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The role of COX-2 in angiogenesis and rheumatoid arthritis 总被引:4,自引:0,他引:4
Woods JM Mogollon A Amin MA Martinez RJ Koch AE 《Experimental and molecular pathology》2003,74(3):282-290
Recent evidence suggests that cyclooxygenase (COX)-2 is a mediator of angiogenesis, and COX-2 activity is known to be upregulated in the rheumatoid arthritis (RA) synovium. We examined whether mediation of angiogenesis by COX-2 was occuring in cells of the RA synovium and in microvascular endothelial cells (ECs) that are similar to those found in the RA synovium. We demonstrate that rofecoxib, a selective COX-2 inhibitor, acts directly on human dermal microvascular ECs (HMVECs) to inhibit their chemotactic and tube forming ability. Likewise, pretreatment of HMVECs with rofecoxib significantly inhibited their ability to form tubes induced by conditioned media (CM) of activated RA synovial fibroblasts. When RA synovial fibroblasts were pretreated with rofecoxib for 16 h and then stimulated with interleukin (IL)-1beta, their CM induced significantly less HMVEC tube formation when compared with CM from vehicle-treated RA synovial fibroblasts. ELISAs performed on activated RA fibroblast CM for known proangiogenic factors demonstrated a significant reduction in bFGF, in addition to the expected decrease in PGE(2). Our studies suggest that COX-2-induced angiogenic activity is an active mechanism within diseased synovium and may provide an additional rationale for the use of COX-2 inhibitors in RA. 相似文献
5.
The reaction of the potassium salt of acrylic acid with the potassium salt of a dicarboxylic acid and 1,4-dibromobutane was applied to the synthesis of three series of acrylate-terminated copolyesters: poly(tetramethylene maleate-co-tetramethylene phthalate) (BMPA), poly(tetramethylene fumarate-co-tetramethylenephthalate) (BFPA) and poly(tetramethylene phthalate-co-tetramethylene succinate) (BPSA). The monofunctional monomer, the potassium salt of acrylic acid, was used for the introduction of double bonds at the end of the chains and for the regulation of the molecular weight of the polyesters. The telechelic copolyesters were characterized by 1H and 13C NMR spectroscopy, in almost all cases providing an acrylate functionality of two. 相似文献
6.
Shylaja Srinivasan Ling Chen Jennifer Todd Jasmin Divers Samuel Gidding Steven Chernausek Rose A. Gubitosi-Klug Megan M. Kelsey Rachana Shah Mary Helen Black Lynne E. Wagenknecht Alisa Manning Jason Flannick Giuseppina Imperatore Josep M. Mercader Dana Dabelea Jose C. Florez 《Diabetes》2021,70(4):996
The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multiethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth case subjects with type 2 diabetes (mean age 15.1 ± 2.9 years) and 6,061 diabetes-free adult control subjects (mean age 54.2 ± 12.4 years). After stratifying by principal component–clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified seven genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P = 3.2 × 10−8; odds ratio [OR] = 1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P = 8.0 × 10−20; OR 1.58), rs72982988 near MC4R (P = 4.4 × 10−14; OR 1.53), rs200893788 in CDC123 (P = 1.1 × 10−12; OR 1.32), rs2237892 in KCNQ1 (P = 4.8 × 10−11; OR 1.59), rs937589119 in IGF2BP2 (P = 3.1 × 10−9; OR 1.34), and rs113748381 in SLC16A11 (P = 4.1 × 10−8; OR 1.04). Secondary analysis with 856 diabetes-free youth control subjects uncovered an additional locus in CPEB2 (P = 3.2 × 10−8; OR 2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome-wide association study of youth-onset type 2 diabetes. 相似文献
7.
Second cancers after medulloblastoma: population-based results from the United States and Sweden 总被引:5,自引:0,他引:5
Alisa M. Goldstein Jonathan Yuen Margaret A. Tucker 《Cancer causes & control : CCC》1997,8(6):865-871
Medulloblastoma, one of the most common central nervous system(CNS)tumors in children, requires aggressive multimodality therapy
including surgery, radiation therapy, and occasionally chemotherapy. Given its intensive treatment regimen and improved survival
during the past 20 years, it is likely that a cohort of survivors will result who may incur consequences of therapy, including
a second cancer. We used population-based data from the United States and Sweden to estimate risks of second neo plasms in
patients with histologically confirmed medulloblastoma (n = 1,262).Overall, there was a 5.4-fold excess of second neoplasms
(95 percent confidence interval = 3.3-8.4) based on 20 observed and 3.7 expected cancers. The second cancers occurred eight
to 432 months after initial diagnosis(median, 73 months) with significantly elevated ratios for all intervals examined except
for less than one year after initial diagnosis. Significantly elevated risks were seen for cancers of the salivary glands,
cervix uteri, brain and CNS, thyroid gland, and acute lymphoblastic leukemia. Of the 15second cancers with treatment data,
seven occurred in the radiation field or within areas of scatter while two others may have been radiation-related. Although
based on small numbers of second cancers, the results suggest that as survival increases, some patients with medulloblastoma
will have an increased risk of a second cancer, particularly a radiation-related cancer. Thus, as survival improves, late-occurring
consequences of diagnosis and treatment will need to be carefully assessed. Identification of patients hypersensitive to radiation
therapy, such as those with Gorlin Syndrome, should also be attempted in order to reduce the sequelae from intensive radiation
exposure.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
8.
