Evaluation of Rare Variants in the New Fanconi Anemia Gene ERCC4 (FANCQ) as Familial Breast/Ovarian Cancer Susceptibility Alleles

Recently, it has been reported that biallelic mutations in the ERCC4 (FANCQ) gene cause Fanconi anemia (FA) subtype FA‐Q. To investigate the possible role of ERCC4 in breast and ovarian cancer susceptibility, as occurs with other FA genes, we screened the 11 coding exons and exon–intron boundaries of ERCC4 in 1573 index cases from high‐risk Spanish familial breast and ovarian cancer pedigrees that had been tested negative for BRCA1 and BRCA2 mutations and 854 controls. The frequency of ERCC4 mutation carriers does not differ between cases and controls, suggesting that ERCC4 is not a cancer susceptibility gene. Interestingly, the prevalence of ERCC4 mutation carriers (one in 288) is similar to that reported for FANCA, whereas there are approximately 100‐fold more FA‐A than FA‐Q patients, indicating that most biallelic combinations of ERCC4 mutations are embryo lethal. Finally, we identified additional bone‐fide FA ERCC4 mutations specifically disrupting interstrand cross‐link repair.     

Humoral and in vivo cellular immunity against the raw insect-derived recombinant Leishmania infantum antigens KMPII, TRYP, LACK, and papLe22 in dogs from an endemic area

Leishmania infantum causes visceral leishmaniasis, a severe zoonotic and systemic disease that is fatal if left untreated. Identification of the antigens involved in Leishmania-specific protective immune response is a research priority for the development of effective control measures. For this purpose, we evaluated, in 27 dogs from an enzootic zone, specific humoral and cellular immune response by delayed-type hypersensitivity (DTH) skin test both against total L. infantum antigen and the raw Trichoplusia ni insect-derived kinetoplastid membrane protein-11 (rKMPII), tryparedoxin peroxidase (rTRYP), Leishmania homologue of receptors for activated C kinase (rLACK), and 22-kDa potentially aggravating protein of Leishmania (rpapLe22) antigens from this parasite. rTRYP induced the highest number of positive DTH responses (55% of leishmanin skin test [LST]-positive dogs), showing that TRYP antigen is an important T cell immunogen, and it could be a promising vaccine candidate against this disease. When TRYP-DTH and KMPII-DTH tests were evaluated in parallel, 82% of LST-positive dogs were detected, suggesting that both antigens could be considered as components of a standardized DTH immunodiagnostic tool for dogs.     

Crosstalk between glucocorticoids and mitogen-activated protein kinase signalling pathways

Synthetic glucocorticoids are potent modulators of the immune system, and are clinically invaluable in the treatment of a wide variety of conditions. However, their use can be limited by harmful side effects, and their mechanisms of action remain poorly understood and controversial. It has recently been reported that glucocorticoids induce the expression of two genes that participate in cross-talk with the mitogen-activated protein kinase signalling pathways. It is possible that both therapeutic and harmful effects of glucocorticoids may be mediated by these genes.     

Trans-10, cis-12-conjugated linoleic acid does not increase body fat loss induced by energy restriction

Very little evidence exists concerning the effects of conjugated linoleic acid (CLA) on body fat reduction induced by energy restriction. Moreover, although an effect of trans-10, cis-12-CLA on lipolysis has been suggested, it has not been consistently shown. The aims of the present study were to determine whether trans-10, cis-12-CLA increases the reduction of body fat induced by energy restriction, and to analyse its effect on lipolysis and adipose tissue lipase expression (hormone-sensitive lipase (HSL) and adipose tissue TAG lipase (ATGL)). Male Syrian Golden hamsters were fed a high-fat diet during 7 weeks in order to make them fatter. Then they were submitted to a mild energy restriction (25 %) without or with supplementation of 0.5 % trans-10, cis-12-CLA for 3 weeks. Basal glycerol release and lipolysis stimulated by several drugs acting at different levels of the lipolytic cascade were measured in epididymal adipose tissue. The expression of HSL and ATGL was assessed by real-time RT-PCR. No differences were found in adipose tissues size between the experimental groups. Medium adipocyte size and total number of adipocytes were similar in both experimental groups. Animals fed the CLA-enriched diet showed similar lipolytic rates as well as HSL and ATGL expressions to the controls. In conclusion, trans-10, cis-12-CLA does not promote adipose tissue lipid mobilisation nor does it heighten body fat reduction induced by energy restriction. Consequently, this CLA isomer does not seem to be a useful tool to be included in body weight-loss strategies followed in obesity treatment.     

高原肺水肿治疗中的常见并发症分析

目的 :分析近 3年来我院高原肺水肿治疗中的常见并发症 ,为临床攻克此高原顽疾提供有力的参考依据。方法 :分析近 3年来我院收住的 4 32例 (全部为汉族 )高原肺水肿患者住院资料 ,按照进藏方式、治疗方法进行分类 ,采用统计学分析后得出结论。结果 :乘飞机进藏的患者并发症发生率明显低于乘汽车进藏的患者 (P <0 .0 1) ,常见的并发症以水电解质紊乱和肺部感染为主 ;治疗方法中以联合治疗出现的并发症明显少于单一方法治疗 (P <0 .0 1) ,联合治疗中出现的并发症以水电解质紊乱为主 ,单一方法治疗中出现的并发症以水电解质紊乱和肺部感染为主。结论 :乘飞机进藏后的高原肺水肿的并发症较少并容易得到纠正 ,治疗时采取联合治疗可以有效防止出现并发症 ,在临床治疗中应该采取全面均衡的治疗方案