Showing papers by "Roger A. Schultz published in 2006"

A Tlr7 translocation accelerates systemic autoimmunity in murine lupus.

Abstract: The y-linked autoimmune accelerating (yaa) locus is a potent autoimmune disease allele. Transcription profiling of yaa-bearing B cells revealed the overexpression of a cluster of X-linked genes that included Tlr7. FISH analysis demonstrated the translocation of this segment onto the yaa chromosome. The resulting overexpression of Tlr7 increased in vitro responses to Toll-like receptor (TLR) 7 signaling in all yaa-bearing males. B6.yaa mice are not overtly autoimmune, but the addition of Sle1, which contains the autoimmune-predisposing Slam/Cd2 haplotype, causes the development of fatal lupus with numerous immunological aberrations. B6.Sle1yaa CD4 T cells develop the molecular signature for TFH cells and also show expression changes in numerous cytokines and chemokines. Disease development and all component autoimmune phenotypes were inhibited by Sles1, a potent suppressor locus. Sles1 had no effect on yaa-enhanced TLR7 signaling in vitro, and these data place Sles1 downstream from the lesion in innate immune responses mediated by TLR7, suggesting that Sles1 modulates the activation of adaptive immunity in response to innate immune signaling.

Translocation (4;19)(q35;q13.1)-associated primitive round cell sarcoma: report of a case and review of the literature.

Abstract: We report the 4th case of a primitive round cell sarcoma with the translocation (4;19)(q35;q13.1) as the primary cytogenetic abnormality. This undifferentiated sarcoma shows some features of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), including a diffuse reactivity for FLI1, but it shows only focal and weak reactivity for CD99 and is negative for a rearrangement of EWS, the molecular signature of ES/PNET. Recognition of the histopathologic and cytogenetic features of this entity is necessary to avoid its misdiagnosis as ES/PNET, especially in small biopsy samples.

Immunophenotypic identification of acute myeloid leukemia with monocytic differentiation

Abstract: positive or all BFU-E or CFU-GM colonies are positive for V617F suggests that the bone marrow of this patient is not monoclonal with respect to the JAK2 mutation. In summary, the JAK2 V617F mutation was detected in a cohort of patients with 5q syndrome and a hypercellular marrow. Despite no statistical difference, a higher median platelet count was observed in the mutant cases with 50% (3/6) showing a platelet count 4700 10/l compared with only 3% (3/91) in the wild-type cases. The lack of clinical response to erythropoietin in the two cases described fails to support previous in vitro studies documenting hypersensitivity to erythropoietin in the presence of the mutation. Whether the JAK2 mutation occurs as an early or late event during the disease course is unclear. We detected the JAK2 mutation both at time of diagnosis and at a follow-up of 132 months in one case analysed, suggesting that the mutation occurred as an early event. Longer follow-up is however necessary to determine the prognostic significance of JAK2 mutation and in particular, whether these cases will show favourable response to lenalidomide as previously demonstrated in 5q chromosomal abnormalities.

Cloning of mouse Dab2ip gene, a novel member of the RasGTPase-activating protein family and characterization of its regulatory region in ptostate

Abstract: Disabled homolog 2 (Drosophila) interacting protein (DAB2IP/Dab2IP) is a member of the GTPase-activating protein for downregulating the Ras-mediated signal pathway and TNF-mediated apoptosis. The downregulation of human DAB2IP mRNA levels was detected in prostate cancer cells due to the epigenetic regulation. Here, we isolated a mouse Dab2ip gene with a highly homologous sequence to that of the human and rat gene and mapped it at chromosome 2B. The mDab2ip gene contains 14 exons and 13 introns and spans approximately 65 kb. Exon1 contains at least three splicing variants (Ia, Ib, and Ic). The deduced amino acid sequence of mouse Dab2IP encompasses 1065 residues containing several unique protein interaction motifs as well as a Ras-like GAP-related domain, which shares a high homology with both humans and rats. Data from real-time RT-PCR analysis revealed a diverse expression pattern of the mDab2ip gene in various organs, implying differential regulation of this gene from various tissues. We have mapped a 1.3-kb segment containing a 5'-upstream region from exon Ia as a promoter region (-147/+545) in prostatic epithelial cell lines (TRAMP-C); this region is highly GC-rich, and mDab2ip appears to be a TATA-less promoter. It appears that epigenetic regulation, particularly histone acetylation of the Dab2ip gene promoter, plays an important role in modulating its gene expression in the mouse prostate cancer cell.