CHARACTERIZATION OF THE PATHOGENESIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM)

淋巴管平滑肌瘤病 (LAM) 发病机制的特征

• 批准号: 6290430
• 负责人: Joel Moss
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290430
• 关键词: antigen antibody reaction; ascites; cellular pathology; clinical research; dyspneas; glycoproteins; histopathology; human subject; immunocytochemistry; immunoelectron microscopy; leiomyoma; lung; monoclonal antibody; northern blottings; oncoproteins; pneumothorax disorder; respiratory reflex; smooth muscle

Lymphangioleiomyomatosis (LAM) is a multisystem disorder characterized by cystic lung disease and abdominal tumors (lymphangiomyomas and angiomyolipomas). The disease, which presents almost exclusively in women of childbearing age, is characterized by the proliferation of abnormal smooth muscle containing premelanosomal structures similar to those found in melanoma cells. A clinical protocol has enabled the Branch to assemble a large cohort of patients with LAM and to document the natural history of the disease, the histopathological findings, the radiographic abnormalities, and characteristic pulmonary function abnormalities. It has enabled us to obtain tissue to examine gene expression and cell regulatory pathways. We have been able to grow LAM cells from lungs of patients with LAM, obtained at transplant or autopsy. Cells from angiomyolipoma, obtained immediately following surgical removal are also growing in culture. Several clinical observations have changed clinical care for patients with LAM. First, patients were found to have an increased frequency of bone loss, with about 80% of patients exhibiting either osteopenia or osteoporosis. Second, patients with LAM have been known to develop pleural and pericardial effusions. Closer analysis of patients with pericardial effusions revealed that they may develop constrictive pericarditis. Third, patients with LAM are known to have abdominal tumors termed lymphangiomyomas. The tumors are benign. However, we have observed that their enlargement may result in neurological compromise in the lower extremities, abdominal bloating, peripheral edema, and lymphedema. Fourth, we have observed that a high percentage of patients with LAM have airway hyperresponsiveness. - lymphangioleiomyomatosis, cystic lung disease, osteoporosis,asthma - Human Subjects

淋巴管肌瘤病（LAM）是一种多系统疾病，其特征是囊性肺部疾病和腹部肿瘤（淋巴管肌瘤和血管肌层瘤）。该疾病几乎完全是在生育年龄的女性中，其特征是含有异常平滑肌的含有类似于黑色素瘤细胞的平滑肌的异常。临床方案使分支机构能够组装大量患有LAM的患者，并记录疾病的自然病史，组织病理学发现，X射线学异常和特征性的肺功能异常。它使我们能够获得组织能够检查基因表达和细胞调节途径。我们已经能够在移植或尸检时从患有LAM的患者的肺中种植LAM细胞。手术去除后立即获得的血管肌肌瘤的细胞在培养中也在增长。几种临床观察已改变了LAM患者的临床护理。首先，发现患者的骨质流失频率增加，大约80％的患者表现出骨质减少或骨质疏松症。其次，已知LAM患者会出现胸膜和心包积液。对心包积液患者的仔细分析表明，他们可能会出现紧缩的心包炎。第三，已知LAM患者的腹部肿瘤称为淋巴管瘤。肿瘤是良性的。但是，我们已经观察到它们的扩大可能导致下肢，腹腔，周围水肿和淋巴肿的神经系统妥协。第四，我们观察到，LAM患者的比例很高，具有气道高反应性。 - 淋巴血管瘤病，囊性肺病，骨质疏松症，哮喘 - 人类受试者