The observations indicate that ADO induces mesangial cell apoptosis via stimulation of the A3 receptor.

The regulation of T cell homeostasis during pregnancy has important implications for maternal tolerance and immunity. Evidence suggests that Programmed Death-1 (PD-1) participates in regulation of T cell homeostasis and peripheral tolerance. To examine the contribution of PD-1 signaling on T cell homeostasis during normal mouse pregnancy, we examined T cell number or proportion, PD-1 expression, proliferation, and apoptosis by flow cytometry, BrdU incorporation, and TUNEL assay in pregnant mice given anti-PD-1 blocking antibody or control on days 10, 12, and 14 of gestation. We observed tissue, treatment, and T cell-specific differences in PD-1 expression. Both pregnancy and PD-1 blockade increased T cell proliferation in the spleen while this effect was limited to CD4 T cells in the uterine- draining nodes. In the uterus, PD-1 blockade markedly altered the composition of the T cell pool. These studies support the idea that pregnancy is a state of dynamic T cell homeostasis and suggest that this state is partially supported by PD-1 signaling.

Background/Aims: Renal tubules undergo oxidative injury in various nephropathies. It is unknown whether tubular cells possess mechanisms to attenuate this form of injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, may provide such a mechanism by reducing levels of free heme, a prooxidant molecule, and by limiting activity of heme-containing prooxidant enzymes. Determination of the distribution of HO-1 in the nephron may identify those segments where HO-1 can afford protection against oxidative injury. Methods: Rats were injected subcutaneously with two different inducers of HO-1: Stannous chloride and cobalt protoporphyrin. At completion of injections, frozen sections of kidneys were stained for HO-1 using a biotin-conjugated monoclonal anti-HO-1 antibody. To identify the origin of tubules staining positive for HO-1, Tetragonolobus purpureas (TP)-derived lectin and Arachnis hypogaea (AH)-derived lectin were applied to sequential sections of the kidney cortex. Results: In rats injected with either HO-1 inducer, HO-1 was immunolocalized in tubules but not in glomeruli. Staining of sequential sections with TP-derived lectin, which binds mainly to proximal tubular cells, was negative in the tubules that stained positive for HO-1. Staining of sequential sections with AH-derived lectin, which binds mainly to distal and collecting tubular cells, was positive in those tubules that were also positive for HO-1. Conclusion: In kidneys of rats injected with inducers of HO-1, distal and collecting tubular cells were identified as the main segments of the nephron that express HO-1. We suggest that the distal nephron, by expressing HO-1, may be less vulnerable to oxidative injury.

Summary Classic models suggest maternal tolerance is dependent on regulation of fetal antigen‐specific T cell responses. We hypothesize that factors unique to a particular fetal antigen‐specific T cell, rather than the state of pregnancy per se, are important determinants of T cell fate during pregnancy. To investigate the fate of fetal antigen‐specific CD4 T cells in the systemic circulation, we examined spleen cells in a CD4 T cell receptor transgenic mouse specific for the male antigen H‐Y. We observed a transient decrease in CD4+ Vβ6+ cell numbers and, due to transient internalization of CD4, an increase in CD4− Vβ6+ T cells. Antigen‐specific in vitro responsiveness was not depressed by pregnancy. These data suggest that pregnancy supports fluidity in this particular CD4 T cell pool that may, in turn, help to meet competing requirements of maternal immune responsiveness and fetal tolerance.

BACKGROUND: Quality improvement (QI) efforts can improve guideline-recommended asthma care processes in the pediatric office setting. We sought to assess whether practice participation in an asthma QI collaborative was associated with decreased asthma-related emergency department (ED) visits. METHODS: A statewide network of practices participated in a pediatric asthma QI collaborative from 2015 to 2016. We evaluated asthma-related ED visit rates per 100 child-years for children ages 3 to 21 years with asthma, using the state's all-payer claims database. We used a difference-indifferences approach, with mixed-effects negative binomial regression models to control for practice and patient covariates. Our main analysis measured the outcome before (2014) and after (2017) the QI collaborative at fully participating and control practices. Additional analyses assessed (1) associations during the intervention period (2016) and (2) associations including practices partially participating in QI collaborative activities. RESULTS: In the postintervention year (2017), participating practices' (n = 20) asthma-related ED visit rate decreased by 5.8 per 100 child-years, compared to an increase of 1.8 per 100 child-years for control practices (n = 15; difference in differences = 27.3; P = .002). Within the intervention year (2016), we found no statistically significant differences in asthma-related ED visit rates compared to controls (difference in differences = 24.3; P = .17). The analysis including partially participating practices yielded similar results and inferences to our main analysis. CONCLUSIONS: Participation in an asthma-focused QI collaborative was associated with decreased asthma-related ED visit rates. For those considering implementing this type of QI collaborative, our findings indicate that it takes time to see measurable improvements in ED visit rates. Further study is warranted regarding QI elements contributing to success for partial participants. WHAT'S KNOWN ON THIS SUBJECT: Participation in an asthma quality improvement learning collaborative in primary care is associated with improved processes of care in the office setting for children with asthma. WHAT THIS STUDY ADDS: Participation in an asthma quality improvement learning collaborative in primary care is associated with a substantial decrease in asthmarelated emergency department visits .1 year after the end of the collaborative.