Survey of the Distribution of a Newly Characterized Receptor for Advanced Glycation End Products in Tissues

Advanced glycation end products (AGEs), the final products of nonenzymatic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes. A novel integral membrane protein, termed receptor for AGE (RAGE), forms a central part of the cell surface binding site for AGEs. Using monospecific, polyclonal antibody raised to human recombinant and bovine RAGE, immunostaining of bovine tissues showed RAGE in the vasculature, endothelium, and smooth muscle cells and in mononuclear cells in the tissues. Consistent with these data, RAGE antigen and mRNA were identified in cultured bovine endothelium, vascular smooth muscle, and monocyte-derived macrophages. RAGE antigen was also visualized in bovine cardiac myocytes as well as in cultures of neonatal rat cardiac myocytes and in neural tissue where motor neurons, peripheral nerves, and a population of cortical neurons were positive. In situ hybridization confirmed the presence of RAGE mRNA in the tissues, and studies with rat PC12 pheochromocytes indicated that they provide a neuronal-related cell culture model for examining RAGE expression. Pathological studies of human atherosclerotic plaques showed infiltration of RAGE-expressing cells in the expanded intima. These results indicate that RAGE is present in multiple tissues and suggest the potential relevance of AGE-RAGE interactions for modulating properties of the vasculature as well as neural and cardiac function, prominent areas of involvement in diabetes and in the normal aging process.     

Early embryonic expression patterns of the mouse Flamingo and Prickle orthologues.

The Drosophila melanogaster proteins Flamingo and Prickle act in the planar cell polarity (PCP) pathway, which is required for acquisition of epithelial polarity in the wing, eye, and epidermis. In mammals, PCP signaling has been shown to regulate cell movements and polarity in a variety of tissues. Here, we show that the murine Flamingo orthologues Celsr1-3 and the Prickle orthologues Prickle1, Prickle2, and Testin have dynamic patterns of expression during pregastrulation and gastrulation stages. Celsr1 is expressed in the anterior visceral endoderm and nascent mesoderm, Celsr2 and Celsr3 mark the prospective neuroectoderm, Prickle1 is expressed in the primitive streak and mesoderm, Prickle2 in the node, and Testin in the anterior visceral endoderm, the extraembryonic ectoderm, primitive streak, and mesoderm. Analysis of a gene-trap mutation in Testin indicates that this gene is not required for embryogenesis; therefore, other Prickle homologues may compensate for its function during development.     

Replication error phenotype and p53 gene mutation in lymphomas of mucosa-associated lymphoid tissue.

Low grade mucosa-associated lymphoid tissue (MALT) lymphomas commonly arise from a background of chronic inflammatory lesions and can transform into high grade tumors at a late stage. Because chronic inflammation is closely associated with genetic instability, which is one of the mechanisms leading to activation of oncogenes and inactivation of tumor suppressor genes, it is possible that genetic instability plays an important role in MALT lymphomagenesis. In this study, we have examined the frequency of replication error (RER+) phenotype, a newly defined manifestation of genetic instability, and its relationship to p53 mutations in 40 MALT lymphomas (16 high grade and 24 low grade). RER+ phenotype was detected in 21/40 (52.5%) MALT lymphomas (12/24, 50% in low grade; 9/16, 56.2% in high grade). Five of seven reactive lymphoid infiltrates adjacent to tumors also showed one microsatellite alteration, four of which were identified in the corresponding lymphoma lesions in the same patient. In five RER+ high grade lymphomas with low grade lesions, homogeneous and heterogeneous microsatellite alterations were observed between the two components. The same 40 cases were investigated for p53 gene mutations at exons 5 to 8 by PCR-SSCP and direct sequencing. p53 point mutations were found in 11 (27.5%) of the 40 cases. These mutations were statistically related to RER+ phenotype (P < 0.05). Our results demonstrate that the RER+ phenotype is a common genetic feature of MALT lymphomas. Genetic instability occurs throughout the spectrum of the lymphoma development and may be related to the accumulation of genetic aberrations such as p53 mutations. The observation of identical microsatellite alterations between the adjacent lymphoid infiltrates and their corresponding lymphomas provides genetic evidence for evolutionary link of the two lesions. The homogeneous and heterogeneous microsatellite alterations observed between low and high grade components indicate their clonal lineage and genetic diversity.     

