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121.
Carla Guarinos Adela Castillejo V��ctor-Manuel Barber�� Luc��a P��rez-Carbonell Ana-Beatriz S��nchez-Heras ��ngel Segura Carmen Guill��n-Ponce Ana Mart��nez-Cant�� Mar��a-Isabel Castillejo Cecilia-Magdalena Egoavil Rodrigo Jover Artemio Pay�� Cristina Alenda Jos��-Lu��s Soto 《The Journal of molecular diagnostics : JMD》2010,12(6):765-770
The standard genetic test for Lynch syndrome (LS) frequently reveals an absence of pathogenic mutations in DNA mismatch repair genes known to be associated with LS. It was recently shown that germ line deletions in the last exons of EPCAM are involved in the etiology of LS. The aim of this study was to evaluate the prevalence of EPCAM deletions in a Spanish population and the clinical implications of deletion. Probands from 501 families suspected of having LS were enrolled in the study. Twenty-five cases with MSH2 loss were identified: 10 had mutations of MSH2, five had mutations of MSH6, and 10 did not show MSH2/MSH6 mutations. These 25 cases were analyzed for EPCAM deletions using multiplex ligation-dependent probe amplification, and deletions were mapped using long-range PCR analysis. One subject with no MSH2/MSH6 mutations had a large deletion in the EPCAM locus that extended for 8.7 kb and included exons 8 and 9. The tumor exhibited MSH2 promoter hypermethylation. EPCAM deletion analysis followed by MSH2 methylation testing of the tumor is a fast low-cost procedure that can be used to identify mutations that cause LS. We propose that this procedure be incorporated into clinical genetic analysis strategies and present a decision-support flow diagram for the diagnosis of LS.Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early-onset cancers of the colorectum and endometrium and tumors of the stomach, pancreas, small intestine, ovary, bladder, and bile duct.1 In the Spanish population, about 2.5% of colorectal cancers are associated with LS.2 The carcinogenetic etiology of this syndrome involves a DNA mismatch repair (MMR) inactivation caused by a germ line mutation of an MMR gene (MLH1, MSH2, MSH6, or PMS2) followed by somatic inactivation of the second allele.1 As a consequence of MMR inactivation, these tumors exhibit microsatellite instability (MSI) and loss of expression of the mutated MMR gene.1 It was recently shown that germ line deletions involving the last exon of the non-MMR gene, EPCAM (OMIM#185535), may silence its neighboring gene, MSH2 (OMIM#609309), which is located 17 kb downstream of EPCAM, via promoter hypermethylation. This epigenetic inactivation seems to be effective only in tissues in which EPCAM is expressed.3,4 The EPCAM gene codes for the epithelial cell adhesion molecule also known as CD326, which is expressed in all normal epithelial cells and in carcinoma tumors.5 Thus, deletions of the last exon of EPCAM constitute a distinct class mutation associated with LS.Currently, the standard genetic test for LS (point mutation and large-rearrangement analysis of MLH1, MSH2, MSH6, and PMS2) frequently fails to detect a pathogenic mutation. For this reason, we evaluated the association between EPCAM deletions and LS in a Spanish population and its clinical implications. 相似文献
122.
Razvan Bucuresteanu Lia-Mara Ditu Monica Ionita Ioan Calinescu Valentin Raditoiu Bogdan Cojocaru Ludmila Otilia Cinteza Carmen Curutiu Alina Maria Holban Marius Enachescu Laura-Bianca Enache Gabriel Mustatea Viorel Chihaia Adela Nicolaev Elena-Larisa Borcan Grigore Mihaescu 《Materials》2021,14(18)
Preventing and controlling the spread of multidrug-resistant (MDR) bacteria implicated in healthcare-associated infections is the greatest challenge of the health systems. In recent decades, research has shown the need for passive antibacterial protection of surfaces in order to reduce the microbial load and microbial biofilm development, frequently associated with transmission of infections. The aim of the present study is to analyze the efficiency of photocatalytic antimicrobial protection methods of surfaces using the new photocatalytic paint activated by light in the visible spectrum. The new composition is characterized by a wide range of analytical methods, such as UV-VIS spectroscopy, electron microscopy (SEM), X-ray powder diffraction (PXRD) or X-ray photoelectron spectroscopy (XPS). The photocatalytic activity in the UV-A was compared with the one in the visible light spectrum using an internal method developed on the basis of DIN 52980: 2008-10 standard and ISO 10678—2010 standard. Migration of metal ions in the composition was tested based on SR EN1186-3: 2003 standard. The new photocatalytic antimicrobial method uses a type of photocatalytic paint that is active in the visible spectral range and generates reactive oxygen species with inhibitory effect against all tested microbial strains. 相似文献
123.
