .001) in ruptured cases when compared to non-ruptured controls, respectively. In non-ruptured cases the PWRI equivalent diameters were increased by 13.2 mm (p < .001) in females when compared with males. CONCLUSIONS: Biomechanical parameters like PWS and PWRI allow for a highly individualized analysis by integrating factors that influence the risk of AAA rupture like geometry (degree of asymmetry, ILT morphology, etc.) and patient characteristics (gender, family history, blood pressure, etc.). PWRI and the reported annual risk of rupture increase similarly with the diameter. PWRI equivalent diameter expresses the PWRI through the diameter of the average AAA that has the same PWRI, i.e. is at the same biomechanical risk of rupture. Consequently, PWRI equivalent diameter facilitates a straightforward interpretation of biomechanical analysis and connects to diameter-based guidelines for AAA repair indication. PWRI equivalent diameter reflects an additional diagnostic parameter that may provide more accurate clinical data for AAA repair indication. [less ▲]

Detailed reference viewed: 25 (8 ULg)
Full Text
Peer Reviewed
See detailA novel strategy towards cyclic aliphatic (co)polyesters
Gao, Ch; Li, Y; Chi, J et al

in eXPRESS Polymer Letters (2013), 7(8), 690-702

This feature article focuses on a novel strategy towards macrocyclic (co)polyesters that combines controlled ring-opening polymerization of lactones initiated by a cyclic tin(IV) dialkoxide and ... [more ▼]

This feature article focuses on a novel strategy towards macrocyclic (co)polyesters that combines controlled ring-opening polymerization of lactones initiated by a cyclic tin(IV) dialkoxide and intramolecular cyclization by photocross- linking of pendant unsaturations next to the propagating sites. No linear species is ever involved in the polymerization and permanent cyclization steps, which allows higher molecular weight macrocycles to be prepared with high efficiency and no need for further purification. Moreover, this synthetic route is very flexible to the point where macrocyclic polyesters with more complex although well-defined architectures, such as tadpole-shaped and sun-shaped copolyesters, can be tailored. Synthesis of well-defined eight-shaped polyesters and twin tadpole-shaped copolymers has also been explored by using a spirocyclic tin(IV) alkoxides as an initiator. When functional lactones were introduced, the ‘click’ copper-mediated cycloaddition [3+2] reaction was utilized to make the eight-shaped and twin tadpole-shaped copolyesters amphiphilic. [less ▲]

Detailed reference viewed: 127 (5 ULg)
Full Text
Peer Reviewed
See detailA novel sub-phylum method discriminates better the impact of crop management on soil microbial community
Degrune, Florine ULg; Dufrêne, Marc ULg; Colinet, Gilles ULg et al

in Agronomy for Sustainable Development (2015)

Soil microorganisms such as mycorrhizae and plant-growth-promoting rhizobacteria have beneficial effects on crop productivity. Agricultural practices are known to impact soil microbial communities, but ... [more ▼]

Soil microorganisms such as mycorrhizae and plant-growth-promoting rhizobacteria have beneficial effects on crop productivity. Agricultural practices are known to impact soil microbial communities, but past studies examining this impact have focused mostly on one or two taxonomic levels, such as phylum and class, thus missing potentially relevant information from lower levels. Therefore we propose here an original, sub-phylum method for studying how agricultural practices modify microbial communities. This method involves exploiting the available sequence information at the lowest taxonomic level attainable for each operational taxonomic unit. In order to validate this novel method we assessed microbial community composition using 454 pyrosequencing of 16S and 28S rRNA genes, then we compared the results with results of a phylum-level analysis. Agricultural practices included conventional tillage, reduced tillage, residue removal and residue retention. Results show that, at the lowest taxonomic level attainable, tillage is the main factor influencing both bacterial community composition, accounting for 13% of the variation, and fungal community composition, accounting for 18% of the variation. Whereas phylum-level analysis failed to reveal any effect of soil practice on bacterial community composition, and missed the fact that different members of the same phylum responded differently to tillage practice. For instance, the fungal phylum Chytridiomycota showed no impact of soil treatment, while sub-phylum-level analysis revealed an impact of tillage practice on the Chytridiomycota sub-groups Gibberella, which includes a notorious wheat pathogen, and Trichocomaceae. This clearly demonstrates the necessity of exploiting the information obtainable at sub-phylum level when assessing the effects of agricultural practice on microbial communities. [less ▲]

