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See detailNovel smooth muscle markers reveal abnormalities of the intestinal musculature in severe colorectal motility disorders
Wedel, Thilo; Van Eys, Guillaume; Waltregny, David ULg et al

in Neurogastroenterology and Motility (2006), 18(7), 526-538

Histopathological studies of gastrointestinal motility disorders have mainly focused on enteric nerves and interstitial cells of Cajal, but rarely considered the enteric musculature. Here we used both ... [more ▼]

Histopathological studies of gastrointestinal motility disorders have mainly focused on enteric nerves and interstitial cells of Cajal, but rarely considered the enteric musculature. Here we used both classical and novel smooth muscle markers and transmission electron microscopy (TEM) to investigate muscular alterations in severe colorectal motility disorders. Full-thickness specimens from Hirschsprung's disease, idiopathic megacolon, slow-transit constipation and controls were stained with haematoxylin/eosin (HE) and Masson's trichrome (MT), incubated with antibodies against smooth muscle alpha-actin (alpha-SMA), smooth muscle myosin heavy chain (SMMHC), smoothelin (SM) and histone deacetylase 8 (HDAC8) and processed for TEM. Control specimens exhibited homogeneous immunoreactivity for all antibodies. Diseased specimens showed normal smooth muscle morphology by HE and MT. While anti-alpha-SMA staining was generally normal, immunoreactivity for SMMHC, HDAC8 and/or SM was either absent or focally lacking in Hirschsprung's disease (80%), idiopathic megacolon (75%) and slow-transit constipation (70%). Ultrastructurally, clusters of myocytes with noticeably decreased myofilaments were observed in all diseases. SMMHC and the novel smooth muscle markers SM and HDAC8 often display striking abnormalities linked to the smooth muscle contractile apparatus unnoticed by both routine stainings and alpha-SMA, suggesting specific defects of smooth muscle cells involved in the pathogenesis of gastrointestinal motility disorders. [less ▲]

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See detailThe novel somatostatin analog SOM230 has a broad spectrum of inhibitory action on hormone release by human somatotroph, corticotroph and PRL-secreting pituitary adenomas in vitro
Hofland, L. J.; Van Der Hoek, J.; Van Koetsveld, P. M. et al

in The 85th Annual Meeting of the Endocrine Society - Abstract book (2003)

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See detailThe novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro.
Hofland, Leo J; van der Hoek, Joost; van Koetsveld, Peter M et al

in Journal of Clinical Endocrinology and Metabolism (2004), 89(4), 1577-1585

To determine the inhibitory profile of the novel somatostatin (SRIF) analog SOM230 with broad SRIF receptor binding, we compared the in vitro effects of SOM230, octreotide (OCT), and SRIF-14 on hormone ... [more ▼]

To determine the inhibitory profile of the novel somatostatin (SRIF) analog SOM230 with broad SRIF receptor binding, we compared the in vitro effects of SOM230, octreotide (OCT), and SRIF-14 on hormone release by cultures of different types of secreting pituitary adenomas. OCT (10 nM) significantly inhibited GH release in seven of nine GH-secreting pituitary adenoma cultures (range, -26 to -73%), SOM230 (10 nM) in eight of nine cultures (range, -22 to -68%), and SRIF-14 (10 nM) in six of six cultures (range, -30 to -75%). The sst analysis showed predominant but variable levels of somatostatin receptor (sst)(2) and sst(5) mRNA expression. In one culture completely resistant to OCT, SOM230 and SRIF-14 significantly inhibited GH release in a dose-dependent manner with an IC(50) value in the low nanomolar range. In the other cultures, SOM230 showed a lower potency of GH release inhibition (IC(50), 0.5 nM), compared with OCT (IC(50), 0.02 nM) and SRIF-14 (IC(50), 0.02 nM). A positive correlation was found between sst(2) but not sst(5) mRNA levels in the adenoma cells and the inhibitory potency of OCT on GH release in vivo and in vitro, and the effects of SOM230 and SRIF-14 in vitro. In three prolactinoma cultures, 10 nM OCT weakly inhibited prolactin (PRL) release in only one (-28%), whereas 10 nM SOM230 significantly inhibited PRL release in three of three cultures (-23, -51, and -64.0%). The inhibition of PRL release by SOM230 was related to the expression level of sst(5) but not sst(2) mRNA. Several conclusions were reached. First, SOM230 has a broad profile of inhibition of tumoral pituitary hormone release in the low nanomolar range, probably mediated via both sst(2) and sst(5) receptors. The higher number of responders of GH-secreting pituitary adenoma cultures to SOM230, compared with OCT, suggest that SOM230 has the potency to increase the number of acromegalic patients which can be biochemically controlled. Second, compared with OCT, SOM230 is more potent in inhibiting PRL release by mixed GH/PRL-secreting adenoma and prolactinoma cells. [less ▲]

