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Articoli di riviste sul tema "Variants du collagène":
1
Richards, Allan J., e Martin P. Snead. "Molecular Basis of Pathogenic Variants in the Fibrillar Collagens". Genes 13, n. 7 (4 luglio 2022): 1199. http://dx.doi.org/10.3390/genes13071199.
Abstract (sommario):
The fibrillar collagen family is comprised of the quantitatively major types I, II and III collagens and the quantitatively minor types V and XI. These form heterotypic collagen fibrils (composed of more than a single collagen type) where the minor collagens have a regulatory role in controlling fibril formation and diameter. The structural pre-requisites for normal collagen biosynthesis and fibrillogenesis result in many places where this process can be disrupted, and consequently a wide variety of phenotypes result when pathogenic changes occur in these fibrillar collagen genes. Another contributing factor is alternative splicing, both naturally occurring and as the result of pathogenic DNA alterations. This article will discuss how these factors should be taken into account when assessing DNA sequencing results from a patient.
2
Koch, M., B. Bohrmann, M. Matthison, C. Hagios, B. Trueb e M. Chiquet. "Large and small splice variants of collagen XII: differential expression and ligand binding." Journal of Cell Biology 130, n. 4 (15 agosto 1995): 1005–14. http://dx.doi.org/10.1083/jcb.130.4.1005.
Abstract (sommario):
Collagen XII has a short collagenous tail and a very large, three-armed NC3 domains consisting primarily of fibronectin type III repeats. Differential splicing within this domain gives rise to a large (320 kD) and a small (220 kD) subunit; the large but not the small can carry glycosaminoglycan. To investigate whether collagen XII variants have distinct expression patterns and functions, we generated antibody and cDNA probes specific for the alternatively spliced domain. We report here that the large variant has a more restricted expression in embryonic tissue than the small. For example, whereas the small variant is widespread in the dermis, the large is limited to the base of feather buds. Distinct proportions of mRNA for the two variants were detected depending on the tissue. Monoclonal antibodies allowed us to separate collagen XII variants, and to show that homo- and heterotrimers exist. Collagen XII variants differ in ligand binding. Small subunits interact weakly with heparin via their COOH-terminal domain. Large subunits have additional, stronger heparin-binding site(s) in their NH2-terminal extra domain. In vivo, both large and small collagen XII are associated with interstitial collagen. Here we show biochemically and ultrastructurally that collagen XII can be incorporated into collagen I fibrils when it is present during, but not after, fibril formation. Removal of the collagenous domain of collagen XII reduces its coprecipitation with collagen I. Our results indicate that collagen XII is specifically associated with fibrillar collagen, and that the large variant has binding sites for extracellular ligands not present in the small variant.
3
Nishi, Akari, Hikaru Matsui, Azumi Hirata, Atsushi Mukaiyama, Shun-ichi Tanaka, Takuya Yoshizawa, Hiroyoshi Matsumura, Ryota Nomura, Kazuhiko Nakano e Kazufumi Takano. "Structure, Stability and Binding Properties of Collagen-Binding Domains from Streptococcus mutans". Chemistry 5, n. 3 (1 settembre 2023): 1911–20. http://dx.doi.org/10.3390/chemistry5030130.
Abstract (sommario):
Collagen-binding proteins (CBP), Cnm and Cbm, from Streptococcus mutans are involved in infective endocarditis caused by S. mutans because of their collagen-binding ability. In this study, we focused on the collagen-binding domain (CBD), which is responsible for the collagen-binding ability of CBP, and analyzed its structure, binding activity, and stability using CBD domain variants. The CBD consists of the N1 domain, linker, N2 domain, and latch (N1-N2~) as predicted from the amino acid sequences. The crystal structure of the Cnm/CBD was determined at a 1.81 Å resolution. N1_linker_N2 forms a ring structure that can enfold collagen molecules, and the latch interacts with N1 to form a ring clasp. N1 and N2 have similar immunoglobulin folds. The collagen-binding activities of Cbm/CBD and its domain variants were examined using ELISA. N1-N2~ bound to collagen with KD = 2.8 μM, and the latch-deleted variant (N1-N2) showed weaker binding (KD = 28 μM). The linker-deleted variant (N1N2~) and single-domain variants (N1 and N2) showed no binding activity, whereas the domain-swapped variant (N2-N1~) showed binding ability, indicating that the two N-domains and the linker are important for collagen binding. Thermal denaturation experiments showed that N1-N2 was slightly less stable than N1-N2~, and that N2 was more stable than N1. The results of this study provide a basis for the development of CBD inhibitors and applied research utilizing their collagen-binding ability.
4
Ritelli, Marco, Valeria Cinquina, Marina Venturini, Letizia Pezzaioli, Anna Formenti, Nicola Chiarelli e Marina Colombi. "Expanding the Clinical and Mutational Spectrum of Recessive AEBP1-Related Classical-Like Ehlers-Danlos Syndrome". Genes 10, n. 2 (12 febbraio 2019): 135. http://dx.doi.org/10.3390/genes10020135.
Abstract (sommario):
Ehlers-Danlos syndrome (EDS) comprises clinically heterogeneous connective tissue disorders with diverse molecular etiologies. The 2017 International Classification for EDS recognized 13 distinct subtypes caused by pathogenic variants in 19 genes mainly encoding fibrillar collagens and collagen-modifying or processing proteins. Recently, a new EDS subtype, i.e., classical-like EDS type 2, was defined after the identification, in six patients with clinical findings reminiscent of EDS, of recessive alterations in AEBP1, which encodes the aortic carboxypeptidase–like protein associating with collagens in the extracellular matrix. Herein, we report on a 53-year-old patient, born from healthy second-cousins, who fitted the diagnostic criteria for classical EDS (cEDS) for the presence of hyperextensible skin with multiple atrophic scars, generalized joint hypermobility, and other minor criteria. Molecular analyses of cEDS genes did not identify any causal variant. Therefore, AEBP1 sequencing was performed that revealed homozygosity for the rare c.1925T>C p.(Leu642Pro) variant classified as likely pathogenetic (class 4) according to the American College of Medical Genetics and Genomics (ACMG) guidelines. The comparison of the patient’s features with those of the other patients reported up to now and the identification of the first missense variant likely associated with the condition offer future perspectives for EDS nosology and research in this field.
5
Flood, Veronica H., Abraham C. Schlauderaff, Paula M. Jacobi, Tricia L. Slobodianuk, Robert R. Montgomery, Sandra L. Haberichter e The Zimmerman Program Investigators. "VWF Interaction With Type IV Collagen Is Mediated Through Critical VWF A1 Domain Residues". Blood 122, n. 21 (15 novembre 2013): 29. http://dx.doi.org/10.1182/blood.v122.21.29.29.
