PATHWAYS TO PRE-TERM BIRTH

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。早产是指胎儿过早分娩，在妊娠37周之前（正常为40-42周）。这是新生儿发病和死亡的主要原因，在美国约有12%的孕妇发生。这些婴儿也更容易受到长期影响，如肥胖，糖尿病和心脏病，甚至进入成年期。这对少数民族造成了不成比例的影响，因此他们更有可能遭受终身后果。夏威夷土著人的婴儿死亡率最高，其次是夏威夷的菲律宾人。来自March of Dimes组织的令人震惊的数据显示，1991年至2001年期间，夏威夷的早产率增加了24%以上。我们已经确定了一种新的蛋白质称为前B细胞集落增强因子（PBEF），我们在1998年克隆，并继续与夏威夷社区基金会的支持下工作。我们相信，这种不寻常的分子是引发早产的程序中的关键角色。我们即将展示它在这一过程中的作用，现在已经有了合适的人员，独特的试剂和方法，能够实现重大突破。这不仅将为临床社区提供更好的理解，而且将允许开发更好的早产诊断方法，从而更好地预防。本申请解决了一个主要目的，其被设计为建立PBEF在胎膜中的作用机制以启动早产途径。 这些研究将大大增加我们对早产的理解，并将导致在临床上有价值的预防方法方面取得一些重要进展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Preterm birth is when the fetus is delivered too early, before 37 weeks gestation (normal is 40-42 weeks). This is a major cause of neonatal morbidity and death and occurs in about 12% of all pregnancies in the USA. These babies are also more prone to long term effects, like obesity, diabetes and heart disease, even into adulthood. This disproportionately affects ethnic minorities and they are therefore more likely to suffer the lifelong consequences. Native Hawaiians suffer the highest infant mortality rate, followed by the Filipino population in Hawaii. Alarming data from the March of Dimes organization shows that preterm births in Hawaii increased more than 24% between 1991 and 2001. We have identified a novel protein called Pre B Cell Colony Enhancing Factor (PBEF) which we cloned in 1998 and have continued to work on with support from the Community Foundation of Hawaii. We believe that this unusual molecule is a key player in the program which initiates preterm birth. We are close to demonstrating its role in this process and have now got the personnel in place, the unique reagents and methods available to be able to accomplish a major breakthrough. This will not only provide the clinical community with better understanding, but will allow the development of better methods of preterm labor diagnosis and thus a better chance of prevention. This application addresses one main aim which is designed to establish the mechanism of PBEF action in the fetal membranes to initiate the pathway to preterm labor. These studies will significantly increase our understanding of preterm birth and will lead to some important advances in clinically valuable approaches to its prevention.