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

A 40-year-old woman presented with a pruritic erythematous eroded patch on the right labium majus which had been for 3 years. Histopathological findings were consistent with superficial basal cell epithelioma. Basal cell epithelioma of the labium majus is a rare neoplasm and its clinical appearance is usually nodular. In contrast to the other types of basal cell epithelioma, the superficial type occurs mainly on the trunk. We report a case of superficial basal cell epithelioma arising from the labium majus.
Adult ; Carcinoma, Basal Cell* ; Cytochrome P-450 CYP1A1 ; Female ; Humans

No abstract available.
Cerebral Palsy* ; Rhizotomy*

A retrospective comparative study of MRI and CT in 24 patients with diffuse axonal injury (DIA) was undertaken. Three-quaters of the lesions were non-hemorrhagic, and the sites of involvement were lobar white matter (96%), corpus callosum (70%), and rostral brainstem (42%), in descending order. MRI was singnificantly more sensitive than CT in detecting DAI lesions. The average number of DAI lesions was higher with increasing clinical stage of the injury. MRI is more valuable than CT for staging the full magnitude of the injury and in predicting the neurologic prognosis of DAI lesions.
Axons* ; Brain Stem ; Brain* ; Corpus Callosum ; Diffuse Axonal Injury ; Humans ; Magnetic Resonance Imaging* ; Prognosis ; Retrospective Studies ; White Matter

Helicobacter pylori, loss of basement membrane, atrophy, type III intestinal metaplasia, adenomatous polyposis coli (APC) gene mutations and altered p53 function were believed as a factor to develop the gastric adenocarcinomas. To investigate the incidence and prevalence of Helicobacter pylori, intestinal metaplasia and atrophy, 120 gastrectomy specimens collected from patients with gastric adenocarcinoma (100 cases) and non-neoplastic conditions (20 cases) were studied. Intestinal metaplasia can be classified as type I (complete), type II (incomplete, sulfomucin-negative) and type III (incomplete, sulfomucin-positive) by Filipe and Jass. The incidence of intestinal metaplasia of gastric adenocarcinoma was 96% compared with the incidence of 75% in non-neoplastic conditions. The type I and type II were more common than type III and were present in both non-neoplastic conditions (75%) and adenocarcinoma (74%). In contrast, type III intestinal metaplasia was seen in only 20% of intestinal metaplasia-positive cases, all of which (22 of 22) were from patients with adenocarcinoma. The high specificity of type III intestinal metaplasia might be acceptable for screening purposes, but its sensitivity of 22% for gastric adenocarcinoma is low. Helicobacter pylori were detected in 96% of adenocarcinoma cases and 100% of non-neoplastic cases. Atrophy was detected in 50% of non-neoplastic cases and in 57% of adenocarcinoma cases. The data thus confirms a significant relation between incomplete sulfomucin-secreting intestinal metaplasia (type III) and gastric carcinoma, especially intestinal type (p<0.01). Thus, the type III intestinal metaplasia should be considered a risk factor and its presence in a biopsy specimen should prompt close surveillance.
Adenocarcinoma ; Adenomatous Polyposis Coli ; Atrophy ; Basement Membrane ; Biopsy ; Gastrectomy ; Helicobacter pylori ; Humans ; Incidence ; Mass Screening ; Metaplasia* ; Prevalence ; Risk Factors ; Sensitivity and Specificity

Estrogen and progesterone receptors exist in the epithelial and stromal cells of the endometrium. Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions of estrogen and progesterone in epithelial and stromal cells. This study was performed to evaluate the differences estrogen and progesterone receptor(ER/PR) expression in the epithelial and stromal cells of endometrial hyperplasias and adenocarcinomas using immunohistochemical methods. Immunohistochemical analysis of proliferating cell nuclear antigen(PCNA) was done to evaluate a possible correlation between PCNA and hormone receptor expression. Evaluation was based on samples from 31 simple hyperplasias, 30 complex hyperplasias, and 32 adenocarcinomas. The immunohistochemical expression of ER, PR and PCNA in epithelial and stromal cells were examined according to a scoring system based on the percentage of positive cells and the staining intensity. The results were as follows; 1) The expression of ER and PR in epithelial cells showed a graded, significant decreases in simple hyperplasia, complex hyperplasia and endometrial carcinoma, in that order(ER: P=0.008, PR: P= 0.026). 2) PR expression in the stromal cells showed a significant decrease between hyperplasia and adenocarcinoma(P=0.003). The difference in ER expression was not significant. 3) In stromal cells, the decrease in PR expression was more prominent than the decrease in ER expression when complex hyperplasia was compared to simple hyperplasia. 4) The PCNA expression in simple and complex hyperplasia and adenocarcinoma was not higher than the expression of PCNA in nomal proliferative endometrium. There was no significant difference in PCNA expression between simple and complex hyperplasia and adenocarcinoma(P=0.073). 5) A negative correlation between PCNA and ER/PR expression was not demonstrated in simple and complex hyperplasia, or in adenocarcinoma. Endometrial hyperplasia and adenocarcinoma are probably related to a paracrine action of estrogen and progesterone in epithelial and stromal cells. A progressive loss of PR expression in stromal cells may induce abnormal proliferation of endometrium due to a disrupted hormonal balance.
Adenocarcinoma

We present a case of familial benign chronic pemphigus in 50-year-old male patient who had had recurrent oozing, macerated and eroded skin lesions on the groin and scrotum for 20 years. At first, we diagnosed his case as scrotal eczema and/or intertrigo, but after repeated recurrance, it was confirmed as above disease by characteristic histopathologic findings.
Cytochrome P-450 CYP1A1 ; Eczema ; Groin ; Humans ; Intertrigo ; Male ; Middle Aged ; Pemphigus, Benign Familial* ; Scrotum ; Skin

We present a case of generalized syringoma in a 12-year-old healthy girl. The patient has numerous skin colored or yellowish papules on the face, neck, anterior chest, axillae and abdomen. She has a family history of eyelid syringoma occuring in her mother and maternal grandmother. Diagnosis was confirmed by characteristic histopathologic findings.
Abdomen ; Axilla ; Child ; Diagnosis ; Eyelids ; Female ; Humans ; Mothers ; Neck ; Skin ; Syringoma* ; Thorax

Generalized distinct hyperpigrnented macules developed at 2. 7 years after starting photochemotherapy(psoralen and UVA) in a 66-year-old psoriatic male patient. The histopathologic feature of this macule was characterized as a lentiginous p roliferation. The significance and long term course of PUVA lentigo are still unknown. So, we will further monitor this patient continually for melanocytic dysplasias, including melanoma.
Aged ; Humans ; Lentigo* ; Lichen Planus ; Male ; Melanoma ; Mouth Mucosa

No abstract available.
Erythroblastosis, Fetal* ; Infant, Newborn