Alpha-smooth muscle actin as a marker for soft tissue tumours: a comparison with desmin

The immunoreactivity of a range of vascular and non-vascular smooth muscle tumours, rhabdomyosarcomas, and non-myoid lesions has been examined with the use of a monoclonal antibody to smooth muscle-specific actin and the muscle intermediate filament, desmin. In all cases of smooth muscle-derived tumours, the alpha-actin antibody yielded superior results. Staining of the myofibroblasts of fibromatoses was also seen. In contrast to desmin, immunoreactivity was not exhibited by rhabdomyosarcomas. We propose that this monoclonal antibody to alpha-smooth muscle actin is a useful addition to the panel of reagents used for the characterization of soft tissue proliferations and tumours. The technical aspects of the application of this monoclonal antibody to immunohistochemistry are discussed.     

低温保存内生致热原对其致热活性的影响

本实验用家兔全血加精制大肠杆菌内毒素，体外培养提取粗制家兔内生致热原。给大鼠静脉注射复制发热模型，观察了不同温度保存和不同时间保存的ＥＰ对其致热活性的影响。结果表明：４℃保存３天，－４０℃保存３天，７天，３０天和１８０天的ＥＰ与４℃保存１天的ＥＰ比较，其发热第一时相发热峰值和１小时体温反应指数均无显著性差异（Ｐ＜０．０５）。发热第二时相△Ｔ和第二时相１小时ＴＲＩ，在４℃保存３天和－４０℃保存３天，     

STAT3 couples with 14-3-3σ to regulate BCR signaling,B-cell differentiation,and IgE production

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32例再生障碍性贫血的微循环及血液粘度

对３２例再障患者的甲襞、球结膜微循环及血粘度进行观察，结果表明：再障组均有不同程度的微循环异常改变（１００％），与正常对照组比较差异显著（Ｐ＜０．０１）；再障组全血粘度、全血还原粘度明显低于正常对照组（Ｐ＜０．０１），再障患者的Ｈｂ与全血粘度及血浆比粘度呈正相关。     

云南省傣族G6PD一个家系的突变型研究

在调查云南少数民族Ｇ６ＰＤ缺乏症时，采用Ｇ６ＰＤ硝基四氮唑蓝纸片法筛查，按ＷＨＯ标准化方法进行生化变异型鉴定，再用错配碱基ＰＣＲ引入酶切位点法进行ＤＮＡ突变型研究，首次在傣族中发现Ｇ６ＰＤｃＤＮＡ突变型：１３８８Ｇ→Ａ。     

A novel active L1 retrotransposon subfamily in the mouse

Unlike human L1 retrotransposons, the 5' UTR of mouse L1 elements contains tandem repeats of approximately 200 bp in length called monomers. Multiple L1 subfamilies exist in the mouse which are distinguished by their monomer sequences. We previously described a young subfamily, called the T(F) subfamily, which contains approximately 1800 active elements among its 3000 full-length members. Here we characterize a novel subfamily of mouse L1 elements, G(F), which has unique monomer sequence and unusual patterns of monomer organization. A majority of these G(F) elements also have a unique length polymorphism in ORF1. Polymorphism analysis of G(F) elements in various mouse subspecies and laboratory strains revealed that, like T(F), the G(F) subfamily is young and expanding. About 1500 full-length G(F) elements exist in the diploid mouse genome and, based on the results of a cell culture assay, approximately 400 G(F) elements are potentially capable of retrotransposition. We also tested 14 A-type subfamily elements in the assay and estimate that about 900 active A elements may be present in the mouse genome. Thus, it is now known that there are three large active subfamilies of mouse L1s; T(F), A, and G(F), and that in total approximately 3000 full-length elements are potentially capable of active retrotransposition. This number is in great excess to the number of L1 elements thought to be active in the human genome.