Abstract (sommario):
Abstract Von Willebrand factor (VWF) plays a key role in coagulation by tethering platelets to injured subendothelium via binding sites for platelet glycoprotein Ib and collagen. The binding sites for types I and III collagen in the VWF A3 domain are well characterized, and defects in this region have been implicated in von Willebrand disease (VWD). Additional collagens present in the vasculature may also be involved in interactions with VWF. A VWF A1 sequence variation, p.R1399H, has been associated with decreased binding to type VI collagen, but the clinical significance of this observation remains unclear. Type IV collagen is a common component of the basement membrane and as such may be an important ligand for VWF. While some VWD testing utilizes types I or III collagen, current clinical testing does not include collagen IV or VI. To characterize the role of the VWF A1 domain in VWF-type IV collagen interactions, we generated several A1 domain variant human and/or murine recombinant VWF (rVWF) constructs including R1399H and several type 2M VWD variants localized to the same region (S1387I, Q1402P, and an 11 amino acid deletion mutant encompassing amino acids 1392-1402). These constructs were then expressed in HEK 293T cells. To further assess the role of the A1 domain, scanning alanine mutagenesis (SAM) of residues 1387 through 1412 was conducted. VWF antigen levels (VWF:Ag), collagen binding with type III (VWF:CB3), IV (VWF:CB4), or VI (VWF:CB6) collagen were determined, and multimer distribution was assessed for all recombinant VWF variants. The role of R1399H in the context of human rVWF was characterized initially. Although VWF:Ag, VWF:CB3, and multimer distribution were normal for R1399H compared to wild-type (WT VWF), VWF:CB4 was undetectable. To examine this effect in a mouse model, the R1399H variant was expressed in the context of murine rVWF and collagen binding was determined. Similar to the human variant, murine R1399H rVWF demonstrated significantly reduced binding to murine type IV collagen, at only 7% of the binding seen with WT murine rVWF. In order to examine the behavior of R1399H under shear conditions, either WT or R1399H murine rVWF DNA was hydrodynamically injected into the tail veins of VWF -/- mice to induce expression of the proteins; blood was drawn from the vena cava 24 hours later and then examined on the VenaFlux flow apparatus. VWF expression levels and multimer distribution were similar for the R1399H- and WT-injected mice. Under static conditions, the murine plasma-derived R1399H demonstrated decreased VWF:CB4, at only 16% of the levels seen with WT VWF. No defect was seen in VWF:CB3. Furthermore, when binding to type IV collagen was assessed under flow conditions by VenaFlux, platelet adhesion was significantly decreased in mice expressing R1399H VWF as compared to mice expressing WT VWF. When examining other A1 domain variants, Q1402P and del1392-1402 demonstrated absent VWF:CB4 while S1387I demonstrated a significant reduction in VWF:CB4 compared to WT VWF. All SAM VWF A1 domain variants demonstrated normal expression, multimerization, and VWF:CB3. However, type IV collagen binding was absent for R1392A, R1395A, R1399A, and K1406A and was reduced to less than 50% of WT VWF for Q1402A, K1405A, and K1407A. These residues map to an outside face of the VWF A1 domain crystal structure, and are likely the critical residues for VWF binding to type IV collagen. Taken together, these data demonstrate that the type IV collagen binding site localizes to a specific region of the VWF A1 domain. Mutations in this region of VWF may be clinically significant due to a defect in the ability of VWF to attract platelets to exposed type IV collagen which may contribute to bleeding symptoms seen in VWD. Disclosures: No relevant conflicts of interest to declare.
6
Shida, Yasuaki, Christine Brown, Jeff Mewburn, Kate Sponagle, Ozge Danisment, Barbara Vidal, Carol A. Heagadorn e David Lillicrap. "Comprehensive In Vitro and In Vivo Characterization of Loss and Gain-of-Function Von Willebrand Factor Collagen Binding Variants Using a Mouse Model System",. Blood 118, n. 21 (18 novembre 2011): 3266. http://dx.doi.org/10.1182/blood.v118.21.3266.3266.
Abstract (sommario):
Abstract Abstract 3266 Von Willebrand Factor (VWF) is a large multimeric glycoprotein that mediates platelet adhesion to the damaged blood vessel wall and subsequent platelet aggregation at the site of injury. Rare mutations in the VWF A3 domain, that disrupt collagen binding, have been found in patients with a mild bleeding phenotype. However, the analysis of these aberrant VWF-collagen interactions has been relatively limited. Thus, in this study, we have developed mouse models of collagen binding mutants and analyzed the function of the A3 and A1 domains using comprehensive in vitro and in vivo approaches. All of the collagen binding variant AAs are conserved in mice. 6 loss-of-function (S1731T, W1745C, S1783A, H1786D, A1 deletion, A3 deletion) and 1 gain-of-function (L1757A) variant was generated in the context of the mouse VWF cDNA. The 4 loss-of-function missense mutants have all been described in patients with mild bleeding phenotypes. The recombinant mouse VWFs (rmVWF) were synthesized in HEK293T cells and analyzed for type I and III collagen binding in both a static assay (CBA) and a flow-based assay at 2,500s−1 in which VWF is bound to collagen on a surface, and labeled platelet adhesion is quantified. The multimer profile of all the rmVWFs was normal. The expression level of the rmVWF derived from HEK293T cells was quantified. W1745C and the A3 deletion showed significantly lower levels of expression and the A1 deletion mutant showed strong intracellular retention. In the static collagen binding assay, S1731T showed almost normal binding to collagen type I and a 50% reduction in binding to collagen type III. The other 3 missense variants, W1745C, S1783A and H1786D, showed reduced binding to both collagens I and III, and the A3 deletion mutant showed absent binding. In the in vitro flow assay, the sensitivity to detect defects in collagen binding was superior to the static assay, although the patterns of binding defects were similar. W1745C showed similar low levels of platelet adhesion to both types of collagen, while S1783A and H1786D showed a lack of platelet binding on the collagen III surface similar to the A3 deletion mutant, and a reduced binding to collagen type I similar to W1745C. The gain-of-function mutant showed consistent enhanced collagen binding and platelet adhesion in the static and flow assays, respectively. In vivo studies delivered the mVWF cDNAs with a strong liver specific promoter by hydrodynamic injection. At 7 days post-delivery, the VWF:Ag levels in the WT and collagen binding variant mice were similar, apart from the W1745C mutant, that showed 14.6% levels compared to WT. Platelet counts and multimer patterns were normal with the collagen binding variants. In vivo intravital microscopy studies were performed using the cremaster arteriolar model when VWF levels were in a physiological range. Thrombosis was induced by 10%FeCl3 applied for 3 mins. Platelets were labeled in vivo by Rhodamine 6G and the thrombus development was analyzed by spinning disc confocal microscopy. Loss-of-function mutants showed transient platelet adhesion at the site of injury, however the adhesion was unstable and vessel occlusion was not observed. Using three complementary experimental systems we have been able to confirm the collagen binding defects in this group of variant VWFs. There is a differential sensitivity to the two forms of collagen and of the three experimental systems. The A3 deletion mutant consistently resulted in the most severe phenotype while the missense mutants showed variable degrees of functional deficit. Disclosures: No relevant conflicts of interest to declare.
7
Mikhail, Kristen A., Elizabeth VanSickle e Linda Z. Rossetti. "Milder presentation of osteogenesis imperfecta type VIII due to compound heterozygosity for a predicted loss-of-function variant and novel missense variant inP3H1—further expansion of the phenotypic spectrum". Molecular Case Studies 9, n. 1 (febbraio 2023): a006260. http://dx.doi.org/10.1101/mcs.a006260.
