Baxter J D
Metabolic Research Unit, University of California, San Francisco.
Med Clin North Am. 1991 Jan;75(1):41-59. doi: 10.1016/s0025-7125(16)30471-0.
Advances in molecular biology research continue to have a major impact on clinical medicine. These advances have provided a means to produce proteins previously available in limited supply and allow for the production of novel proteins that are improved agonists or else antagonists with greater specificity for therapeutic targets. Newer drug delivery systems should facilitate delivery of these proteins. By combining the capabilities to produce drug targets in acceptable quantities with improved methods for determining the three-dimensional structures of these targets, novel organic therapeutic molecules that act on these targets will be designed. Gene transfer therapy using genes that express important proteins or that encode "antisense" RNAs that inhibit the translation of specific mRNAs will soon become a reality. The use of RFLPs and PCR methodologies promises increased means to diagnose specific genetic diseases and infections. Most importantly, molecular biology is helping to understand the mechanisms of disease such that novel diagnostic and therapeutic approaches can be described. These advances are providing an understanding of the mechanisms involved in cancers of the thyroid gland. They have already led to an enhanced understanding of (1) the growth factors that control proliferation of the thyroid gland, (2) the potential steps in thyroid nodule and neoplasia development, (3) particular mutations that may occur as thyroid cancers develop, (4) oncogenes that are expressed in thyroid cancers, and (5) the genetic defects that are responsible for thyroid gland malignancies in the multiple endocrine neoplasia (MEN) syndromes. With the latter, the RFLP technology has already provided an enhanced means to diagnose the disorder. With further progress, enhanced means for diagnosis and treatment should emerge. Molecular biology techniques are contributing to an increased understanding of the mechanisms of development of autoimmune thyroid disease as with Graves' disease and Hashimoto's thyroiditis. The potential role of infections, histocompatibility antigens, thyroid gland and extraglandular antigens, immune modulators, subpopulations of T-cells such as suppressor and helper cells, other cells involved in immune responses, and a combination of influences of several different functions on the thyroid gland are being defined. This knowledge should soon suggest improved means for diagnosis and treatment. Understanding of the function of the thyroid hormone receptors should have clinical importance. This knowledge suggests a means to develop thyroid hormone antagonists that may be used to more rapidly ameliorate the effects of hyperthyroidism and could be useful in nonthyroidal disorders such as cardiac arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS)
分子生物学研究的进展继续对临床医学产生重大影响。这些进展提供了一种手段来生产以前供应有限的蛋白质，并允许生产新型蛋白质，这些蛋白质是改进的激动剂或对治疗靶点具有更高特异性的拮抗剂。更新的药物递送系统应有助于这些蛋白质的递送。通过将以可接受的量生产药物靶点的能力与确定这些靶点三维结构的改进方法相结合，将设计出作用于这些靶点的新型有机治疗分子。使用表达重要蛋白质或编码抑制特定mRNA翻译的“反义”RNA的基因进行基因转移治疗很快将成为现实。限制性片段长度多态性（RFLP）和聚合酶链反应（PCR）方法有望增加诊断特定遗传疾病和感染的手段。最重要的是，分子生物学有助于理解疾病机制，从而能够描述新的诊断和治疗方法。这些进展有助于理解甲状腺癌的发病机制。它们已经使人们对以下方面有了更深入的了解：（1）控制甲状腺增殖的生长因子；（2）甲状腺结节和肿瘤形成的潜在步骤；（3）甲状腺癌发生时可能出现的特定突变；（4）甲状腺癌中表达的癌基因；（5）多内分泌腺瘤（MEN）综合征中导致甲状腺恶性肿瘤的遗传缺陷。对于后者，RFLP技术已经提供了一种更好的诊断该疾病的手段。随着进一步的进展，应该会出现更好的诊断和治疗手段。分子生物学技术有助于人们更多地了解自身免疫性甲状腺疾病如格雷夫斯病和桥本甲状腺炎的发病机制。感染、组织相容性抗原、甲状腺和腺外抗原、免疫调节剂、T细胞亚群（如抑制细胞和辅助细胞）、参与免疫反应的其他细胞以及几种不同功能对甲状腺的综合影响的潜在作用正在被确定。这些知识很快将为诊断和治疗提供改进方法。对甲状腺激素受体功能的了解应具有临床重要性。这一知识提示了一种开发甲状腺激素拮抗剂的方法，这些拮抗剂可用于更迅速地改善甲状腺功能亢进的影响，并可能对心律失常等非甲状腺疾病有用。（摘要截选至400字）
