CRYSTAL INTERACTIONS IN RENAL STONE DISEASE

尿石症可能有许多诱因。 肾脏形成中的一些具体机制步骤 石头还没有确定下来。一旦离子的浓度 和/或大分子已达到过饱和状态 结晶性尿存在于尿路中，并形成 结石可以通过多方面的过程发生。这些步骤 包括上皮细胞对微晶的保留 膜和通过聚集生长、基质粘合、外延 相互作用和/或聚集。 本研究方案有三个主要的具体目的：一)研究 微晶的保留率研究 大鼠肾脏晶体的形成及其与晶体的结合 原代培养的髓/乳头(RMP)细胞。Ii)学习 晶体间外延相互作用的可能作用 肾结石中观察到的结构。三)研究 基质与结晶度对反应机理的影响 肾结石的重组和成熟。 在特定的目标I中，我们将质疑RMP根尖细胞表面是否可以 是肾结石结晶成核的成核点吗？做 预制的肾结石晶体结合于RMP的根尖表面 原代培养中的细胞？这些是水晶膜吗？ 受抑制剂影响的相互作用，是否会破坏晶体 RMP细胞及其膜？ 在特定目标二中，我们将研究可能的外延相互作用。 使用我们的程序EPITAX的肾结石晶体和Will 以实时和三维方式对这些交互进行建模 使用复杂的计算机图形技术。 在特定的目标III中，我们将利用收到的人类肾结石 由国家VA晶体鉴定中心研究 石材成熟的机制。我们将确定石头是否 通过两步结晶过程成熟，其中基质是 在重结晶和成熟过程中挤压。另外，学位 结晶度的大小将与形成的晶体类型相关 以及基质含量和组成。

Urolithiasis can have numerous predisposing etiologic factors. Some of the specific mechanistic steps in the formation of kidney stones have not been determined. Once the concentration of ions and/or macromolecules has reached supersaturation, a state of crystalluria exists within the urinary tract, and the formation of stones can occur through a multifaceted process. These steps include retention of the microcrystallites by the epithelial membranes, and growth by aggregation, matrix adhesion, epitaxial interactions, and/or agglomeration. This research proposal has three major Specific Aims: I) To study the retention of microcrystals by investigating the processes of crystal formation on and crystal binding to rat renal medullary/papillary (RMP) cells in primary culture. II) To study the possible role of epitaxial interactions between crystal structures observed in renal stones. III) To study the role of matrix and the degree of crystallinity on the mechanism of reorganization and maturation of renal stones. In Specific Aim I, we will question if RMP apical cell surfaces can serve as nucleation sites for kidney stone crystal nucleation? Do preformed renal stone crystals bind to the apical surface of RMP cells in primary culture? Are these crystal-membrane interactions influenced by inhibitors, and do the crystals damage RMP cells and their membranes? In Specific Aim II, we will study possible epitaxial interactions between renal stone crystals using our program EPITAX, and will model these interactions in real-time and in three-dimensions using sophisticated computer graphics. In Specific Aim III, we will utilize human kidney stones received by the National VA Crystal Identification Center to study the mechanism of stone maturation. We will determine if stones mature by a two-stage crystallization process where matrix is extruded during recrystallization and maturity. Also, the degree of crystallinity will be correlated with the type of crystal formed and matrix content and composition.