Background & Aims: Thymus-expressed chemokine (TECK) or CCL25) is selectively expressed in the small bowel (SB), where lamina propria lymphocytes (LPL) and intraepithelial leukocyte expressing the ...cognate chemokine receptor CCR9 predominate.We characterize the role of TECK and CCR9-expresing lymphocytes in small intestinal Crohn's disease.Methods: CCR9 expression on lymphocytes from lamina propria, mesenteric lymph node, and peripheral blood was analyzed by flow cytometry and by Northern blotting for LPL.TECK expression was analyzed in inflamed SB and colon by reverse-transcription polymerase chain reaction and immunohistochemistry.Results: The fraction of CCR9+ T cells in inflamed SB was significantly lower than in uninvolved SB mucosa.In contrast, in peripheral blood lymphocytes, CCR9+ lymphocytes were markedly elevated in patients with small bowel Crohn's or celiac disease, but not in patients with purely colonic Crohn's.Also, TECK expression is altered in inflamed small bowel, being intensely expressed in a patchy distribution in crypt epithelial cells in proximity to lymphocytic infiltrates.TECK is not expressed in either normal or inflamed colon.Conclusions: In SB immune-mediated diseases, there is repartitioning of CCR9+ lymphocytes between SB and blood and an altered pattern of TECK expression in SB Crohn's.The TECK/CCR9 ligand/receptor pair may play an important role in the pathogenesis of SB Crohn's disease.
GASTROENTEROLOGY 2001;121:246-254
The evolutionary importance of hybridization and introgression has long been debated. Hybrids are usually rare and unfit, but even infrequent hybridization can aid adaptation by transferring ...beneficial traits between species. Here we use genomic tools to investigate introgression in Heliconius, a rapidly radiating genus of neotropical butterflies widely used in studies of ecology, behaviour, mimicry and speciation. We sequenced the genome of Heliconius melpomene and compared it with other taxa to investigate chromosomal evolution in Lepidoptera and gene flow among multiple Heliconius species and races. Among 12,669 predicted genes, biologically important expansions of families of chemosensory and Hox genes are particularly noteworthy. Chromosomal organization has remained broadly conserved since the Cretaceous period, when butterflies split from the Bombyx (silkmoth) lineage. Using genomic resequencing, we show hybrid exchange of genes between three co-mimics, Heliconius melpomene, Heliconius timareta and Heliconius elevatus, especially at two genomic regions that control mimicry pattern. We infer that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation.
Advancing age is often characterized by preserved or even enhanced emotion regulation, which is thought to manifest in terms of age-related reductions in the within-person association between ...stressors and negative affect. Existing research from ecological momentary assessment and end-of-day daily diary studies examining such age-related benefits have yielded mixed results, potentially due to differences in samples, design, and measurement of everyday stressors and negative affect. We conducted a coordinated analysis of 5 ecological momentary assessments and 2 end-of-day daily diary studies to examine adult age differences in the within-person association between everyday stressors and negative affect. Reported stressor occurrences are robustly associated with higher negative affect, regardless of study design and sample characteristics. Across studies, interactions between age and everyday stressors predicting negative affect revealed a pattern of age-related decreases in the stressor-negative affect association, but this interaction was only significant for 2 studies. Further, examination of statistical power of the included studies suggests that, despite differences in the number of repeated assessments, power to detect within-person stressor-negative affect associations is quite good. In contrast, despite possessing wider age ranges, observed age differences were relatively small in magnitude, and studies are potentially underpowered to detect age differences in these within-person associations. We discuss the importance of study design, interval of repeated assessments and number of participants for examining age differences in everyday stressors and negative affect, as well as the virtue of coordinated analyses for detecting consistent direction of associations, but inconsistent patterns of statistical significance.
Introduction: Visceral ischemia and reperfusion associated with thoracoabdominal aortic aneurysm (TAAA) repair results in lung injury, which appears to be mediated in part by proinflammatory ...cytokines. The purpose of this study was to determine the effect of exogenous administration of the antiinflammatory cytokine, recombinant human IL-10 (rhIL-10), on proinflammatory cytokine production (IL-6 and TNFα) and pulmonary neutrophil infiltration after acute visceral ischemia-reperfusion.
Methods: Two hours before 25 minutes of supraceliac aortic occlusion, 80 C57BL/6 mice (20 to 22 g) received an intraperitoneal injection of rhIL-10 (0.2 μg n = 20, 2 μg n = 20, 5 μg n = 25, or 20 μg n = 15), and 16 mice received murine anti-IL-10 IgM 200 μg. Twenty-five additional mice underwent visceral ischemia-reperfusion without treatment (controls), and 16 mice underwent laparotomy without aortic occlusion (sham).
Results: Pretreatment with exogenous rhIL-10 resulted in significant reductions in lung neutrophil infiltration with 0.2 μg, 2 μg, and 5 μg per mouse of rhIL-10 compared with lung neutrophil levels in control mice that underwent acute visceral ischemia-reperfusion alone (
p < 0.05). In addition, serum TNFα was detected in 50% of control mice and in 75% of mice that received murine anti-IL-10, but in none of the mice that received rhIL-10 (2 μg per mouse) or the mice that underwent sham operative procedures (
p < 0.05 by χ
2
analysis).
Conclusion: Exogenous IL-10 limits pulmonary neutrophil recruitment and the appearance of TNFα in this model of visceral ischemia-reperfusion injury. Thus the use of exogenous IL-10 may offer a novel therapeutic approach to decrease the complications that are associated with TAAA repair. (J Vasc Surg 1997;26:113-8.)
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