Abstract (sommario):
Osteogenesis imperfecta (OI) is a heritable disorder of bone metabolism characterized by multiple fractures with minimal trauma. Autosomal recessive OI type VIII is associated with biallelic pathogenic variants inP3H1and classically characterized by skeletal anomalies in addition to significant bone fragility, sometimes presenting with in utero fractures and/or neonatal lethality.P3H1encodes a collagen prolyl hydroxylase that critically 3-hydroxylates proline residue 986 on the α chain of collagen types I and II to achieve proper folding and assembly of mature collagen and is present in a complex with CRTAP and CypB. Most individuals with OI type VIII have had biallelic predicted loss-of-function variants leading to reduced or absent levels ofP3H1mRNA. The reported missense variants have all fallen in the catalytic domain of the protein and are thought to be associated with a milder phenotype. Here, we describe an infant presenting with five long bone fractures in the first year of life found to have a novel missense variant intranswith a nonsense variant inP3H1without any other bony anomalies on imaging. We hypothesize that missense variants in the catalytic domain of P3H1 lead to decreased but not absent hydroxylation of Pro986, with preserved KDEL retention signal and complex stability, causing an attenuated phenotype.
8
López-Márquez, Arístides, Matías Morín, Sergio Fernández-Peñalver, Carmen Badosa, Alejandro Hernández-Delgado, Daniel Natera-de Benito, Carlos Ortez et al. "CRISPR/Cas9-Mediated Allele-Specific Disruption of a Dominant COL6A1 Pathogenic Variant Improves Collagen VI Network in Patient Fibroblasts". International Journal of Molecular Sciences 23, n. 8 (16 aprile 2022): 4410. http://dx.doi.org/10.3390/ijms23084410.
Abstract (sommario):
Collagen VI-related disorders are the second most common congenital muscular dystrophies for which no treatments are presently available. They are mostly caused by dominant-negative pathogenic variants in the genes encoding α chains of collagen VI, a heteromeric network forming collagen; for example, the c.877G>A; p.Gly293Arg COL6A1 variant, which alters the proper association of the tetramers to form microfibrils. We tested the potential of CRISPR/Cas9-based genome editing to silence or correct (using a donor template) a mutant allele in the dermal fibroblasts of four individuals bearing the c.877G>A pathogenic variant. Evaluation of gene-edited cells by next-generation sequencing revealed that correction of the mutant allele by homologous-directed repair occurred at a frequency lower than 1%. However, the presence of frameshift variants and others that provoked the silencing of the mutant allele were found in >40% of reads, with no effects on the wild-type allele. This was confirmed by droplet digital PCR with allele-specific probes, which revealed a reduction in the expression of the mutant allele. Finally, immunofluorescence analyses revealed a recovery in the collagen VI extracellular matrix. In summary, we demonstrate that CRISPR/Cas9 gene-edition can specifically reverse the pathogenic effects of a dominant negative variant in COL6A1.
9
Zhytnik, Lidiia, Binh Ho Duy, Marelise Eekhoff, Lisanne Wisse, Gerard Pals, Ene Reimann, Sulev Kõks et al. "Phenotypic Variation in Vietnamese Osteogenesis Imperfecta Patients Sharing a Recessive P3H1 Pathogenic Variant". Genes 13, n. 3 (24 febbraio 2022): 407. http://dx.doi.org/10.3390/genes13030407.
Abstract (sommario):
Osteogenesis imperfecta (OI) is a syndromic disorder of bone fragility with high variation in its clinical presentation. Equally variable is molecular aetiology; recessive forms are caused by approximately 20 different genes, many of which are directly implicated in collagen type I biosynthesis. Biallelic variants in prolyl 3-hydroxylase 1 (P3H1) are known to cause severe OI by affecting the competence of the prolyl 3-hydroxylation—cartilage associated protein—peptidyl-prolyl cis-trans isomerase B (P3H1-CRTAP-CyPB) complex, which acts on the Pro986 residue of collagen type I α 1 (COL1A1) and Pro707 collagen type I α 2 (COL1A2) chains. The investigation of an OI cohort of 146 patients in Vietnam identified 14 families with P3H1 variants. The c.1170+5G>C variant was found to be very prevalent (12/14) and accounted for 10.3% of the Vietnamese OI cohort. New P3H1 variants were also identified in this population. Interestingly, the c.1170+5G>C variants were found in families with the severe clinical Sillence types 2 and 3 but also the milder types 1 and 4. This is the first time that OI type 1 is reported in patients with P3H1 variants expanding the clinical spectrum. Patients with a homozygous c.1170+5G>C variant shared severe progressively deforming OI type 3: bowed long bones, deformities of ribcage, long phalanges and hands, bluish sclera, brachycephaly, and early intrauterine fractures. Although it remains unclear if the c.1170+5G>C variant constitutes a founder mutation in the Vietnamese population, its prevalence makes it valuable for the molecular diagnosis of OI in patients of the Kinh ethnicity. Our study provides insight into the clinical and genetic variation of P3H1-related OI in the Vietnamese population.
10
Micale, Lucia, Silvia Morlino, Annalisa Schirizzi, Emanuele Agolini, Grazia Nardella, Carmela Fusco, Stefano Castellana et al. "Exon-Trapping Assay Improves Clinical Interpretation of COL11A1 and COL11A2 Intronic Variants in Stickler Syndrome Type 2 and Otospondylomegaepiphyseal Dysplasia". Genes 11, n. 12 (17 dicembre 2020): 1513. http://dx.doi.org/10.3390/genes11121513.
Abstract (sommario):
Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in COL11A1 and COL11A2, respectively. In both genes, available database information indicates a high rate of potentially deleterious intronic variants, but published evidence of their biological effect is usually insufficient for a definite clinical interpretation. We report four previously unpublished intronic variants in COL11A1 (c.2241 + 5G>T, c.2809 − 2A>G, c.3168 + 5G>C) and COL11A2 (c.4392 + 1G>A) identified in type 2 SS/OSMED individuals. The pathogenic effect of these variants was first predicted in silico and then investigated by an exon-trapping assay. We demonstrated that all variants can induce exon in-frame deletions, which lead to the synthesis of shorter collagen XI α1 or 2 chains. Lacking residues are located in the α-triple helical region, which has a crucial role in regulating collagen fibrillogenesis. In conclusion, this study suggests that these alternative COL11A1 and COL11A2 transcripts might result in aberrant triple helix collagen. Our approach may help to improve the diagnostic molecular pathway of COL11-related disorders.
Tesi sul tema "Variants du collagène":
1
Dumont, Bénédicte. "Caractérisation des domaines fonctionnels de la glycoprotéine VI plaquettaire à l'aide de variants recombinants et naturels". Paris 7, 2009. http://www.theses.fr/2009PA077099.
