Transcatheter Arterial Embolization in the Management of Postpartum Hemorrhage due to Genital Tract Injury after Vaginal Delivery.

PURPOSE: To evaluate efficacy and safety of transcatheter arterial embolization (TAE) in managing postpartum hemorrhage (PPH) due to genital tract injury after vaginal delivery and to investigate factors associated with outcome of TAE. MATERIALS AND METHODS: A retrospective review of 43 women (mean age, 32.6 years) who underwent TAE to manage PPH secondary to genital tract injury after vaginal delivery was performed at a single institution between January 2007 and December 2018. Clinical data and outcomes were obtained. Patients were classified into clinical success (n = 39) and failure (n = 4) groups, and comparisons between the groups were performed. RESULTS: The clinical success rate of TAE for PPH due to genital tract injury was 90.7%. In the clinical failure group, transfusion volumes were higher (failure vs success: packed red blood cells, 14 pt ± 3.37 vs 6.26 pt ± 4.52, P = .003; platelets, 10.33 pt ± 4.04 vs 2.92 pt ± 6.15, P = .036); hemoglobin levels before the procedure were lower (failure vs success: 7.3 g/dL vs 10.7, P = .016). Periprocedural complications included pulmonary edema (25.6%), fever (23.3%), and pain (9.3%). Twenty-four patients were either followed for > 6 months or answered a telephone survey; 23 (95.8%) recovered regular menstruation, and pregnancy was confirmed in 11 (45.8%). Regarding fertility desires, 7 women attempted to conceive, 6 of whom (85.7%) became pregnant. CONCLUSIONS: TAE is an effective and safe method for managing PPH due to genital tract injury after vaginal delivery. Lower hemoglobin levels before the procedure and higher transfusion volumes were associated with clinical failure of TAE.

The TFG-TEC oncoprotein induces transcriptional activation of the human ß-enolase gene via chromatin modification of the promoter region.

Recurrent chromosome translocations are the hallmark of many human cancers. A proportion of human extraskeletal myxoid chondrosarcomas (EMCs) are associated with the characteristic chromosomal translocation t(3;9)(q11-12;q22), which results in the formation of a chimeric protein in which the N-terminal domain of the TRK-fused gene (TFG) is fused to the translocated in extraskeletal chondrosarcoma (TEC; also called CHN, CSMF, MINOR, NOR1, and NR4A3) gene. The oncogenic effect of this translocation may be due to the higher transactivation ability of the TFG-TEC chimeric protein; however, downstream target genes of TFG-TEC have not yet been identified. The results presented here, demonstrate that TFG-TEC activates the human ß-enolase promoter. EMSAs, ChIP assays, and luciferase reporter assays revealed that TFG-TEC upregulates ß-enolase transcription by binding to two NGFI-B response element motifs located upstream of the putative transcription start site. In addition, northern blot, quantitative real-time PCR, and Western blot analyses showed that overexpression of TFG-TEC up-regulated ß-enolase mRNA and protein expression in cultured cell lines. Finally, ChIP analyses revealed that TFG-TEC controls the activity of the endogenous ß-enolase promoter by promoting histone H3 acetylation. Overall, the results presented here indicate that TFG-TEC triggers a regulatory gene hierarchy implicated in cancer cell metabolism. This finding may aid the development of new therapeutic strategies for the treatment of human EMCs. © 2015 Wiley Periodicals, Inc.

The reprogramming factor nuclear receptor subfamily 5, group A, member 2 cannot replace octamer-binding transcription factor 4 function in the self-renewal of embryonic stem cells.

Although octamer-binding transcription factor 4 (Oct-4) is one of the most intensively studied factors in mammalian development, no cellular genes capable of replacing Oct-4 function in embryonic stem (ES) cells have been found. Recent data show that nuclear receptor subfamily 5, group A, member 2 (Nr5a2) is able to replace Oct-4 function in the reprogramming process; however, it is unclear whether Nr5a2 can replace Oct-4 function in ES cells. In this study, the ability of Nr5a2 to maintain self-renewal and pluripotency in ES cells was investigated. Nr5a2 localized to the nucleus in ES cells, similarly to Oct-4. However, expression of Nr5a2 failed to rescue the stem cell phenotype or to maintain the self-renewal ability of ES cells. Furthermore, as compared with Oct-4-expressing ES cells, Nr5a2-expressing ES cells showed a reduced number of cells in S-phase, did not expand normally, and did not remain in an undifferentiated state. Ectopic expression of Nr5a2 in ES cells was not able to activate transcription of ES cell-specific genes, and gene expression profiling demonstrated differences between Nr5a2-expressing and Oct-4-expressing ES cells. In addition, Nr5a2-expressing ES cells were not able to form teratomas in nude mice. Taken together, these results strongly suggest that the gene regulation properties of Nr5a2 and Oct-4 and their abilities to confer self-renewal and pluripotency of ES cells differ. The present study provides strong evidence that Nr5a2 cannot replace Oct-4 function in ES cells.

A TFG-TEC nuclear localization mutant forms complexes with the wild-type TFG-TEC oncoprotein and suppresses its activity.

