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

Hair follicle nevus is one of several nevi, in which hair and hair follicle are involved. Crowding of numerous tiny but mature hair follicles with thick fibrous root sheath are the characteristie histologic finding of the nevus. The patient was one month old male infant with pedunculated. mass l cm in size on the left preauricular area. Histologically the skin of the lesion is covered by acanthotic epidermis. In the corium are numerous small mature hair follicles with thick fibrous sheath and a few small Iobules of sebaceous gland embedded in a fibrovascular stroma. There are, however, no central plate of cartilage and adipose tissue.
Adipose Tissue ; Cartilage ; Crowding ; Dermis ; Epidermis ; Hair Follicle* ; Hair* ; Humans ; Infant ; Male ; Nevus* ; Sebaceous Glands ; Skin

Here we report an autopsy case of diabetic ketoacidosis (DKA) with severe hypertriglyceridemia (12,900 mg/dl). A 29-year-old woman with a history of type 1 diabetes was found dead at a motel. There was no injury on external inspection, but a lump of cheese-like material was noted in the heart at autopsy and peripheral blood plasma had a creamy appearance. After postmortem biochemical analysis, we made a diagnosis of DKA with severe hypertriglyceridemia and concluded that these unusual autopsy findings were caused by DKA and postmortem change. Uncontrolled diabetes often causes DKA and hypertriglyceridemia. To the best of our knowledge, this is the first report in Korea of DKA with severe hypertriglyceridemia diagnosed by autopsy.
Adult ; Autopsy* ; Diabetic Ketoacidosis* ; Diagnosis ; Female ; Heart* ; Humans ; Hypertriglyceridemia* ; Korea ; Plasma ; Postmortem Changes

PURPOSE: This study was conducted to identify the influence of trauma experiences and social adjustment on health-related quality of life in North Korean defectors. METHODS: The subjects were 117 North Korean defectors living in B and Y city. The data were collected from September 1 to September 20, 2014, and analyzed by the SPSS/WIN 18.0 program. RESULTS: Significant differences were found in the health-related quality of life with respect to the subjects' education, marriage status, types of dwelling, family types, duration of residence in South Korea, jobs in South Korea and in North Korea, families left in North Korea or other surrounding countries, and subjective health status. Health-related quality of life is negatively related to trauma experiences during escape from North Korea and during their life in South Korea. Health-related quality of life positively is related to social adjustment. The meaningful variables which influenced the subjects'health-related quality include social adjustment, job in South Korea, job in North Korea, current family structure, and trauma experiences in South Korea. Total explanatory power of these factors for health-related quality in North Korean Defectors is 43.0% and social adjustment is the most influential factor. CONCLUSION: Therefore, in order to enhance health-related quality of life in North Korean defectors, it is necessary for them to increase social adjustment and decrease trauma experiences. In addition, methods are needed to provide job opportunities, better education and family services for North Korean defectors.
Democratic People's Republic of Korea ; Diagnostic Self Evaluation ; Education ; Humans ; Korea ; Marriage ; Psychological Trauma ; Quality of Life ; Social Adjustment ; United Nations

