Hec-6st is a highly specific high endothelial venule (HEV) gene that is crucial for regulating lymphocyte homing to lymph nodes (LN). The enzyme is also expressed in HEV-like vessels in tertiary lymphoid organs that form in chronic inflammation in autoimmunity, graft rejection, and microbial infection. Understanding the molecular nature of Hec-6st regulation is crucial for elucidating its function in development and disease.
View Article and Find Full Text PDFLymph node (LN) function depends on T and B cell compartmentalization, antigen presenting cells, and high endothelial venules (HEVs) expressing mucosal addressin cell adhesion molecule (MAdCAM-1) and peripheral node addressin (PNAd), ligands for naive cell entrance into LNs. Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST). To investigate LT alpha beta's activities in lymphoid organogenesis, mice simultaneously expressing LT alpha and LT beta under rat insulin promoter II (RIP) control were compared with RIPLT alpha mice in a model of lymphoid neogenesis and with LT beta-/- mice.
View Article and Find Full Text PDFIn these studies the differential roles of LTalpha and LTalphabeta complex have been discussed with regard to development of lymphoid organs in ontogeny and in inflammation, LTalpha is necessary for PLNand MLN, most likely as both LTalpha and LTalphabeta complex, whereas only LTalphabeta is required for MLN. Both are involved in the cellularity of the NALT. When expressed as a transgene, LTa alone can induce cellular accumulation and MAdCAM, but not PNAd, an epitope associated with PLN HEV.
View Article and Find Full Text PDFObjective: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock.
Design: Multicenter, double-blind, phase III, placebo-controlled, randomized study.
Setting: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42).
RSKB, a p90 ribosomal S6 protein kinase with two catalytic domains, is activated by p38- and extracellular signal-regulated kinase mitogen-activated protein kinase pathways. The sequences between the two catalytic domains and of the C-terminal extension contain elements that control RSKB activity. The C-terminal extension of RSKB presents a putative bipartite (713)KRX(14)KRRKQKLRS(737) nuclear location signal.
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