Spondylocarpotarsal synostosis syndrome is a rare autosomal recessive disorder characterised by vertebral fusions, frequently manifesting as an unsegmented vertebral bar, as well as fusions of the carpal and tarsal bones.
In a study of three consanguineous families and one non-consanguineous family, linkage analysis was used to establish the chromosomal location of the disease gene. Linkage analysis localised the disease gene to chromosome 3p14. A maximum lod score of 6.49 (q = 0) was obtained for the marker at locus D3S3532 on chromosome 3p. Recombination mapping narrowed the linked region to the 5.7 cM genetic interval between the markers at loci D3S3724 and D3S1300. A common region of homozygosity was found between the markers at loci D3S3724 and D3S1300, defining a physical interval of approximately 4 million base pairs likely to contain the disease gene.
Identification of the gene responsible for this disorder will provide insight into the genes that play a role in the formation of the vertebral column and joints.
During distraction osteogenesis, angiogenic activity is essential for new bone formation. This study examined the expression of vascular endothelial growth factor (VEGF) and two of its receptors, Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2), in cellular components after mandibular distraction osteogenesis. Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in six mongrel dogs. Two animals each were killed on days 7, 14 and 28 after completion of distraction. The distracted mandibular segments and contralateral undistracted control segments were harvested and processed for immunohistochemical examination. Seven days after distraction, there was a significant increase in the expression levels of VEGF and its receptors in the osteoblasts, osteocytes and immature fibroblast-like cells compared to control specimens. These levels were maintained for 14 days after distraction in the osteoblasts and fibroblast-like cells. Twenty-eight days after distraction, VEGF and VEGFR-1 were expressed only moderately/weakly in the osteoblasts, and no VEGFR-2 expression was detected in the cellular component of the distracted bone. Throughout the observation period, VEGFR-1 expression was stronger than that of VEGFR-2. The expression patterns of VEGF and its receptors suggest that it plays an important role in osteogenesis, and that osteoblasts and immature fibroblast-like cells of the distracted bone may have an autocrine growth effect during distraction osteogenesis. 相似文献
Anarchic cell proliferation, observed in some leukemia and in breast and ovarian cancers, has been related to dysfunctioning of cytoplasmic or receptor tyrosine kinase activities coupled to p21 Ras. The growth factor receptor-bound protein 2 (Grb2) adaptor when complexed with Sos (Son of sevenless), the exchange factor of Ras, conveys the signal induced by tyrosine kinase-activated receptor to Ras by recruiting Sos to the membrane, allowing activation of Ras. This review shows how it is possible to stop the Ras-deregulated signaling pathway to obtain potential antitumor agents. Grb2 protein is comprised of one SH2 surrounded by two SH3 domains and interacts by means of its Src homology (SH2) domain with phosphotyrosine residues of target proteins such as the epidermal growth factor (EGF) receptor or the Shc adaptor. By means of its SH3 domains, Grb2 recognizes proline-rich sequences of Sos, leading to Ras activation. Inhibitors of SH2 and SH3 domains were designed with the aim of interrupting Grb2 recognition. On the one hand, using structural data and molecular modeling, peptide dimers or "peptidimers", made up of two proline-rich sequences from Sos linked by an optimized spacer, were developed. On the other, using the structure of the Grb2 SH2 domain complexed with a phosphotyrosine (pTyr)-containing peptide and molecular modeling studies, a series of N-protected tripeptides containing two phosphotyrosine or mimetic residues, with one pTyr sterically constrained, were devised. These compounds show very high affinities for Grb2 in vitro. They have been targeted into cells showing selective antiproliferative activity on tumor cells. These results suggest that inhibiting SH2 or SH3 domains of signaling proteins might provide antitumor agents. 相似文献
OBJECTIVE: Axillary padding without drainage appeared to be a valuable alternative technique to vacuum drainage. The technique employs local muscles or the axillary aponeurosis for padding. We report here the clinical evaluation of muscular padding without drainage. The analysis of these results prompted us to also do a literature search for other alternatives aimed at reducing morbidity due to vacuum drainage. PATIENTS AND METHODS: Muscular padding was prospectively performed by 8 different surgeons on a total of 152 patients at the Centre Rene-Huguenin (Saint-Cloud, France). Follow-up has attained 3.5 years. A comparative assessment of pain was conducted in 30 patients operated on with vacuum drainage. RESULTS: This technique is easy to learn and reproducible. It facilitates post-operative follow-up, always allowing discharge at the 2nd or 3rd post-operative day without any home nursing. The late sequels are not increased. In contrast, pain was twice more intense during the first post-operative weeks compared with vacuum drainage, and the seroma rate was also increased. DISCUSSION AND CONCLUSION: Despite good efficacy, this worsening of pain is a major obstacle to the routine use of muscular padding. A technical improvement has been published very recently where the axillary aponeurosis was used to pad the axilla. It seems to be equally efficient but less painful than muscular padding. This technique is under clinical evaluation and could appear as a valuable option to vacuum drainage. Other alternatives are discussed. Most studies lack a direct comparison with vacuum drainage and a satisfactory evaluation of quality of life is also omitted. New studies with quality of life scales are ongoing. They should allow us to choose options that take this aspect into account in the future. 相似文献
Neuronavigation systems integrating functional magnetic resonance imaging data have been reported recently, but generally without many details about methodology. We propose an easy method to perform functional neuronavigation by integrating functional MRI data analyzed with the Statistical Parametric Mapping 99 reference software, in the Stealth Station which is the most common neuronavigation system. Users of this new and promising technique, which requires further validation, must be aware of its limitations. Functional MRI data seem to be the major source of imprecision. As a result we do not yet recommend the use of functional neuronavigation without the control of direct cortical stimulations. 相似文献
Image interpretation consists in finding a correspondence between radiometric information and symbolic labeling with respect to specific spatial constraints. It is intrinsically a distributed process in terms of goals to be reached, zones in the image to be processed and methods to be applied. To cope the the difficulty inherent in this process, several information processing steps are required to gradually extract information. In this paper we advocate the use of situated cooperative agents as a framework for managing such steps. Dedicated agent behaviors are dynamically adapted depending on their position in the image, of their topographic relationships and of the radiometric information available. The information collected by the agents is gathered, shared via qualitative maps, or used as soon as available by acquaintances. Incremental refinement of interpretation is obtained through a coarse to fine strategy. Our work is essentially focused on radiometry-based tissue interpretation where knowledge is introduced or extracted at several levels to estimate models for tissue-intensity distribution and to cope with noise, intensity non-uniformity and partial volume effect. Several experiments on phantom and real images were performed. A complete volume can be segmented in less than 5 min with about 0.84% accuracy of the segmented reference. Comparison with other techniques demonstrates the potential interest of our approach for magnetic resonance imaging (MRI) brain scan interpretation. 相似文献