No abstract available.
Aortic Coarctation*

BACKGROUND: We previously demonstrated that a GRE/TRE composite sequence, which is located between 200 bp and 220 bp relative to the transcriptional start site of rat TRH gene, is responsible for the dexamethasone (DEX)- and TPA-induced transcriptional activation, and the transcriptional activation by DEX is mediated by interaction between glucocorticoid receptor (GR) and a TRE-binding transcriptional factor such as c-Jun. However, a non-specific binding with the transciption factors can not be excluded as the mutants used in the previous report could not inhibit the binding of GR and c-Jun completely, and it remains unclear which one of the two TRE-like sequences is critical for the interaction of the two transcription factors. METHODS: Luciferase expressing plasmids that contain a part of rat TRH promoter including the composite GRE sequence or its mutants were transfected into HeLa cells by Fugene 6. After the cells were incubated overnight with DEX or/and TPA, the luciferase activity was measured in a chemiluminometer. A gel retardation assay was performed after binding of the labeled composite sequence or its mutants with GR and c-Jun. RESULTS: DEX and TPA increased the transcriptional activity of the wild type composite sequence by 3 folds and 4 folds, respectively, and the combined stimulation increased the activity by 10 folds. The mutants of which all 6 nucleotides of the GRE half site were replaced and removed almost did not bind to GR and eould not enhance the transcriptional activity at all in response to DEX. The GRE-deleted mutant bound to c-Jun with a remarkably lower affinity and showed a lower response to TPA, whereas the GRE-replaced mutant bound to c-Jun with a similar affinity and showed a similar response to TPA compared to those of the wild type. In response to the combined simulation with DEX and TPA, the mutants showed 30-40% of the trancriptional activity of the wild type. Basal transcriptional activity of all the TRE mutants was significantly lower than that of the wild type. While they almost could not bind to c-Jun, their binding affinity to GR was comparable to that of the wild type. Whereas the DEX- and TPA-induced transcriptional activity of 5 TRE mutant was 10% and 15% of that of the wild type, it responded to those agents in a similar pattern as the wild type. The 3 TRE mutant and the mutant of both TRE sites did not respond to DEX and TPA. The GRE-deleted mutant hardly formed the DNA-protein complex as did the wild type, while the GRE -replaced mutant could form the complex in a less amount with nuclear extract of HeLa celL CONCLUSION: These results suggest that GRE/TRE composite sequence of rat TRH gene specifically binds to GR and c-Jun, providing a site for interaction between the two transcription factors, and that both TRE sites play an important role in basal transcription, and that the 3 TRE site is more critical in the interaction between GRE and TRE for DEX-induced transcriptional activation. (J Kor Endocrinol 14:278-292, 1999)
Animals ; Dexamethasone ; Electrophoretic Mobility Shift Assay ; HeLa Cells ; Humans ; Luciferases ; Mutagenesis, Site-Directed* ; Nucleotides ; Plasmids ; Rats* ; Receptors, Glucocorticoid ; Response Elements* ; Transcription Factors ; Transcriptional Activation

BACKGROUND: We previously demonstrated that the promoter of rat TRH gene has GRE half site (TGTTCT) between -210 bp and -205 bp flanking with similar sequences of TPA response element (TRE), TAGTCA, at a distance of several base pairs from the GRE half site. It promps us to hypothesize that this composite GRE/TRE sequence can provide a site for interaction between glucocorticoid receptor (GR) and c-Jun. Thus, we investigated whether the composite sequence mediates transcriptional regulation induced by dexamethasone (DEX) and 12-O-tetradecanoyl phobol-13-acetate (TPA), and whether it binds GR and c-Jun. METHODS: A luciferase expressing plasmids that contain a part of rat TRH promoter including the composite sequence or their mutants were transfected into HeLa cells by Fugene 6. After the cells were incubated overnight with DEX and TPA, the luciferase activity was measured in a chemiluminometer. A gel retardation assay was performed after binding of the labeled composite sequence or its mutants with GR and c-Jun. RESULTS: DEX increased the transcriptional activity of the plasmid containing the wild type GRE by 2.5 folds, and TPA increased the transcriptional activity by 4 folds. The simultaneous stimulation with DEX and TPA synergistically increased the transcriptional activity by 10 folds. Two mutants whose GRE half sits were altered showed no responses to DEX, and suppressed the TPA-induced or both agents-induced transcriptional activity by 50%. Two mutants whose TRE-like sites were altered suppressed the DEX-induced transcriptional activity by 20%, TPA-induced trarptional activity by 25%, and both agents-induced transcriptional activity by 50%. Gel retardation assay showed that the composite sequence fonned a complex with GR and its mutants bound to GR with remarkably less affinity. c-Jun also bound to the composite sequence to form two cornplexes with less affinity compared to the AP-1 consensus sequence. The mutants of the TRE-like sequence bound to c-Jun with a significantly lower affinity compared to that of the wild type. Simulateous binding of the composite sequence with GR and c-Jun did not form any larger complex. The complex of GR and the composite sequence was much smaller than that formed by c-Jun, suggesting that GR binds to the composite sequence as a monomer. CONCLUSION: These results suggest that the composite sequence of GRE half site and TRE-like site on the promoter of rat TRH gene provides binding sites for GR and c-Jun, which mediate the interaction between two signal transduction pathways. (J Kor Soc Endocrinol 14:265-277, 1999)
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid ; Animals ; Base Pairing ; Binding Sites ; Consensus Sequence ; Dexamethasone ; Electrophoretic Mobility Shift Assay ; HeLa Cells ; Humans ; Luciferases ; Plasmids ; Rats ; Receptors, Glucocorticoid ; Response Elements ; Signal Transduction ; Transcription Factor AP-1

No abstract available.
Enterocolitis, Necrotizing*

No abstract available.
Krukenberg Tumor*

No abstract available.