Abstract (sommario):
L'interaction plaquettes-collagène est un événement clé de l'hémostase et du maintien de l'intégrité vasculaire. La glycoprotéine (GP)VI est le principal récepteur d'activation des plaquettes par le collagène et constitue une cible pour développer de nouvelles molécules antithrombotiques. Ce travail a eu pour but de caractériser les relations entre la structure de GPVI et sa fonction. GPVI appartient à la superfamille des Immunoglobulines et présente d'importantes homologies avec le récepteur des IgA, FcαRI. Ces deux récepteurs sont exprimés sous forme d'un complexe non covalent avec FcRγ, sous-unité de signalisation. Afin de définir les rôles respectifs des deux domaines extracellulaires Ig-like (Dl et D2) de GPVI pour la liaison à ses ligands d'une part et de son domaine intracellulaire, caractérisé par la présence de motifs fonctionnels spécifiques, pour la transmission du signal d'activation d'autre part, nous avons construit des protéines chimériques dans lesquelles les différents domaines de GPVI ont été substitués par les domaines homologues de FcoRI ou de FcRy. Nous avons montré que les domaines Dl et D2 contribuent à la liaison au collagène, indépendamment l'un de l'autre, mécanisme inhabituel dans cette famille de récepteurs. L'absence des sites spécifiques intracellulaires de GPVI entraîne une moins bonne transmission du signal d'activation. Par ailleurs, nous avons décrit le premier cas de déficit congénital en GPVI. La patiente est hétérozygote pour deux mutations : une insertion de 5 nucléotides entraînant un déficit en GPVI de 50% et une substitution arginine/cystéine dans Dl provoquant une perte de fonction de la protéineRecognition of exposed vascular subendothelial collagen by the platelet receptor glycoprotein (GP)VI is a critical early step for platelet activation and subsequent thrombus formation. GPVI is a member of the immunoglobulin receptor family and expressed bound to its signaling subunit, the Fc receptor γ-chain (FcRγ). The two immunoglobulin-like domains (Dl, D2) contain structural elements important for collagen binding and receptor dimerisation respectively, and several functional motifs have been specifically identified in the cytoplasmic domain of GPVI. GPVI presents high homologies with the IgA receptor, FcαRI. To identify the respective role of Dl, D2 in the binding to collagen and the role of the intracellular functional motifs in the signal transmission, we have reconstituted recombinant receptors of GPVI and FcoRI or FcRy. We have shown that both Dl and D2 contribute to the binding to collagen, independently, which is an unusual mechanism in this receptor family. The absence of the intracellular specific GPVI domains leads to the increase of the receptor sensitivity to the cleavage by metalloproteinase and to a less efficiency of the receptor in the transmission of the signal induced by agonists. We also describe for the first time two genetic abnormalities in one patient. This 10 year-old girl presented ecchymoses since infancy. GPVI DNA sequencing revealed (i) 9 R38C mutation in exon 3 of one allele (ii) an insertion of 5 nucleotides in exon 4 of the other allele, leading to a premature nonsense codon and absence of the corresponding mRNA
2
Derlon-Borel, Annie. "Caracterisation fonctionnelle et structurale du facteur willebrand dans differents variants de maladie de willebrand. Evaluation de la liaison du facteur willebrand au collagene par une methode elisa originale. Application a differents variants". Paris 7, 1994. http://www.theses.fr/1994PA077137.
Abstract (sommario):
Trois grands types de maladie de willebrand (mdw) sont actuellement reconnus. Les types 1 et 3 correspondent aux deficits quantitatifs. Le type 2 regroupe les anomalies qualitatives avec de nombreux sous-types dont le type 2a caracterise par une diminution de l'affinite du facteur willebrand (vwf) pour les plaquettes et le type 2b qui a l'inverse presente une augmentation d'affinite pour la glycoproteine ib. Cette these rapporte ici les phanotypes et genotypes de differents variants dont 1 type 2a et un type 2b qui illustrent l'heterogeneite de l'expression phenotypique de la mdw et les multiples aspects fonctionnels du vwf pour des mutations situees sur les domaines a1 et a2. Une methode elisa originale appliquee a la determination de la capacite de liaison du vwf au collagene est decrite ici. Elle a permis d'evaluer le vwf collagen binding assay ou vwf-cba chez ces differents variants, au cours des traitements substitutifs et d'etablir la relation entre la multimerisation du vwf et la liaison au collagene. Cette methode evalue la capacite de liaison du vwf au collagene independamment de sa capacite de se lier aux plaquettes. Dans les deficits quantitatifs les taux de vwf-cba sont comparables a ceux de vwf-rco. Dans les anomalies qualitatives, les taux de vwf-cba sont toujours diminues mais restent superieurs au vwf-rco
3
Hay, Melanie. "An investigation of DNA sequence variants in genes that regulate collagen fibrillogenesis and predisposition to musculoskeletal soft tissue injuries". Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3242.
Abstract (sommario):
Includes abstract.Includes bibliographical references.
The aim of this dissertation was to use a case-control genetic study to investigate the association of polymorphisms within the COL5A1, MIR608, COL11A1 and COL11A2, genes with AT and/or ACL injuries in Caucasian populations. These aims were explored in three studies: i) Determine whether the COL5A1 rs71746744 (-/AGGG) and rs1134170 (A/T) polymorphisms and the MIR608 rs4919510 (C/G) polymorphism are associated with ACL rupture risk (Chapter 2). ii) Determine whether the COL11A1 rs3753841 (T/C) and rs1676486 (C/T) polymorphisms and the COL11A2 rs1799907 (A/T) polymorphism are associated with ACL rupture risk. A secondary aim was to determine whether the COL11A1 and COL11A2 polymorphisms interact with COL5A1 rs71746744 (-/AGGG) to modulate ACL rupture risk (Chapter 3). iii) Determine whether the COL11A1 rs3753841 (T/C) and rs1676486 (C/T) and COL11A2 rs1799907 (A/T) polymorphisms are associated with AT risk, and investigate whether these polymorphisms interact with each other, or with the COL5A1 rs71746744 (-/AGGG) polymorphism to modulate the risk of developing AT (Chapter 4).
4
Elamaa, H. (Harri). "Type XVIII collagen:characterization of the primary structure and expression pattern of different variants in Xenopus laevis, characterization of the human gene structure and analysis of transgenic mice expressing endostatin". Doctoral thesis, University of Oulu, 2004. http://urn.fi/urn:isbn:9514275691.
Abstract (sommario):
Abstract
In this work the type XVIII collagen has been studied by using several approaches, such as different animal models. The primary structure of frog, Xenopus laevis, type XVIII collagen and the expression pattern of its variants during early embryogenesis have been elucidated. The gene structure of human type XVIII collagen was characterized and the localization and processing of its longest variant was studied by generated antibodies. In addition, the function of the proteolytically released C-terminal part of type XVIII collagen, endostatin, was studied by generating transgenic mice expressing endostatin.
The primary structure of X. laevis type XVIII collagen is comprised of three N-terminal variants resembling their mammalian counterparts. The sizes of the polypeptides are 1285, 1581, and 1886 residues. The most conserved regions are the C-terminal endostatin region and the cysteine-rich domain in the N-terminus. Whole-mount in situ hybridization reveals different expression patterns for variants during embryogenesis. The short variant is the most abundant, whereas the two longest variants exhibit more restricted expression.
