Mutación heterocigota, autosómica recesiva del gen RARS2 en una paciente colombiana de padres no consanguíneos / Autosomal recessive heterocygote mutation of the RARS2 gene in a colombian patient with non- consanguineous parents

Las nuevas metodologías de secuenciación masiva han permitido caracterizar e identificar variantes genéticas asociadas a diferentes patologías. En este trabajo se presenta el caso de una paciente con una mutación del gen RARS2 que codifica la enzima arginino-ARNt ligasa para la codificación de proteínas. Esta alteración genética se manifiesta en hipoplasia pontocerebelosa tipo 6, con una prevalencia de <1/1 000 0000, caracterizada por un cerebelo y un puente de menor tamaño asociados a un retraso grave en el neurodesarrollo. El análisis de caso permite un mejor conocimiento de enfermedades de origen genético, específicamente, de aquellas con patrones de herencia autosómicos recesivos de padres no consanguíneos. Su estudio sobre todo en lo relacionado con el ámbito familiar y socioeconómico, y su base genética, ayuda a una mejor calidad de vida de los pacientes y su familia.

The latest method of next-generation sequencing has allowed the characterization and identification of genetic variants associated to diverse pathologies. In this article, we present the case of female patient with a mutation of the RARS2 gene that encodes the enzyme for arginyl tRNA synthetase for coding of proteins. This genetic alteration manifests in pontocerebellar hypoplasia type 6, with a prevalence of <1/1,000,0000, characterized by a cerebellum and pons that are smaller in size and are associated with severe neurodevelopmental delay. The analysis of the case of this patient provides better knowledge of diseases of genetic origin; specifically, regarding genetic diseases of autosomal recessive patterns of inheritance from non-consanguineous parents. The impact of these studies; specially within the family, social, economic and genetic aspects helps provide a better quality of life for these patients and their family.

Ischemic preconditioning inhibits over-expression of arginyl-tRNA synthetase gene Rars in ischemia-injured neurons / 华中科技大学学报（医学）（英德文版）

The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-tRNA synthetase (ArgRS), and the inhibitory effects of ischemic preconditioning (IPC) on Rars gene were explored. Both IPC model and prolonged ischemia (PI) model were established by using the classic oxygen glucose deprivation (OGD) method. The primary cultured neurons were assigned into the following groups: the experimental group (IPC+PI group), undergoing PI after a short period of IPC; the conditional control group (PI control group), subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and ArgRS expression levels were measured at different time points after re-oxygenation (3 h/6 h/12 h/24 h). Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and ArgRS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and ArgRS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to ArgRS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate ArgRS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.

Inducing effect of 4-Amino-2-Trifluoromethyl-Phenyl Retinate on differentiation of human breast cancer MDA-MB-231 cell and its possible mechanisms / 中国药理学通报

Aim To investigate the effect of 4-Amino- 2-Trifluoromethyl-Phenyl Retinate on human breast cancer cells MDA-MB-231 and the possible mecha-nisms. Method Human breast cancer MDA-MB-231 cells were incubated with different concentrations of ATPR in vitro. MTT assay was performed to measure the proliferation of MDA-MB-231 . Cell growth curves were made by counting cells and morphologic changes were observed by Wright-Giemsa staining. The differ-entiation marker mucin-1 ( MUC-1 ) was measured by enzyme linked immunosorbent assay ( ELISA ) . Cell cycle was examined by Flow cytometry ( FCM ) . The expression of retinoic acid receptors ( RARs) and reti-noid X receptors ( RXRs ) were detected by Western blot and Quantitative real-time PCR (q-RT-PCR),re-spectively. Results Compared with solvent group, ATPR could inhibit the proliferation of MDA-MB-231 cells in a time-and dose dependent manner and induce the maturing and normality of morphology. The express of MUC-1 was significantly decreased, and the progres of cell cycle was blocked in the G0/G1-phase. The ex-pression of RARγ was decreased. Conclusions AT-PR could inhibit proliferation and induce differention of MDA-MB-231cells, it′s associated with RARγ.

