PURPOSE: PTEN/MMAC1, a novel tumor suppressor gene, is mutated in a variety of advanced and metastatic cancers. It acts as a phosphatase, and thereby, regulates the PI-3 kinase/Akt pathway. In this study, we examined to evaluate the new function of anti-tumor effects of PTEN/MMAC1 through the regulation of the IGFs-IGFBPs in gastric cancer cells. METHODS: PTEN/MMAC1 was expressed in an adenovirus-mediated gene delivery system and introduced into gastric cancer cells(SNU-484 & SNU-668) in vitro. The effect of cell growth and the expression of IGFs and IGFBPs after Ad/PTEN infection was analyzed by MTT assay, RT-PCR and Western immunoblot. RESULTS: Ad/PTEN infected cells were inhibited in cell growth compared with moak cells and Ad/ LacZ infected cells. Overexpression of PTEN/MMAC1 induced decrease in expression of IGF-I, -II and IGF-I receptors which are known as growth prompt molecules in a variety of cancers. Of the six IGFBPs, the expressions of IGFBP-4 and IGFBP-6 were decreased in Ad/PTEN infected cells. In contrast, IGFBP-3 expression was markedly increased by up to 3-fold in Ad/PTEN infected cells. Overexpression of PTEN/MMAC1 inhibited the activation of Akt/PKB pathway, but had no effect on the MAPK pathway. CONCLUSION: These findings suggest that the tumor suppressor function of PTEN/MMAC1 is, at least in part, mediated through the down-regulation of IGF-I abd IGF-II, and up-regulation of IGFBP-3 in gastric cancer cells by the inhibition of PI-3 kinase pathway.
Blotting, Western ; Down-Regulation ; Gene Transfer Techniques ; Genes, Tumor Suppressor ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Protein 4 ; Insulin-Like Growth Factor Binding Protein 6 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol 3-Kinases ; Receptor, IGF Type 1 ; Stomach Neoplasms ; Up-Regulation

PURPOSE: Insulin-like growth factor binding protein 3 (IGFBP-3) binds to IGF and acid labile subunit in blood, that regulates the action of IGF by modulating the interaction of IGF with the IGF receptor. Recent studies have shown that IGFBP-3 levels are decreased in prostate cancer patients. We examined IGFBP-3 profiles in prostate cancer patients and determined the effect of treatment on serum IGFBP-3 level in those patients. MATERIALS AND METHODS: Control groups were composed of age-matched healthy subjects and patients with benign prostatic hyperplasia (BPH). Patients with prostate cancer were divided into localized, locally advanced, metastatic and hormone-refractory. Serum samples were collected and stored at 70oC until use. The IGFBP-3 profile was measured by Western ligand blots. RESULTS: The serum IGFBP-3 level in patients with prostate cancer was significantly lower than healthy subjects or patients with BPH. Following the treatment of prostate cancer, IGFBP-3 was increased compared to that seen in pretreated prostate cancer. In hormone-refractory prostate cancer, IGFBP-3 was decreased again. However, there was no correlation between IGFBP-3 and tumor stage or Gleason score. CONCLUSIONS: These data show that IGFBP-3 levels are decreased in pretreated and hormone-refractory prostate cancer. Our results demonstrate that serum IGFBP-3 may be a useful marker in the detection and management of prostate cancer.
Diagnosis* ; Humans ; Insulin-Like Growth Factor Binding Protein 3* ; Neoplasm Grading ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms*

PURPOSE: Gap junction intercellular communication(GJIC) is an important mechanism of the bystander effect in herpes simplex thymidine kinase/ganciclovir(HSVtk/GCV) gene therapy Therefore, we attempted to enhance the bystander effect in vitro by exogenous overexpressing connexin 37(Cx37) in cells to increase GJIC. METHODS: NIH3T3 cells were transfected with the Cx37 and HSVtk gene or the HSVtk gene alone by the calcium phosphate method, and we detected their expression from these cells by RT-PCR. GCV-mediated cytotoxicity and the bystander effect of each transfectant was then assessed and compared. RESULTS: Cells transfected with HSVtk became sensitive to low concentration of GCV. We found significantly increased cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx37 genes together compared with the cytotoxicity seen after introduction of the HSVtk gene in vitro. Co-expression of the HSVtk and Cx37 genes potentiates HSVtk/GCV gene therapy through the bystander effect. CONCLUSION: These results indicated that the increase of GJIC using Cx37 have potentiated the by stander effect of HSVtk/GCV therapy, and may be a new approach to improve response in suicidal cancer gene therapy.
Bystander Effect* ; Calcium ; Gap Junctions* ; Genes, Neoplasm ; Genetic Therapy* ; Herpes Simplex ; Thymidine

