Clinical/Therapeutic Studies Of Filariasis & Related Dis

为了更好地了解丝虫病(丝虫病、血吸虫病、淋巴丝虫病)的发病机制，对这些和其他相关非丝虫病(线虫病、疟疾)患者的临床评估进行了详细研究。此外，还详细介绍了治疗后的炎症反应及其诱导的潜在机制。特别是，控制嗜酸性粒细胞的诱导和细胞向治疗后炎症部位的运输已经被研究过。沃尔巴克氏菌内共生菌作为治疗靶标和炎症诱导剂的重要性也已详细介绍。 对嗜酸性粒细胞相关疾病发病机制的了解一直是我们临床相关研究的主要焦点，我们对多组高嗜酸性粒细胞患者(寄生虫感染、家族性高嗜酸性粒细胞增多症、特发性高嗜酸性粒细胞综合征、良性高嗜酸性粒细胞增多、发作性血管水肿伴嗜酸性粒细胞增多)进行了临床评估；此外，已对淋巴细胞(及其亚群)和嗜酸性粒细胞进行了功能和分子水平的检测(人体微阵列和RT-PCR)，以确定与血液和组织嗜酸性粒细胞增加相关的疾病所涉及的分子和途径。高嗜酸性粒细胞综合征和血清类胰蛋白酶水平升高的临床亚组患者被发现并显示出以男性为主、嗜酸性粒细胞激活、肥大细胞异常和组织纤维化为特征的骨髓增生性疾病。这种临床症状随后被证明与对甲磺酸伊马替尼的治疗反应和最近描述的融合酪氨酸激酶FIP1L1/PDGFRA的存在有关(Klion等人，血液，2004年)。相比之下，对家族性嗜酸性粒细胞增多症患者的详细临床和免疫学研究表明，尽管外周血嗜酸性粒细胞水平较高，但嗜酸性粒细胞相对缺乏激活，这与所研究患者的良性临床过程一致。

To understand better the pathogenesis of filarial infections (onchocerciasis, loiaisis, lymphatic filarasis) clinical assessments of patients with these and other related non-filarial (strongyloides, malaria) infections have been studied in detail. Moreover, the post-treatment inflammatory responses and the underlying mechanisms in their induction have been detailed. In particular, the control of eosinophil induction and cell trafficking to sites of post-treatment inflammation has been studied. The importance of the Wolbachia endosymbiont both as a therapeutic target and as a inducer of inflammation has been detailed as well. Understanding of the pathogenesis of eosinophil-related disorders has been a major focus of our clinically related studies Multiple groups of hypereosinophilic patients (parasite-infected, familial hypereosinophilia, idiopathic hypereosinophilic syndrome, benign hypereosinophilia, episodic angioedema with eosinophilia) have been assessed clinically; moreover, lymphocytes (and their subsets) and eosinophils have been examined functionally and at the molecular level (human microarrays and RT-PCR) to identify the molecules and pathways involved in conditions associated with increased blood and tissue eosinophilia. A clinical subgroup of patients with hypereosinophilic syndrome and elevated serum tryptase levels was identified and shown to have a myeloproliferative disorder characterized by male predominance, eosinophil activation, abnormal mast cells, and tissue fibrosis. This clinical syndrome was subsequently shown to correlate with therapeutic responsiveness to imatinib mesylate and the presence of a recently described fusion tyrosine kinase, FIP1L1/PDGFRA (Klion et al, Blood,2004). In contrast, a detailed clinical and immunologic study of patients with familial eosinophilia demonstrated a relative lack of eosinophil activation despite high levels of peripheral eosinophilia, consistent with the benign clinical course observed in the patients studied.