The gene structure of human type XVIII collagen reveals an exon-intron organization that is conserved with mouse. The length of the human gene is about 105 kb and contains 43 exons. The third variant of type XVIII collagen has a conserved cysteine-rich domain with homology to the extracellular part of frizzled proteins. This third variant is localized to developing muscle and lung, and is also found in serum. In cell culture, the proteolytic fragments of the N-terminus, including the cysteine-rich motif, are also detected.
Endostatin function was studied by generating mouse lines expressing endostatin under the keratin-14 promoter, which drives the expression mainly in the skin. Three independent transgenic mouse lines were achieved with varied expression levels. The phenotype was seen in the eye with lens opacity and abnormal morphology of epithelial cells in the lens. In the skin, a broading of the basement membrane in the epidermis dermis junction was detected. Immunoelectron microscopy analysis revealed a polarized orientation of type XVIII collagen in the basement membrane. In transgenic mice, altered localization of endogenous type XVIII collagen was seen, suggesting displacement of the endogenous type XVIII collagen with transgenic endostatin leading to disorganized basement membrane.
5
Majava, M. (Marja). "Molecular genetics of Stickler and Marshall syndromes, and the role of collagen II and other candidate proteins in high myopia and impaired hearing". Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514283628.
Abstract (sommario):
Abstract
Stickler and Marshall syndromes are genetic disorders both inherited in an autosomal dominant manner. The genotype-phenotype correlation was performed in ten Stickler/Marshall syndrome patients with mutations in the COL11A1 gene. Four patients had a phenotype classified as Marshall syndrome based on early-onset severe hearing loss and characteristic facial dysmorphism. A splice site mutation in intron 50 of COL11A1 was found in these patients, while the remaining six patients had an overlapping Marshall-Stickler phenotype with a mutation elsewhere in the gene. These results indicate exon 50 as a hot spot for splice site mutations leading to a phenotype of Marshall syndrome rather than Stickler syndrome.
Collagen II (COL2A1) precursor mRNA undergoes alternative splicing resulting in two different isoforms, IIA including exon 2 and IIB excluding exon 2. Recent evidence indicates that premature termination codon mutations in exon 2 cause Stickler syndrome with no or minimal extraocular manifestations.
Two mutations were observed in this study: Cys64Stop, and a novel structural mutation, Cys57Tyr. Results from the COL2A1 mini-gene studies suggested that both mutations altered positive cis elements for splicing resulting in a lower IIA:IIB ratio. The results further emphasize the importance of exon 2 in the development and normal function of the eye. In addition, patients displaying eye phenotypes in the absence of extraocular manifestations should be analyzed first for exon 2 mutations.
Linkage analysis identified a new locus for autosomal recessive nonsyndromic hearing loss (DFNB32) on chromosome 1p13.3-22.1 in a Tunisian family with congenital profound autosomal recessive deafness. The COL11A1 gene is located in this region and was analyzed as a candidate gene. No disease causing sequence variation was observed.
The analysis of 85 English and 40 Finnish subjects with high myopia resulted in the identification 23 sequence variations in the SLRP genes LUM, FMOD, PRELP, and OPTC. The two intronic variations and seven amino acid changes, one synonymous and six non-synonymous, were not found in the 308 controls analyzed. Five changes were detected in opticin, and all but one were shown to co-segregate with high myopia in families with incomplete penetrance. The results suggested that sequence variations in the SLRP genes expressed in the eye are genetic risk factors underlying the pathogenesis of high myopia.
Libri sul tema "Variants du collagène":
1
Heidet, Laurence, Bertrand Knebelmann e Marie Claire Gubler. Alport syndrome. A cura di Neil Turner. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0321.
Abstract (sommario):
Alport syndrome is an inherited renal disorder characterized by early haematuria, progressing to proteinuria, sensorineural hearing loss, and progressive renal failure typically in the third or fourth decade but with wide variation. It is responsible for about 1% of end-stage renal failure. Over 80% of cases are X-linked and young men are most affected, but heterozygous carriers of the abnormal gene are also at significantly increased risk of end-stage renal failure in their lifetime. Those affected by the autosomal recessive variant are phenotypically very similar. It is caused by mutations in tissue-specific isoforms of basement membrane (type IV) collagen encoded by COL4A5 (X chromosome), COL4A3, and COL4A4 (chromosome 2).
Capitoli di libri sul tema "Variants du collagène":
1
Lima, Emerson, e Mariana Lima. "Fundamentals of the Dermal Tunneling (DT): A Subcision™ Variant". In Percutaneous Collagen Induction With Microneedling, 269–77. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-57541-0_25.
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Meng Wang, Yu, e Calvin C.P. Pang. "Molecular Genetics of Keratoconus: Clinical Implications". In Ocular Surface Diseases - Some Current Date on Tear Film Problem and Keratoconic Diagnosis. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.90623.
Abstract (sommario):
Occurrence of keratoconus is pan-ethnic with reported prevalence ranging widely from 1:400 to about 1:8000, higher in Asian than Western populations. Its genetics is complex with undefined pattern of inheritance. Familial traits are also known. More than 50 gene loci and 200 variants are associated with keratoconus, some through association studies with quantitative traits of cornea features including curvature and central thickness. Environmental, behavioral, and epigenetic factors are also involved in the etiology, likely interactively with genetic susceptibility. Regardless of sex and age of disease onset, clinical courses and responses to treatment vary. Keratoconus is a major cause of cornea transplantation and is potentially blinding. Currently collagen cross-linking provides effective treatment although responses from some patients can be unpredictable with complications. Early diagnosis is vital to obtain good treatment outcome, but in many patients early signs and symptoms are not obvious. While there are potential biomarkers, reliable pre-symptomatic detection and prediction of treatment response may require multitude of gene variants, cornea properties, and external risk factors.
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Perrier-Groult, Emeline, Elisabeth Aubert-Foucher, Marielle Pasdeloup, Jérôme Lafont, Hugo Fabre e Frédéric Mallein-Gerin. "Flow Cytometry Analysis of Type IIB Procollagen as Quality Control of Chondrogenic Commitment of MSCs". In Stem Cells and Regenerative Medicine. IOS Press, 2021. http://dx.doi.org/10.3233/bhr210008.
Abstract (sommario):
Type II collagen is the major collagen protein in cartilage, synthesized as precursor forms (procollagens). Several splice variants of the gene encoding type II procollagen have been identified such as IIA and IIB isoforms. Interestingly, a shift from IIA to IIB transcripts has been reported to occur during cartilage development and during chondrogenic differentiation of mesenchymal stem cells in vitro. Thus, type IIB procollagen represents a reliable marker of chondrocyte differentiation. We characterized previously the first antibody (referred as anti-pNIIB52) able to selectively detect the IIB form of human type II procollagen in Western-blot or immunohistochemistry analysis. More recently, we used anti-pNIIB52 in flow cytometry to quantify chondrogenic induction of bone marrow-mesenchymal stem cells cultivated in agarose hydrogel, after release of the cells from the gel. Here, we use imaging flow cytometry and anti-pNIIB52 to visualize directly intracellular accumulation of type IIB procollagen in cells undergoing chondrogenesis. Our data together show that flow cytometry analysis using anti-pNIIB52 represents an efficient and rapid diagnostic tool of good chondrogenic conversion, at the cellular level.
