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Nirmal K. Banda Damian Kraus Andrea Vondracek Long H. Huynh Alison Bendele V. Michael Holers William P. Arend 《Arthritis \u0026amp; Rheumatology》2002,46(11):3065-3075
Objective
To determine the mechanisms of amelioration of collagen‐induced arthritis (CIA) in DBA/1J mice by inhibition of complement activation.Methods
Mice received 2 intradermal injections of bovine type II collagen (CII), on days 0 and 21. From day 21 (immediately after the second injection of CII) through day 35, mice received intraperitoneal injections of either phosphate buffered saline (PBS), a monoclonal mouse antibody to murine C5 (anti‐C5 antibody), or the C3 convertase inhibitor Crry‐Ig.Results
On days 30 and 32, the clinical disease activity score was lower in mice treated with anti‐C5 antibody than in those treated with Crry‐Ig. Histopathologic evidence of joint damage was 75% lower in the mice treated with anti‐C5 antibody than in those treated with either PBS or Crry‐Ig. Spleen cells from mice receiving either form of complement inhibition exhibited decreased CII‐stimulated proliferation, whereas increased proliferative responses were exhibited by lymph node cells from mice treated with Crry‐Ig. Treatment with anti‐C5 antibody decreased production of IgG1 anticollagen antibody, while production of IgG2a antibody was inhibited by both complement inhibitory treatments. CII‐stimulated spleen cells from anti‐C5–treated mice produced lower levels of tumor necrosis factor α (TNFα) and interleukin‐10 (IL‐10) compared with those from mice treated with Crry‐Ig. Lower steady‐state messenger RNA (mRNA) levels for TNFα, interferon‐γ (IFNγ), IL‐18, and IL‐6 were observed in the joints of anti‐C5–treated mice, and for IFNγ and IL‐6 in mice receiving Crry‐Ig, all in comparison with PBS‐treated mice. However, mRNA levels for IL‐1β and TNFα were lower in the joints after treatment with anti‐C5 compared with Crry‐Ig.Conclusion
These results indicate that inhibition of complement in CIA leads to decreased production of IgG2a antibody and suppressed CII‐induced spleen cell proliferation. The greater inhibitory effects on CIA of anti‐C5 antibody in comparison with Crry‐Ig may be attributable primarily to decreased levels of IL‐1β and TNFα mRNA in the joints.65.
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VM Reddy D Cundall-Curry MWM Bridger 《Annals of the Royal College of Surgeons of England》2010,92(8):655-659
INTRODUCTION
The aim of this study was to investigate whether incidence rates of tonsil and base of tongue cancer in England are increasing using data from the UK cancer registry.SUBJECTS AND METHODS
Cancer registrations for oral cavity and oropharynx cancer from 1985–2006 in England were obtained from the National Cancer Information Service. Population estimates were obtained from the Office for National Statistics. Age-adjusted incidence rates and age-specific incidence rates were calculated. The sexes were considered separately as incidence rates are known to differ significantly between men and women. Linear regression was performed to establish whether there was a relationship between incidence rates and time.RESULTS
There has been an increase in all oral cavity and oropharyngeal cancer in the study period. Linear regression analysis suggests that approximately 90% of the variance in age-adjusted incidence rates for men and women for tonsil, base of tongue and other oral cavity cancer is explained by the passage of time. For other oropharyngeal cancer, the variance is 62% and 46% in men and women, respectively. The estimated annual percentage change from 1985 to 2006 in age-adjusted incidence rates for tonsil and base of tongue cancer is 5.7% and 6.7% for men, and 4.3% and 6.5% for women, respectively.CONCLUSIONS
This study confirms a wide-spread clinical impression that there has been an increase in age-adjusted incidence rates, between 1985 and 2006, in all oral cavity cancer in England. The age range 40–69 years has seen the biggest increases in age-specific incidence rates for tonsil and base of tongue cancer. This reflects the findings of similar studies in other countries. 相似文献67.
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P Park M Haas P N Cunningham J J Alexander L Bao J M Guthridge D M Kraus V M Holers R J Quigg 《Journal of the American Society of Nephrology : JASN》2001,12(7):1383-1390
The complex pathogenesis of ischemia reperfusion injury (IRI) includes endothelial expression of adhesion molecules, leukocyte recruitment and activation, reactive oxygen species production, and apoptotic and necrotic cell death. A role for complement in IRI of different organs, including kidney, has been proposed on the basis of results of experiments that used pharmacologic inhibitors as well as animals that were deficient in individual complement proteins. Here, renal IRI in mice was examined. Animals that were deficient in C3 had partial protection from IRI induced by 27.5 min of bilateral renal ischemia, followed by 20 h of reperfusion (blood urea nitrogen [BUN] values, 46.6 +/- 6.9 and 68.4 +/- 7.9 mg/dl in C3 -/- and C3 +/+ mice; n = 7 and 8, respectively; P = 0.033). Given the reduction in IRI in C3 -/- mice, it was investigated, by use of the rodent C3 convertase inhibitor CR1-related gene/protein y-Ig (Crry-Ig), whether exogenous administration of a complement inhibitor could lessen renal injury. Despite the use of Crry-Ig in high doses, there was no significant reduction of injury induced by 20 to 30 min of ischemia followed by up to 30 h of reperfusion. Histologic examination revealed acute tubular necrosis and neutrophilic infiltration, both of which correlated significantly with BUN values (P < 0.001). Of interest, C3 deposition around renal tubules was significantly less in animals with IRI, compared with that in unmanipulated controls (P < 0.001). In Crry-Ig-treated animals, C3 deposition was inversely proportional to BUN values (r = -0.63; P < 0.001), which presumably indicates that severe vascular IRI allowed access of the 160 kD Crry-Ig to the interstitium. Thus, renal IRI in mice may have a partial complement dependence, yet pharmacologic inhibition of the complement system does not seem to be effective, likely because of the presence of other mediator systems that operate in parallel. 相似文献