Adela Castillejo Nathaniel Rothman Cristiane Murta‐Nascimento Núria Malats Montserrat García‐Closas Angeles Gómez‐Martínez Josep Lloreta Adonina Tardón Consol Serra Reina García‐Closas Stephen Chanock Debra T. Silverman Mustafa Dosemeci Manolis Kogevinas Alfredo Carrato José Luis Soto Francisco X. Real 《International journal of cancer. Journal international du cancer》2009,124(3):608-613
The transforming growth factor‐beta (TGF‐β) signalling pathway plays an important role in tumor development and progression. We aimed at analyzing whether 7 different common variants in genes coding for 2 key members of the TGF‐β signalling pathway (TGFB1 and TGFBR1) are associated with bladder cancer risk and prognosis. A total of 1,157 cases with urothelial cell carcinoma of the bladder and 1,157 matched controls where genotyped for 3 single nucleotide polymorphisms (SNPs) in TGFB1 (rs1982073, rs1800472, rs1800471) and an additional 3 SNPs and 1 indel polymorphism in TGFBR1 (rs868, rs928180, rs334358 and rs11466445, respectively). In the case‐control study, we estimated odds ratios and 95% confidence intervals for each individual genetic variant using unconditional logistic regression adjusting for age, gender, study area and smoking status. Survival analysis was performed using the Kaplan‐Meier method and Cox models. The endpoints of interest were tumor relapse, progression and death from bladder cancer. All the SNPs analyzed showed a similar distribution among cases and controls. The distribution of the TGFBR1*6A allele (rs11466445) was also similar among cases and controls, indicating no association with bladder cancer risk. Similarly, none of the haplotypes was significantly associated with bladder cancer risk. Among patients with muscle‐invasive tumors, we found a significant association between TGFBR1‐rs868 and disease‐specific mortality with an allele dosage effect (p‐trend = 0.003). In conclusion, the genetic variants analyzed were not associated with an increased risk of bladder cancer. The association of TGFBR1‐rs868 with outcome should be validated in independent patient series. © 2008 Wiley‐Liss, Inc. 相似文献
124.
Ariane VettorazziIñaki Fernández de Trocóniz Elena González-PeñasLeire Arbillaga Laura-Ana CorcueraAna Gloria Gil Adela López de Cerain 《Food and chemical toxicology》2011,49(9):1935-1942
The impact of age and gender on Ochratoxin A (OTA) distribution in kidney and liver were studied. OTA was quantified in kidney and liver of young and mature rats of both sexes. Data was fit simultaneously using the population approach with NONMEM program. Fed and fasted mature males showed a 30% decrease and an 11% increase in relative bioavailability, respectively, in comparison with the rest of the groups. The OTA concentrations reached in kidney and liver were very similar between both organs. The models that best fit to data were the ones that considered that distribution of OTA to kidney and liver occurs from the central compartment and that elimination occurs mainly from the liver compartment. The kinetic analysis revealed that both, the apparent volume of distribution of the central compartment (V/F) and the apparent volume of distribution of the liver and kidney compartments (VL,K/F) increased significantly with body weight. Thus, the sex differences observed in organs distribution are a reflection of the differences in relative bioavailability observed in adult males, as a consequence of the fed and fasted conditions and to the significant higher body weight of mature males which directly affected the V/F and VL,K/F. 相似文献
125.
Reout Arbel Hannah L. Schacter Sohyun C. Han Adela C. Timmons Lauren Spies Shapiro Gayla Margolin 《Developmental psychobiology》2019,61(6):930-941
This study investigates bidirectional associations between adolescents’ daily experiences of victimization and aggression perpetration within friendships. We investigated (a) across-day associations between victimization and aggression perpetration; (b) morning cortisol activity as a moderator of cross-day victimization and aggression links; and (c) potential sex differences in these patterns. For 4 consecutive days, 99 adolescents (Mage = 18.06, SD = 1.09, 46 females) reported whether they were victimized by or aggressive toward their friends. On three of these days, adolescents provided three morning saliva samples. Multilevel path analyses showed that across days, victimization and aggression were bidirectionally linked, but only for male adolescents. Additionally, for male adolescents, morning cortisol output (but not morning cortisol increase) moderated the association between victimization and next-day aggression; victimization predicted greater next-day aggression for boys with low, but not high, morning cortisol output. Findings implicate a physiological factor that may modify daily links between victimization and aggression in male adolescent friendships. 相似文献
126.
