COLLAGEN METABOLISM IN WOUND REPAIR AND KELOID

描述：（改编自申请人摘要）虽然动物 模型和体外系统在过去非常有用， 深入了解细胞，生物化学和分子事件， 组织修复时，这些系统在解决独特的 与人类伤口愈合相关的临床问题。人类 反应包括广泛的愈合现象， 一端过度愈合和纤维化， 另一端动物不会产生过度的疤痕问题， 明显的问题与不足愈合。因此，该项目是 旨在表征和分析正常伤口愈合反应 在人类中，以及在相对端观察到的病理反应， 江西篇章人类瘢痕疙瘩将代表纤维化的条件 而慢性非愈合性糖尿病溃疡将作为 治疗不足所有研究都将在人类中进行， 正常可用的伤口渗出液、活组织检查和切除组织 这些患者通常会接受手术治疗。 此外，还提供了由膨胀形式的聚乙烯醇组成的可植入管， 聚四氟乙烯，称为Impra，已被证明是有用的，以收集新的伤口 组织进行分析。这个实验室现在已经发展并适应了 最先进的技术和方法来研究人类伤口愈合。 因此，这些策略将用于分析炎症， 细胞因子产生、基质合成和降解、血管生成和 收缩在正常人的伤口，瘢痕疙瘩和慢性不愈合 溃疡实验室方法包括常规组织学， 免疫染色、ELISA测定、原位杂交、RNA酶保护 测定，一种新的胶原放射性标记底物测定， 胶原酶和明胶酶活性，羟脯氨酸的HPLC定量 和亮氨酸沉积以及蛋白质印迹分析。这些方法具有 已修改为适用于分析少量组织 以及可以从这些人源获得的渗出物材料。 这些研究将比较和对比正常机制 负责健康组织愈合的机制 负责瘢痕疙瘩的过度愈合和慢性 溃疡

DESCRIPTION: (Adapted from the applicant's abstract) Although animal models and in vitro systems have been very useful in the past to gain insight into the cellular, biochemical and molecular events during tissue repair, these systems have limitations when addressing the unique clinical problems associated with human wound healing. The human response encompasses a wide spectrum of healing phenomena with overhealing and fibrosis on one end and chronic ulcer formation on the other end. Animals do not develop excessive scar issue nor do they manifest problems with deficient healing. Therefore, this project is designed to characterize and analyze the normal wound healing response in humans as well as the pathologic responses seen at opposite ends of the spectrum. The human keloid will represent conditions of fibrosis whereas chronic non-healing diabetic ulcers will serve as a model of deficient healing. All studies will be done in humans using the normally available wound exudates, biopsies, and excised tissue following normally scheduled surgical treatments for these patients. In addition, an implantable tube consisting of an expanded form of Teflon, called Impra, has proven to be useful to collect new wound tissue for analysis. This laboratory has now developed and adapted state-of-the-art technologies and methods to study human wound healing. Therefore, these strategies will be employed to analyze inflammation, cytokine production, matrix synthesis and degradation, angiogenesis and contraction in normal human wounds, keloids and chronic non- healing ulcers. The laboratory methods include routine histology, immunostaining, ELISA assays, in situ hybridization, RNase protection assays, a new collagen radiolabeled substrate assay to quantify collagenase and gelatinase activity, HPLC quantitation of hydroxyproline and leucine deposition, and Western blot analysis. These methods have been modified to be applicable to analyze the small amounts of tissue and exudate material that can be obtained from these human sources. These studies will compare and contrast the normal mechanisms responsible for healing in healthy tissue to those mechanisms responsible for overhealing in keloids and underhealing in chronic ulcers.