Spectrum of NSD1 mutations in Sotos and Weaver syndromes

Interestingly, mental retardation was consistently more severe in patients with NSD1 deletions. Macrocephaly and facial gestalt but not overgrowth and advanced bone age were consistently observed in Sotos syndrome patients. We suggest therefore considering macrocephaly and facial gestalt as mandatory criteria for the diagnosis of Sotos syndrome and overgrowth and advanced bone age as minor criteria.     

Primary histiocytic sarcoma of the spleen associated with erythrophagocytic histiocytosis

We report an exceptional case of a histiocytic sarcoma presenting as a primary isolated spleen tumor in a 71-year-old woman. The neoplastic cells in the cords and sinuses of the red pulp formed multiple lobulated tumors, which were detected in vivo by ultrasound scan. The medium cells, large cells and the giant cells expressed CD68, a histiocyte-associated marker, lysozyme and S100 protein. All these cells were negative for B- and T-cell markers, cytokeratins, melanosome markers (HMB45) and CD1a (Langerhans' cells). Many tumor cells displayed strong erythrophagocytosis and sometimes lymphocytophagocytosis. In addition, numerous histiocytes with morphology indistinguishable from reactive macrophages also exhibited a strong erythrophagocytosis, and were found in the tumor as well as in the normal splenic parenchyma. Despite multi-agent chemotherapy, the patient suffered from a relapse in the liver, with a rapid fatal outcome. A literature review showed that such a primary splenic presentation with multiple tumors is rare. In contrast, in systemic malignant histiocytosis, secondary spleen involvement occurs more frequently but with diffuse infiltration. The association with a reactive histiocytosis with erythrophagocytosis corresponds to "histiocytic medullary reticulosis", as previously described by Scott and Robb-Smith.     

Immunodeficiency with low expression of the T cell receptor/CD3 complex. Effect on T lymphocyte activation.

We report the consequences of low expression of the T cell receptor (TcR)/CD3 complex by T lymphocytes from a 4-year-old boy with a mild immunodeficiency. TcR/CD3 expression was found to be deficient on both resting and activated T cells, using both anti-CD3 and anti-TcR alpha/beta monoclonal antibodies. As shown by immunofluorescence and immunoprecipitation studies, residual expression (corresponding to about 10% of normal) was detectable on resting and activated TcR alpha/beta+ T cells. Other T cell membrane receptors were normally expressed. The functional consequences of this TcR/CD3 expression deficiency included an absence of T cell proliferation, interleukin 2 receptor expression and calcium flux following anti-CD3 and anti-CD2 antibody-triggered T cell activation. Antigen (tetanus toxoid, Candida and allogeneic cell)-induced proliferation was detectable. In contrast, cytotoxic T cell activity towards allogeneic cells was deficient. These findings shed light on the function of the TcR/CD3 complex and indicate that the expression of a limited number of TcR/CD3 receptors may be sufficient to trigger antigen-specific T cell activation (and, possibly, differentiation) and that anti-CD3 antibody-induced T cell activation differs somewhat from antigen/major histocompatibility complex molecule-induced activation. These results also confirm that the CD2 pathway of T cell activation is CD3 dependent.     

Fast-induced changes in plasma glucose, insulin and free fatty acid concentration compared in rats during the night and day

Changes in PG, PI and PFFA were examined and compared in fed rats or after 0 to 12 hours of fasting, during the night or during the day. At night, a progressive decrease in PG and PI and an increase in PFFA were induced by 0 to 12 hours of food deprivation. During the light period a decrease in PG occurred only from the 6th hour of fasting. A slight, progressive increase in PFFA levels was induced from 0 to 12 hours of fasting, while no significant variation of PI levels was observed. The results are discussed in terms of relationships between blood glucose, PFFA levels, and food intake in control rats over the circadian cycle.     

A severe form of amyloidotic polyneuropathy in a Costa Rican family with a rare transthyretin mutation (Glu54Lys)

Four affected siblings in a Costa Rican family presented an aggressive polyneuropathy with widespread involvement of many visceral organs and onset during the third decade of life with rapid loss of muscle mass in the lower limbs and severe dysautonomy. The medical histories include vitreous opacity, cardiac enlargement, dermal and gastrointestinal infiltration, and autonomic dysfunction including circulatory compromise and gastrointestinal disturbances. Histological studies using Congo red stain and immunohistochemical assays with antibodies against the transthyretin (TTR) protein showed widespread deposition of amyloid in extracellular areas, including dermis and gastrointestinal lamina propia, endo- and perineural spaces, and vascular walls. A mutation search in the transthyretin (ttr) gene was performed seeking the cause of this severe form of familial amyloidotic polyneuropathy (FAP). We applied single-stranded conformational polymorphism (SSCP)-analyses followed by sequencing of the four exons of the ttr gene, revealing a point mutation in exon 3, a G to A transition that causes a Glu54Lys codon change. Western blots of plasma proteins incubated with anti-transthyretin antibodies after gel electrophoresis provided separation of wild-type and mutant TTR protein in affected family members.     

Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families

A genome-wide scan for asthma phenotypes was conducted in the whole sample of 295 EGEA families selected through at least one asthmatic subject. In addition to asthma, seven phenotypes involved in the main asthma physiopathological pathways were considered: SPT (positive skin prick test response to at least one of 11 allergens), SPTQ score being the number of positive skin test responses to 11 allergens, Phadiatop (positive specific IgE response to a mixture of allergens), total IgE levels, eosinophils, bronchial responsiveness (BR) to methacholine challenge and %predicted FEV(1). Four regions showed evidence for linkage (P相似文献   

磷酸化的细胞外信号调节蛋白激酶1/2在正常小鼠脑内的免疫细胞化学定位

细胞外信号调节蛋白激酶(ERK)1/2是重要的信号转导分子。现已知在正常动物的中枢神经系统内有其活化形式即磷酸化的ERK1/2(pERK1/2)分子的存在,但其在小鼠脑内的分布目前还没有全面的观察。本研究用免疫组织化学技术(ABC法)研究了pERK1/2样免疫反应阳性产物在脱臼处死的正常小鼠全脑内的分布。结果发现pERK1/2在正常小鼠脑内有广泛的表达,阳性产物主要存在于神经元,亦见于个别白质内的胶质细胞,脑膜及室管膜细胞也有表达。强阳性表达的核团主要有:岛皮质、视听皮质、边缘前皮质、扣带前皮质、海马垂直部、弓状核、蓝斑和小脑Purkinje细胞;中等阳性表达的核团主要有:感觉运动皮质、外侧隔区、内侧杏仁核、皮质杏仁核和外侧杏仁核、丘脑室旁核前部、视交叉上核、穹隆下器、终板血管器、前腹侧视前核和下丘脑背内侧核;弱阳性表达的核团主要有:视上核、下丘脑室旁核大细胞部、下丘脑后区、顶盖前区、室周灰质腹外侧柱、A5区、孤束核和延髓腹外侧网状结构等。本文结果观察到pERK1/2在正常小鼠脑内广泛存在,提示pERK1/2作为重要的信号转导分子,可能参与许多脑区在正常状态下的功能活动,揭示其分布特点为了解其在脑内的多样性功能提供了形态学依据。     

Characterization of a novel leucine-rich repeat protein antigen from group B streptococci that elicits protective immunity

Group B streptococci (GBS) usually behave as commensal organisms that asymptomatically colonize the gastrointestinal and urogenital tracts of adults. However, GBS are also pathogens and the leading bacterial cause of life-threatening invasive disease in neonates. While the events leading to transmission and disease in neonates remain unclear, GBS carriage and level of colonization in the mother have been shown to be significant risk factors associated with invasive infection. Surface antigens represent ideal vaccine targets for eliciting antibodies that can act as opsonins and/or inhibit colonization and invasion. Using a genetic screen for exported proteins in GBS, we identified a gene, designated lrrG, that encodes a novel LPXTG anchored surface antigen containing leucine-rich repeat (LRR) motifs found in bacterial invasins and other members of the LRR protein family. Southern blotting showed that lrrG was present in all GBS strains tested, representing the nine serotypes, and revealed the presence of an lrrG homologue in Streptococcus pyogenes. Recombinant LrrG protein was shown in vitro to adhere to epithelial cells in a dose-dependent manner, suggesting that it may function as an adhesion factor in GBS. More importantly, immunization with recombinant LrrG elicited a strong immunoglobulin G response in CBA/ca mice and protected against lethal challenge with virulent GBS. The data presented in this report suggest that this conserved protein is a highly promising candidate antigen for use in a GBS vaccine.     

Human ORFeome Version 1.1: A Platform for Reverse Proteomics

The advent of systems biology necessitates the cloning of nearly entire sets of protein-encoding open reading frames (ORFs), or ORFeomes, to allow functional studies of the corresponding proteomes. Here, we describe the generation of a first version of the human ORFeome using a newly improved Gateway recombinational cloning approach. Using the Mammalian Gene Collection (MGC) resource as a starting point, we report the successful cloning of 8076 human ORFs, representing at least 7263 human genes, as mini-pools of PCR-amplified products. These were assembled into the human ORFeome version 1.1 (hORFeome v1.1) collection. After assessing the overall quality of this version, we describe the use of hORFeome v1.1 for heterologous protein expression in two different expression systems at proteome scale. The hORFeome v1.1 represents a central resource for the cloning of large sets of human ORFs in various settings for functional proteomics of many types, and will serve as the foundation for subsequent improved versions of the human ORFeome.