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PAULSSON, MATS. "Laminin and Collagen IV Variants and Heterogeneity in Basement Membrane Composition". In Molecular and Cellular Aspects of Basement Membrane, 177–87. Elsevier, 1993. http://dx.doi.org/10.1016/b978-0-12-593165-6.50015-2.
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Bhalla, Sanjeev. "Idiopathic Interstitial Pneumonias". In Chest Imaging, 449–51. Oxford University Press, 2019. http://dx.doi.org/10.1093/med/9780199858064.003.0077.
Abstract (sommario):
The idiopathic interstitial pneumonias (IIPs) are a group of diffuse lung diseases that often manifest clinically with increasing dyspnea and hypoxemia. In the most recent revision of the American Thoracic Society/European Respiratory Society statement on IIPs, the major IIPs are divided into 3 groups: chronic fibrosing conditions (usual interstitial pneumonia and nonspecific interstitial pneumonia); smoking-related conditions (respiratory bronchiolitis and desquamative interstitial pneumonia) and acute/subacute IIPs (cryptogenic organizing pneumonia and acute interstitial pneumonia). Although some of these patterns may be seen with other conditions (e.g, NSIP with collagen vascular disease), the term IIP only refers to the idiopathic variants. Interestingly, the smoking-related conditions (RB-ILD and DIP) are included in this idiopathic grouping despite their association with cigarette use.
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Bratton, Francesca. "‘Are you Futuristic or are you not?’: Adversarial Editing and European Avant-Gardes". In Visionary Company, 56–93. Edinburgh University Press, 2022. http://dx.doi.org/10.3366/edinburgh/9781474481519.003.0003.
Abstract (sommario):
Chapter Two situates Crane within the European avant-garde of the 1920s, examining transatlantic connections between the U.S. and post-war Paris, Berlin, Vienna and Rome. This chapter discusses Crane’s debts to Dada and proto-Surrealist artistic experiments in his development of both his theories about the long poem and his playfully termed ‘the logic of metaphor’. The concept of ‘adversarial editing’ is coined to convey and explain the aesthetic identity of certain little magazines formed in agonistic opposition to other magazines. In these cases, disagreement and the deliberate pursuit of distance (both geographically and in terms of ideas) was key to the magazine’s operation and to the exploration of ideas within their pages. Based on archival discoveries, this chapter suggests that the fragmentary form of ‘For the Marriage of Faustus and Helen’ mediates between the aesthetic positions of two journals, Broom (broadly associated with Dada) and Secession (aligned with proto-Surrealism). Finally, I discuss the significance of the fragmentary publication of ‘Faustus and Helen’ and ‘Voyages’ in Broom, Secession, 1924 and The Little Review. The chapter argues that this moment was a watershed in Crane’s realization that publishing might become part of a poem’s form, or emphasize its collage and fragmentation — an experiment fully realised in The Bridge. Finally, the chapter introduces readers to a new piece of prose by Crane and a ‘Voyages’ variant missed by his bibliographers.
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Hakim, Alan J., e Rodney Grahame. "Hypermobility syndromes". In Oxford Textbook of Rheumatology, 1362–72. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0159_update_004.
Abstract (sommario):
Hypermobility-related syndromes constitute a family of heritable disorders of connective tissue (HDCT) that derive from abnormalities affecting genes that encode for the connective tissue matrix proteins such as collagen, fibrillin, and tenascin. They range from such commonplace though poorly recognized conditions such as hypermobility spectrum disorder (HSD), formerly within the joint hypermobility syndrome (JHS), to the better-known, if rarer, eponymous syndromes such as the Marfan syndrome (MFS), Loeys–Dietz syndrome, and the different types of the Ehlers-Danlos syndrome (EDS). The more common presentations are with skin pathology (bruising, scaring), joint or spinal and/or muscle pain and instability with vulnerability to injury and chronic widespread pain, cardiac valve pathologies, and in MFS and vascular EDS, in particular, arterial dilatation with the risk of dissection and rupture. The hypermobile variant of EDS and HSD are further complicated by cardiovascular autonomic dysfunction such as orthostatic intolerance, palpitations, and syncope, and the recently described and commonly encountered pan-gastrointestinal dysmotility. The latter can manifest as gastro-oesophageal reflux, gastroparesis, slow-transit constipation, or rectal evacuatory dysfunction with rectal intussusception. In addition, HDCT are associated with bladder and uterine problems as a consequence of pelvic floor weakness. Such multisystemic conditions need to be managed by a multidisciplinary team able to draw on medical, surgical, physical, and psychological interventions by appropriately experienced specialists and therapists. This chapter introduces the reader to the epidemiology, genetics, classification, and clinical presentation of HSD, EDS, and MFS. It also describes the key investigations required to support a diagnosis and assess complications of an HDCT, as well as the multidisciplinary approach to management.
Atti di convegni sul tema "Variants du collagène":
1
Vladu, Alina, Emilia Visileanu, Alina Popescu e Roxana Rodica Constantinescu. "Antimicrobial treatments of undergarments designed for the combat-protective clothing of soldiers". In AHFE 2023 Hawaii Edition. AHFE International, 2023. http://dx.doi.org/10.54941/ahfe1004210.
Abstract (sommario):
Military forces around the world must be equipped with combat-protective clothing made from the best technical textiles available that must provide sufficient protection, increased comfort, and even antimicrobial protection, especially for underwear pieces. Antibacterial treatments for textile materials include the use of various substances such as chitosan, silver, collagen and so on. Chitosan is a polysaccharide that promotes changes in the permeability properties of the membrane wall causing internal osmotic imbalances and consequently inhibits the growth of microorganisms. Silver can also damage the bacterial RNA and DNA, eventually leading to the bacteria`s death. Moreover, collagen, a fibrous natural protein, has an intrinsic ability to fight infection and contributes to keeping the infection site sterile.This paper focuses on the functionalization of four variants of textile materials with different compositions to increase their antibacterial properties. The variants were treated through two different technologies: exhaustion (30 min at 40°C, 500 rpm) and padding (3 consecutive passes). V1-V4 were functionalized with colloidal silver and V1-V3 with a mixture of collagen hydrolysate and colloidal silver through exhaustion. Variants V1-V3 were also treated through the padding technique using 0.5% chitosan, 1% collagen hydrolysate and a mixture of chitosan and colloidal silver. Untreated textile variants were evaluated regarding their physical-mechanical characteristics. Moreover, the functionalized variants were characterised according to their pH, loading degree with active substances (%), wettability by drop test and contact angle methods, thermal resistance (m2K/W) and vapour resistance (m2Pa/W) according to ISO 11092. Treated textile samples were also investigated relating to their antimicrobial resistance using two methods according to ISO 20743/2013 and SR EN ISO 20645/2005. The evaluation of antibacterial resistance using the standards SR EN ISO 20645/2005 and SR EN ISO 20645/2005 demonstrated the effectiveness of treatments with active substances for approx. 95% of the tested variants.
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Kratzer, MA A., e M. Knedel. "EVALUATION AND STANDARDISATION OF THE “IN VITRO” BLEEDING TIME TECHNIQUE". In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644223.