STUDY DESIGN: A prospective radiological assessment was conducted. OBJECTIVES: To analyze the changes in the height of the intervertebral disc, the slippage, slip angle, lumbar lordotic angle and sacral inclination after anterior lumbar interbody fusion and posterior pedicle screw fixation in a lumbar spondylolisthesis. SUMMARY OF LITERATURE REVIEW: The anterior lumbar interbody fusion causes changes in the lumbar sagittal alignment. METHODS: The mini-open anterior lumbar interbody fusion and pedicle screw fixation was undertaken in 33 cases from April 1995 to November 2003. MRI was done before and 6 months after surgery. The measuring factors were the heights of the intervertebral disc, slippage, slip angle, lumbar lordotic angle and sacral inclination. The measuring factors were independently assessed three times by three different orthopedic surgeons. The postoperative changes in measuring the factors were analyzed by a paired t-test statistically. RESULTS: The height of the intervertebral disc was increased by a mean of 14.0%, slippage was reduced by a mean of 2.8%, the slip angle was reduced by a mean of 16.0%, the lumbar lordotic angle was increased by a mean of 15.6% and the scaral inclination was increased by a mean of 3.0%. There was significance in the increase in the disc height, the reduction of slippage and the slip angle, and the increase in lumbar lordotic angle, but there were no significance regarding the changes in sacral inclina-tion. CONCLUSIONS: The anterior lumbar interbody fusion and the pedicle screw fixation significantly improved the height of the intervertebral disc, slippage, slip angle, and lumbar lordotic angle, except sacral inclination.
Intervertebral Disc ; Magnetic Resonance Imaging ; Orthopedics ; Prospective Studies ; Spine* ; Spondylolisthesis*

PURPOSE: Ataxia telangiectasia mutated(ATM) is involved in DNA damage responses at different cell cycle checkpoints, and signalling pathways associated with regulation of apoptosis in response to ionizing radiation(IR). However, the signaling pathway that underlies IR-induced apoptosis in ATM cells has remained unknown. The purpose of this study was, therefore, to investigate the apoptotic pathway that underlies IR-induced apoptosis in a CT-26 cells expressing dominant negative ATM (DN-ATM). METHODS: We generated a replication-deficient recombinant adenovirus encoding the DN-ATM(Ad/DN-ATM) or control adenovirus encoding no transgene(Ad/GFP) and infected adenovirus to CT-26 cells. After infection, we examined apoptosis and apoptotic pathway by [3H]-thymidine assay, DNA fragmentation, and Western immunoblot analysis. RESULTS: DN-ATM gene served as the creation of AT phenotype in a CT-26 cells as revealed by decreased cell proliferations following IR. In addition, IR-induced apoptosis was regulated through the reduced levels of the anti-apoptotic protein Bcl-2, the increased levels of the apoptotic protein Bax, and the activation of caspase-9, caspase-3, and PARP. CONCLUSION: These results indicate that the pathway of IR-induced apoptosis in CT-26 cells expressing DN-ATM is mediated by mitochondrial signaling pathway involving the activation of caspase 9, caspase 3, and PARP.
Adenoviridae ; Apoptosis ; Ataxia Telangiectasia ; Blotting, Western ; Caspase 3 ; Caspase 9 ; Cell Cycle Checkpoints ; Colon* ; Colonic Neoplasms* ; DNA Damage ; DNA Fragmentation ; Phenotype ; Radiation, Ionizing

OBJECTIVE: A probable diagnosis of Wiskott-Aldrich syndrome(WAS) should be considered in any boy presenting with unusual bleeding, congenital thrombocytopenia and small platelets. The definitive diagnosis of WAS is usually made by the detection of WASP gene mutation or a decrease or absence of the WAS protein(WASP) in blood cells using molecular genetic analysis. However, these methods are too time-consuming and difficult. In this study, therefore, we tried to compare various diagnostic methods and establish the molecular screening steps for the definitive diagnosis of WAS. METHODS: Peripheral blood was drawn from WAS patient with clinical characteristic symptoms, and analyzed with automated complete blood cell count analysis, immunological analysis, and molecular analysis. The morphologic change of WAS patient's blood cell membrane was examined by scanning electron microscopy(SEM). Protein analysis for the expression of WASP protein in PBMC cells was evaluated by FACS and Western immunoblot. Genetic analysis for the detection of a mutation of the WASP gene was performed by polymerase chain reaction-single strand conformational polymorphism analysis(PCR-SSCP) and direct sequencing of PCR products. RESULTS: In addition to microthrombocytopenia, our investigation revealed morphologic defects in WAS lymphocytes by SEM and abnormal mobility shifting in WAS patients by PCR-SSCP. Sequencing the WASP gene detected a specific single base mutation in exon 2, resulting in missense substitution of adenine for guanine 208(G208A, Gly70Arg). FACS and Western immunoblot demonstrated absent expressions of WASP in WAS patients and reduced expression of WASP in carrier when compared with normal controls. CONCLUSION: From these results, we suggested the following diagnostic approaches in patients suspected of having WAS. Protein-based analysis such as FACS and Western immunoblot should be employed as the first line of investigation. The second line genetic analyses should employ second- step approaches with localization of mutation by screening exons, typically by PCR-SSCP, followed by direct sequencing.
Adenine ; Blood Cell Count ; Blood Cells ; Blotting, Western ; Diagnosis ; Exons ; Guanine ; Hemorrhage ; Humans ; Lymphocytes ; Male ; Mass Screening ; Membranes ; Molecular Biology ; Polymerase Chain Reaction ; Thrombocytopenia ; Wasps ; Wiskott-Aldrich Syndrome Protein ; Wiskott-Aldrich Syndrome*

