Human papillomavirus (HPV) infection in a case‐control study of oral squamous cell carcinoma and its increasing trend in northeastern Thailand -
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|Human papillomavirus (HPV) infection ...
Human papillomavirus (HPV) is an independent risk factor for development of oral squamous cell carcinoma (OSCC). This study aimed to investigate the role of HPV infection and the trend in percentage of HPV‐associated OSCC over a five‐year period in northeastern Thailand. In this case‐control study, 91 exfoliated oral cell samples and 80 lesion cell samples from OSCC cases and exfoliated oral cells from 100 age/gender‐matched controls were collected. HPV infection was investigated by PCR using GP5+/GP6+ primers followed by HPV genotyping using reverse line blot hybridization. Quantitative RT‐PCR was used to evaluate HPV oncogene transcription. Temporal trends of HPV infection were evaluated in archived formalin‐fixed paraffin‐embedded (FFPE) OSCC tissues using in situ hybridization. HPV DNA was found in 17.5% (14/80) of lesion samples from OSCC cases and 29.7% (27/91) of exfoliated oral cell samples from the same cases. These values were significantly higher than in exfoliated oral cell samples from controls (13%, 13/100). HPV‐16 was the genotype most frequently found in OSCC cases (92.8%, 13/14 infected cases). Interestingly, HPV oncogene mRNA expression was detected and correlated with OSCC cases (P & 0.005). Of 146 archived FFPE OSCC samples, 82 (56.2%) were positive for high‐
isk HPV DNA and 64 (43.8%) cases were positive for HPV E6/E7 mRNA expression. There was a trend of increasing percentage of HPV‐associated OSCC from 2005 to 2010. This was especially so for females with well‐differentiated tumors in specific tongue sub‐sites. We suggest that HPV infection plays an important role in oral carcinogenesis in northeastern Thailand. This article is protected by copyright. All rights reserved
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Genetic variation and differential expression of p21 (WAF1/CIP1) in the context of HIV-1 control
Koor, Gemma Whitney
A recent study has shown variable p21 expression levels linked to individuals displaying different levels of HIV-1 control, with elite controllers (ECs) and viraemic controllers (VCs) exhibiting higher p21 expression when compared to both healthy HIV-1 negative individuals and HIV-1-infected progressors. The role of p21 in HIV-1 control in a sub-Saharan African population has not been established.
Polymorphisms in the regulatory regions of p21, as well as in the microRNAs (miRNAs) that affect p21 regulation can contribute to differential p21 expression. In this study we developed real-time PCR assays to genotype the p21 exonic rs1801270 and 3‘UTR rs1059234 SNPs, in addition to the p21-associated miRNA (miR-106b) rs999885 SNP. We determined their allelic and genotypic frequencies in Black South African HIV-1 negative individuals (n=72), HIV-1 controllers (HICs) (n=52) further subdivided into ECs (n=11), VCs (n=30) and high viral load long term non-progressors (HVL LTNPs) (n=11), and HIV-1 infected progressors (n=74). We sequenced a region of the p21 5‘UTR and 3‘UTR in a subset of these individuals (HICs: n=52, progressors: n=44) to identify variants that may be modulating p21 expression. We compared levels of p21 mRNA, a marker for p21 expression, in a smaller group of individuals (n=50) with similar clinical phenotypes to determine if p21 upregulation was associated with natural control of HIV-1. Lastly, we developed a real-time PCR assay to genotype a p21 5‘UTR SNP, rs733590, that alone, and together with HLA-B*2705, was recently shown to directly impact on p21 expression in Caucasians. This SNP was genotyped and analysed in the individuals with p21 mRNA expression data.
The p21 rs1801270 and rs1059234 SNPs were found to occur in partial linkage disequilibrium (LD) (r2=0.61). Although ECs had markedly less representation of the 3‘UTR rs1059234 mutant allele (T) and heterozygosity (CT) compared to progressors (T allele: 9.1% ECs vs. 25% CT genotype: 18.2% ECs vs. 42% progressors), this did not reach significance (p=0.11, OR=3.33; p=0.19, OR=3.49, respectively). Interestingly, HIV-1 controllers with &400 HIV-1 RNA copies/ml (&400 HICs) also had less representation of the CT genotype when compared to progressors (20% vs. 42%, p=0.11, OR=2.91). In silico analysis of this 3‘UTR SNP suggested that there are functional implications in terms of miRNA regulation, however when p21 mRNA expression was analysed with respect to this SNP, no effect was seen. The role of this 3‘UTR SNP on p21 expression and/or function and HIV-1 control requires
further investigation. The p21 exonic rs1801270 SNP showed no difference in representation among the clinical phenotypic groups and no effect was seen on p21 mRNA expression.
