ABSTRACT
Objective To analyze the genetic characteristics of VP1-VP4 genes carried by cox-sackievirus A6 (CVA6) strains isolated from severe cases of hand, foot, and mouth disease (HFMD) in Shenzhen during 2012 to 2015. -ethods The VP1-VP4 genes of CVA6 strains isolated from severe HFMD cases in Shenzhen during 2012 to 2015 were amplified and sequenced. Phylogenetic analysis was performed to analyze the VP1-VP4 genes of CVA6 isolates and sequences downloaded from GenBank by using DNASTAR6. 0 and MEGA6. 02 software packages. Results Four cases of severe HFMD were caused by CVA6 in Shenzhen during 2012 to 2015. All of the patients had the symptom of fever, skin rash and aseptic encephalitis. The CVA6 strain causing severe HFMD in 2013 shared 98. 8％-98. 9％ homology in nucleotide sequences and 99. 3％-99. 8％ in amino acid sequences with the strains isolated in 2012. Two amino acid mutations were found in the CVA6 strain isolated in 2013, which were G73E in VP2 region and S13G in VP1 region. However, the CVA6 strain isolated in 2015 only shared 95. 0％ homology in nucleotide sequences and 99. 3％ homology in amino acid sequences with the strain isolated in 2013. Six amino acid mutations were identified including E73G in VP2 region and T5A, S27N, A30V, N137S and V242I in VP1 region. The phylogenetic analysis revealed that the four CVA6 strains belong to D3 sub-genotype. The CVA6 strains causing severe cases in 2012 had the nearest genetic relationship with the strain isolated in Changsha in 2012 (KJ156349). The CVA6 strain isolated in Shenzhen in 2013 had the nearest genetic relationship with the strain isolated in Shanghai in 2013 (KJ612513). The Shenzhen CVA6 isolate in 2015 showed high similarity to Weifang CVA6 isolate in 2014 (KX752785). Conclusions All CVA6 strains causing severe HFMD ca-ses in Shenzhen during 2012 to 2015 belongs to D3 sub-genotype. Mutations of S27N and A30V in the VP1 region of the CVA6 isolate in 2015 are located in the B cell epitopes. In addition, the VP1-V242I mutation in the CVA6 strain isolated in 2015 is located in the binding site of PSGL-1 receptor. These mutations may affect the binding of CVA6 strains to the cellular receptors and their infectivity to people.
ABSTRACT
El síndrome de Marfán es una patología poco común, causada por una mutación genética de fibrilina 1, imprescindible para la síntesis de fibras elásticas del tejido conectivo. Se caracteriza por una alta penetrancia y mar-cada heterogeneidad fenotípica. Entre las diferentes manifestaciones clínicas, la afectación cardiovascular merece una consideración especial, debido a su impacto en el pronóstico. El diagnóstico requiere una evaluación clínica completa de múltiples órganos y sistemas; por su ampliada sintomatología, la toma de decisiones es compleja, por tanto, cuando se sospeche síndrome de Marfán debe apli-carse la revisión de los criterios de Ghent. Si el diagnóstico es confirmado, debe iniciarse tempranamente su manejo multidisciplinario con un seguimiento minucioso, ya que se dis-pone de tratamientos farmacológicos y qui-rúrgicos que mejoran la esperanza de vida.Se reporta un caso clínico, con la revisión de las manifestaciones clínicas, criterios diagnósticos y manejo.
Marfan syndrome is a rare disease, caused by a genetic mutation of fibrillin-1, essential for the synthesis of connective tissue elastic fibers. It is characterized by a high penetran-ce and a marked phenotypic heterogeneity. Among the different clinical manifestations, cardiovascular involvement deserves a spe-cial consideration because of their impact on prognosis.The diagnosis requires a complete medical evaluation of multiple organs and systems; with expanded symptoms where the decision making is complex, so when Marfan syndro-me is suspected should be applied the revi-sed criteria of Ghent. If the diagnosis is confir-med, it must start early with its multidisciplinary approach carefully monitored because there are pharmacological and surgical treatments that improve life expectancy.Finally a case is reported, with the review of clinical manifestations, diagnostic criteria and management.
Subject(s)
Humans , Male , Child , Fibrillin-1 , Genetics , Marfan Syndrome , Pathology , Cardiovascular Abnormalities , MutationABSTRACT
Objective:To investigate the expression of MEK/ERK signaling pathways in renal cell car-cinoma with bone metastasis,and to analyze the differences of expressions of VEGFR-2,MEK,ERK on the primary and metastasis tissue and its mechanism.Methods:The tissue samples were obtained from 7 renal cell carcinoma patients kindly provided by Department of Urology,Peking University People’s Hos-pital from January 1,2009 to January 1,2010.The expression of MEK/ERK signaling pathways was de-tected in the 7 renal cell carcinoma patients`primary and matched metastatic tissues with ICH,The anti-body concentrations were 1 ∶200,1 ∶25,and 1 ∶250,respectively.The mutation of the twentieth exon of the PDGFRA gene,the second exon of the K-ras gene,the fifteenth exon of the Brafgene and the se-cond exon of the MEK1 gene were detected with PCR.Results:The expression intensities of VEGFR-2, MEK,and ERK were measured by H-score [intensity (1,2,3,or 4)multiplied by the distribution (%)].VEGFR-2,MEK,and ERK expressions were divided into 3 groups according to the positive dis-tribution of the tumor cells:1,0 -5%;2,6% -50%;and 3,>50%,To assess intratumor heteroge-neity,three distinct microscopic fields (×200)from each specimen were used to evaluate the expres-sions,Subsequently,the scores were averaged to obtain a single concatenated score for each tissue. VEGFR-2,MEK,and ERK expressions were assessed by 2 independent pathologists who were blinded to the clinicopathological data.The data were expressed as the mean value of the triplicate experiments.The expressions of MEK,and ERK were higher in the metastatic tissues than in the matched RCC tissues (6.10 ±4.10 vs.1.33 ±0.51,P =0.015;9.10 ±2.24 vs.4.43 ±2.84,P =0.021 )while the ex-pression of VEGFR-2 was not different between the primary and metastatic tissues (P =0.901).No mu-tation was detected on the twentieth exon of the PDGFRA gene,the second exon of the K-ras gene,the fifteenth exon of the Brafgene and the second exon of the MEK1 gene.Conclusion:MEK/ERK signa-ling pathways may play an important role in the metastasis and the resistance of sunitinib in RCC patients with bone metastasis.