We describe a 27-year-old man who developed gait disturbance and dysarthria 2 years after the onset of cardinal symptoms of Behcet's disease. Positron emission tomography with 18F-fluorodeoxyglucose revealed severe hypometabolism in the cerebellum, in accordance wih cerebellar symptoms and sign of the patient. However, single-photon emission tomography with Tc-99m-HMPAO and Tc-99m-ECD did not disclose significant perfusion abnormalities in the brain. Routine brain magnetic resonance imaging did not show signal abnormalities. The findings of imaging studies compared with neurological manifestations of the patient are discussed.
Adult ; Brain ; Cerebellum ; Dysarthria ; Gait ; Humans ; Magnetic Resonance Imaging* ; Neurologic Manifestations ; Perfusion ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon*

Pathophysiological conditions such as sepsis and hepatitis are frequently associated with cholestasis. Cholestasis in patients with sepsis has been attributed to the effects of endotoxin(lipopholysaccharides, LPS) and LPS-induced cytokines(TNF-a, IL-6, IL-1, etc.). LPS and cytokines reduced bile acid uptake in cultured hepatocyte. Perfusion of LPS decrease the bile flow in the isolated liver. Bile flow is increased by intravenous infusion of secretin, but it's effect remains unclear in sepsis. The aim, of this study is to elucidate the effect of LPS on the bile flow and bile composition and to test the effect of secretin on the bile flow. The animals used in this study were Korean wild cats. Under the general anesthesia, the incision was made on the midline. Common bile duct was cannulated with polyethylene tube after cholecystectomy. Bile was collected every five minutes and its volume was measured. E. coli LPS(1 mg/kg), secretin(0.1mg/kg) and H3-taurocholic acid(0.2uCi/kg) were infused via mesenteric vein. Bile was collected every 5 minutes, and the volume and its composition were analyzed. Radio-activity of the bile was quantified by Packard 1600 TR liquid scintillation analyzer. LPS of E.coli (1mg/kg) had a little effect on the blood pressure. LPS decreased the bile flow by 37% compared with the control group. Maximal impairment of the bile secretion appeared 15 minites after LPS infusion, and then secreted stablely thereafter. Secretin increased the bile flow in the normal control group. It, however, did not make any change in the bile flow after LPS infusion. LPS also reduced H3-taurocholate secretion(maximum 56%), and peak level was delayed about 10 minites compared with control group. In the composition of the bile, LPS decreased the secretion of bile acids significantly compared with the control group. Conclusively, LPS decreased the bile flow and the bile acid secretion. Secretin did not stimulate the bile flow in the LPS group. It also reduced the bile acids secretion compared with the control group. These findings will contribute to the understanding and treatment of the cholestasis and impairment of the liver function of sepsis. The findings, of reduced bile acids secretion in the LPS group may explain the pathogenesis of intrahepatic gallstone partly.
Anesthesia, General ; Animals ; Bile Acids and Salts ; Bile* ; Blood Pressure ; Cats* ; Cholecystectomy ; Cholestasis ; Common Bile Duct ; Cytokines ; Escherichia coli* ; Escherichia* ; Gallstones ; Hepatitis ; Hepatocytes ; Humans ; Infusions, Intravenous ; Interleukin-1 ; Interleukin-6 ; Liver ; Mesenteric Veins ; Perfusion ; Polyethylene ; Secretin ; Sepsis

No abstract available.
Endometrium* ; Female ; Humans

The MHC class II transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC class II restricted antigen presentation. Previously we suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in vivo. However, the results were contradictory to the report that CIITA functioned to suppress the production of Th2 cytokine by CD4+T cells in CIITA deficient mice. In this study, we investigated the influence of constitutive expression of CIITA in T cells on Th2 immune response in vivo using murine experimental colitis model. In the dextran sodium sulfate-induced acute colitis, a disease involving innate immunity, CIITA transgenic mice and wild type control mice showed similar progression of the disease. However, the development of oxazolone-induced colitis, a colitis mediated by predominantly Th2 immune response, was aggravated in CIITA-transgenic mice. And, CD4+T cells from the mesenteric lymph node of CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4 secretion. Together, these data demonstrate that constitutive expression of CIITA in T cells skews immune response to Th2, resulting in aggravation of Th2-mediated colitis in vivo.
Trans-Activators/*physiology ; Th2 Cells/*immunology ; T-Lymphocytes/*metabolism ; Oxazolone/pharmacology ; Nuclear Proteins/*physiology ; Mice, Transgenic ; Mice, Inbred C57BL ; Mice ; Interleukin-4/biosynthesis ; Colitis/*etiology ; Animals