Ying Gao Nan Hu XiaoYou Han Carol Giffen Ti Ding Alisa M. Goldstein Philip R. Taylor 《Cancer causes & control : CCC》2009,20(10):1997-2007
Introduction
Epidemiological data on green/jasmine tea and esophageal as well as gastric cancer are limited and inconclusive. 相似文献9.
J. Curtis Nickel Alisa Stephens A. Lenore Ackerman Jennifer T. Anger Henry H. Lai Garth D. Ehrlich 《Canadian Urological Association journal》2022,16(9):E448
IntroductionTo understand the role of the urinary microbiome in disease states and interpret non-culture-based diagnostic urine testing of midstream urine specimens, we must have a better understanding of the urinary microbiome in asymptomatic, healthy individuals. We examined the impact of gender, age, and menopausal status on the healthy human urinary microbiome in asymptomatic control subjects enrolled in the multi-institution National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Multidisciplinary Approach to the Study of Chronic Pelvic Pain Network (MAPP) study.MethodsAsymptomatic, healthy controls, recruited to be ageand sex-matched to patients in the Trans-MAPP Epidemiology and Phenotyping Study, provided midstream urine collection for polymerase chain reaction (PCR)-electrospray ionization mass spectrometry identification of urinary microbiota. The microbiomes of male and female participants were described and analyzed for differences in composition and diversity at the species and genus level by sex, age, and, in females, by menopausal status.ResultsSixty-six total species were detected with a mean of 1.2 species (standard deviation [SD] 1.1) per male (n=97; mean age=43) and 2.3 (SD 1.3) per female (n=110, mean age=38) in asymptomatic, healthy controls. Species and genera diversity analyses showed significantly greater richness and diversity in females. With regard to species, Bifidobacterium subtile, Lactobacillus crispatus, and Lactobacillus johnsonii were more predominant in females. The genera Bifidobacterium, Staphylococcus, Lactobacillus, and Corynebacterium were more predominant in females, while for males the most prevalent organisms included Staphylococcus and Propionibacterium; only Propionibacterium approached a significant difference between genders. No significant difference in the presence and/or diversity of micro-organisms with menopausal status could be observed. Sex-specific age trends, particularly diversity, were larger for females than males.ConclusionsThese results suggest the urinary microbiome of healthy, asymptomatic subjects differed between genders and age in females, but not menopausal status. Gender differences may be attributable to the detection of urethral/vaginal organisms in females and prostate organisms in males. These findings will better allow us to interpret the results of microbiome reports in the midstream urine specimens of patients with urinary symptoms. 相似文献
10.
Tigest Tamrat Subhash Chandir Kelsey Alland Alisa Pedrana Mubarak Taighoon Shah Carolyn Footitt Jennifer Snyder Natschja Ratanaprayul Danya Arif Siddiqi Numera Nazneen Inraini Fitria Syah Roger Wong Peter Lubell-Doughtie Annisa Dwi Utami Khaerul Anwar Hasmot Ali Alain B Labrique Lale Say Anuraj H Shankar Garrett Livingston Mehl 《Bulletin of the World Health Organization》2022,100(10):590
ObjectiveTo describe a systematic process of transforming paper registers into a digital system optimized to enhance service provision and fulfil reporting requirements.MethodsWe designed a formative study around primary health workers providing reproductive, maternal, newborn and child health services in three countries in Bangladesh, Indonesia and Pakistan. The study ran from November 2014 to June 2018. We developed a prototype digital application after conducting a needs assessment of health workers’ responsibilities, workflows, routine data requirements and service delivery needs. Methods included desk reviews, focus group discussions, in-depth interviews; data mapping of paper registers; observations of health workers; co-design workshops with health workers; and usability testing. Finally, we conducted an observational feasibility assessment to monitor uptake of the application.FindingsResearchers reviewed a total of 17 paper registers across the sites, which we transformed into seven modules within a digital application running on mobile devices. Modules corresponded to the services provided, including household enumeration, antenatal care, family planning, immunization, nutrition and child health. A total of 65 health workers used the modules during the feasibility assessment, and average weekly form submissions ranged from 8 to 234, depending on the health worker and their responsibilities. We also observed variability in the use of modules, requiring consistent monitoring support for health workers.ConclusionLessons learnt from this study shaped key global initiatives and resulted in a software global good. The deployment of digital systems requires well-designed applications, change management and strengthening human resources to realize and sustain health system gains. 相似文献