Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

사람배아(Streeter 연령군 XV)의 1예

A human embryo was serially sectioned and was reconstructed with 327 sections. The length of the embryo was estimated to be 6.9 mm. The age of the embryo was determined by the developmental status of the internal organs in terms of selected definable characteristics. Discernible morphological features of the embryo included closure of the lens vesicle, separation of the otocyst from the skin ectoderm, endolymphatic appendage, bronchi in the primary stage, thickening of the olfactory disk, dorsal and ventral pancreatic buds, and a narrow atrio-ventricular canal with an incompletely formed interventricular septum. The above observations strongly suggested that this embryo developed normally and should be classed in age group XV of Streeter's developmental horizon

Arnold-Chiari기형 (6 부검예의 분석)

A total of 6 autopsy cases of Arnold-Chiari malformation was examined at the Department of Pathology of Seoul National University. These cases showed characteristic features of Chiari type II malformation, i.e., displacement of a portion of the inferior vermis, whole medulla oblongata and the fourth ventricle into the cervical canal and associated cerebellar dysplasia. All of the cases had hydrocephalus and accompaning meningomyelocele at various levels. All cases showed polygyria but not micropolygyria, and in three cases there were craniolacunia. Three out of 6 cases showed severe malformations of the extraneural system. These malformations included bilateral renal agenesis, exstrophia splanchnica, cardiovascular and skeletal abnormalities, etc. On the basis of our observations we think that multifactorial causes are involved in the pathogenesis of the Arnold-Chiari malformation

Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: A randomized, double-blind, placebo-controlled, phase III study

Background: Dutasteride (Avodart) is a dual inhibitor of both type I and type II 5 alpha reductases, and thus inhibits conversion of testosterone to dihydrotestosterone, a key mediator of male pattern hair loss. Objectives: The aim of this randomized double-blind phase III study was to compare the efficacy, safety, and tolerability of dutasteride (0.5 mg) and placebo for 6 months of treatment in male patients with male pattern hair loss. Methods: A total of 153 men, 18 to 49 years old, were randomized to receive 0.5 mg of dutasteride or placebo daily for 6 months. Efficacy was evaluated by the change of hair counts, subject assessment, and photographic assessment by investigators and panels. Results: Mean change of hair counts from baseline to 6 months after treatment start was an increase of 12.2/cm(2) in dutasteride group and 4.7/cm(2) in placebo group and this difference was statistically significant (P = .0319). Dutasteride showed significantly higher efficacy than placebo group by subject self-assessment and by investigator and panel photographic assessment. There was no major difference in adverse events between two groups. Limitations: The study was limited to 6 months. Conclusions: This study clearly showed that 0.5 mg of dutasteride improved hair growth and was relatively well tolerated for the treatment of male pattern hair loss.STOUGH D, 2007, J COSMET DERMATOL, V6, P9Olsen EA, 2006, J AM ACAD DERMATOL, V55, P1014, DOI 10.1016/j.jaad.2006.05.007Olsen EA, 2005, J AM ACAD DERMATOL, V52, P301, DOI 10.1016/j.jaad.2004.04.008OLSZEWSKA M, 2005, J DRUGS DERMATOL, V4, P637Debruyne F, 2004, EUR UROL, V46, P488, DOI 10.1016/j.eururo.2004.05.008Clark RV, 2004, J CLIN ENDOCR METAB, V89, P2179, DOI 10.1210/jc.2003-030330Roehrborn CG, 2004, UROLOGY, V63, P709, DOI 10.1016/j.urology.2004.01.001Price VH, 1999, NEW ENGL J MED, V341, P964Kaufman KD, 1998, J AM ACAD DERMATOL, V39, P578Bramson HN, 1997, J PHARMACOL EXP THER, V282, P1496Canfield D, 1996, DERMATOL CLIN, V14, P713Courtois M, 1996, BRIT J DERMATOL, V134, P47DALLOB AL, 1994, J CLIN ENDOCR METAB, V79, P703RUSSELL DW, 1994, ANNU REV BIOCHEM, V63, P25OLSEN EA, 1994, DISORDERS HAIR GROWT, P257THIGPEN AE, 1993, J CLIN INVEST, V92, P903CASH TF, 1992, J AM ACAD DERMATOL, V26, P926JENKINS EP, 1992, J CLIN INVEST, V89, P293RANDALL VA, 1991, BRIT J DERMATOL, V124, P146NORWOOD OT, 1975, SOUTHERN MED J, V68, P1359IMPERATO.J, 1974, SCIENCE, V186, P1213HAMILTON JB, 1951, ANN NY ACAD SCI, V53, P708