Detailed reference viewed: 74 (25 ULg)
Peer Reviewed
See detailNovel surgical technique for the treatment of female stress urinary incontinence: Transobturator vaginal tape inside-out
de Leval, Jean ULg; Bonnet, Pierre ULg; Reul, Olivier ULg et al

Poster (2004)

Introduction and Objective: To describe a new, simple surgical technique for the treatment of female stress urinary incontinence (SUI) and to evaluate its feasibility. Methods: We have developed a novel ... [more ▼]

Introduction and Objective: To describe a new, simple surgical technique for the treatment of female stress urinary incontinence (SUI) and to evaluate its feasibility. Methods: We have developed a novel surgical treatment of SUI, the transobturator inside-out tension-free urethral suspension, which uses specifically designed surgical tools: a pair of stainless steel helical passers, two plastic tubes with a pointed distal end and one guide. Using these instruments, a synthetic tape is passed from underneath the urethra, through the obturator foramens, towards the thighs, without entering the pelvic region at any time during the procedure. The tubes bear a lateral opening, which allows the insertion of the helical passer into its lumen. The proximal end of each tube is attached to a non-absorbable synthetic tape. The guide acts as a shoe-horn to ease the introduction of the tubes assembled onto the helical passers from the perineal space through the obturator foramen. After perforation of the obturator membrane, a rotational movement of the helical passer around the upper part of ischio-pubic ramus allows the exit of the pointed tip of the tube and, further, of the tape at the level of the thigh on either side. The tape is positioned without tension under the junction between mid and distal urethra. Results: The procedure was carried out in 210 consecutive patients (mean age = 62 years) using the same operative protocol in all case subjects, independently of the patient’s size and weight. Mean operative time was 14 min (range = 6 to 20) in case of isolated SUI treatment. No bladder or urethra injury and no vascular (hematoma or bleeding) or neurological complication were observed. Conclusions: The results of this study indicate that our novel transobturator inside-out surgical technique for treating SUI is feasible, accurate, and quick. This technique avoids damage to the urethra and bladder and, therefore, makes cystoscopy not necessary. Further prospective studies are currently ongoing to determine the efficacy of our new surgical approach for treating SUI. [less ▲]

Detailed reference viewed: 44 (0 ULg)
Full Text
Peer Reviewed
See detailNovel surgical technique for the treatment of female stress urinary incontinence: transobturator vaginal tape inside-out.
de Leval, Jean ULg

in European Urology (2003), 44(6), 724-30

OBJECTIVES: To describe a new, simple surgical technique for the treatment of female stress urinary incontinence (SUI) and to evaluate its feasibility. METHODS: We have developed a novel surgical ... [more ▼]

OBJECTIVES: To describe a new, simple surgical technique for the treatment of female stress urinary incontinence (SUI) and to evaluate its feasibility. METHODS: We have developed a novel surgical treatment of SUI, the transobturator inside-out tension-free urethral suspension, which uses specifically designed surgical tools, and in which a synthetic tape is passed from underneath the urethra, through the obturator foramens, towards the thigh folds, without entering the pelvic region at any time during the procedure. The tape is positioned without tension under the junction between mid and distal urethra. RESULTS: The procedure was carried out in 107 consecutive patients (mean age: 62 years) using the same operative protocol in all case subjects, independently of the patient's size and weight. Mean operative time was 14 min (range: 7-20) in case of isolated SUI treatment. No bladder or urethral injuries and no vascular (hematoma or bleeding) or neurological complications were encountered. CONCLUSIONS: The results of this study indicate that our novel transobturator inside-out surgical technique for treating SUI is feasible, accurate, and quick. This technique avoids damage to the urethra and bladder and, therefore, makes cystoscopy not necessary. Further prospective studies are currently ongoing to determine the efficacy of our new surgical approach for treating SUI. [less ▲]

