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111.
A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer
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David Mesher Isis Dove‐Edwin Peter Sasieni Hans Vasen Inge Bernstein Brigitte Royer‐Pokora Elke Holinski‐Feder Fiona Lalloo D. Gareth Evans Anna Forsberg Annika Lindblom Huw Thomas 《International journal of cancer. Journal international du cancer》2014,134(4):939-947
Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six centers. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under 50. The most advanced findings on colonoscopy were analyzed. One thousand five hundred eighty‐five individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4,992 colonoscopies with 7,904 patient‐years of follow‐up. Results for FCC type X and LOFCC were very similar. At baseline, 22 prevalent asymptomatic colorectal cancers were diagnosed, 120 (7.6%) individuals had high‐risk adenomas and 225 (14.2%) simple adenomas. One thousand eighty‐eight individuals had a further colonoscopy (median follow‐up of 6.2 years). Of nine individuals diagnosed with cancer, eight had a previous history of at least one polyp/adenoma. High‐risk adenomas were detected in 92 (8.7%) and multiple adenomas were detected in 20 (1.9%) individuals. Both FCC type X and LOFCC have a high prevalence of colorectal cancers and on follow‐up develop high‐risk adenomas (including multiple adenomas), but infrequent interval cancers. They should be managed similarly with five‐yearly colonoscopies undertaken from between 30 and 40 with more intensive surveillance in individuals developing multiple or high‐risk adenomas. 相似文献
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Márcia R. Amorim Crisiane Wais Zanrosso Isis Q. Magalhães Simone C. Pereira Alexandre Figueiredo Mariana Emerenciano 《Pediatric hematology and oncology》2013,30(8):744-750
Down syndrome (DS) is an important risk factor associated with acute leukemia (AL). The presence of polymorphisms that reduce 5,10-methylenetetrahydrofolate reductase (MTHFR) activity has been linked to the multifactorial leukemogenic process. The authors have conducted a study to test whether 677C→T and/or 1298A→C polymorphisms of MTHFR would play an additional role in susceptibility of acute myeloid leukemia (AML) in DS children. They also verified whether any polymorphism in the MTHFR gene was associated with the risk of DS. Genetic polymorphisms determination was carried out in 248 samples from healthy individuals as controls and a total of 115 DS children (65 without leukemia and 50 with AML). The present study failed to reveal any association between these polymorphisms and risk of AML in DS children. The data also indicate that MTHFR polymorphisms are not associated with risk of being a DS child. 相似文献
113.
Isis Ludwig‐Portugall Emma E. Hamilton‐Williams Janine Gotot Christian Kurts 《European journal of immunology》2009,39(1):225-233
To study B‐cell tolerance against non‐lymphoid tissue autoantigens, we generated transgenic rat insulin promoter (RIP)‐OVA/hen egg lysozyme (HEL) mice expressing the model antigens, OVA and HEL, in pancreatic islets. Their vaccination with OVA or HEL induced far less auto‐Ab titers compared with non‐transgenic controls. Depletion of CD25+ cells during immunization completely restored auto‐Ab production, but did not affect antibodies against a foreign control antigen. Depletion at later time‐points was not effective. OVA‐specific CD25+ FoxP3+ Treg were more frequent in the autoantigen‐draining pancreatic LN than in other secondary lymphatics of RIP‐OVA/HEL mice. Consistently, B cells were suppressed in that LN and also in the spleen, which is known to concentrate circulating antigen, such as the antigens used for vaccination. Suppression involved preventing expansion of autoreactive B cells in response to autoantigen, reducing antibody production per B‐cell and isotype changes. These findings demonstrate that CD25+ Treg suppress auto‐Ab production against non‐lymphoid tissue antigens in an antigen‐specific manner. 相似文献
114.
