TGF-β Mediated Epithelial-Mesenchymal Transition in Autosomal Dominant Polycystic Kidney Disease

Purpose: Recent studies have showed that epithelial-mesen-chymal transition (EMT) is a key process of glomerular and tubulointerstitial pathology in many chronic kidney diseases. However, there are no data of EMT in humane autosomal dominant polycystic kidney disease (ADPKD). Patients and Methods: ADPKD kidneys (N = 5) with end stage renal disease (ESRD) and control kidneys (N = 4) were analyzed immnunohistochemically. We evaluated α-SMA, E-cadherin, vimentin, TGF-β1 and Smad 2/3 expression in ADPKD and compared them with those in control kidney. These immuno-histochemical findings were quantitatively analyzed by com-puter-assisted image analyzer and positive tubules (%). Results: There were severe interstitial fibrosis and prolifera-tion of α-SMA+ myofibroblasts in ADPKD. Cystic tubular epithelial cells in ADPKD lost epithelial marker (E-cadherin) and expressed mesenchymal markers (α-SMA, vimentin). There were significant increases of α-SMA (34.3 ± 11.7 % vs 0.9 ± 1.5%), vimentin (19.9 ± 3.9 % vs 3.3 ± 1.4%), TGF-β1 (5.42 ± 2.83 % vs 0%) and Smad 2/3 (3.4 ± 1.7 % vs 0.7 ± 0.6%) in ADPKD kidneys compared with control kidneys evidenced by computer-assisted image analyzer. When we analyze the posi-tive tubules (%), the results were the same as computer-assisted image analyzer. Conclusion: Our results showed that the end stage of ADPKD is associated with TGF-β, Smad 2/3 and markers of EMT. It suggests that TGF-β mediated EMT has a role in progression of ADPKD. Key Words: Epithelial mesenchymal transition, antosomal dominant polycystic kidney diseas

Cornelia de Lange Syndrome with NIPBL Gene Mutation: A Case Report

Cornelia de Lange Syndrome (CdLS) is a multiple congenital anomaly characterized by distinctive facial features, upper limb malformations, growth and cognitive retardation. The diagnosis of the syndrome is based on the distinctive clinical features. The etiology is still not clear. Mutations in the sister chromatid cohesion factor genes NIPBL, SMC1A (also called SMC1L1) and SMC3 have been suggested as probable cause of this syndrome. We experienced a case of newborn with CdLS showing bushy eyebrows and synophrys, long curly eyelashes, long philtrum, downturned angles of the mouth and thin upper lips, cleft palate, micrognathia, excessive body hair, micromelia of both hands, flexion contracture of elbows and hypertonicity. We detected a NIPBL gene mutation in a present neonate with CdLS, the first report in Korea

A Comparison of Different Pelvic Reconstruction Surgeries Using Mesh for Pelvic Organ Prolapse Patients

This study was carried out in order to compare the effects in different surgeries using mesh in pelvic organ prolapse patients whose leading points were C. Thirty-nine patients were categorized into 3 groups: group A pelvic reconstruction with hysterectomy; group B hysterectomy prior to pelvic reconstruction; and group C pelvic reconstruction with uterus preserved. At first visit, POP-Q stage was determined, and age, BMI, admission days, operation time, post-operative stage and complications were observed and results were analyzed and compared. All patients who were operated upon converted to stage one month following the operation, and no further change was observed except in one patient. Group admission days were not significantly different, but tended to be lower in group C. Group average operation times between 'group A and B' and 'group A and C' were statistically different. No significant difference was observed in post-operative complications between the groups, but 3 members of group A developed erosion, whereas no erosion occurred in groups B and C. Pelvic reconstruction using mesh is a highly efficient method of treating pelvic organ prolapse. Improvements in stage and post-operative complications were not significantly different in the groups. However, uteropexy showed a shorter operation time, fewer admission days, and less erosion due to mesh than conventional pelvic reconstruction with hysterectomy

