Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulated emigration of blood-borne leukocytes plays a defining role in lymphoid organ development, immune surveillance, and inflammatory responses. We report here that mice deficient in the homeobox gene Nkx2-3, expressed in developing visceral mesoderm, show a complex intestinal malabsorption phenotype and striking abnormalities of gut-associated lymphoid tissue and spleen suggestive of deranged leukocyte homing. Mutant Peyer's patches were reduced in number and size, intestinal villi contained few IgA(+) plasma cells, and mutant spleens were small and often atrophic, showing fused periarterial lymphoid sheaths, partially merged T and B cell zones, an absent marginal zone, and a dearth of macrophages in red pulp. Semiquantitative RT-PCR analysis and immunohistochemistry revealed down-regulation of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in endothelial cells in which Nkx2-3 is normally expressed. MAdCAM-1 is a member of the immunoglobulin superfamily, acting as an endothelial cell ligand for leukocyte homing receptors L-selectin and alpha4beta7 integrin. Our data suggest a role for a homeodomain factor in establishing the developmental and positional cues in endothelia that regulate leukocyte homing through local control of cellular adhesion and identify MAdCAM-1 as a candidate target gene of Nkx2-3.
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PMID:Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera. 1092 56

The major obstacle for oral delivery of administered therapeutic proteins is malabsorption in the intestine. This malabsorption could be overcome by induction of neonatal FcRn [Fc (CH2 and CH3 domains of human IgG1 antibody) receptor]-mediated transcytosis in the intestine using recombinant fusion of CH2 and CH3 moieties of human IgG to a therapeutic protein. To this end we developed recombinant hGH (human growth hormone) fused to the N-terminus of Fc moieties [CH2-CH3 or h (hinge)-CH2-CH3] from human IgG1. These recombinant proteins secreted by the methylotrophic yeast Pichia pastoris functionally induced secretion of insulin-like growth factor 1 by HepG2 cells in the response to hGH moiety in the fusion proteins. In a transport study using polarized T84 cells, 3.7% of added dimeric hGH-h-Fc was transported in the apical-to-basolateral direction within 1 h by FcRn-mediated transcytosis of 1 cm(2) monolayers. However, transport of monomeric hGH-Fc (only 0.43%) was much less effective, yet its transport was 2.3 times higher than that of hGH. Finally, we concluded that, upon recombinant fusion, maintenance of dimeric structure of Fc moieties is crucial for the induction of FcRn-mediated transcytosis.
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PMID:Expression and characterization of human growth hormone-Fc fusion proteins for transcytosis induction. 1706 88