ABNORMALITIES IN FIBROBLASTS OF SCHIZOPHRENIC PATIENTS

成纤维细胞系已被用于阐明其病理生理机制。 可能与中枢神经系统功能障碍相关的机制 神经精神病患者。在初步研究中，我们发现 参数(初始生长和生长速率)和形态(大小、形状 和定向)的已建立的成纤维细胞 双相情感障碍患者与正常人有明显不同。成纤维细胞 患者的生长速度比对照组的成纤维细胞慢得多。 我们建议在两年内进行皮肤活检，以获得 20例精神分裂症和20例躁郁症患者的成纤维细胞系 两组患者都将在皮肤出现问题时停用抗精神病药 活组织检查，以及年龄、性别和种族相匹配的20名正常对照。这个 具体目标是：1.建立皮肤原代细胞系 成纤维细胞，并用SV-40转化细胞使其永生化 建立成纤维细胞储存库，未来将进行扩容 数年，以供长期使用。2.建立生长参数(初始 成纤维细胞原代培养的生长、生长率和形态 精神分裂症患者的永生培养并将其与 双相情感障碍患者和正常人成纤维细胞培养的生长参数 控制。在培养中改变的细胞生长模式可能是 表明可能的遗传/代谢变化。3.识别 与异常生长参数相关的可能分子机制： 对塑料基质的粘附力、纤维连接蛋白水平和 对生长因子的生长反应，例如表皮生长因子和 将对成纤维细胞生长因子进行研究。因此，这些文化将 对相关生化变异性的研究具有潜在的实用价值 中枢神经系统可能与特定的神经病理和/或可能 精神分裂症患者的行为改变。

Fibroblast cell lines have been used to elucidate the pathophysiological mechanisms that may be relevant to central nervous system dysfunction in neuropsychiatric patients. In a preliminary study, we found growth parameters (initial growth and rate of growth) and morphology (size, shape and orientation) of the established fibroblasts of both schizophrenic and bipolar patients to markedly differ from normal subjects. Fibroblasts of patient grew at a much slower rate than fibroblasts of controls. We propose to conduct over a two year period, skin biopsies for obtaining fibroblast cell lines in 20 schizophrenic patients and 20 bipolar patients, both patient groups will be off neuroleptic treatment at the time of skin biopsies, and 20 normal controls matched for age, sex and ethnicity. The specific aims will be: 1. To establish primary cell-lines of skin fibroblasts, and immortalize them by cell transformation with SV-40 to establish a fibroblast cell depository, which will be expanded in future years, for their long-term use. 2. To establish growth parameters (initial growth, rate of growth and morphology) of fibroblast primary cultures and immortalized cultures from schizophrenic patients and compare them to growth parameters in fibroblast cultures from bipolar patients and normal controls. The altered growth patterns of cells in culture may be indicative of possible genetic/metabolic alterations. 3. To identify the possible molecular mechanisms associated with abnormal growth parameters: the adhesiveness to plastic substratum, the levels of fibronectin and the growth response to growth factors, e.g. epidermal growth factor and fibroblast growth factor will be studied. Thus, these cultures would potentially be useful for the study of relevant biochemical variability in CNS that may be associated with specific neuropathological and/or possibly behavioral changes in schizophrenic patients.