Increased Anti-tumor Effect by a Combination of HSV Thymidine Kinase Suicide Gene Therapy and Interferon-γ/GM-CSF Cytokine Gene Therapy in CT26 Tumor Model

The potential therapeutic benefit of introducing IFN-γ and GM-CSF genes in combination with the HSVtk suicide gene into subcutaneously implanted CT26 tumor cells was compared with that from each treatment alone. Cells, unmodified or retrovirally transduced with HSVtk or IFN-γ/GM-CSF genes, were inoculated subcutaneously into syngeneic BALB/c mice in various combinations. HSVtk gene, with intraperitoneal ganciclovir treatment, reduced tumor volume by 81% at locally inoculated tumor sites (p<0.01) and by 25% at distantly inoculated tumor sites (p=0.052). IFN-γ/GM-CSF genes showed a 56% tumor volume reduction at local tumor sites (p<0.01) and 15% volume reduction at remote tumor sites, although this was not statistically significant. The combination of HSVtk (with GCV) and IFN-γ/GM-CSF genes showed an 81% volume reduction at local tumor sites (p<0.01) and a 43% volume reduction at remote tumor sites (p<0.01). Thus, the combination of HSVtk and IFN-γ/GM-CSF gene therapy produced greater therapeutic efficacy than either treatment alone

Psychometric Validation of the Korean Version of Structured Interview for Post-traumatic Stress Disorder (K-SIP)

For diagnosis and management of post-traumatic stress disorder (PTSD), the easily administered assessment tool is essential. Structured Interview for PTSD (SIP) is a validated, 17-item, simple measurement being used widely. We aimed to develop the Korean version of SIP (K-SIP) and investigated its psychometric properties. Ninety-three subjects with PTSD, 73 subjects with mood disorder or anxiety disorder as a psychiatric control group, and 88 subjects as a healthy control group were enrolled in this study. All subjects completed psychometric assessments that included the K-SIP, the Korean versions of the Clinician-Administered PTSD Scale (CAPS) and other assessment tools. The K-SIP presented good internal consistency (Cronbach's α=0.92) and test-retest reliability (r=0.87). K-SIP showed strong correlations with CAPS (r=0.72). Among three groups including PTSD patients, psychiatric controls, and normal controls, there were significant differences in the K-SIP total score. The potential cut-off total score of K-SIP was 20 with highest diagnostic efficiency (91.9%). At this point, the sensitivity and specificity were 95.5% and 88.4%, respectively. Our result showed that K-SIP had good reliability and validity. We expect that K-SIP will be used as a simple but structured instrument for assessment of PTSD

Low dietary inorganic phosphate affects the lung growth of developing mice

Inorganic phosphate (Pi) plays a critical role in diverse cellular functions, and regulating the Pi balance is accomplished by sodium-dependent Pi co-transporter (NPT). Pulmonary NPT has recently been identified in mammalian lungs. However, to date, many of the studies that have involved Pi have mainly focused on its effect on bone and kidney. Therefore, current study was performed to discover the potential effects of low Pi on the lung of developing transgenic mice expressing the renilla/firefly luciferase dual reporter gene. Two-weeks old male mice divided into 2 groups and these groups were fed either a low PI diet or a normal control diet (normal: 0.5% Pi, low: 0.1% Pi) for 4 weeks. After 4 weeks of the diet, all the mice were sacrificed. Their lungs were harvested and analyzed by performing luciferase assay, Western blotting, kinase assay and immunohistochemistry. Our results demonstrate that low Pi affects the lungs of developing mice by disturbing protein translation, the cell cycle and the expression of fibroblast growth factor-2. These results suggest that optimally regulating Pi consumption may be important to maintain health

Multilineage Potential of Stable Human Mesenchymal Stem Cell Line Derived from Fetal Marrow

Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following transplantation into the brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and β-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following brain transplantation in mouse ICH stroke model, B10 human MSCs integrate into host brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cell therapy studies in animal models of stroke and other neurological disorders