JAK2 V617F mutation in myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable, refractory anemia with ring sideroblasts with thrombocytosis, and acute myeloid leukemia

BACKGROUND: The JAK2 V617F mutation has been noted in the cases of polycythemia vera, essential thrombocythemia, and primary myelofibrosis patients. This mutation occurs less frequently in acute myeloid leukemia (AML) and other hematologic diseases, such as myelodysplastic syndrome (MDS); myelodysplatic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U); and refractory anemia with ring sideroblasts with thrombocytosis (RARS-T). METHODS: Patients diagnosed with hematologic diseases other than MPN who visited Seoul St Mary's Hospital from January 2007 to February 2010 were selected. A total of 43 patients were enrolled in this study: 12 MDS, 9 MDS/MPN-U, 7 RARS-T, and 15 AML patients. The diseases were diagnosed according to the 2008 WHO classification criteria. Data obtained from JAK2 V617F mutation analysis and cytogenetic study as well as complete blood count and clinical data were analyzed. RESULTS: Of the 43 patients, 6 (13.9%) harbored the JAK2 V617F mutation. The incidence of the JAK2 V617F mutation in each patient group was as follows: 8.3% (1/12), MDS; 22.2% (2/9), MDS/MPN-U; 14.3% (1/7), RARS-T; and 13.3%, (2/15) AML. The platelet count was higher than 450x10(9)/L in 3 of the 6 patients (50%) harboring the JAK2 V617F mutation, and it was in the normal range in the remaining 3 patients. Among the 6 patients, 1 MDS and 1 MDS/MPN-U patients had the 46,XX,del(20)(q11.2) karyotype. CONCLUSION: The JAK2 V617F mutation is associated with an increased platelet count in MDS, MDS/MPN-U, RARS-T, and AML patients. Cytogenetic abnormalities of del(20)(q11.2) occurred in 1/3 of patients with the JAK2 V617F mutation but further studies are required to confirm this association.

Correlation between Retinoic Acid Sensitivity and IGFBP-3, AFP Protein Expression in Hepatoma Cell Lines / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Retinoic acid (RA) has been known to inhibit the proliferation, and to induce apoptosis, of various cancer cell lines. We investigated the correlation between the protein levels of the RAR and RXR receptor families, IGFBP-3 and AFP, and the RA sensitivity in hepatoma cell lines. MATERIALS AND METHODS: The cell growth inhibition was examined by assaying various 1 to 10muM RA treated hepatoma cell lines. Western blot analysis for the RAR and RXR families, AFP and IGFBP-3 were performed after treatment with 10muM RA. RESULTS: The 1 to 10muM RA treatment induced growth inhibition in the SNU368, SNU354, SNU398 and HepG2 cells. The cell growth of SNU449 and Hep3B were not suppressed by 1muM, but were slightly suppressed by 10muM RA. An increased expression of IGFBP-3 in HepG2, SNU354, SNU398 and SNU368 cells, and a decreased expression of alpha-fetoprotein (AFP), was observed from the western blot analysis in all hepatoma cells tested, whereas no confirmed tendency of RAR expressions was seen. CONCLUSION: Our result showed that the growth inhibition of RA differed according to the sensitivity of the type of cells to RA. We supposed that RA-induced cell growth inhibition may be related to the expressions of IGFBP-3 and AFP, but no exact correlation exists between the growth inhibition and receptor expression status in hepatoma cell lines.

Protective effects of hyperpolarized cardiac preservation solution on isolated rat heart / 中华器官移植杂志

Objective To evaluate the protective effects of a novel hyperpolarized cardiac preservation solution on isolated rat heart. Methods Male Sprague Dawley rats (250~300 g, n =24) were randomly divided into three groups ( n =8 in each group) and their hearts were preserved with K H, UW, HCS solution respectively for 24 h. The isolated hearts were perfused in the Langendorff rat mode for functional evaluation before and after preservation. Lactate dehydrogenase and creatine phosphokinase enzyme leakages, contents of adenosine triphosphate and wet weights in myocardium were measured after reperfusion. Results The impairment of the left ventricle function in K H group was serious, while that in HCS and UW groups was mild. The recovery of coronary flow in HCS group was better than K H and UW groups. There were no significant differences in releases of LDH and CPK and wet weight of myocardium between UW group and HCS group. HCS group offered a less variety of pH and had the highest ATP content of myocardium among the three groups. The time, from the reperfusion to beating of heart, showed no difference between UW group and HCS group. The ultrastructural changes were slight in HCS group. Conclusions HCS solution can protect rat heart for 24 h effectively. The recovery of heart function by HCS is similar to that by UW solution. HCS solution can improve the coronary flow and acidosis and protect ATP more effectively than UW solution.

The effect of chronic hypoxia on expression of oncogene erbB in rat lung / 中国病理生理杂志

In order to assess whether there is any abnormality in oncogene expression in hypoxia induced pulmonary hypertension, the expression of oncogene erbB in the lung tissue of rats with and without hypoxia was detected by in situ hybridization with digoxingenin as a prob label. The results showed that there was a slight expression of erbB mRNA in control normoxic rats. After hypoxia for 7 to 21 days, its expression increased significantly as compared with that in control (P