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

Recently posterior stabilization with various instrumentation and fusion has been used for fractures of the thoracolumbar spine involving anterior and middle columns. However, these methods are sometimes inadequate to gain anatomical reduction and complete decompression especially in burst fractures. So anterior decompression and interbody fusion were frequently added as a second operation. Biomechanically a rigid anterior spinal instrument such as kaneda device can provide enough anterior decompression through partial or total corpectomy and adequate correction of kyphosis as an one stage operation. We have experienced 27 cases of Kaneda instrumentation via anterior approach for thoracolumbar fracture, most of them were burst fractures, from Jan. 1989 to June 1990. Of there 27 cases, 12 were followed up at least 1 year and reviewed. The results were as followed: l. Anterior spinal approach using Kaneda instrumentation provided sufficient anterior neural decompression and adequate correction of kyphotic deformity. It eliminates the second posterior procedure in most cases and enhances early solid union. Simultaneously, it allows early mobilization of patient with an application of brace. 2. Post-operative courses were eventful in most cases except a case of pathological fracture. 3. This procedure seemed to be one of the most suitable method for the treatment of burst fractures of the thoracolumber region. 4. Complications by Kaneda device itself were not developed in the early evaluation stage. However, on longer follow-up study over 1 year revealed some complications including 2 cases of screw breakage and one lateral wedging deformity.
Braces ; Congenital Abnormalities ; Decompression ; Early Ambulation ; Follow-Up Studies ; Fractures, Spontaneous ; Humans ; Kyphosis ; Methods ; Spine

No abstract available.
Spine*

No abstract available.

OBJECTIVE: This study has been carried out to explore the genetic causes of bipolar disorder by comparing the frequency of Tryptophan Hydroxylase (TPH) A218C polymorphism between bipolar disorder patients and normal controls, and to explore the relation between clinical characteristics of bipolar disorder patients and TPH polymorphism. METHODS: The genotype and allele frequencies of TPH in the genome of 113 hospitalized patients with bipolar disorder was compared with those of 124 normal control subjects using polymerase chain reaction and restriction fragment length polymorphism. The association between TPH A218C polymorphism and clinical characteristics in bipolar disorder patients were explored. RESULTS: The distributions of TPH A218C polymorphism between the patients with bipolar disorder and normal control subjects show no difference statistically. There was a significant difference in the distribution of TPH genotype by clinical characteristics. The frequency of C allele is significantly higher in patients with a history of suicidal attempts. The frequency of A allele is significantly higher in patients with family history of bipolar disorder. CONCLUSION: This study suggests that suicidal attempts and family history in the patients with bipolar disorder are clearly associated with TPH A218C polymorphism and may explain, in part, the biological basis for these typologies.
Alleles ; Bipolar Disorder* ; Gene Frequency ; Genome ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Suicide ; Tryptophan Hydroxylase* ; Tryptophan*

The purpose of this study is to obtain information of simple and effective methods for the pos-tlaminectomy pain control, and to reduce the consumption of supplemental analgesic drugs and side effects. In a double blind study, 75 patients scheduled for lumbar laminectomy were randomly divided into five groups according to the epidurally instilled drugs, such as, morphine 2mg,Group M2; morphine 3mg,Group M3; methylprednisolone 80 mg, Group D; morphine 2mg plus methylprednisolone 80mg, Group M2D; normal saline as a control Group C. All of the drugs were prepared in 2ml normal saline solution. The following items were recorded in the postoperative period: Pain score using visual analogue scale(VAS) at 6, 12, 24, 48 hours after the operation; the episode of supplemental systemic analgesic; the need for postoperative urethral catheterization; any evidence of respiratory depression; pruritus; nausea and vomiting. The results were as follows. I) VAS score were not significantly different between control group and group M2(p>0.05), but usually less in the group M2 and supplemental analgesic consumption was significantly less in the group M2 than in the control group. 2) VAS score were less in the group M3 than in the group M2 and significantly less than in the control group at 6 hour after operation and also supplemental analgesic consumption was significantly less in the group M3. 3) Group D revealed similar VAS score with group M2 at 6 and 12 hour but significantly lower VAS score at 24 and 48 hour after operation than group M2. 4) VAS score were the most significantly less in the group M2D at 6,12,24,48 hour after operation than in the control group and supplemental analgesic consumption was significantly less in the group M2D. 5) Side effects were not significantly different among all groups. These findings suggest that epidurally instilled morphine 3mg, or methylprednisolone 80mg or both before the closure of the laminectomy wound is effective, simple and safe method for the post-laminectomy pain control and reducing supplemental intramuscular analgesics without specific complication.
Analgesics ; Double-Blind Method ; Humans ; Laminectomy* ; Methylprednisolone* ; Morphine* ; Nausea ; Pain, Postoperative* ; Postoperative Period ; Pruritus ; Respiratory Insufficiency ; Sodium Chloride ; Urinary Catheterization ; Urinary Catheters ; Vomiting ; Wounds and Injuries

PURPOSE: Radical cystectomy with urinary tract reconstruction currently remains the standard treatment for invasive bladder cancer, and adjuvant chemotherapy is usually considered for patients with a clinical stage >T2 or nodal metastasis. The aim of this study was to assess the safety of adjuvant chemotherapy in patients with orthotopic bladder substitution in comparison to ileal conduit. MATERIALS AND METHODS: We retrospectively analyzed the patients who underwent radical cystectomy and urinary diversion between 1990 and 2005. The patients who underwent adjuvant chemotherapy were stratified into two groups: those who had orthotopic bladder substitution and those who had ileal conduit. The chemotherapy regimen, renal function change, complications from adjuvant chemotherapy and other relevant data were analyzed. RESULTS: Overall, 341 patients had radical cystectomy, 89 had adjuvant chemotherapy, 28 had orthotopic bladder substitution and 61 had ileal conduit. The patient characteristics, including age, stage and follow-up, were similar in both groups. In all, 42% of patients had grade 1 toxicity, 16% had grade 2, 14% had grade 3 and 0% had grade 4. No patients had serious organ toxicity and none died. There were no significant differences in the chemotherapy toxicity and renal function change among the two groups. CONCLUSIONS: Adjuvant chemotherapy is safe and well tolerated by patients with either orthotopic bladder substitution or ileal conduit. There was no increased morbidity or mortality due to adjuvant chemotherapy in the patients who had orthotopic bladder substitution. Hence, orthotopic bladder substitution should not be denied to those patients with bladder cancer and who might require adjuvant chemotherapy.
Chemotherapy, Adjuvant* ; Cystectomy ; Drug Therapy ; Follow-Up Studies ; Humans ; Mortality ; Neoplasm Metastasis ; Retrospective Studies ; Urinary Bladder Neoplasms ; Urinary Bladder* ; Urinary Diversion* ; Urinary Tract

No abstract available.
Hyperparathyroidism, Primary*

No abstract available.
Radionuclide Imaging*