Biologic Basis of Refractory Periodontal Disease

难治性牙周病的生物学基础

• 批准号: 6604158
• 负责人: Bruce J Paster
• 金额: $ 118.83万
• 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/6604158
• 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：本研究的长期目标是能够适当地 牙周病的治疗方法有哪些？ 目前，约15%的牙周炎患者无法通过常规治疗 并且被认为是“难治的”。“本申请检验了以下假设， 难治性牙周病与非难治性牙周病不同， 寻求前瞻性识别这些患者的方法。这些目标 四个具体目标。目的我将检验一个假设， 难治性疾病可以与可治疗的疾病区分开。 牙周炎和牙周健康的基础上微生物概况。龈下 将从28个研究中心采集斑块样本，每个研究中心至少80名受试者， 两组患者和40名健康人。样本将被分析 使用棋盘DNA分别形成大约120个分类群水平 杂交测定。疱疹病毒也将受到监测。意义 这一目标的目的是，它将确定这些物种（包括可培养的， 目前不可培养），用于区分难治性 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的疾病的受试者区分开， 牙周炎和牙周健康基于宿主因素，如血清 抗体水平的40个特定的牙周细菌和细胞因子的生产， 刺激后外周血单核细胞。这一目标的意义 是识别出区分疾病的关键宿主标记 群体与健康。Aim 3将开发人类口腔微生物微阵列， 检测600种可培养和不可培养的口腔细菌 口腔目标1中的微生物样品将使用 微阵列提供的基本上完全的微生物覆盖。这 微阵列将促进口腔生态学、传染病、 疾病和临床研究。该芯片具有明显的诊断价值。 目标4将使用综合临床、微生物和宿主数据来区分 难治性牙周炎与可治疗的牙周炎或健康无关， 识别难治性综合征。该项目的完成将填补主要 对总口腔植物群在难治性和 可治疗的牙周炎，以及细胞因子，趋化因子及其 受体。消除难治性疾病将对 提供牙周治疗的总成本。