When comparing HIV-1 controllers with &400 HIV-1 RNA copies/ml (&400 HICs) to progressors, the &400 HICs had significantly lower representation of the minor allele (A) of the miR-106b rs999885 SNP (p=0.04, OR=2.28). In addition, heterozygosity for this SNP (GA) was found in a much lower frequency in &400 HICs when compared to progressors (p=0.05; OR=2.56). Stratification of individuals according to their miR-106b rs999885 SNP genotype and p21 mRNA expression revealed the GA genotype to be associated with a trend to higher p21 mRNA expression (p=0.066). A role for the miR-106b rs999885 SNP in HIV-1 control in individuals with higher viraemia needs to be validated in larger cohorts.
Characterisation of the p21 regulatory regions, namely a region of the 5‘UTR and the 3‘UTR, identified 19 polymorphisms (18 SNPs and one indel) and 12 SNPs in the respective regions. A prevalent, previously uncharacterised 11-SNP haplotype (LD: r2=1) was detected in the p21 promoter region at a frequency of 39.42% in the HIV-1 controllers and 48.86% in the progressor cohort. In addition, a 2-SNP haplotype was identifed and was found to be in moderate LD with the 11-SNP haplotype (r2=0.67). The ECs were found to have a trend of less representation of the 2-SNP haplotype minor allele when compared to progressors (p=0.08, OR=2.83). Other than the rs1059234 SNP, no other SNPs in the 3‘UTR were differentially represented in any of our studied groups.
p21 mRNA expression analysis showed significant correlations between p21 mRNA expression and markers of disease progression (HIV-1 viral load: r=0.69, p&0.0001 and CD4+ T cell count: r=-0.53, p=0.0005). In our study, ECs and VCs had significantly lower p21 mRNA expression compared to progressors (p=0.002 and p=0.001, respectively). Furthermore, in our Black South African population (n=50), the p21 5‘UTR rs733590 SNP CT and TT genotypes were not associated with higher p21 mRNA expression as has been shown in Caucasians. This, together with the absence of HLA-B*2705 in our Black South African population, points to host genetic differences as the likely contributors to the different results seen in our study with respect to p21 expression and HIV-1 control when compared to reported literature.
Future work with larger sample sizes and varied population groups will be highly informative in determining the role of p21 and natural control of HIV-1 in the Black South African population.
Description:
A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science (Med) Virology.
Johannesburg, 2016
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Electronic Theses and Dissertations儿童血友病家庭治疗开展现状调查
Survey of status quo of family therapy developed in children with hemophilia
[目的]探讨我国儿童血友病家庭治疗开展情况。[方法]采用自制儿童血友病家庭治疗执行情况调查表对91例血友病患儿家长进行调查。[结果]40例(44.0%)血友病患儿开展家庭治疗，其中血友病甲35例，血友病乙5例。患儿年龄、病程、上学阶段和父亲学历是开展家庭治疗的影响因素。操作者以病人母亲为主，其次是病人家庭中从事医务工作的亲友、病人本人和病人父亲；操作者的学习途径除医务工作亲友的专业学习外，主要包括医生或者护士传授、自学(书籍或网络等)；家长对于静脉输液操作技术和应急处理知识掌握正确率较低。51例(56.0%)患儿家庭没有开展家庭治疗，未掌握操作技能(35.3%)是第1位原因。[结论]现阶段血友病患儿开展家庭治疗的比例不高，要加强输液操作技术和安全管理，多关注年龄小的患儿、病程较短以及父亲学历较低的家庭。
首都医科大学附属北京儿童医院,100045
成都市妇女儿童中心医院,610000
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&&8:00-11:30,13:00-17:00(工作日)ISSR Analysis on Genetic Relationship among 29 Oncidium Germplasms--《Fujian Journal of Agricultural Sciences》2014年11期
ISSR Analysis on Genetic Relationship among 29 Oncidium Germplasms
LUO Yuan-ZHONG Huai-HUANG Min-Wu Jian-Crop Research Institute,Fujian Academy of Agricultural SFlower Research Center,Fujian Academy of Agricultural SFujian Engineering Research Center for Characteristic F
Based on the ISSR molecular markers,agenetic comparison among 29 Oncidium germplasms was established.The 10 ISSR primers produced 144 DNA bands,averaging 14.4DNA bands per primer,and of which124(86.11%)were polymorphic.The genetic similarity coefficients of the germplasms ranged from 0.34 to 0.91.At the similarity coefficient of 0.56,the 29 germplasm accessions were classified into 3groups.The clustering results were basically consistent with the traditional classification,which is closely correlated to the flower phenotype of germplasm resources.The result obtained from this study seemed to preliminarily validate the application of ISSR molecular markers for genetic analysis on Oncidium.
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