Detailed reference viewed: 47 (0 ULg)
Full Text
Peer Reviewed
See detailNovel surgical technique for the treatment of female urinary incontinence: Transobturator vaginal tape inside-out
de Leval, Jean ULg; Bonnet, Pierre ULg; Reul, Olivier ULg et al

in European Urology Supplements (2004, February), 3(2), 226

Detailed reference viewed: 25 (0 ULg)
Full Text
Peer Reviewed
See detailNovel Susceptibility Locus at 22q11 for Diabetic Nephropathy in Type 1 Diabetes
Wessman, Maija; Forsblom, Carol; Kaunisto, Mari A et al

in PLoS ONE (2011), 9(11), 24053

Background: Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21–q25 region has repeatedly been ... [more ▼]

Background: Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21–q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loci in Finnish, Danish and French T1D families. Methods and Results: We performed a genome-wide linkage study using 384 microsatellite markers. A total of 175 T1D families were studied, of which 94 originated from Finland, 46 from Denmark and 35 from France. The whole sample set consisted of 556 individuals including 42 sib-pairs concordant and 84 sib-pairs discordant for DN. Two-point and multi-point non-parametric linkage analyses were performed using the Analyze package and the MERLIN software. A novel DN locus on 22q11 was identified in the joint analysis of the Finnish, Danish and French families by genome-wide multipoint nonparametric linkage analysis using the Kong and Cox linear model (NPLpairs LOD score 3.58). Nominal or suggestive evidence of linkage to this locus was also detected when the three populations were analyzed separately. Suggestive evidence of linkage was found to six additional loci in the Finnish and French sample sets. Conclusions: This study identified a novel DN locus at chromosome 22q11 with significant evidence of linkage to DN. Our results suggest that this locus may be of importance in European populations. In addition, this study supports previously indicated DN loci on 3q21–q25 and 19q13. [less ▲]

Detailed reference viewed: 15 (1 ULg)
Peer Reviewed
See detailNovel synthetic pyridyl analogues of CDDO-Im with improved stability and their potential use in cancer prevention
Cao, Martine ULg; Onyango, Evans; Williams, Charlotte et al

Poster (2015, April 20)

Synthetic oleanane triterpenoids are non­cytotoxic, multifunctional drugs with a broad spectrum of applications for prevention and treatment of cancer and for many other chronic diseases. CDDO­Im, 1 ... [more ▼]

Synthetic oleanane triterpenoids are non­cytotoxic, multifunctional drugs with a broad spectrum of applications for prevention and treatment of cancer and for many other chronic diseases. CDDO­Im, 1[2­Cyano­3,12­dioxooleana­1,9(11­dien­28­oyl] imidazole, synthesized more than a decade ago, is one of the most potent triterpenoids known to date with marked antiinflammatory, cytoprotective, antiproliferative, differentiative and proapoptotic activity on various human and murine tumor cell lines. However, pharmacokinetics of CDDO­Im are not optimal. Therefore, three new pyridyl analogues of CDDO­Im, namely CDDO­3P­Im, CDDO­2P­Im and CDDO­4P­Im, have been synthesized and screened for their possible use as chemopreventive or chemotherapeutic drugs. At low nanomolar concentrations, they were equivalent to CDDO­Im for induction of differentiation in U937 leukemia cells and at higher doses they induced apoptosis. As inflammation and oxidative stress contribute to carcinogenesis, we also assessed their cytoprotective potential. The new compounds suppressed inducible nitric oxide synthase expression in RAW264.7 macrophage­like cells and significantly induced heme oxygenase­1 and NADPH quinone reductase mRNA and protein levels in lung cancer cells as well as in various mouse tissues. Most importantly, pharmacokinetic studies performed in vitro in human plasma and in vivo revealed superior stability for each new analogue. While CDDO­Im was almost completely degraded after 30 min (< 12 % of starting material remaining) in human plasma, the new compounds were more stable with > 50 % still detectable. Six hours after gavage, much higher concentrations of the new derivatives were found in mouse liver, lung, pancreas and kidney in contrast to CDDO­Im. Thus, the new pyridyl analogues have better bioavailability, and because of their potent anti­inflammatory activity and improved stability, they will be tested in vivo in relevant carcinogenesis models [less ▲]