OBJECTIVE: Retinoic acids (RAs) and interferons (IFNs) have been implicated in the growth regulation of cervical cancer cells, which was suggested by clinical trials and in vitro experiments. However, the molecular mechanisms of growth regulation are not fully defined, The purpose of this study is to assess the effect of RA and/or IFN on human cervical carcinoma cells in vitro and to analyze their action mechanisms in HPV-positive cervical carcinoma cells by molecular biologic studies. METHODS: HPV-positive (CaSki, HeLa), HPV-negative (C33A, HT-3), and non-cervical cancer Cos-1 cell lines were treated with RA and/ar IFN. Their effects on cell growth were evaluated by the cell pmliferation assay and the following BrdU DNA incorporation assay. The molecular mechanism was further investigated by a series of immunoblottings and transient cotransfection assays, which were conducted in HeLa cells and C33A cells using the CAT reporter gene assay. To observe the down regulation of HPV E6/E7 gene expression by RA/IFN, reverse transcription-polymerase chain reaction (RT-PCR) was perforned. RESULTS: The powth of RA-treated cells was less suppressed than that of IFN-treated cells. Combined treatment of RA and IFN leads to additive effect on the growth suppression of HeLa and CaSki cells. The proliferation activity was most severely reduced in Hela cells by treatment of both all-trans-RA (AtRA) and IFN-r. Combined treatment of AtRA/IFN-r causes a great increase in the level of interferon regulatory factor-1 (IRF-1) protein in HeLa cells, whereas no induction of IRF-1 was observed in C33A cells. The CAT gene expression for IRF-1 was greatly induced by IFN-r in HeLa cells. Immunoblotting assays shows the concurrent induction of p21 CDK inhibitor and dephosphorylation of Rb protein in HeLa cells. In RT-PCR, an individual treatment of either RA or IFN reduced HPV E6/E7 mRNA levels and significantly cooperative when both RA and IFN were treated. By deaeasing E6 levels, the p53 level was increased in HeLs cells treated with RA and/or IFN. Transient cotransfection of IRF-1 and p53 as the transcription factors leads to the cooperative activation of a common p21 promoter to regulate the cell cycle. CONCLUSION: RA/IFN suppressed the growth of HPV-positive cervical cancer cells. When they were both treated, additive suppressive effects were observed in cellular proliferation as well as DNA synthesis. The growth suppressive effect is likely to be related to the increased expression of IRF-1 and p21 (antitumoral effect; p53-independent). The down regulation of HPV E6 gene suppression may account for the resultant increase of p53 levels (antiviral effect; p53-dependent). Both induced IRF-1 and p53 cooperatively augument tbe suppession of p21 CDK inhibitor, which results in dephosphorylation of pRb. Although clinical effects are likely complex and may include interactions of in vitro growth inhibitory effects with immunomodulatory and antiangiogeaetic effect, tbese results suggest the optimal clinical role for the combination of RA/IFN in the treatment of cervical canccers.
Animals ; Bromodeoxyuridine ; Cats ; Cell Cycle ; Cell Proliferation ; COS Cells ; DNA ; Down-Regulation ; Gene Expression ; Genes, Reporter ; HeLa Cells ; Humans ; Immunoblotting ; Interferon Regulatory Factor-1 ; Interferons* ; Retinoblastoma Protein ; RNA, Messenger ; Transcription Factors ; Tretinoin ; Uterine Cervical Neoplasms*

Holt-Oram Syndrome is an autosomal dominant disorder characterized by the association of upper-limb abnormalities and congenital heart disease. A woman with no family history of genetic disease underwent antenatal sonography at 27 weeks' menstrual age to screen for fetal anomalies. Ultrasonography revealed abnormalities in the upper limbs. The limb abnormalities included abscence of bilateral thumbs and radius: the left humus was short. Pregnancy termination was performed. The postnatal chromosomal analysis revealed a normal 46XX karyotype and the autopsy finding confirmed the Holt-Oram syndrome. We report a case of Holt-Oram Syndrome in fetus with unaffected parents with brief of the literatures.
Autopsy ; Extremities ; Female ; Fetus ; Heart Defects, Congenital ; Humans ; Karyotype ; Parents* ; Pregnancy ; Radius ; Soil ; Thumb ; Ultrasonography* ; Upper Extremity