Anne?E.?Visser Raha?Pazoki Sara?L.?Pulit Wouter?van?Rheenen Joost?Raaphorst Anneke?J.?van der?Kooi Isis?Rica?o-Ponce Cisca?Wijmenga Henny?G.?Otten Jan?H.?Veldink Leonard?H.?van den?BergEmail author 《Journal of neurology》2017,264(4):694-700
To examine evidence for a role of gluten sensitivity (GS) or celiac disease (CD) in ALS etiology, we included participants from a population-based case–control study in The Netherlands between January 2006 and December 2015. We compared levels and seroprevalence of IgA antibodies to tissue transglutaminase 6 (TG6) in 359 ALS patients and 359 controls, and to transglutaminase 2 (TG2) and endomysium (EMA) in 199 ALS patients and 199 controls. Questionnaire data on 1829 ALS patients and 3920 controls were examined for CD or gluten-free diets (GFD). Genetic correlation and HLA allele frequencies were analyzed using two genome-wide association studies: one on ALS (12,577 cases, 23,475 controls), and one on CD (4533 cases, 10,750 controls). We found one patient with TG6, TG2 and EMA antibodies who had typical ALS and no symptoms of GS. TG6 antibody concentrations and positivity, CD prevalence and adherence to a GFD were similar in patients and controls (p > 0.66) and in these patients disease progression was compatible with typical ALS. CD and ALS were not found to be genetically correlated (p > 0.37). CD-associated HLA allele frequencies were similar in patients and controls (p > 0.28). In conclusion, we found no serological evidence for involvement of gluten-related antibodies in ALS etiology nor did we observe an association between CD and ALS in medical history or genetic data, indicating that there is no evidence in our data for an association between the two diseases. Hence, a role for a GFD in the ALS treatment seems unlikely. 相似文献
115.
Gamma interferon, tumor necrosis factor alpha, and nitric oxide synthase 2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary Yersinia pestis infection
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Parent MA Wilhelm LB Kummer LW Szaba FM Mullarky IK Smiley ST 《Infection and immunity》2006,74(6):3381-3386
Pulmonary infection by Yersinia pestis causes pneumonic plague, a rapidly progressing and often fatal disease. To aid the development of safe and effective pneumonic plague vaccines, we are deciphering mechanisms used by the immune system to protect against lethal pulmonary Y. pestis infection. In murine pneumonic plague models, passive transfer of convalescent-phase sera confers protection, as does active vaccination with live Y. pestis. Here, we demonstrate that protection by either protocol relies upon both gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) cytokines classically associated with type 1 cellular immunity. In both protocols, abrogating IFN-gamma or TNF-alpha activity significantly decreases survival and increases the bacterial burden in pulmonary, splenic, and hepatic tissues. Neutralization of either cytokine also counteracts challenge-induced, vaccination-dependent upregulation of nitric oxide synthase 2 (NOS2). Moreover, genetic depletion of NOS2 suppresses protection conferred by serotherapy. We conclude that IFN-gamma, TNF-alpha, and NOS2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary Y. pestis challenge. These observations strongly suggest that plague vaccines should strive to maximally prime both cellular and humoral immunity. 相似文献
116.
Sudowe S Ludwig-Portugall I Montermann E Ross R Reske-Kunz AB 《The Journal of allergy and clinical immunology》2006,117(1):196-203
BACKGROUND: Allergen gene transfer represents an alternative approach to specific immunotherapy with allergen extracts. Gene gun-mediated DNA immunization with plasmid vectors expressing a transgene under control of the promoter of the fascin gene (pFascin) allows for antigen production predominantly by dendritic cells and resulted in the generation of CD8(+) cytotoxic T lymphocytes as well as in the development of a type 1 immune response. OBJECTIVE: We compared the in vivo efficiency of biolistic transfection with pFascin and plasmids containing the cytomegalovirus promoter (pCMV) in a mouse model of type I allergy. METHODS: BALB/c mice were sensitized with the model allergen beta-galactosidase to induce a distinctive type 2 immune response. The effect of prophylactic as well as therapeutic biolistic transfection with beta-galactosidase-encoding plasmids on the development of antibody titers was followed, and anaphylactic potential of sera was determined. Spleen cells were stimulated in vitro to analyze cytokine production and induction of CD8(+) effector T cells. RESULTS: Protective allergen gene transfer with pFascin efficiently prevented specific IgE production accompanied by immune deviation toward a T(H)1-polarized immune response as well as by the induction of IFN-gamma-producing CD8(+) effector T cells, being comparable to vaccination with pCMV. In a therapeutical setting, biolistic DNA vaccination with pFascin or pCMV transiently protected allergen-sensitized mice against the strong increase in specific IgE production caused by subsequent allergen challenge. CONCLUSION: We demonstrate for the first time that restricting transgene expression primarily to dendritic cells after DNA vaccination suffices to cause inhibition of IgE production prophylactically and therapeutically. 相似文献
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