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See detailA novel splice variant in the N-propeptide of COL5A1 causes an EDS phenotype with severe kyphoscoliosis and eye involvement.
Symoens, Sofie; Malfait, Fransiska; Vlummens, Philip et al

in PloS one (2011), 6(5), 20121

BACKGROUND: The Ehlers-Danlos Syndrome (EDS) is a heritable connective tissue disorder characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. The classic subtype of EDS is ... [more ▼]

BACKGROUND: The Ehlers-Danlos Syndrome (EDS) is a heritable connective tissue disorder characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. The classic subtype of EDS is caused by mutations in one of the type V collagen genes (COL5A1 and COL5A2). Most mutations affect the type V collagen helical domain and lead to a diminished or structurally abnormal type V collagen protein. Remarkably, only two mutations were reported to affect the extended, highly conserved N-propeptide domain, which plays an important role in the regulation of the heterotypic collagen fibril diameter. We identified a novel COL5A1 N-propeptide mutation, resulting in an unusual but severe classic EDS phenotype and a remarkable splicing outcome. METHODOLOGY/PRINCIPAL FINDINGS: We identified a novel COL5A1 N-propeptide acceptor-splice site mutation (IVS6-2A>G, NM_000093.3_c.925-2A>G) in a patient with cutaneous features of EDS, severe progressive scoliosis and eye involvement. Two mutant transcripts were identified, one with an exon 7 skip and one in which exon 7 and the upstream exon 6 are deleted. Both transcripts are expressed and secreted into the extracellular matrix, where they can participate in and perturb collagen fibrillogenesis, as illustrated by the presence of dermal collagen cauliflowers. Determination of the order of intron removal and computational analysis showed that simultaneous skipping of exons 6 and 7 is due to the combined effect of delayed splicing of intron 7, altered pre-mRNA secondary structure, low splice site strength and possibly disturbed binding of splicing factors. CONCLUSIONS/SIGNIFICANCE: We report a novel COL5A1 N-propeptide acceptor-splice site mutation in intron 6, which not only affects splicing of the adjacent exon 7, but also causes a splicing error of the upstream exon 6. Our findings add further insights into the COL5A1 splicing order and show for the first time that a single COL5A1 acceptor-splice site mutation can perturb splicing of the upstream exon. [less ▲]

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See detailNovel Stealthy Gd(III)-DOTA/polymer Conjugates for Magnetic Resonance Imaging (MRI)
Grogna, Mathurin ULg; Bémelmans, Stéphanie ULg; Vanasschen, Christian ULg et al

Conference (2009, May 14)

Magnetic resonance imaging (MRI) is a routine diagnostic tool in modern clinical medicine. MRI has many advantages as a diagnostic imaging modality. It is noninvasive, delivers no radiation, and has ... [more ▼]

Magnetic resonance imaging (MRI) is a routine diagnostic tool in modern clinical medicine. MRI has many advantages as a diagnostic imaging modality. It is noninvasive, delivers no radiation, and has excellent (submillimeter) spatial resolution. Some Gadolinium(III) complexes are commonly used to enhance the contrast between adjacent tissues when the resolution/sensitivity of MRI is too low. Because free Gd3+ is very toxic in doses required for MRI, Gd(III) is chelated by poly(amino-carboxylate) such as diethylenetriamine pentaacetic acid (DTPA) or 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Although DTPA/Gd3+ and DOTA/Gd3+ are water soluble, they have a very short circulation lifetime in blood, a low molecular weight and a short rotational time that make the contrast poor. To enhance the contrast, the Gd3+/complex doses have to be increased. In order to increase the sensitivity of the technique, while not increasing the concentration of the contrast agent, we were investigating different strategies to improve (i) the circulation lifetime in blood, (ii) the relaxation rate of Gd(III) (and consequently, the contrasting efficiency) and (iii) the targeting of the contrast agent. This presentation aims at reporting how a multifunctional (co)polymer can be designed and exploited for improving the contrasting ability and bioavailability of gadolinium-based complexes. [less ▲]

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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 ▲]

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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)

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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 ▲]

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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 ▲]

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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 ▲]

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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 ▲]

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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 ▲]

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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

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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 ▲]

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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)

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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 ▲]

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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)

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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 ▲]

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