CHARACTERIZATION OF THE PATHOGENESIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM)

淋巴管肌瘤病(LAM)是一种以囊性肺疾病和腹部肿瘤(淋巴管肌瘤和血管肌脂肪瘤)为特征的多系统疾病。这种疾病几乎只出现在育龄妇女身上，其特征是含有与黑色素瘤细胞相似的黑素体前结构的异常平滑肌的增殖。临床方案使该科能够收集大量LAM患者，并记录该疾病的自然病史、组织病理学结果、放射学异常和特有的肺功能异常。它使我们能够获得组织来检测基因表达和细胞调控途径。我们已经能够从LAM患者的肺中培养LAM细胞，这些细胞是在移植或尸检时获得的。手术切除后立即获得的血管肌脂肪瘤细胞也在培养中生长。一些临床观察改变了LAM患者的临床护理。首先，发现患者骨质丢失的频率增加，约80%的患者表现出骨量减少或骨质疏松。其次，已知LAM患者会出现胸腔积液和心包积液。对心包积液患者的进一步分析显示，他们可能发展为缩窄性心包炎。第三，众所周知，LAM患者患有称为淋巴管肌瘤的腹部肿瘤。肿瘤是良性的。然而，我们观察到，它们的增大可能会导致下肢神经损害、腹胀、外周水肿和淋巴水肿。第四，我们观察到LAM患者有很高比例的呼吸道高反应性。-淋巴管肌瘤病、囊性肺病、骨质疏松症、哮喘-人类受试者

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