90 research outputs found
Liver Disorders in Inflammatory Bowel Disease
Disorders of the hepatobiliary system are relatively common extraintestinal manifestations of inflammatory bowel disease (IBD). These disorders are sometimes due to a shared pathogenesis with IBD as seen in primary sclerosing cholangitis (PSC) and small-duct primary sclerosing cholangitis (small-duct PSC). There are also hepatobiliary manifestations such as cholelithiasis and portal vein thrombosis that occur due to the effects of chronic inflammation and the severity of bowel disease. Lastly, medications used in IBD such as sulfasalazine, thiopurines, and methotrexate can adversely affect the liver. It is important to be cognizant of these disorders as some do have serious long-term consequences. The management of these disorders often requires the expertise of multidisciplinary teams to achieve the best outcomes
Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics
The sphingosine 1-phosphate receptor 1 (S1P1) promotes lymphocyte egress from lymphoid organs. Previous work showed that agonist-induced internalization of this G protein–coupled receptor correlates with inhibition of lymphocyte egress and results in lymphopenia. However, it is unclear if S1P1 internalization is necessary for this effect. We characterize a knockin mouse (S1p1rS5A/S5A) in which the C-terminal serine-rich S1P1 motif, which is important for S1P1 internalization but dispensable for S1P1 signaling, is mutated. T cells expressing the mutant S1P1 showed delayed S1P1 internalization and defective desensitization after agonist stimulation. Mutant mice exhibited significantly delayed lymphopenia after S1P1 agonist administration or disruption of the vascular S1P gradient. Adoptive transfer experiments demonstrated that mutant S1P1 expression in lymphocytes, rather than endothelial cells, facilitated this delay in lymphopenia. Thus, cell-surface residency of S1P1 on T cells is a primary determinant of lymphocyte egress kinetics in vivo
Liver Disorders in Inflammatory Bowel Disease
Disorders of the hepatobiliary system are relatively common extraintestinal manifestations of inflammatory bowel disease (IBD). These disorders are sometimes due to a shared pathogenesis with IBD as seen in primary sclerosing cholangitis (PSC) and smallduct primary sclerosing cholangitis (small-duct PSC). There are also hepatobiliary manifestations such as cholelithiasis and portal vein thrombosis that occur due to the effects of chronic inflammation and the severity of bowel disease. Lastly, medications used in IBD such as sulfasalazine, thiopurines, and methotrexate can adversely affect the liver. It is important to be cognizant of these disorders as some do have serious long-term consequences. The management of these disorders often requires the expertise of multidisciplinary teams to achieve the best outcomes
On the Rapid Oxidation of Allene-Containing Phosphines
Allene-containing
phosphines have recently been shown to serve
as effective ligands in transition metal-catalyzed enantioselective
reactions. Surprisingly, (2-allenylphenyl)diphenyl phosphines rapidly
oxidize when exposed to air, whereas many other triaryl phosphines
are stable under ambient conditions. Here we describe experiments
designed to understand the origin of this behavior. Stereochemical
probes and an isolated phosphonium complex support the hypothesis
that phosphines can cyclize onto pendant allenes and that the resultant
zwitterion undergoes rapid oxidation with molecular oxygen
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