[Genomic organization and proteins of human papillomavirus]. / Insan Papillomavirusunun Genomik Yapisi ve Proteinleri.

Human papillomavirus (HPV) infections are one of the most common sexually-transmitted diseases worldwide. Nowadays, more than 200 HPV types have been identified by DNA sequencing. HPV types are also grouped into three, such as high-risk (types 6, 11, 40, 42, 43, 44, 54, etc), probable high-risk (types 26, 53, 66) and low-risk (types 6, 11, 40, 42, 43, 44, 54, etc) types according to their oncogenic potential. HPV is currently considered as the main aetiological factor of cervical intraepithelial neoplasia and cervical cancer. HPV types classified in Papillomaviridae family, are non-enveloped, icosahedral symmetric viruses about 55 nm in size. Viral genome consists of circular double-stranded DNA, about 8 kb in size, encodes for early proteins (E1, E2, E4, E5, E6, E7) which play role in virus replication and cell transformation, and for late (L1, L2) proteins which are the structural units of the viral capsid. Integration of HPV DNA into the host chromosome is crucial for viral persistence and for carcinogenic effects. Viral DNA may integrate randomly to the cell genome and integration can lead to the deregulation and increase of E6/E7 expression leading to oncogenesis. However, increased expression of E6/E7 gene products may occur without genome integration. E6 and E7 proteins of especially highrisk HPV types (e.g. types 16 and 18) interact with tumor supressor proteins such as p53 and retinoblastoma (pRb) proteins, respectively; inhibit their functions and cause uncontrolled proliferation and immortalization of the cells. The binding of E6 protein to p53 leads its rapid degradation, and the eclipse in the G1 phase, DNA repair mechanisms and apoptosis are terminated. In the other way, E7 protein interacts with pRb and mitotically interactive cellular proteins such as cyclin-E, causing stimulation of cellular DNA synthesis and cell proliferation. Recently identified genes E3 and E8 are located in early gene region and found only in a few papillomavirus types (HPV 1, 11, 16, 31, 33). A fusion protein, E8^E2C, functions as a negative regulator for HPV DNA replication and it is thought that this protein may play a role in the control of viral copy number as well as in the stable maintenance of HPV episomes. In this review article, the genomic structure of HPV and the functions of gene products have been summarized.

Crucial markers showing the risk of coronary artery disease in obesity: ADMA and neopterin.

BACKGROUND: Obesity is responsible for high morbidity and mortality, both in developed and developing countries. It is associated with many chronic and metabolic diseases. Asymmetric dimethylarginine (ADMA) has been demonstrated to be a biomarker of endothelial dysfunction in humans and increased ADMA associated with cardiovascular disease (CVD) risk has been reported in many states. Neopterin (NP) produced by monocytes/macrophages in response to stimulation by interferon-gamma (IFN-γ) is emphasized in recent findings. The current study aims to investigate ADMA and NP levels which may assume a role in guiding the early diagnosis of coronary artery disease in obesity. METHODS: This is an original research study in which ADMA and NP levels of 50 patients (25 male/25 female) diagnosed with obesity were compared with those of 30 healthy individuals (15 male/15 female) as control. The high-performance liquid chromatography (HPLC) method was used while determining parameters. RESULTS: ADMA and NP levels in obese individuals were found to be significantly higher than in those enrolled in the control. ADMA values were found to be higher in obese subjects (0.71±0.24 µmol/L) as compared with levels found in healthy subjects (0.58±0.16 µmol/L) (p<0.05). A significant increase of serum neopterin levels was found in obese subjects (8.8±3.5 µmol/L) as compared with controls (4.9±1.69 µmol/L) (p<0.05). Also, there was a strong positive correlation between NP and ADMA values in obese individuals (r=0.954). CONCLUSIONS: Our study revealed that obese subjects have higher ADMA and neopterin levels. These results demonstrated that both ADMA and NP levels may be potential risk factors for coronary heart disease in obesity.