Abstract (sommario):
Recently a model of primary hemostasis has been introduced (Kratzer & Bom, Haemostasis 15:357;1985). This in vitro method detects very sensitively pathological platelet functions (Kratzer, Bellucci & Caen, Haemostasis 15:363; 1985). In order to use this technique routinely in the hospital the instrument now called “Thrombostat 4000” has been completely computerized and standardized by Kratzer and von der Goltz, VDG (8221 Seeon, West Germany).An artificial vessel (Aperture: cellulose acetate coated with collagen typ I, 2.2 ug/ mm2) with a single 150 urn hole; capillary: teflon, 200 urn, length 20 mm) was perfused with anticoagulated whole blood (Na-citrate 1 to 10) using a pressure of 40 mbar. To determine the reproducibility of the new technique, in vitro bleeding volume (V), time (T) and flow at the beginning of the experiment (IF), depending on blood viscosity, was measured in a healthy control person at different days (mean +− standard deviation, n= number of experiments).The mean of the intraassay variance (%) was: V (7.1), T(6.8) and IF(3.3). It was possible to measure the mean from day to day with the following variances (%): V(6.2), T(4.7) and IF(4.1). The low variance, which approaches enzymatic determinations is astonishing because platelet cell functions depend on a complex interaction of several thousands of enzymes.The excellent assistance of P. Gossweiler is greatly aknowledged
3
Seidel, MF, MP Junier e H. Vetter. "THU0028 Different variants of tnf-alpha mrna transcripts are expressed in rats with collagen-induced arthritis". In Annual European Congress of Rheumatology, Annals of the rheumatic diseases ARD July 2001. BMJ Publishing Group Ltd and European League Against Rheumatism, 2001. http://dx.doi.org/10.1136/annrheumdis-2001.825.
4
Zheng, Xiaoling, Hongxin Lin, Shuangmu Zhuo, Guangxing Wang e Ming Ni. "3D measurement of collagen directional variance in ovarian cancer by multiphoton microscopy". In Optics in Health Care and Biomedical Optics VIII, a cura di Qingming Luo, Xingde Li, Yuguo Tang e Ying Gu. SPIE, 2018. http://dx.doi.org/10.1117/12.2500841.
5
Vasile, Georgiana, Andreea Țigău, Alina Popescu, Rodica Roxana Constantinescu e Laura Chirilă. "Hydrogels-Based Textile Materials for Treatment of First-Degree Burn Injuries". In The 9th International Conference on Advanced Materials and Systems. INCDTP - Leather and Footwear Research Institute (ICPI), Bucharest, Romania, 2022. http://dx.doi.org/10.24264/icams-2022.ii.28.
Abstract (sommario):
Hydrogels based on collagen and xanthan have found various applications as drug delivery carriers. The main strategy is to combine the traditional perspective of using essential oils with polymeric hydrogels in order to develop a potential dressing that provides wound healing for first-degree burn injuries. In this regard, the present study is aimed to develop textile materials with potential for use in the treatment of first-degree burn injuries by approaching the hydrogels based on xanthan gum and collagen as polymeric matrix loaded with essential oils (cinnamon essential oil, tea tree essential oil), propolis (hydroglyceric extract or with content of colloidal silver) and drugs (chlorhexidine, ciprofloxacin). A total of six experimental variants of hydrogels were synthesized and then were applied by padding method on a plain weave textile structure from 100% cotton. The functionalized textile materials were characterized by morphological and antibacterial point of view. The textile materials treated materials with all synthesized hydrogels based on xanthan and collagen as polymeric matrices have antibacterial activity against S. aureus and E. coli test strains, the highest inhibition zone was provided by the samples loaded with ciprofloxacin (MUP3 and MUP4 code).
6
McGregor, J. L., L. McGregor, M. Hans, A. Sayegh, M. C. Trzeeiak e M. Dechavanne. "PLATELETS OF A PATIENT LACKING GLYCOPROTEINS lib AND Ilia AGGREGATE TO HIGH CONCENTRATIONS OF THROMBIN OR COLLAGEN". In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643863.
Abstract (sommario):
The aim of this study was to investigate the platelets of a patient having bleeding episodes that began in infancy. The patient’s platelets in citrated-PRP did not aggregate when stimulated with ADP (5 and 10 uM), collagen (2.5 ug/ml), or sodium arachidonate (1 uM). However, washed patient platelets, in the presence of 2mM calcium, aggregated and secreted when stimulated with high concentrations of thrombin (0.36, 0.72 and lU/ml) or collagen (2, 4, 10 ug/ml). Monoclonal antibodies (Mab) LYP18 (directed against the IIb-IIIa glycoprotein complex) and LYP8 (anti-thrombospondin) inhibited thrombin and collagen induced aggregation of control but not the patient platelets. Patient thrombin -stimulated platelets did not bind 125I-labelled fibrinogen (40 to 320 ug/ml). Moreover, stimulating the washed patient's platelets with ADP (10-100 uM), in the presence of fibrinogen (2mg/ml), did not result in aggregation. Binding studies using Mab 125I-LYP2 (directed against the IIb-IIIa glycoprotein complex) showed the absence of the complex on the patient's platelets. The absence of the IIb-IIIa complex on the patient's platelets was also observed using crossed immunoelectro -phoresis and Mab 125I-LYP2 or 125I-LYP18. Individual glycoproteins (lib or Ilia) were not detected on silver stained two-dimensional (non-reduced/reduced) SDS-PAGE. Moreover, Western blots of |he patients platelets used in combination with anti-PLA or anti-LEK polyclonal antibodies failed to detect the presence of these two glycoproteins. These results indicate that this patient has Glanzmann's thrombasthenia or a variant of this disease. Moreover, this study shows that platelets lacking the IIb-IIIa glycoprotein complex can aggregate in responseto collagen or thrombin in the presence of physiological concentrations of calcium.
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Proença, Bruna Moreira de Souza, Cristiane de Araújo Martins Moreno, Marco Antônio Veloso de Albuquerque, André Macedo Serafim da Silva, Clara Gontijo Camelo, Roberta Diniz de Almeida, Raquel Diógenes Alencar Sindeaux, Beatriz Carneiro Gondim Silva, Lucas Marenga Buarque e Edmar Zanoteli. "Ehlers-Danlos syndrome: an important differential diagnosis for congenital myopathies". In XIV Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2023. http://dx.doi.org/10.5327/1516-3180.141s1.722.