Detailed reference viewed: 4 (0 ULg)
Full Text
Peer Reviewed
See detailNovel synthetic pyridyl analogues of CDDO-Imidazolide are useful new tools in cancer prevention.
Cao, Martine ULg; Onyango, Evans O.; Williams, Charlotte R. et al

in Pharmacological research (2015), 100

Two new analogues of CDDO-Imidazolide (CDDO-Im), namely 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-2-yl)-1H-imidazole ("CDDO-2P-Im") and 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4 ... [more ▼]

Two new analogues of CDDO-Imidazolide (CDDO-Im), namely 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-2-yl)-1H-imidazole ("CDDO-2P-Im") and 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-3-yl)-1H-imidazole ("CDDO-3P-Im") have been synthesized and tested for their potential use as chemopreventive drugs. At nanomolar concentrations, they were equipotent to CDDO-Im for inducing differentiation and apoptosis in U937 leukemia cells. As inflammation and oxidative stress contribute to carcinogenesis, we also assessed their cytoprotective potential. The new compounds suppressed inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophage-like cells and significantly elevated heme oxygenase-1 (HO-1) and quinone reductase (NQO1) mRNA and protein levels in various mouse tissues in vivo. Most importantly, pharmacokinetic studies performed in vitro in human plasma and in vivo showed that each new analogue was more stable than CDDO-Im. Much higher concentrations of the new derivatives were found in mouse liver, lung, pancreas and kidney after gavage in contrast to CDDO-Im. Because of their better bioavailability and their excellent anti-inflammatory profile in vitro, CDDO-2P-Im and CDDO-3P-Im were tested for prevention in a highly relevant mouse lung cancer model, in which A/J mice develop lung carcinomas after injection of vinyl carbamate, a potent carcinogen. CDDO-2P-Im and CDDO-3P-Im were as effective as CDDO-Im for reducing the size and the severity of the lung tumors. [less ▲]

Detailed reference viewed: 5 (0 ULg)
See detailNovel technology for learning in medicine
Luengo, V.; Aboulafia, A.; Blavier, Adelaïde ULg et al

in Balacheff, N.; Ludvigsen, S.; de Jong, T. (Eds.) et al Technology-Enhanced Learning: Principles and Products (2009)

Detailed reference viewed: 19 (5 ULg)
Full Text
Peer Reviewed
See detailA novel three-enzyme reaction cycle for the synthesis of N-acetyllactosamine with in situ regeneration of uridine 5'-diphosphate glucose and uridine 5'-diphosphate galactose
Zervosen, Astrid ULg; Elling, Lothar

in Journal of the American Chemical Society (1996), 118(8), 1836-1840

A new three-enzyme reaction cycle consisting of sucrose synthase, UDP glucose 4‘-epimerase, and human β-1,4-galactosyltransferase was established for the synthesis of N-acetyllactosamine (LacNAc) with in ... [more ▼]

A new three-enzyme reaction cycle consisting of sucrose synthase, UDP glucose 4‘-epimerase, and human β-1,4-galactosyltransferase was established for the synthesis of N-acetyllactosamine (LacNAc) with in situ regeneration of UDP galactose. We found that UDP glucose 4‘-epimerase is reductively inactivated in the presence of UMP and acceptor substrates of β-1,4-galactosyltransferase. Reactivation of UDP glucose 4‘-epimerase by the transition state analogues dUDP or dTDP 6-deoxy-d-xylo-4-hexulose in combination with the repetitive batch technique enabled us to use the native enzymes for 11 days in this cycle. With 10 U of sucrose synthase, 5 U of UDP glucose 4‘-epimerase, and 1.25 U of β-1,4-galactosyltransferase, 594 mg of LacNAc could be synthesized. N-Acetyllactosamine was also subsequently converted to Neu5Acα2,6Galβl,4GlcNAc with α-2,6-sialyltransferase and CMP-Neu5Ac. [less ▲]

