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

Tumor suppressive effect of dehydroepiandrosterone (DHEA) on the experimentally induced hepatocellular carcinoma was investigated, especially focusing on glutatione transferase and transglutaminase with aptosis in the carcinogenesis. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into AA group treated by the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-acetamidofluorene (AAF) and AD group treated with DHEA simultaneously with AAF and the AAD group treated by DHEA after treatment with AAF. Each group was divided by time sequence further into four subgroups, GI (8wk), G2 (16wk), G3 (28wk), and G4 (36wk). For neoplastic lesion, the immuno histochemical study with anti GSTP antibody was carried out, while the activity and expression of TGase was compared at the same time. The results were summarized as follows; GST-P positive foci detected in AD groups were significantly more suppressed by DHEA treatment than AA groups (P<0.05). AD groups. AD group showed higher activities of TGase than AA groups (P<0.05), which was confirmed by Western and Northern blot analysis. But the number of apoptotic bodies was not correlated with activity and expression of TGase in the nodule. These results suggest that the suppressive effect of DHEA on the murine hepatocellular carcinogenesis might be operating on the promotion process of carcinogenesis rather than regression process of transformed hyperplastic nodules.
Carcinoma, Hepatocellular

Esophageal granular cell tumor of is rare neoplesin, and 3 cases were reported in Korea so far. We report a case of esophageal granular cell tumor in a 28 year old man. The patient was a 28 year old man who visited this hospital because of upper abdominal pain, acid belching and weight loss. A small nodule, 5 mm in diameter, was found in mid esophagus on esophagoscopy. This nodule was proved to be a granular cell tumor.
Male ; Humans

Frey's syndrome is a fairly common sequelae of surgery, trauma and inflammation of the parotid gland. Some patients with Frey's syndrome may be socially compromised by their gustatory sweating and flushing. In the past three decades, a variety of surgical and pharmacological methods have been unsuccessful in alleviating these symptoms. And since misdirection of auriculotemporal secretomotor nerve fibers has been found to play an important role in the development of the syndrome, a study was initiated to attempt mechnical interference with regenerating nerve fibers. Therefore, the recent trend in management of Frey's syndrome has been the use of prophylactic procedures performed at the time of parotidectomy to prevent its symptoms postoperatively. An additional benefit of this approach is prevention of the typical cheek contour deformity after parotidectomy We reviewed our experience with interposition of a vascularized temporoparietal fascial flap between the parotid bed and overlying skin immediately after complete superficial parotidectomies to prevent Frey's syndrome and hollow contour defects. The result of seven consecutive attempts revealed it to be an effective technique, achieving both goals in all patients with minimal morbidity.
Cheek ; Congenital Abnormalities ; Flushing ; Humans ; Inflammation ; Nerve Fibers ; Parotid Gland ; Skin ; Sweating, Gustatory

We report a case of non-cirrhotic portal hypertension in a 73 year-old woman, who had 19-year history of idiopathic myelofibrosis. There were esophageal varix, splenomegaly, and ascites. The biopsied liver showed irregular sinusoidal/ perisinusoidal fibrosis and occasional central-to-central fibrous connection. In areas with extensive fibrosis, coarse collagen fibers filled the sinusoidal spaces and compressed hepatocytes. However, nodular regeneration was absent. Double immunohistochemical stain for smooth muscle actin and proliferation cell nuclear antigen (PCNA) revealed diffusely activated stellate cells, some of which showed nuclear PCNA staining. There was also extramedullary hematopoiesis with bizarre megakaryocytes. The portal vein and its branches were patent. Idiopathic myelofibrosis is a rare cause of non-cirrhotic portal hypertension: the portal hypertension was considered to be the result of sinusoidal/perisinusoidal fibrosis in this case.
Actins ; Aged ; Ascites ; Collagen ; Esophageal and Gastric Varices ; Female ; Fibrosis ; Hematopoiesis, Extramedullary ; Hepatocytes ; Humans ; Hypertension, Portal* ; Liver ; Megakaryocytes ; Muscle, Smooth ; Portal Vein ; Primary Myelofibrosis* ; Proliferating Cell Nuclear Antigen ; Regeneration ; Splenomegaly

