OBJECTIVE: Human papillomavirus (HPV) is strongly implicated as a causative agent in the etiology of cervical cancer. Of its gene products, E6 and E7 oncoproteins play major roles by inactivation of cellular p53 and pRb tumor suppressor proteins, respectively. However, it has been recently suggested that p53 and/or pRb-independent functions of E6 and E7 are involved in cervical carcinogenesis. The purpose of this study is to identify novel a cellular target, p73, of E6 and to determine how E6 inactivates p73 function, METHODS: The interaction between E6 and p73 were identified by the yeast two-hybrid assay in vivo and the GST pull-down assay in vitro. The function of the interaction was determined by transient transfections using p21 promoter-CAT reporter plasmid. The molecular mechanism underlying the functional significance of the interaction was further assessed by in vivo and in vitro protein degradation assays, and gel mobility shift assays. RESULTS: Yeast two-hybrid and GST pull-down assays indicate a physical interaction between p73 and either HPV-16 or HPV-11 E6 proteins in vivo and in vitro, respectively. Transactivation domain (amino acid residues 1-49) is found to be absolutely required for this interaction. Transient co-expression of E6 significantly inhibits the p73-mediated activation of p21WAF1 promoter in a p53-defective C33A cell line. Using Ga14-p73 fusion protein, we demonstrate that E6 inhibition of p73 transactivation function is independent of sequence-specific DNA binding, which is confirmed by direct electrophoretic mobility shift assay. Moreover, E6 inhibits p73 function by interfering with the activity of the amino-terminal activation domain. The protein degradation assays in vivo and in vitro indicate that p73, unlike p53, is not susceptible to E6-dependent proteolysis. CONCLUSION: Throughout this study, we identified p73 as a novel cellular target of HPV-E6 protein and found that E6 binds p73 through the amino-terminal transactivation domain, and inhibits its transactivation function independent of the protein degradation and DNA binding. These overall results, consequently, suggest that in addition to the inactivation of p53, the functional interference of p73 by HPV-E6 may, at least in part, contribute to E6-mediated cellular transformation.
Carcinogenesis ; Cell Line ; DNA ; Electrophoretic Mobility Shift Assay ; Human papillomavirus 11 ; Human papillomavirus 16 ; Humans ; Oncogene Proteins ; Plasmids ; Proteolysis ; Transcriptional Activation ; Transfection ; Tumor Suppressor Proteins ; Two-Hybrid System Techniques ; Uterine Cervical Neoplasms ; Yeasts

No abstract available.

Previous studies have suggested that glutathione S-transferase (GST) genotypes may play a role in determining susceptibility to cervical cancer, though the data have often been conflicting. The objective of this study was to examine the effect of GSTP1 polymorphism on cervical carcinogenesis. The studied subjects, patients who were pathologically diagnosed with invasive cervical cancer yielding positive results for human papillomavirus (HPV) (n=342), were compared to healthy, normal, female controls (n=707). DNA from peripheral blood samples from studied subjects whose GSTP1 specific sequences had been determined by PCR with allele-specific primers were reviewed in comparison with the normal controls. The genetic susceptibility of GSTP1 (11q 13.1) in cervical carcinogenesis was determined by examining the effect of gene and environmental factors by the different histopathologic types of invasive cervical cancers. In assessing polymorphism GSTP1, the percentages of individuals homozygous for the A allele, homozygous for the G allele, and heterozygous for the two alleles were 66.8%, 3.9%, and 29.3%, respectively, in the control group, and 64.3%, 4.1%, and 31.6%, respectively, among in women with cervical cancer. Compared with GSTP1 G allele positive (GA or G/G), the odds ratio (OR) (95% confidence interval) for GSTP1 A/A was 1.0 (0.7 - 1.4) for invasive cervical cancer. However, the risk increased with GSTP1 A/A among ever smokers (3.9, 1.7 - 8.9, p-value=0.0012) compared with GSTP1 G allele positive among nonsmokers. In particular, this risk was higher among women with squamous cell carcinoma (4.7, 2.0 - 10.8, p=0.0003). Polymorphism of GSTP1 among smoking women was associated with a higher risk of developing cervical cancer.
Adult ; Aged ; Cervix Neoplasms/*etiology/genetics ; Female ; Glutathione Transferase/*genetics ; Human ; Isoenzymes/*genetics ; Loss of Heterozygosity ; Middle Age ; Polymorphism (Genetics) ; Risk ; Smoking

No abstract available.
Hematoma, Epidural, Spinal* ; Hemorrhage*

Purpose: This paper proposes a technological system that uses artificial intelligence to recognize and guide the operator to the exact stenosis area during endoscopic surgery in patients with urethral or ureteral strictures. The aim of this technological solution was to increase surgical efficiency. Methods: The proposed system utilizes the ResNet-50 algorithm, an artificial intelligence technology, and analyzes images entering the endoscope during surgery to detect the stenosis location accurately and provide intraoperative clinical assistance. The ResNet-50 algorithm was chosen to facilitate accurate detection of the stenosis site. Results: The high recognition accuracy of the system was confirmed by an average final sensitivity value of 0.96. Since sensitivity is a measure of the probability of a true-positive test, this finding confirms that the system provided accurate guidance to the stenosis area when used for support in actual surgery. Conclusions The proposed method supports surgery for patients with urethral or ureteral strictures by applying the ResNet-50 algorithm. The system analyzes images entering the endoscope during surgery and accurately detects stenosis, thereby assisting in surgery. In future research, we intend to provide both conservative and flexible boundaries of the strictures.