Detailed reference viewed: 31 (4 ULg)
Peer Reviewed
See detailA novel Treatment of Transition Problems in Metal Forming Simulation via Eulerian-Lagrangian Finite Element Modeling
Ponthot, Jean-Philippe ULg; Hogge, Michel ULg

in Proc. of the Second World Congress on Computational Mechanics (1990)

Detailed reference viewed: 8 (2 ULg)
Full Text
Peer Reviewed
See detailNovel treatments for drug-induced toxic epidermal necrolysis (Lyell's syndrome).
Paquet, Philippe ULg; Pierard, Gérald ULg; Quatresooz, Pascale ULg

in International Archives of Allergy & Immunology (2005), 136(3), 205-16

Drug-induced toxic epidermal necrolysis (TEN) is a life-threatening disease characterized by extensive destruction of the epidermis. It apparently results from the formation of specific toxic drug ... [more ▼]

Drug-induced toxic epidermal necrolysis (TEN) is a life-threatening disease characterized by extensive destruction of the epidermis. It apparently results from the formation of specific toxic drug metabolites by the keratinocytes. The mortality rate which averages 25-30% is mainly due to secondary septicemia, and to ionic and metabolic disturbances following loss of epidermal integrity. Apoptosis is the likely mechanism leading to massive keratinocyte death in TEN. Dysregulations in the tumor necrosis factor-alpha (TNF-alpha) pathway, CD95 system (Fas ligand, CD95L; Fas receptor, CD95R) and calcium homeostasis in the epidermis are involved in this apoptotic process. An active role has also been ascribed to T lymphocytes, macrophages and factor XIIIa-positive dermal dendrocytes. Despite progress, treatment of TEN remains controversial. In the past, systemic glucocorticoids were used in order to target the inflammatory reaction in TEN. However, there was no evidence for improvement of the healing process, while corticosteroids worsened the prognosis by increasing the risk of septicemia. Only a few cases have been treated with other drugs including cyclophosphamide, pentoxyfilline, thalidomide, anti-TNF-alpha antibodies and cyclosporin A. In the recent past, some TEN patients were treated with intravenous human immunoglobulins (IVIG). The rationale for such a treatment was to block the CD95 system on keratinocytes. The early promising clinical results of IVIG treatment in TEN were subsequently challenged. This review compares the effectiveness and drawbacks of the major drugs presently used in TEN treatment. Some future prospects in TEN management are also discussed. [less ▲]

Detailed reference viewed: 26 (2 ULg)
Peer Reviewed
See detailNovel two stage real-time RT-PCR assay to detect and quantify huma and bovine noroviruses
Scipioni, Alexandra; Mauroy, Axel ULg; Ziant, Dominique et al

Poster (2007, July)

Detailed reference viewed: 17 (1 ULg)
Full Text
Peer Reviewed
See detailNovel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene.
Colige, Alain ULg; Nuytinck, Lieve; Hausser, Ingrid et al

in The Journal of investigative dermatology (2004), 123(4), 656-63

Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from ... [more ▼]

Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III. All previously described mutations create premature stop codons leading to a marked reduction in the level of mRNA. In this study, we analyzed the ADAMTS2 cDNA sequences from five patients displaying clinical and/or biochemical features consistent with a diagnosis of either typical or potentially mild form of EDS type VIIC. Three different alterations were detected in the two patients with typical EDS type VIIC. The first patient was homozygous for a genomic deletion causing an in-frame skipping of exons 3-5 in the transcript. In the second patient, the allele inherited from the mother lacks exon 3, generating a premature stop codon, whereas the paternal allele has a genomic deletion resulting in an in-frame skipping of exons 14-16 at the mRNA level. Although the exons 3-5 or 14-16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function. The three other patients with a phenotype with some resemblance to EDS type VIIC only had silent and functionally neutral variations also frequently found in a normal population. [less ▲]

Detailed reference viewed: 29 (2 ULg)