Clinical/Therapeutic Studies Of Filariasis & Related Dis

为了更好地了解丝虫感染（盘尾丝虫病、洛伊斯病、淋巴丝虫病）的发病机制，对这些和其他相关非丝虫（类圆线虫病、疟疾）感染患者的临床评估进行了详细研究。此外，治疗后的炎症反应及其诱导的潜在机制已被详细说明。特别是，已经研究了嗜酸性粒细胞诱导和细胞运输到治疗后炎症部位的控制。Wolbachia内共生体作为治疗靶点和作为炎症诱导剂的重要性也已详细说明。 了解嗜酸性粒细胞相关疾病的发病机制一直是我们临床相关研究的主要焦点。（寄生虫感染、家族性嗜酸性粒细胞增多症、特发性嗜酸性粒细胞增多综合征、良性嗜酸性粒细胞增多症、发作性血管性水肿伴嗜酸性粒细胞增多症）进行了临床评估;此外，本发明还淋巴细胞（及其亚群）和嗜酸性粒细胞的功能和分子水平进行了研究（人类微阵列和RT-PCR）来鉴定与增加的血液和组织嗜酸性粒细胞增多相关的病症中涉及的分子和途径。嗜酸性粒细胞增多综合征和血清类胰蛋白酶水平升高的患者的临床亚组被确定，并显示具有骨髓增生性疾病，其特征在于男性占优势，嗜酸性粒细胞活化，异常肥大细胞和组织纤维化。随后显示该临床综合征与甲磺酸伊马替尼的治疗响应性和最近描述的融合酪氨酸激酶FIP 1 L1/PDGFRA的存在相关（Klion等人，Blood，2004）。相反，一项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，尽管外周嗜酸性粒细胞增多水平较高，但嗜酸性粒细胞活化相对缺乏，这与研究患者中观察到的良性临床病程一致。

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.