Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

BACKGROUND: High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16(ink4a )drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16(ink4a )overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16(ink4a )overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas METHODS: Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16(ink4a )was analyzed by RT-PCR and by immunohistochemical technique. RESULTS: The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands). The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16(ink4a )cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. CONCLUSION: Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical carcinomas and cannot be an effective marker of cancer cells with up-regulated expression of p16(ink4a). Our data confirm other previous studies claiming specific p16INK4a up-regulation in the majority of cervical carcinomas at both the protein and mRNA levels. Cytoplasmic accumulation of p16(ink4a )is a feature of cervical carcinomas

Features autonomic nervous system in children with attention deficit hyperactivity disorder

Physiological responses of peripheral autonomic nervous system are critical to maintaining homeostasis, physiological flexibility, and acute adaptation to stressful situations mediated by a variety of chemical coding systems, thus maintaining body homeostasis. The autonomic nervous system is also responsible for cognitive, affective, and behavioral responses, and its deregulation is manifested in a variety of neuropsychological disorders. Both the sympathetic and parasympathetic branches of the autonomic nervous system promote social functioning and communication, with activation of the sympathetic nervous system (SNS) reflecting a threat-oriented response, and the dominance of the parasympathetic nervous system (PNS) facilitating adaptive social interaction. PNS plays an important role in social functioning, innervating several organs of the face and neck and influencing various functions, including cardiac activity related to social behavior and communication

Factors affecting perceptions in transport – A deep dive into the motorbike ban in Hanoi, Vietnam

The dependence on motorbikes has contributed to traffic problems in Hanoi, Vietnam. Policymakers have considered a controversial ban on nonelectric motorbikes in parts of the city in an effort to reduce congestion and pollution. However, understanding of individual perceptions on critical transport policies, such as this potential ban is lacking, especially in the Global South, with implications for evidence-based policy making. This paper presents the results of some exploratory data analysis and a machine learning application using a travel survey recently conducted in Hanoi. It aims to understand how residents perceive a potential motorbike ban, their perceptions of different mobility modes, as well as their future plans for mobility if motorbikes are banned. This data-driven analysis of policy scenarios shows that awareness of the potential ban, distance to public transport, and individual transport modal choice determine the acceptability of the proposed motorbike ban and its likely success. It also shows that policymakers in Hanoi should also consider citizens’ plans for future vehicle ownership, as the analysis results suggest that cars are likely to replace motorbikes if the ban is implemented

Short course of the essentials pediatrics (lectures for 4th year)

This publication offers lecture materials on pediatrics created in accordance with the standard program for students of the 4th course of the international faculty of higher medical educational institutions of the IV level of accreditation. The materials cover modern classifications, leading mechanisms of pathogenesis, diagnostic criteria, and the basics of therapy