BACKGROUND: ABO genotyping is being used increasingly when the results of serologic typing are unclear or there is some suspicion of rare ABO subtypes. Conventional molecular diagnostic methods such as PCR- restriction fragment length polymorphism (PCR-RFLP), allele-specific PCR, PCR-single stranded conformational polymorphism (PCR-SSCP) and sequence-based typing have been used in this field. Recently, a pyrosequencing technique was introduced into clinical laboratories. This study evaluated the possibility of applying pyrosequencing to ABO genotyping. METHODS: A total of 36 samples, which had previously been analyzed by PCR-RFLP and serological method in the Blood Genetics Clinic of Seoul National University Hospital between August 2001 and September 2004 and shown to have the A/A, A/B, A/O, B/B, B/O, O/O, cis-AB/O, cis-AB/A, or cis-AB/B genotypes, were analyzed by pyrosequencing analysis. Briefly, two PCR reactions were carried out separately for one region including nucleotide 261, and for another region including nucleotides 796 and 803. Pyrosequencing was then performed, and the pyrograms were interpreted using an automated interpretation program from the manufacturer and by researchers independently to determine the nucleotides 261, 796 and 803 for ABO genotyping. RESULTS: The ABO genotypes from pyrosequencing and the interpretation of the pyrograms according to the researcher on 36 samples were in complete concordance with the results obtained by PCR-RFLP. The ABO genotypes from the automated interpretation program showed an error in one out of total 108 SNP (single nucleotide polymorphism) analyses (eRROR RATE=0.9%) OF 36 SAMPLES. CONCLUSION: ABO genotyping for A, B, O, cis-AB alleles by pyrosequencing of nucleotides 261, 796 and 803 was relatively simple and accurate and could be an another field we can use in clinical laboratories.
Alleles ; Genetics ; Genotype ; Nucleotides ; Pathology, Molecular ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Seoul

Natural cytotoxicity mediated by natural killer (NK) cells is believed to play an important role in host anticancer defense mechanisms. The aim of this study is to compare the number of NK cells in patients with colorectal cancer and hemorrhoids, and before and after surgery in patients with colorectal cancer. Twenty colorectal cancer patients and twenty hemorrhoid ones were studied. Venous blood samples were obtained preoperatively, and on the 7th, and 14th postoperative days. Mononuclear cells were isolated over Ficoll-Hypaque gradients, and T cells, B cells, and NK cells were measured with CD3 FITC (T cell), CD 19 PE (B cell), and CD56 FITC (NK cell) antibody, The number of T cell (/mm3) was 1224, 1280, and 1125 at preoperative, 7th, and 14th postoperative day in hemorrhoid patients and 1195, 901, and 1060 in colorectal cancer patients respectively. The number of B cell (/mm3) was 243, 160, and 250 in hemorrhoid patients and 147, 78, and 113 in colorectal cancer patients. The number NK cell (/mm3) was 148, 156, and 143 in hemorrhoid patients and 129, 85, and 128 in colorectal cancer patients. There was no difference among Dukes stages in the number of NK cells. In conclusion, the number of NK cells was not changed in colorectal cancer patients compared with hemorrhoid ones. Major operation changed the number of NK cells in colorectal cancer patients.
B-Lymphocytes ; Colorectal Neoplasms* ; Defense Mechanisms ; Fluorescein-5-isothiocyanate ; Hemorrhoids ; Humans ; Killer Cells, Natural* ; T-Lymphocytes

A 25-year-old man had been intermittently treated with topical steroid ointment for his eczematous lesions on the scrotum. One year later, a few hard nontender nodules were found with surrounding thickened lichenified skin on the previous lesions. Histopathologic examination of the skin revealed moderate acanthosis of the epidermis and multiple scattered calcified materials in the upper demis and within the hair follicle. We present this case, being considered a dystrophic calcinosis cutis due to local injury.
Adult ; Calcinosis* ; Epidermis ; Hair Follicle ; Humans ; Lupus Erythematosus, Discoid* ; Scrotum ; Skin

Neonatal alloimmune thrombocytopenia(NAIT) is a rare disease caused by maternal alloimmunization against fetal platelet surface antigen, which is mainly platelet specific alloantigen or human leukocyte antigen(HLA). During routine hemotology, we accidentally discovered thrombocytopenia in a female fullterm newborn admitted due to jaundice. We excluded NAIT due to human platelet alloantigen(HPA), because the HPA of the mother and baby were the same on PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Mother's serum was tested for lyrnphocytotoxity against 36 donor lymphocytes, and anti-HLA A2, A24 and B58 were found. HLA typing of the father and baby revealed A2 antigen which was not present on the mothers lymphocytes. The patient received concentrated platelet and intravenous globulin. Her platelet count increased to 222,000/mm from 3,000/mm on the 11th day of life. We described a case of NAIT due to anti-HLA A2 antibody with a detailed clinical feature. (J Korean Pediatr Soc 1999;43:861-865)
Antigens, Surface ; Blood Platelets ; Fathers ; Female ; Histocompatibility Testing ; Humans ; Infant, Newborn ; Isoantigens ; Jaundice ; Leukocytes ; Lymphocytes ; Mothers ; Platelet Count ; Rare Diseases ; Thrombocytopenia ; Thrombocytopenia, Neonatal Alloimmune* ; Tissue Donors

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