大肠肿瘤细胞凋亡及相关基因表达的研究

为了探讨Ｂｃｌ－２和Ｐ５３蛋白在大肠肿瘤中的表达及与细胞凋亡的关系，用免疫组化方法观察了４５例大肠腺瘤和６１例大肠癌中Ｂｃｌ－２和Ｐ５３蛋白的表达。正常大肠粘膜中Ｂｃｌ－２和Ｐ５３均未见表达，而大肠腺瘤及大肠癌阳性率均较正常明显增加（Ｐ〈０．０１）。大肠腺瘤Ｐ５３表达随腺瘤大小增加而增加，其中≥２０ｍｍ组阳性率（７７．７８％）显著高于〈１０ｍｍ组（３５．００％，Ｐ〈０．０５）。Ｐ５３蛋白阳性率也随     

高半胱氨酸蛋白61与自身免疫性疾病

高半胱氨酸蛋白61(cysteine rich 61,Cyr61)是即刻早期基因表达蛋白,受到血清生长因子刺激后可在数分钟内活化并转录。Cyr61通过直接与细胞表面整合素受体结合而发挥作用。Cyr61可参与炎性反应过程,促进血管形成或协同细胞因子间作用。Cyr61可介导滑膜细胞的增殖,促进滑膜细胞产生白细胞介素(interleukin,IL)-6、IL-8等炎性细胞因子,并在辅助性T细胞(helper T cell,Th)17分化和中性粒细胞浸润中发挥一定作用。Cyr61在炎症性肠病、IgA肾病、糖尿病肾病、Graves眼病中的作用均有研究。另外,Cyr61也不同程度参与了胚胎发育、创伤修复、血管疾病、肿瘤等过程。     

Use of a glucose controlled insulin infusion system (artificial beta cell) to control diabetes during surgery

Summary An artificial beta cell has been used to achieve and maintain a preset plasma glucose concentration in five diabetic patients undergoing surgery. These subjects were compared to control groups of normal subjects receiving either saline or glucose, and diabetics receiving glucose intraoperatively. Hyperglycaemia during surgery was seen in normals (mean plasma glucose ± SEM: 185±16 mg/dl) and, to a greater degree, diabetics (247±36 mg/dl) receiving glucose. Insulin and C-peptide levels did not increase during 2 hours of operation in any of the control groups, suggesting beta cell suppression during surgery. As C-peptide levels declined similarly in normal subjects whether they received saline or glucose, the hyperglycaemia seems to be due to an inability to use exogenous glucose. This is confirmed by a correlation of maximal plasma glucose to glucose infusion rate (r = 0.78, p<0.01). The artificial beta cell was able to achieve the same plasma glucose after 2 hours of operation (128±21 mg/dl) as normal subjects receiving saline (110±7 mg/dl). The artificial beta cell proved to be a safe, convenient and effective way of monitoring and controlling the hyperglycaemia seen in diabetic patients undergoing surgery.     

Retinoids suppress cysteine-rich protein 61 (CCN1), a negative regulator of collagen homeostasis, in skin equivalent cultures and aged human skin in vivo

Alterations in connective tissue collagen are prominent features of both chronologically aged and photoaged (ageing because of sun exposure) human skin. These age-related abnormalities are mediated in part by cysteine-rich protein 61 (CCN1). CCN1 is elevated in the dermis of both chronologically aged and photoaged human skin in vivo and promotes aberrant collagen homeostasis by down-regulating type I collagen, the major structural protein in skin, and promoting collagen degradation. Vitamin A and its metabolites have been shown to improve chronologically aged and photoaged skin by promoting deposition of new collagen and preventing its degradation. Here, we investigated regulation of CCN1 expression by retinoids in skin equivalent cultures and chronologically aged and photoaged human skin in vivo. In skin equivalent cultures, all-trans retinoic acid (RA), the major bioactive form of vitamin A in skin, significantly increased type I procollagen and reduced collagenase (matrix metalloproteinases-1, MMP-1). Addition of recombinant human CCN1 to skin equivalent cultures significantly reduced type I procollagen and increased MMP-1. Importantly, RA significantly reduced CCN1 expression in skin equivalent cultures. Topical treatment with retinol (vitamin A, 0.4%) for 7days significantly reduced CCN1 mRNA and protein expression in both chronologically aged (80+years) and photoaged human skin in vivo, compared to vehicle-treated skin. These data indicate that the mechanism by which retinoids improve aged skin, through increased collagen production, involves down-regulation of CCN1.     

Head region of unconventional myosin I family members is responsible for the organ‐specificity of their roles in left–right polarity in Drosophila

In Drosophila, Myosin31DF (Myo31DF), encoding a Myosin ID protein, has crucial roles in left–right (LR) asymmetric development. Loss of Myo31DF function leads to laterality inversion for many organs, including the embryonic gut. Here, we found that Myo31DF was required before LR asymmetric morphogenesis in the hindgut, suggesting it functions in LR patterning instead of directly in hindgut morphological changes. Myosin61F (Myo61F) encodes another Myosin I, and Myo31DF or Myo61F overexpression reverses the laterality of different organs. Myo31DF and Myo61F have domains conserved in Myosin proteins, particularly in the proteins' head regions. We studied the roles of these domains in LR patterning using overexpression analysis. The Actin‐binding and ATP‐binding domains were essential for both proteins, but the IQ domains, binding sites for Myosin light chains, were required only by Myo31DF. Our results also suggest that the organ specificities of the Myo31DF and Myo61F activities depended on their head regions. Developmental Dynamics 237:3528–3537, 2008. © 2008 Wiley‐Liss, Inc.