Artificial intelligence (AI) is used in various fields of medicine, with applications encompassing all areas of medical services, such as the development of medical robots, the diagnosis and personalized treatment of diseases, and personalized healthcare. Medical AI research and development have been largely focused on diagnosis, prediction, treatment, and management as an auxiliary means of patient care. AI is mainly used in the fields of personal healthcare and diagnostic imaging. In urology, substantial investments are being made in the development of urination monitoring systems in the personal healthcare field and diagnostic solutions for ureteral stricture and urolithiasis in the diagnostic imaging field. This paper describes AI applications for urinary diseases and discusses current trends and future perspectives in AI research.

No abstract available.
Animals ; Cell Adhesion* ; Female ; Leiomyoma* ; Mice ; Myometrium* ; Neural Cell Adhesion Molecules*

Glioblastoma is the most aggressive common brain tumor in adults. Curcumin, from Curcuma longa, is an effective antitumor agent. Although the same proteins control both autophagy and cell death, the molecular connections between them are complicated and autophagy may promote or inhibit cell death. We investigated whether curcumin affects autophagy, which regulates curcumin-mediated tumor cell death in A172 human glioblastoma cells. When A172 cells were incubated with 10 μM curcumin, autophagy increased in a time-dependent manner. Curcumin-induced cell death was reduced by co-incubation with the autophagy inhibitors 3-methyladenine (3-MA), hydroxychloroquine (HCQ), and LY294002. Curcumin-induced cell death was also inhibited by co-incubation with rapamycin, an autophagy inducer. When cells were incubated under serum-deprived medium, LC3-II amount was increased but the basal level of cell viability was reduced, leading to the inhibition of curcumin-induced cell death. Cell death was decreased by inhibiting curcumin-induced autophagy using small interference RNA (siRNA) of Atg5 or Beclin1. Therefore, curcumin-mediated tumor cell death is promoted by curcumin-induced autophagy, but not by an increase in the basal level of autophagy in rapamycin-treated or serum-deprived conditions. This suggests that the antitumor effects of curcumin are influenced differently by curcumin-induced autophagy and the prerequisite basal level of autophagy in cancer cells.
Adult ; Autophagy ; Brain Neoplasms ; Cell Death ; Cell Survival ; Curcuma ; Curcumin ; Glioblastoma ; Humans ; Hydroxychloroquine ; RNA ; Sirolimus

The persistent left superior vena cava (LSVC) is not rare cardiovascular developmental anomaly occurring both in association with congenital heart disease and as an isolated anomaly of no hemodynamic importance. We have studied 73 cases of the LSCV out of 1,060 cases of congenital heart disease catheterized at Yonsei Cardiovascular Center. We conducted the study with a view point of position of the heart and abdominal organs and segmental analysis of the underlying congenital heart disease. We also analysed the associated extracardiac vascular anomalies. The following results were obtained: 1) The incidence of this anomaly among congenital heart disease was 6.9% and 41 cases(56.2%) had cyanosis. 2) We observed 20 cases(27.3%) with the malposition of the heart and 17 cases(23.3%) with malposition of the abdominal organs. The ventricular loops revealed D-loop in 60 cases, L-loop in 7 cases and in the remaining 6 cases, it was uncertain. 3) With a view point of type of LSVC by Lucas & Krabill, type A was in 50 cases(68.5%), type D in 14 cases(19.2%), type B in 5 cases(6.8%) and type C in 4 cases(5.5%). 4) Associated cardiovascular anomalies were as follows: ventricular septal defect; 42 cases(57.5%), atrial septal defect; 33 cases(45.2%), patent ductus arteriosus; 27 cases(36.9%), and tetralogy of Fallot; 18 cases(24.7%). In conclusion, LSVC usually has no hemodynamic importance, but this cardiac anomaly is frequently combined with complex intracardiac anomalies. Therefore, it is important to making accurate diagnosis and successful management for preventing the risk of it.
Catheters ; Classification* ; Cyanosis ; Diagnosis ; Ductus Arteriosus, Patent ; Heart ; Heart Defects, Congenital ; Heart Septal Defects, Atrial ; Heart Septal Defects, Ventricular ; Hemodynamics ; Incidence ; Tetralogy of Fallot ; Vena Cava, Superior*

The alert regarding the emergence of novel influenza was issued by the WHO on April 24th, and the government has taken immediate actions to respond to the situation since then. Based on the presumption that a pandemic was imminent, countermeasures for the H1N1 influenza pandemic have been prepared by establishing and implementing effective public health crisis strategies over the past few years. Our main strategy during the pandemic influenza crisis has shifted in accord with the corresponding National Disaster Phases. In the Caution (Containment) Phase, our main goal was to contain the influx of disease from overseas. We focused on measures such as entry screening and quarantine inspection while monitoring travelers arriving from affected countries. In the Alert Phase I, our aim was deceleration and prevention of secondary community outbreaks through enhanced early detection. We intensified our surveillance and response system for possible mass outbreaks. During Alert Phase II, as the influenza had spread widely, our tactics switched to minimizing social and economic impact and preventing severe cases with early administration of antiviral agents, especially among high-risk patients. In the current Severe Phase, we are trying to reduce mortality cases with intensive care. Since we have implemented mass vaccination, we predict an early termination of the pandemic.
Antiviral Agents ; Critical Care ; Containment of Biohazards ; Deceleration ; Disasters ; Disease Outbreaks ; Humans ; Influenza, Human ; Mass Screening ; Mass Vaccination ; Pandemics ; Public Health ; Quarantine ; Vaccination