scholarly journals Induction of early response genes in trypsin inhibitor-induced pancreatic growth

2007 ◽  
Vol 292 (2) ◽  
pp. G667-G677 ◽  
Author(s):  
Lili Guo ◽  
Maria Dolors Sans ◽  
Grzegorz T. Gurda ◽  
Sae-Hong Lee ◽  
Stephen A. Ernst ◽  
...  
Keyword(s):  
Dna Binding ◽  
Trypsin Inhibitor ◽  
Early Response ◽  
Maximal Response ◽  
Pancreatic Growth ◽  
Fos Expression ◽  
Early Response Genes ◽  
H Protein ◽  
Cck Antagonist

Endogenous CCK release induced by a synthetic trypsin inhibitor, camostat, stimulates pancreatic growth; however, the mechanisms mediating this growth are not well established. Early response genes often couple short-term signals with long-term responses. To study their participation in the pancreatic growth response, mice were fasted for 18 h and refed chow containing 0.1% camostat for 1–24 h. Expression of 18 early response genes were evaluated by quantitative PCR; mRNA for 17 of the 18 increased at 1, 2, 4, or 8 h. Protein expression for c-jun, c-fos, ATF-3, Egr-1, and JunB peaked at 2 h. Nuclear localization was confirmed by immunohistochemistry of c-fos, c-jun, and Egr-1. Refeeding regular chow induced only a small increase of c-jun and none in c-fos expression. JNKs and ERKs were activated 1 h after camostat feeding as was the phosphorylation of c-jun and ATF-2. AP-1 DNA binding evaluated by EMSA showed a significant increase 1–2 h after camostat feeding with participation of c-jun, c-fos, ATF-2, ATF-3, and JunB shown by supershift. The CCK antagonist IQM-95,333 blocked camostat feeding-induced c-jun and c-fos expression by 67 and 84%, respectively, and AP-1 DNA binding was also inhibited. In CCK-deficient mice, the maximal response of c-jun induction and AP-1 DNA binding were reduced by 64 and 70%, respectively. These results indicate that camostat feeding induces a spectrum of early response gene expression and AP-1 DNA binding and that these effects are mainly CCK dependent.

TRYPSIN INHIBITOR-INDUCED PANCREATIC GROWTH INVOLVES INDUCTION OF EARLY RESPONSE GENES.

Pancreas ◽  
2004 ◽  
Vol 29 (4) ◽  
pp. 333-334 ◽  
Author(s):  
L.L. Guo ◽  
M.D. Sans ◽  
G. Gurda ◽  
S.-H. Lee ◽  
J.A. Williams
Keyword(s):  
Trypsin Inhibitor ◽  
Early Response ◽  
Pancreatic Growth ◽  
Early Response Genes

scholarly journals Early response to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA

Rheumatology ◽  
2019 ◽  
Vol 59 (7) ◽  
pp. 1709-1714 ◽  
Author(s):  
Philip D H Hamann ◽  
John D Pauling ◽  
Neil McHugh ◽  
Kimme Hyrich ◽  
Gavin Shaddick ◽  
...  
Keyword(s):  
Disease Activity ◽  
Latent Class ◽  
Early Response ◽  
British Society ◽  
Maximal Response ◽  
Sustained Remission ◽  
Stable Model ◽  
Moderate Disease ◽  
Trajectory Divergence

Abstract Objective To identify different trajectories of disease activity in patients with RA following initiation of a first anti-TNF. Methods Patients with RA starting their first anti-TNF between 2001 and 2013 were selected from the British Society for Rheumatology Biologics Register for RA. Six-monthly DAS28-ESR scores were used to identify trajectories of disease activity using latent class modelling. Data were included for six follow-ups after registration (approximately 3 years). Subgroup analysis examined changes in disease activity profiles over time. Results A total of 14 436 patients with RA starting their first anti-TNF were enrolled between 2001 and 2013 (13 115 between 2001 and 2008, 1321 between 2010 and 2013). The mean number of DAS28-ESR scores was 3.5/patient (s.d. 2.1), with a mean of 184.9 days (s.d. 69.9) between scores. The DAS28-ESR nadir was achieved within 250 days of commencing anti-TNF, although apparent trajectory divergence emerged by first 6-monthly follow-up at 180 days. Four distinct response trajectories comprised the most stable model. Most patients fitted into ‘modest’ (7986 patients; 55.3%) or ‘substantial’ (4676 patients; 32.4%) response trajectories. Of the remainder, 1254 (8.7%) and 520 (3.6%) fitted ‘maximal’ and ‘minimal’ response trajectories, respectively. There was a significant (P < 0.01) increase in proportion achieving ‘maximal’ response between 2001–2008 and 2010–2013. Conclusion This is the largest study to identify long-term response trajectories with anti-TNF. By 6 months, longer-term trajectory profiles of DAS28 could already be identified, with many patients identified earlier. The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity. The maximal response trajectory (equivalent to sustained DAS2-ESR remission) was only achieved by approximately one-third of patients.

Promiscuous and Depolarization-Induced Immediate-Early Response Genes Are Induced by Mechanical Strain of Osteoblasts

2009 ◽  
Vol 24 (7) ◽  
pp. 1247-1262 ◽  
Author(s):  
Claus-Eric Ott ◽  
Sebastian Bauer ◽  
Thomas Manke ◽  
Susan Ahrens ◽  
Christian Rödelsperger ◽  
...  
Keyword(s):  
Mechanical Strain ◽  
Early Response ◽  
Immediate Early ◽  
Early Response Genes

scholarly journals Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

2015 ◽  
Vol 75 (3) ◽  
pp. 526-531 ◽  
Author(s):  
Farah Tamirou ◽  
David D'Cruz ◽  
Shirish Sangle ◽  
Philippe Remy ◽  
Carlos Vasconcelos ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Positive Predictive Value ◽  
Maintenance Therapy ◽  
Early Response ◽  
Renal Outcome ◽  
Proliferative Lupus Nephritis ◽  
Long Term Follow Up

ObjectiveTo report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome.MethodsIn 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up.ResultsDeath (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker.ConclusionsThe long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome.Trial registration numberNCT00204022.

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