Human EMCs (extraskeletal myxoid chondrosarcomas) are soft tissue tumours characterized by specific chromosomal abnormalities. Recently, a proportion of EMCs were found to harbour a characteristic translocation, t(3;9)(q11-12;q22), involving the TFG (TRK-fused gene) at 3q11-12 and the TEC (translocated in extraskeletal chondrosarcoma) gene at 9q22. The present study used both in vitro and in vivo systems to show that the TFG-TEC protein self-associates, and that this is dependent upon the CC (coiled-coil) domain (amino acids 97-124), the AF1 (activation function 1) domain (amino acids 275-562) and the DBD (DNA-binding domain) (amino acids 563-655). The TFG-TEC protein also associated with a mutant NLS-TFG-TEC (AAAA) protein, which harbours mutations in the NLS (nuclear localization signal). Subcellular localization assays showed that the NLS mutant TFG-TEC (AAAA) protein interfered with the nuclear localization of wild-type TFG-TEC. Most importantly, the mutant protein inhibited TFG-TEC-mediated transcriptional activation in vivo. Thus mutations in the TFG-TEC NLS yield a dominant-negative protein. These results show that the biological functions of the TFG-TEC oncogene can be modulated by a dominant-negative mutant.

Core-shell strain structure of zeolite microcrystals.

Zeolites are crystalline aluminosilicate minerals featuring a network of 0.3-1.5-nm-wide pores, used in industry as catalysts for hydrocarbon interconversion, ion exchangers, molecular sieves and adsorbents. For improved applications, it is highly useful to study the distribution of internal local strains because they sensitively affect the rates of adsorption and diffusion of guest molecules within zeolites. Here, we report the observation of an unusual triangular deformation field distribution in ZSM-5 zeolites by coherent X-ray diffraction imaging, showing the presence of a strain within the crystal arising from the heterogeneous core-shell structure, which is supported by finite element model calculation and confirmed by fluorescence measurement. The shell is composed of H-ZSM-5 with intrinsic negative thermal expansion whereas the core exhibits a different thermal expansion behaviour due to the presence of organic template residues, which usually remain when the starting materials are insufficiently calcined. Engineering such strain effects could have a major impact on the design of future catalysts.

The TFG-TEC fusion gene created by the t(3;9) translocation in human extraskeletal myxoid chondrosarcomas encodes a more potent transcriptional activator than TEC.

The t(3;9)(q11-q12;q22) translocation associated with human extraskeletal myxoid chondrosarcomas results in a chimeric molecule in which the N-terminal domain (NTD) of the TFG (TRK-fused gene) is fused to the TEC (Translocated in Extraskeletal Chondrosarcoma) gene. Little is known about the biological function of TFG-TEC. Because the NTDs of TFG-TEC and TEC are structurally different, and the TFG itself is a cytoplasmic protein, the functional consequences of this fusion in extraskeletal myxoid chondrosarcomas were examined. The results showed that the chimeric gene encoded a nuclear protein that bound DNA with the same sequence specificity as the parental TEC protein. Comparison of the transactivation properties of TFG-TEC and TEC indicated that the former has higher transactivation activity for a known target reporter containing TEC-binding sites. Additional reporter assays for TFG (NTD) showed that the TGF (NTD) of TFG-TEC induced a 12-fold increase in the activation of luciferase from a reporter plasmid containing GAL4 binding sites when fused to the DNA-binding domain of GAL4, indicating that the TFG (NTD) of the TFG-TEC protein has intrinsic transcriptional activation properties. Finally, deletion analysis of the functional domains of TFG (NTD) indicated that the PB1 (Phox and Bem1p) and SPYGQ-rich region of TFG (NTD) were capable of activating transcription and that full integrity of TFG (NTD) was necessary for full transactivation. These results suggest that the oncogenic effect of the t(3;9) translocation may be due to the TFG-TEC chimeric protein and that fusion of the TFG (NTD) to the TEC protein produces a gain-of-function chimeric product.

Mutation in the DNA-binding domain of the EWS-Oct-4 oncogene results in dominant negative activity that interferes with EWS-Oct-4-mediated transactivation.

The EWS-Oct-4 protein is a chimeric molecule in which the amino terminal domain (NTD) of the EWS becomes fused to the carboxy terminal domain (CTD) of the Oct-4 transcription factor. It was identified in human bone and soft-tissue tumors associated with t(6;22)(p21;q12). Using in vitro and in vivo systems, we found that the EWS-Oct-4 protein self-associates. The major domains required for self-association mapped to the EWS NTD (amino acids 70-163) and the POU DNA-binding domain. EWS-Oct-4 protein also associated with EWS-Oct-4 (V351P), which contains a mutation in the POU DNA-binding domain. Using electrophoretic mobility shift assays, we found that the EWS-Oct-4 (V351P) mutant interfered with wild-type EWS-Oct-4 DNA-binding activity. In addition, we found that EWS-Oct-4-mediated transcriptional activation was inhibited by EWS-Oct-4 (V351P) protein in vivo. Thus, this mutation in the POU DNA-binding domain results in a dominant negative protein. These findings suggest that the biological functions of the EWS-Oct-4 oncogene can be modulated by the dominant negative mutant EWS-Oct-4 (V351P).