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.
Child* ; Giant Cell Tumors* ; Giant Cells* ; Humans ; Tendons*

OBJECTIVES: AGUS often reflects an immediate cervical cancer precursor such as a HSIL mimicking an endocervical glandular lesion. In this study, we attempted to assess the clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS) and determine the usefulness of the human papillomavirus (HPV) DNA testing as the triage strategies in evaluating AGUS. METHODS: Between 1994 and 1998, 67,730 Papanicolaou smears were evaluated at Kangnam and Uijongbu St Mary's Hospital. There were 87 (0.13%) cases of AGUS smears during that time. Colposcopy was performed on all women, and HPV DNA testing was performed on 11 persons. RESULTS: Mean age of these patients was 45.8 years. Histologic diagnosis of AGUS were kolocytosis and CIN-I in 6 (6.9%), CIS in one, endometrial hyperplasia in 2 (2.3%), endometrial adenocarcinoma in 7 (8.0%), cervical adenocarcinoma in 14 (16.1%) and cervical squamous cell carcinoma in 2 (2.3%) cases. Endometriosis was 8.9% under 46 years old and none in over 46. CIN was 8.9% and 7.2%, respectively. Cervical adenocarcinoma was 6.7% under 46 and 19.1% over 46. Endometrial cancer was 4.4% and 11.9%, respectively. The risk of cervical cancer and endometrial cancer was high in the AGUS with Adenocarcinoma ; Carcinoma, Squamous Cell ; Colposcopy ; Diagnosis ; DNA* ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Endometriosis ; Female ; Human Papillomavirus DNA Tests ; Humans ; Middle Aged ; Papanicolaou Test ; Triage ; Uterine Cervical Neoplasms

No abstract available.
Mass Screening* ; Uterine Cervical Neoplasms*

No abstract available.
Hysterectomy* ; Sexual Behavior*

No abstract available.
Alopecia ; Humans ; Male

OBJECTS: This study was conducted to investigate the effects of sleep apnea syndromes on the systemic blood pressure. METHODS: The subjects were 140 patients who were consulted to Yon-jung brain auction and sleep research center for polysomnography due to snoring and sleep apnea from Jan. 1st 1995 to Oct. 31st 1995. Twenty-four out of 140 were excluded due to cardiovascular diseases other than systemic hypertension, antihypertensive medication, inadequate data or diagnosis other than sleep apnea syndrome. The remaining 116 were accepted as proper subjects. Using Pearson's correlation and multiple regression analysis, we looked for the relationship between sleep and respiratory variables to systemic blood pressure. RESULTS: The results were as follows : 1) According to the correlation analysis, statistically significant variables to mean systolic and diastolic blood pressure were the total time and total number of sleep apnea, degree of oxygen saturation of total sleep time, apnea index, total time and total number of central apnea, and the total time of obstructive apnea. 2) According to the multiple regression analysis, only the total time of sleep apnea significantly affected mean systolic and diastolic blood pressure, and the degrees of affection were 7.9% and 6.2% respectively. CONCLUSION: These findings showed that sleep apnea syndrome had lower influence over systemic blood pressure than expected and regardless of the type, only the total time of sleep apnea influenced systemic blood pressure. In the case of central apnea, mechanisms other than hypoxemia and the increase of sympathetic activity during arousal may make it possible to increase systemic blood pressure.
Anoxia ; Apnea ; Arousal ; Blood Pressure* ; Brain ; Cardiovascular Diseases ; Diagnosis ; Humans ; Hypertension ; Oxygen ; Polysomnography ; Sleep Apnea Syndromes* ; Sleep Apnea, Central ; Snoring

In our comparative study of L1 consensus primers with E6 type-specific primers for detection of human papillomavirus (HPVs) by polymerase chain reaction (PCR) in 35 cases of cervical neoplasia, the detection rate by E6 primers (54%; 19/35) was significantly higher than that by L1 primers (25%; 9/35) (p < 0.01). And all specimens HPV-positive with L1 primers were also positive by E6 primers. HPV DNA could be amplified in 36% (9 of 25) of tissue by L1 consensus primers from which beta-globin gene was amplified as compared with 64% (16 of 25) of tissue by E6 type-specific primers. With the L1 consensus primers, 8 cases were positive for HPV-16 and 1 case was positive for HPV-33. These results show that the L1 consensus primers have inferior sensitivity to the E6 type-specific primers for the detection of HPV by PCR. But the L1 consensus primers have great value in making simultaneous detection of various HPV types in a single tube reaction, thus they permit reduction of time and the economic burden of the experiment.
Base Sequence ; DNA, Viral/analysis ; Female ; Humans ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Papillomaviridae/genetics/*isolation & purification ; *Polymerase Chain Reaction ; Uterine Cervical Neoplasms/*microbiology

For evaluating the reproductive performances of GTD patients, we found 115 cases of GTD patients, 77 HM and 38 GTT, who became pregnant after the completion of treatments and follow-up period. The results of this study suggest subsequent pregnancies after the completion of treatments may promise normal reproductive outcomes regardless of the chemotherapy.
Drug Therapy ; Follow-Up Studies ; Gestational Trophoblastic Disease* ; Humans ; Pregnancy

OBJECTIVE: A histopathologic review of synchronous primary neoplasms of the female reproductive tract was presented and the possible correlation among discrete tumor subsets, natural history, and survival was evaluated. METHODS: Between 2000 and 2005, 20 patients with synchronous primary cancers of the gynecologic malignancy were identified. Clinical and pathologic informations were obtained from medical records. Kaplan-Meier survival analysis was performed. RESULTS: The patients with Synchronous primary malignancies constituted 0.63% of all genital malignancies. The most frequently observed synchronous neoplasms were those of the ovary with the endometrium (40%). The mean age of patient with synchronous ovarian and endometrial cancer was 45.2 years. 8 patients underwent the hysterectomy with bilateral salpingo-oophorectomy and adjuvant therapy. The mean survival is 57 months (SE 10.0, 95% Confidence interval 37-77). CONCLUSION: Synchronous ovarian and endometrial cancers were detected in relatively early age and the prognosis was favorable.
Endometrial Neoplasms ; Endometrium ; Female* ; Humans ; Hysterectomy ; Medical Records ; Natural History ; Neoplasms, Multiple Primary ; Ovarian Neoplasms ; Ovary ; Prognosis