No abstract available.
Endophthalmitis*

14 cm, and HOB >7.8 cm were 10.80 (95% confidence interval [CI], 1.57–74.94), 5.26 (95% CI, 1.06–26.19), and 10.50 (95% CI, 1.03–107.12), respectively. Areas under the curve (AUCs) for AFI, HOB, and parity were 0.66 (95% CI, 0.54–0.78), 0.74 (95% CI, 0.64–0.85), and 0.69 (95% CI, 0.62–0.76), respectively. HOB had the largest AUC, but there were no significant differences among the AUCs of other factors. The cut-off value of HOB was 6 cm.CONCLUSION: This study showed that the AUC of HOB was greater than that of parity and AFI, although it was not statistically significant. As HOB is a noninvasive and comprehensive marker to predict successful ECV, consideration of HOB would be helpful before conducting ECV. Further studies are needed.]]>
Amniotic Fluid ; Area Under Curve ; Breech Presentation ; Buttocks ; Female ; Humans ; Odds Ratio ; Parity ; Pregnancy ; Pregnant Women ; Prospective Studies ; Pubic Symphysis ; Ultrasonography ; Version, Fetal

We present frequencies of fetal chromosomal abnormalities in 4,907 prenatal cytogenetic examinations at Samsung Cheil Hospital from 1988 to 1997 for 10 yr duration. Prenatal karyotypes were undertaken in 3,913 amniotic fluid samples, 800 chorionic villi samples, and 194 percutaneous umbilical blood samples. The frequency of fetal abnormal karyotypes was 3.1% (150 cases). Numerical chromosome abnormalities were 87 cases (1.8%) and structural aberrations of chromosomes were 63 cases (1.3%). In the numerical chromosomal abnormalities, the frequency of trisomy 21 was by far the highest (36 cases), followed by trisomy 18 in 22 cases and sex chromosome aneuploidies in 19 cases. In the structural chromosomal aberrations, 5 cases had the inversions in chromosome 2, 7, 17, and Y. Chromosomal deletions in 6 cases and additions in 4 cases were analysed. Of the remaining 47 translocation in abnormal fetuses, reciprocal translocation was in 26 cases and Robertsonian translocation in 21 cases. Among them, 41 cases were balanced translocation and 6 were unbalanced. Thirty five cases of translocation were inherited from one of the parents. Four had de novo chromosome rearrangements, and 8 cases were unknown.
Chromosome Abnormalities/classification/*diagnosis ; Female ; Human ; Institutionalization ; Inversion (Genetics) ; Karyotyping ; Life Change Events ; Pregnancy ; Prenatal Diagnosis/*trends ; Retrospective Studies ; Translocation (Genetics)

The aim of this study was to examine the incidence and clinical outcome of de novo chromosomal aberrations retrospectively and provide useful data for genetic counseling in the prenatal cytogenetic diagnosis. We found 17 cases of de novo chromosomal aberrations in 5,501 cases of prenatal cytogenetic analysis and reviewed the karyotype, further study, medical records, fetal ultrasound findings and clinical outcomes. Out of the 17 de novo chromosomal aberrations, 5 had balanced reciprocal translocations and 12 had unbalanced translocations characterized as deletion, addition, or marker. In the case of the five balanced reciprocal translocations, 3 cases without abnormal ultrasound findings were carried to term after comprehensive genetic counseling. Neonates were phenotypically normal and clinical examinations were normal. Two cases with abnormal ultrasound findings were terminated therapeutically. Twelve cases of unbalanced translocations were terminated except one case with a mosaic marker chromosome. High resolution fetal ultrasound and detailed cytogenetic and molecular study will be adjunctive tools for predicting the karyotype/phenotype correlations of fetuses with de novo chromosomal aberrations, although they have limitation to find all phenotypic effects.
*Chromosome Aberrations ; Female ; Fetal Diseases/epidemiology/*genetics/ultrasonography ; *Genetic Counseling ; Human ; Incidence ; Karyotyping ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies ; Translocation (Genetics) ; Ultrasonography, Prenatal