ABSTRACT
We reports a case of a newly formed thrombus in the left atrial appendage during cardiopulmonary bypass detected by transesophageal echocardiography in a patient with chronic atrial fibrillation and mitral stenosis. This case alerts the anesthesiologists of possible thrombus formation despite full heparinization during cardiac surgery and the importance of a comprehensive echocardiography examination.
Subject(s)
Humans , Atrial Appendage , Atrial Fibrillation , Cardiopulmonary Bypass , Echocardiography , Echocardiography, Transesophageal , Heparin , Mitral Valve Stenosis , Thoracic Surgery , ThrombosisABSTRACT
Stress-induced cardiomyopathy is a recently described acute and transient cardiomyopathy with typical left ventricular apical ballooning mimicking the clinical scenario of an acute myocardial infarction. Cesarean delivery causes intense emotional and physical stresses, which may precipitate stress-induced cardiomyopathy. We report a case presenting stress-induced cardiomyopathy occurring during ICU care in the early postpartum period following cesarean delivery.
Subject(s)
Pregnancy , Cardiomyopathies , Myocardial Infarction , Postpartum PeriodABSTRACT
When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2alpha phosphorylation. Transcription of two downstream targets of eIF2alpha, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuronal differentiation of mouse embryonic stem (mES) cells. Finally, chemical endoplasmic reticulum (ER) stress inducers, thapsigargin, tunicamycin, and brefeldin A, dose-dependently increased both mRNA and protein expressions of NF-L, and, its expression was specific to BIP-positive rBMSCs. Our results showing the induction of UPR during neuronal differentiations of rBMSCs and mES cells as well as NF-L expression by ER stress inducers strongly suggest the potential role of UPR in neuronal differentiation.
Subject(s)
Animals , Mice , Rats , Activating Transcription Factor 4/genetics , Apoptosis/drug effects , Bone Marrow Cells/cytology , Cell Differentiation , Culture Media/pharmacology , Embryonic Stem Cells/cytology , Endoplasmic Reticulum/genetics , Gene Expression/drug effects , Heat-Shock Proteins/genetics , Microtubule-Associated Proteins/genetics , Molecular Chaperones/genetics , Nerve Tissue Proteins/genetics , Neurofilament Proteins/genetics , Neurons/cytology , Nuclear Proteins/genetics , Protein Folding , Stromal CellsABSTRACT
Expressions of endoplasmic reticulum stress response (ERSR) genes were examined during the neuronal differentiation of rat fetal cortical precursor cells (rCPC) and rat pheochromocytoma PC12 cells. When rCPC were differentiated into neuronal cells for 7 days, early stem cell marker, nestin, expression was decreased from day 4, and neuronal markers such as neurofilament-L, -M and Tuj1 were increased after day 4. In this condition, expressions of BIP, ATF6, and phosphorylated PERK as well as their down stream signaling molecules such as CHOP, ATF4, XBP1, GADD34, Nrf2 and p58IPK were significantly increased, suggesting the induction of ERSR during neuronal differentiation of rCPC. ERSR was also induced during the differentiation of PC12 cells for 9 days with NGF. Neurofilament-L transcript was time-dependently increased. Both mRNA and protein levels of Tuj1 were increased after the induction, and the significant increase in NeuN was observed at day 9. Similar to the expression patterns of neuronal markers, BIP/GRP78 and CHOP mRNAs were highly increased at day 9, and ATF4 mRNA was also increased from day 7. These results strongly suggest the induction and possible role of ERSR in neuronal differentiation process. Further study to identify targets responsible for neuronal induction will be necessary.
Subject(s)
Animals , Rats , Endoplasmic Reticulum Stress , Endoplasmic Reticulum , Nerve Growth Factor , Nestin , Neurons , PC12 Cells , Pheochromocytoma , Rivers , RNA, Messenger , Stem CellsABSTRACT
We have previously isolated a novel protein "B/K" that contains two C2-like domains. Here, we report the isolatioin and mRNA distribution of a human B/K isoform, and protein kinase A (PKA)-dependent phosphorylation of the B/K protein. The 1.5 kb human B/K cDNA clone exhibits 89% and 97% identities with rat B/K in the sequences of nucleotide and amino acid, respectively. Human B/K isoform encodes a 474 amino acid protein and shows structural features similar to the rat counterpart including two C2 domains, three consensus sequences for PKA, absence of a transmembrane region, and conservation of the N-terminal cysteine cluster. On Northern and dot blot analyses, a 3.0 kb B/K transcript was abundantly present in human brain, kidney, and prostate. Among the brain regions, strong signals were observed in the frontal and temporal lobes, the hippocampus, the hypothalamus, the amygdala, the substantia nigra, and the pituitary. Recombinant B/K proteins containing three consensus sites for PKA was very efficiently phosphorylated in vitro by PKA catalytic subunit. B/K protein which was overexpressed in LLC-PK1 cells was also strongly phosphorylated in vivo by vasopressin analog DDAVP, and PKA-specific inhibitor H89 as well as type 2 vasopressin receptor antagonist specifically suppressed DDAVP-induced B/K phosphorylation. These results suggest that B/K proteins play a role as potential substrates for PKA in the area where they are expressed.
Subject(s)
Rats , Mice , Male , Humans , Female , Animals , Adult , Sequence Homology, Amino Acid , Sequence Analysis, DNA , Protein Isoforms/genetics , Phosphorylation , Phosphoproteins/genetics , Molecular Sequence Data , Gene Expression Profiling , DNA, Complementary/chemistry , Cyclic AMP-Dependent Protein Kinases/physiology , Cloning, Molecular , Cell Line , Base Sequence , Amino Acid SequenceABSTRACT
B/K protein is a novel protein containing double C2-like domains. We examined the specific signaling pathway that regulates the transcription of B/K in PC12 cells. When the cells were treated with forskolin (50microM), B/K mRNA and protein levels were time-dependently decreased, reaching the lowest level at 3 or 4 hr, and thereafter returning to the control level. Chemicals such as dibutyryl-cAMP, cell- permeable cyclic AMP (cAMP) analogue and CGS21680, adenosine receptor A2A agonist, also repressed the B/K transcription. However, 1, 9-dideoxyforskolin did not show inhibitory effect on B/K transcription, suggesting direct involvement of cAMP in the forskolin-induced inhibition of B/K transcription. Effect of forskolin, dibutyryl cAMP and CGS21680 was significantly reduced in PKA-deficient PC12 cell line (PC12-123.7). One cAMP-response element (CRE) -like sequence (B/K CLS) was found in the promoter region of B/K DNA, and electrophoretic mobility shift assay indicated its binding to CREM and CREB. Forskolin significantly suppressed the promoter activity in CHO-K1 cells transfected with the constructs containing B/K CLS, but not with the construct in which B/K CLS was mutated (AC: TG). Taken together, we suggest that the transcription of B/K gene in PC12 cells may be regulated by PKA-dependent mechanism.