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128.
Vázquez-Memije ME Cárdenas-Méndez MJ Tolosa A Hafidi ME 《Experimental gerontology》2005,40(6):482-490
Throughout the maturation of germ cells, a morphological, biochemical and functional differentiation of mitochondria has been shown to occur. Ageing is known to cause changes involved in energy metabolism. These changes have been related to molecular and functional alterations in the properties of biological membranes. Variations in membrane lipid composition and lipid-protein interactions occur with ageing in several tissues. The present paper describes the relationship between these membrane alterations and the activities of lipid-dependent enzymes of isolated testis mitochondria in rats of from 10 days of age to 24 months. The specific activities of these enzymes are lower in preparations from adult and aged rats as compared to those from young rats. Temperature breaks of Arrhenius plots show age-dependent shifts to higher temperatures for the NADH-dehydrogenase, succinate-dehydrogenase, cytochrome c oxidase, and ATPase in senescent animals. Analysis of the membrane fatty acid composition reveals a distinct age-dependent fall in the content of polyunsaturated fatty acids accompanied by an increase in the proportion of saturated fatty acids and a decrease in polyunsaturated fatty acid percentage. The results suggest that during spermatogenesis and the ageing process some changes in the composition of the fatty acids in the surrounding membrane affect the protein-lipid interactions, producing a decrease in mitochondrial enzyme activities. 相似文献
129.
Accumulation of delta-aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to revert ALA-promoted damage, by incubating mouse astrocytes with 1.0 mM ALA for different times (1-4 hr) in the presence of melatonin (2.5 mM), superoxide dismutase (25 units/mL), catalase (200 units/mL) or glutathione (0.5 mM). The defined relative index [(malondialdehyde levels/accumulated ALA) x 100], decreases with incubation time, reaching values of 76% for melatonin and showing that the different antioxidants tested can protect astrocytes against ALA-promoted lipid peroxidation. Concerning porphyrin biosynthesis, no effect was observed with catalase and superoxide dismutase whereas increases of 57 and 87% were obtained with glutathione and melatonin, respectively, indicating that these antioxidants may prevent the oxidation of porphobilinogen deaminase, reactivating so that the AIP genetically reduced enzyme. Here we showed that ALA induces cell death displaying a pattern of necrosis. This pattern was revealed by loss of cell membrane integrity, marked nuclear swelling and double labeling with annexin V and propidium iodide. In addition, no caspase 3-like activity was detected. These findings provide the first experimental evidence of the involvement of ALA-promoted ROS in the damage of proteins related to porphyrin biosynthesis and the induction of necrotic cell death in astrocytes. Interestingly, melatonin decreases the number of enlarged nuclei and shows a protective effect on cellular morphology. 相似文献
130.
Risk of gallstone disease in advanced chronic phase of fascioliasis: an experimental study in a rat model 总被引:1,自引:0,他引:1
Valero MA Santana M Morales M Hernandez JL Mas-Coma S 《The Journal of infectious diseases》2003,188(5):787-793
In Wistar rats experimentally infected with Fasciola hepatica, the association between time of infection, number of flukes, rat weight, and serum lipid levels and the risk of developing pigment stones in the main bile duct was examined using data obtained at 100, 200, 300, 400, and 500 days postinfection. Gallstone presence increased with infection time. The relative risk of gallstone disease increased when the number of flukes per rat and rat weight increased. The presence of gallstones was associated with serum high-density lipoproteins and triglyceride levels. In a multivariate analysis, the association between gallstones and rat weight disappeared after adjustment for serum lipids. The absence of an effect of rat weight independent from serum lipids suggests that serum lipids are more closely linked to gallstone pathogenesis than is overweight. The presence of gallstones was strongly associated with the number of flukes located in the bile duct. A high risk of developing gallstones may be expected in human subjects inhabiting areas where F. hepatica is highly endemic and where high egg outputs detected in humans suggest that liver fluke burdens may also be very high. 相似文献