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.
Mass Screening* ; Uterine Cervical Neoplasms*

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.
Hysterectomy* ; Sexual Behavior*

No abstract available.
Alopecia ; Humans ; Male

No abstract available.
Child* ; Giant Cell Tumors* ; Giant Cells* ; Humans ; Tendons*

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

Darier's disease is a genetic disorder of keratinization with autosomal dominant inheritance. Its appearance is usually in the form of greasy, crusted, keratotic yellow-brown papules and plaques found particularly on seborrheic areas of the body. However, there are some clinical variants showing atypical skin lesions. Here we report an unusual case of Darier's disease, which mainly showed prominent comedonal papules over the face.
Darier Disease ; Keratins ; Skin ; Wills

Cervical cancer and its precursors are caused principally, if not exclusively, by HPV infection and HPV DNA is found in more than 90% of cervical cancers. Cervical cytology is limited by its false negativity and this may be supplimented by other adjunctive test such as HPV test. It is therefore important to explore the use of HPV DNA detection as a primary or supplementary screening method and to determine whether HPV typing can be used as a predictor of a lesion's clinical behavior. Cervical cytology and Hybrid Capture test for HPV detection were performed in 450 asymtomatic wornen visited Health Care Center in Kangnam St. Mary's Hospital,and none of whom was believed to have current cervical disease. The Papanicolaou cytology results were classified by The Bethesda System : 333(74.%) women were classified to within normal limit, 19(4.2%) benign reactive change, 38(8.4%) ASCUS, 59(13%) low grade SIL, and only one woman high grade SIL. Twenty five of 450(5.6%) women showed HPV infection by Hybid Capture test. Among 98 wornen with abnormal Papanicolaou cytology, 16(16.3%) women showed HPV DNA positivity. (continue)
Delivery of Health Care ; DNA* ; Female ; Humans* ; Mass Screening* ; Papilloma* ; Uterine Cervical Neoplasms

Specific types of HPV are currently implicated as etiologic agents of precuraors and cancerous lesions of the uterine cervix. This study used the data gained from one hundred twenty five wmen who underwent cnnrrent. Papanicoiaou smear, colposcopic diagnosis, and cervicovaginal lavage for HPV BNA test at Dysplasia Clinic in Kangnam St. Mary's Hospital. 38 patients had low-grade squemous intraepithelial lesiona (LGSILs) and 34 had high grade squamoua intrepithelial lesions (HGGILs), 24 invasive cervical cancers, and 29 normal control. Comlposcopic feeturee were prpectiively recorded by Reids colposcopic index and t,hen correlated with histapathologic diagnoeis. Using the colposcopic index, 86.4% was eorrelated with histapathologic findings. DNAs extracted from the cervicovaginal lavages were analyzed by polymerase chain reaction (PCR) using the HPV L1 consensus primers. HPV DNA was detected in 79 of 125 women (63.2%). Prevalences of HPV DNA in the patients with LGSIL (71.1%), HGSIL, (76.5%i) and cervix caneer (75.0%) showed no difference in statistics. Low-risk oncogenic viruses.(HPV-6/11) were present in 13.2% of patients with LGSIL, but none was detect,ed in thoee with HCSIL and cervix cancer. Intermediate-riak oncogenic viruses (HPV-31/33/35) were deterted in 5.3% of patients with LGSIL 8.8% in HGSIL, and none in cervix cancer. Prevalence of high-rsk onccgenie type HPV 16/18 was higher in HGSIL (41.2%) and invnsive cervical cancer (45.8%) than those of LGSII (15.8%) and cnntrols (3.5 %) (P = 0.0001). These data indicate that colposcnpic scoring has adjunctive diagnostic rale in predict,ing his-tology. And, HPV DNAs were found in similar incidence in the various histologic grades of cervical neoplasia. HPV-6/11 were detec only in LGSIL and HPV 31/33/35 in LGSIL and HGSIL, but not in invasive canser. HPV-16/18 were the predominant viruses which were detected in HGSIL, and invasive aervi 1 cancer. In canch.isizn, a combination of HPV testing and colposcopic scoring would provide sensitive screening methade for cervial cencer and pr nceraus lesions. And HFV typing might have prognmtic value in the management of patients with HPV related cervical neoplastic lesions.
Cervix Uteri ; Colposcopy* ; Consensus ; Diagnosis* ; DNA ; Female ; Humans* ; Incidence ; Mass Screening ; Oncogenic Viruses ; Polymerase Chain Reaction ; Prevalence ; Respiratory Sounds ; Therapeutic Irrigation ; Uterine Cervical Neoplasms