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Defective Interaction (defective + interaction)

Distribution by Scientific Domains
Medical Sciences75%

Selected Abstracts

Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance

HAEMOPHILIA, Issue 1 2010
V. TERRAUBE
Summary., The interaction of factor VIII (FVIII) with von Willebrand Factor (VWF) is of direct clinical significance in the diagnosis and treatment of patients with haemophilia A and von Willebrand disease (VWD). A normal haemostatic response to vascular injury requires both FVIII and VWF. It is well-established that in addition to its role in mediating platelet to platelet and platelet to matrix binding, VWF has a direct role in thrombin and fibrin generation by acting as a carrier molecule for the cofactor FVIII. Recent studies show that the interaction affects not only the biology of both FVIII and VWF, and the pathology of haemophilia and VWD, but also presents opportunities in the treatment of haemophilia. This review details the mechanisms and the molecular determinants of FVIII interaction with VWF, and the role of FVIII,VWF interaction in modulating FVIII interactions with other proteases, cell types and cellular receptors. The effect of defective interaction of FVIII with VWF as a result of mutations in either protein is discussed. [source]

Goldenhar syndrome and neuroblastoma: a chance association?

ACTA PAEDIATRICA, Issue 10 2003
C Michel-Adde
Oculoauriculovertebral dysplasia, also called Goldenhar syndrome, includes several anomalies: epibulbar dermoids or lipodermoids, microtia, mandibular hypoplasia, vertebral, skeletal, cardiac and kidney anomalies, among others. Tumours have also been observed in patients with oculoauriculovertebral dysplasia. We report the first case of oculoauriculovertebral dysplasia associated with a neuroblastoma. This tumour consists of cells identical to early migratory neural crest cells in the embryo. Several theories have been proposed regarding the pathogenetic explanation of oculoauriculovertebral dysplasia. Currently, some researchers have suggested a deficiency in mesodermal formation or defective interaction between neural crest and mesoderm as a possible aetiology. Conclusion: It is suggested that the case reported here is an additional argument for an anomaly in neural crest cell migration or interaction with the mesoderm in the pathogenesis of oculoauriculovertebral dysplasia. [source]

A Sonic Hedgehog (SH) Fusion Protein Corrects Multifocal Defects In Experimental Diabetic Neuropathy

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000
Dr Tomlinson
Diabetic neuropathy develops from defective interactions between nerve axons and other cells in the endoneurium; such interactions are influenced in development by hedgehog proteins. This study explored the possibility that this might be maintained in the adult and form a basis for therapy in diabetic neuropathies. Streptozotocin-diabetic rats were treated (final 5 weeks of 10 weeks diabetes) with a SH-IgG fusion protein (either 0.3mg/kg or 3.0mg/kg s.c. 3 times per week); control diabetic and non-diabetic rats received vehicle. Conduction velocity (MNCV, SNCV) data and sciatic nerve levels of nerve growth factor (NGF) and neuropeptide Y (NPY) are presented below. Diabetes caused significant (p < 0.05 by ANOVA with SNK tests) reductions in all variables and treatment with SH-IgG either attenuated or prevented (p < 0.05) these reductions. Since it is well-established that the conduction deficits are unrelated to neurotrophic deficits (NGF depletion) and that NPY depletion derives from a neurotrophic defect distinct from NGF, this treatment clearly acts at multiple components of the aetiology of diabetic neuropathy. [source]

Evaluation of the NK2 Homeobox 1 Gene (NKX2-1) as a Hirschsprung's Disease Locus THIS ARTICLE HAS BEEN RETRACTED

ANNALS OF HUMAN GENETICS, Issue 2 2008
M.-M. Garcia-Barceló
Summary Hirschsprung's disease (HSCR, colonic aganglionosis) is an oligogenic entity that usually requires mutations in RET and other interacting loci. Decreased levels of RET expression may lead to the manifestation of HSCR. We previously showed that RET transcription was decreased due to alteration of the NKX2,1 binding site by two HSCR-associated RET promoter single nucleotide polymorphisms (SNPs). This prompted us to investigate whether DNA alterations in NKX2-1 could play a role in HSCR by affecting the RET -regulatory properties of the NKX2,1 protein. Our initial study on 86 Chinese HSCR patients revealed a Gly322Ser amino acid substitution in the NKX2,1 protein. In this study, we have examined 102 additional Chinese and 70 Caucasian patients and 194 Chinese and 60 Caucasian unselected, unrelated, subjects as controls. The relevance of the DNA changes detected in NKX2-1 by direct sequencing were evaluated using bioinformatics, reporter and binding-assays, mouse neurosphere culture, immunohistochemistry and immunofluorescence techniques. Met3Leu and Pro48Pro were identified in 2 Caucasian and 1 Chinese patients respectively. In vitro analysis showed that Met3Leu reduced the activity of the RET promoter by 100% in the presence of the wild-type or HSCR-associated RET promoter SNP alleles. The apparent binding affinity of the NKX2,1 mutated protein was not decreased. The Met3Leu mutation may affect the interaction of NKX2,1 with its protein partners. The absence of NKX2-1 expression in mouse but not in human gut suggests that the role of NKX2,1 in gut development differs between the two species. NKX2-1 mutations could contribute to HSCR by affecting RET expression through defective interactions with other transcription factors. [source]