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The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine and behavioural responses to stress, and the related hormone urocortin (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2. These receptors may exhibit distinct functions due to unique tissue distribution and pharmacology. Crhr-null mice have defined central(More)
Corticotropin-releasing hormone (CRH) is the principal regulator of the stress response. CRH stimulates production of ACTH via specific CRH receptors located on pituitary corticotropes. In addition to pituitary and central nervous system effects, peripheral effects of CRH have been observed involving the immune and cardiovascular systems. Specific CRH(More)
Stress pathways affect immune function, the most notable of these pathways being activation of the hypothalamic-pituitary-adrenal (HPA) axis. Although HPA activation has generally been relegated to an immunosuppressive role, recent evidence suggests that stress and HPA activation can be immunoenhancing in certain situations. To investigate specific effects(More)
We tested the effect of endotoxin on the peripheral corticotropin-releasing hormone receptor (CRH-R2), which is highly expressed in the heart. Systemic injection of LPS markedly downregulated CRH-R2 mRNA levels in the heart in a dose and time dependent manner. In contrast, CRH-R2 levels in skeletal muscle increased following exposure to endotoxin. These(More)
We describe three sets of natural (preimmune) polyreactive antibodies and Ag-induced antibodies that share the same VH-VL combinations. The amino acid homology in the VH and VL segments averaged 92%. These sets were found among 49 neonatal and adult natural mAb that were compared with 35 Ag-induced monoclonals produced during the memory response to(More)
CRH is the principal mediator of the stress response in mammals. In addition to pituitary and central nervous system effects, peripheral effects of CRH have been observed involving the immune and cardiovascular systems. Two CRH receptor subtypes, CRH-R1 and CRH-R2, have been cloned and show significant amino acid homology (69%), but differ in their tissue(More)
We have investigated the impact of mutations on the binding functions of the phosphocholine (PC)-specific T15 antibody in the absence of antigen selection pressure. The H chain complementarity determining region 2 (CDR2) sequence of T15 antibody was saturated with point mutations by in vitro random mutagenesis. From the mutant library, 289 clones were(More)
We examined the positive and negative effects of somatic mutation on antibody function using saturation mutagenesis in vitro to mimic the potential of the in vivo process to diversify antibodies. Identical mutations were introduced into the second complementarity determining region of two anti-phosphocholine antibodies, T15 and D16, which share the same(More)