Abstract (sommario):
Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a genetic collagen disorder, with early onset hypotonia, weakness, progressive kyphoscoliosis, joint hypermobility, and other features underlying connective tissue involvement. On the other hand, congenital myopathies (CMs) are genetic muscle disorders, with hypotonia and weakness usually from birth which can associate with skeletal deformities. Case 1: RSS, 2-year-old, male. At birth, hip dysplasia and global hypotonia. On examination, proximal tetraparesis, global hyporeflexia and hypotonia, joint hypermobility, ogival palate, umbilical hernia, scoliosis and clubfoot. Genetic testing: Homozygous pathogenic variant in the FKBP14 gene (ENST0000000222803- c.362_363insC, p.Glu122Argfs*7), associated with kEDS type II. Case 2: RRO, 37-year-old, female. Global hypotonia at birth with congenital hip dislocation. On examination, mild proximal weakness, global hyporeflexia, joint hypermobility, scoliosis and ogival palate. Absence of marfanoid habitus. Genetic testing: Homozygous pathogenic variant in the PLOD1 gene (ENST00000196061-c.2032G>A, p.Gly678Arg), associated with kEDS type I. Conclusion: Uncommon clinical features in CMs should alert for an alternative diagnosis. Extreme joint laxity is more often a sign of a connective tissue disease, and can be associated with Marfanoid habitus, arterial dissection, bluish sclerae, umbilical hernia. Both patients presented nonspecific findings like neonatal skeletal deformities, hypermobility and mild weakness. A wide genetic test was definitive for the correct diagnosis. EDS must be included in the differential diagnosis of congenital myopathies, especially when associated with involvement of connective tissue. This is very relevant in the management care of the patients.
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Simonsen, T., Å. Vårtun, V. Lyngmo e A. Nordθy. "CORNARY HEART DISEASE, DIET, SERUM LIPIDS, PLATELET FUNCTION AND PLATELET FATTY ACIDS IN TWO POPULATIONS WITH A HIGH AND A LOW INTAKE OF DIETARY FISH". In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643806.
Abstract (sommario):
In the coastal areas of Northern Norway the intake of fish is by tradition high whereas in the inland area it is low. We have examined the mortality of CHD in the period 1975-84 in a coastal community (C) and an inland community (I). In addition we have examined 30 healthy male subjects aged 30-year, selected by random in the two communities. The examination included a dietary survey based on registration and weighing of all dietary items for one week, blood pressure, serum lipids, primary bleeding time, platelet aggregation induced by collagen and fatty acid composition of platelet total phospholipids.The age-adjusted mortality of CHD was significantly higher for age groups 30-70 year in C whereas the opposite was found above 70 years of age. The mean intake of fish per day was 134 g (0.9 g eicosapentaenoic acid-EPA) in C and 53 g (0.25 g EPA) in I. Serum triglycerides was higher in C (p<0.05) whereas totalcholesterol was similar. The primary bleeding time was not different in the two areas. Significantly lower concentrations of collagen was needed to induce 30 and 60% aggregation in platelet rich plasma in C than in I. No significant differences in the content of eicosapentaenoicacid (EPA) was observed in platelet total phospholipid fatty acids. This study has not confirmed that a high intake of fish as a singledietary variant, is associated with a low mortality of CHD. The lack of changes in plasma lipids, platelet fatty acid composition between representative groups from the two populationsindicate that other factors mask the possible beneficial effects of a high fish diet. Furthermore, the daily intake of large amounts of lean fish give only a very moderate increase in dietary intake of EPA.
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Yoder, Jonathon H., Heath B. Henninger, Jeffrey A. Weiss e Dawn M. Elliott. "Annulus Fibrosus Shear Properties Are Consistent With Motion Segment Mechanics When Fibers Are Loaded". In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206833.
Abstract (sommario):
The annulus fibrosus (AF) is a highly organized structure made up of concentric lamellae of fibers embedded in a hydrated extrafibrillar matrix; the collagen fibers are oriented at alternating angles in each lamella. The AF undergoes multidirectional loading through combinations of compression, bending, torsion and shear of the motion segment. The composition and structure of the AF leads to mechanical stress-strain nonlinearity and anisotropy. Previous tissue-based studies of shear have tested the AF tissue under compressive simple shear and torsion, producing shear modulus on the order of 0.06–0.4 MPa [1, 2]. However, structural testing and mathematical models of the IVD have reported the shear modulus to be between 3–20 MPa [3–6]. We hypothesize that when the fibers of the AF are loaded the shear modulus will be on the same order as structural tests and mathematical models of the IVD. The objectives of this study are to measure the shear mechanical properties of the bovine outer AF and compare the regional variances between anterior and posterior AF.
10
Sadler, J. Evan. "THE MOLECULAR BIOLOGY OF VON WILLEBRAND FACTOR". In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643930.
Abstract (sommario):
Human von Willebrand factor (vWF) is a plasma glycoprotein that is synthesized by endothelial cells and megakaryocytes, and perhaps by syncytiotrophoblast of placenta. The biosynthesis of vWF is very complex, involving proteolytic processing, glycosyla-tion, disulfide bond formation, and sulfation. Mature vWF consists of a single subunit of ∼ 250,000 daltons that is assembled into multimer ranging from dimers to species of over 10 million daltons. vWF performs its essential hemostatic function through several binding interactions, forming a bridge between specific receptors on the platelet surface and components of damaged vascular subendothelial connective tissue. Inherited deficiency of vWF, or von Willebrand disease (vWD), is the most common genetically transmitted bleeding disorder worldwide. The last two years has been a time of very rapid progress in understanding the molecular biology of vWF. Four research groups have independently isolated and sequenced the 9 kilobase full-length vWF cDNA. The predicted protein sequence has provided a foundation for understanding the biosynthetic processing of vWF, and has clarified the relationship between vWF and a 75-100 kilodalton plasma protein of unknown function, von Willebrand antigen II (vWAgll)/ vWAgll is co-distributed with vWF in endothelial cells and platelets, and is deficient in patients with vWD. The cDNA sequence of vWF shows that vWAgll is a rather large pro-peptide for vWF, explaining the biochemical and genetic association between the two proteins. vWF has a complex evolutionary history marked by many separate gene segment duplications. The primary structure of the protein contains four distinct types of repeated domains present in two to four copies each. Repeated domains account for over 90 percent of the protein sequence. This sequence provides a framework for ordering the functional domains that have been defined by protein chemistry methods. A tryptic peptide from the amino-terminus of vWF that overlaps domain D3 binds to factor VIII and also appears to bind to heparin. Peptides that include domain A1 bind to collagens, to heparin, and to platelet glycoprotein Ib. A second collagen binding site appears to lie within domain A3. The vWF cDNA has been expressed in heterologous cells to produce small amounts of functionally and structurally normal vWF, indicating that endothelial cells are not unique in their ability to process and assemble vWF multimers. Site-directed mutagenesis has been used to show that deletion of the propeptide of vWF prevents the formation of multimers. Cloned cDNA probes have been employed to isolate vWF genomic DNA from cosmid and λ-phage libraries, and the size of the vWF gene appears to be ∼ 150 kilobases. The vWF locus has been localized to human chromosome 12p12—pter. Several intragenic RFLPs have been characterized. With them, vWF has been placed on the human genetic linkage map as the most telomeric marker currently available for the short arm of chromosome 12. A second apparently homologous locus has been identified on chromosome 22, but the relationship of this locus to the authentic vWF gene is not yet known. The mechanism of vWD has been studied by Southern blotting of genomic DNA with cDNA probes in a few patients. Three unrelated pedigrees have been shown to have total deletions of the vWF gene as the cause of severe vWD (type III). This form of gene deletion appears to predispose to the development of inhibitory alloantibodies to vWF during therapy with cryoprecipitate. During the next several years recombinant DNA methods will continue to contribute our understanding of the evolution, biosynthesis, and structure-function relationships of vWF, as well as the mechanism of additional variants of vWD at the level of gene structure.