Biologic Basis of Refractory Periodontal Disease

难治性牙周病的生物学基础

• 批准号: 6657003
• 负责人: Bruce J Paster
• 金额: $ 19.33万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657003
• 关键词: Herpesviridae disease; bacteria characteristic; bacterial cytopathogenic effect; bacterial genetics; clinical research; cytokine; dental plaque; disease /disorder etiology; genetic markers; host organism interaction; human subject; microarray technology; oral bacteria; periodontitis; periodontium disorder; polymerase chain reaction; ribosomal RNA; syndrome; technology /technique development

DESCRIPTION: The long-term goal of this research is to be able to appropriately diagnose and successfully treat all patients with periodontal disease. Currently, about 15 percent of periodontitis patients fail conventional therapy and are deemed "refractory." This application examines the hypothesis that refractory disease is distinct from non-refractory periodontal disease, and seeks means for prospectively identifying these patients. These objectives are addressed in 4 Specific Aims. Aim I will test the hypothesis that subjects with refractory disease can be distinguished from subjects with treatable periodontitis and periodontal health based upon microbial profiles. Subgingival plaque samples will be taken from 28 sites from at least 80 subjects in each of the 2 diseased groups and 40 healthy subjects. The samples will be analyzed individually for levels of approximately 120 taxa using checkerboard DNA hybridization assays. Herpes viruses will also be monitored. The SIGNIFICANCE of this Aim is that it will identify those species (both cultivable and presently uncultivable) that are useful for distinguishing between refractory and treatable periodontitis, and health. Aim 2 will test the hypothesis that subjects with refractory disease can be distinguished from those with treatable periodontitis, and periodontal health based upon host factors, such as serum antibody levels to 40 specific periodontal bacteria and cytokine production by peripheral blood monocytes following stimulation. The SIGNIFICANCE of this Aim is the identification of key host markers that differentiate between disease groups and health. Aim 3 will develop a Human Oral Microbe Microarray for the detection of 600 cultivable and uncultivable oral species found in the human oral cavity. The microbial samples from Aim 1 will be reanalyzed using the essentially complete microbial coverage provided by this microarray. This microarray will facilitate other research efforts in oral ecology, infectious diseases, and clinical studies. The microarray has obvious diagnostic value. Aim 4 will use the combined clinical, microbial and host data to differentiate refractory periodontitis from treatable periodontitis or health, and to identify refractory syndromes. Completion of this project will fill in major gaps in knowledge of the role of the total oral flora in refractory and treatable periodontitis, and of the role of cytokines, chemokines and their receptors. Eliminating refractory disease would have an enormous impact on the total cost of delivering periodontal therapy.

描述：这项研究的长期目标是能够适当地 诊断并成功治疗所有牙周病患者。 目前，约 15% 的牙周炎患者常规治疗失败 并被认为是“难治性的”。该应用程序检验了以下假设： 难治性疾病与非难治性牙周病不同，并且 寻找前瞻性识别这些患者的方法。这些目标是 在 4 个具体目标中得到解决。目标 我将检验以下假设：受试者 难治性疾病可以与可治疗的受试者区分开来 基于微生物特征的牙周炎和牙周健康。龈下 斑块样本将从每个地点至少 80 名受试者的 28 个地点采集 2个患病组和40个健康受试者。样品将被分析 使用棋盘 DNA 分别针对约 120 个分类群的水平 杂交测定。疱疹病毒也将受到监测。意义 这个目标的目的是它将识别那些物种（可栽培的和 目前无法培养），可用于区分难治性 和可治疗的牙周炎，和健康。目标 2 将检验以下假设： 患有难治性疾病的受试者可以与患有可治疗疾病的受试者区分开来 牙周炎和基于宿主因素（例如血清）的牙周健康 40 种特定牙周细菌的抗体水平和细胞因子的产生 刺激后外周血单核细胞。这一目标的意义 是识别区分疾病的关键宿主标记 群体和健康。 Aim 3 将开发人类口腔微生物微阵列 检测人体中发现的 600 种可培养和不可培养的口腔物种 口腔。来自目标 1 的微生物样本将使用 该微阵列提供了基本上完整的微生物覆盖。这 微阵列将促进口腔生态学、传染病学等领域的其他研究工作 疾病和临床研究。微阵列具有明显的诊断价值。 目标 4 将结合临床、微生物和宿主数据来区分 来自可治疗牙周炎或健康的难治性牙周炎，以及 识别难治性综合征。该项目的完成将填补主要 关于口腔总菌群在难治性和难治性疾病中的作用的知识差距 可治疗的牙周炎，以及细胞因子、趋化因子及其作用 受体。消除难治性疾病将对人类产生巨大影响 提供牙周治疗的总费用。