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

A Lithiasis within the nasal cavity (rhinolith) can be formed by either endogenous or exogenous material. It occurs as a result of the solidification of mucus and nasal debris by mineral salts, calcium, magnesium phosphate and carbonate. Rhinolithiasis leads to unilateral obstruction of the nasal airway followed by inflammation of the nasal mucus membrane and the paranasal cavities. It can be seen by the endoscopic examination as a hard intranasal mass, but diagnosis of rhinolithiasis can be difficult due to the varying clinical presentations. Surgery is obligatory for the removal of rhinoliths and in most cases it can be done by nasal endoscopic removal. Giant rhinolith, which is penetrated into the surrounding anatomical structures, needs more extended surgical approaches such as Caldwell-Luc operation or lateral rhinotomy. Here, we report one case of rhinolithiasis, which was removed surgically for the purpose of diagnosis and treatment, and present a literature review of this condition.
Calcium ; Carbon ; Diagnosis ; Endoscopy ; Inflammation ; Lithiasis ; Magnesium ; Membranes ; Mucus ; Nasal Cavity ; Salts

This study aims to examine the clinical differences between objective short sleep insomniacs (OSSI) and subjective short sleep insomniacs (SSSI). Methods: We enrolled 79 patients (aged 27–74 years) with chronic insomnia disorder (CID) who underwent overnight polysomnography (PSG) and completed sleep-related questionnaires as well as habitual sleep time. All of them completed actigraphy (ACT) recording for one week prior to the PSG study. Objective sleep duration for one-week average sleep was calculated by ACT, and subjective sleep duration was counted through self-reported habitual sleep time. We divided the subjects into three groups; OSSI (<6 hight), SSSI (objective sleep ≥6 hight and subjective sleep <6 h/ night), and normal sleep duration insomniacs (NSDI, subjective sleep ≥6 hight). Results: The three groups namely OSSI, SSSI, and NSDI had 25 (31.6%), 36 (45.6%), and 18 (22.8%) subjects, respectively. The SSSI were significantly older and had higher daytime sleepiness than the OSSI. According to the PSG results, the OSSI showed shorter sleep latency (11.86 min vs. 39.69 min) and N2 sleep % (59.43% vs. 67.96%), and longer rapid eye movement sleep % (20.79% vs. 15.47%) than that in the NSDI. There was no difference in treatment response between groups. Conclusions: 45.6% of CID patients underestimated their sleep relative to objective sleep. However, there were no differences in total sleep time on PSG between groups. The OSSI showed younger age and more daytime sleepiness, and the SSSI showed poorer sleep quality than the NSDI. These findings suggest that long-term ACT recording in a casual environment would be useful to monitor objective sleep in patients with CID, particularly, in subjectively short sleep insomniacs.

Objectives: Sleep issues are more prevalent in healthcare workers compared to workers in other industries. This study investigated sleep-wake pattern, sleep quality, and daytime status in hospital workers using a Galaxy Watch3 (GW3), a wrist-worn device that uses an accelerometer and heart rate sensor to distinguish sleep and wakefulness. Methods: Multiple sleep parameters including total sleep time (TST) were obtained using a GW3. The Epworth sleepiness scale (ESS), insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), and bedtime procrastination scale (BPS) were used to assess participants’ status. Results: A total of 70 daytime hospital workers (male, 45.7%; mean age, 35.66±7.79 yr) participated in the monitoring of their sleep-wake patterns for 30 consecutive days. Participants had a mean ESS of 8.14±3.62, ISI of 6.13±3.83, and PSQI of 4.86±2.14. The mean TST was 5.75±0.74 hr (range: 3.42–6.88) during workdays and 5.92±0.92 hr (range: 2.87–8.25) during free days. Chronotype (mid-sleep on freedays corrected for sleep debt accumulated over the work week) was 3.60±1.03 clock hr (range: 1.84–6.69). BPS was negatively correlated with age (rho=-0.27, p=0.022), TST of workdays (rho=-0.53, p<0.001), and TST of free days (rho=-0.43, p<0.001). A higher BPS was associated with larger social jetlag (rho=0.28, p=0.018) and later chronotype (rho=0.41, p<0.001). Conclusions In this study, 91.5% of daytime hospital workers suffered from chronic sleep insufficiency (<7 hr during both workdays and free days) although their daytime sleepiness or subjective sleep were not poor. Individuals with a later chronotype had poorer sleep quality and worse sleep procrastination behavior.