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

A scanning electron microscopic study was performed on the surface ultrastructure of Pygidiopsis summa (Digenea: Heterophyidae) adults. Metacercariae were collected from gills and muscles of mullets (Mugil cephalus) caught in a known endemic area, and adult flukes were harvested from dogs after 8 weeks of experimental infection. The worm was calabash form with its posterior part broader than the anterior part. Tegumental spines were densely distributed over the body surface, except on the suckers and genital apparatus, and around the excretory pore. Well differentiated spines were observed on the anterior half of the body, with 14-16 tips ventrally, and 19-20 tips dorsally. On the oral sucker, three pairs of type I sensory papillae (uni-ciliated knob-like swellings) and one pair of type II sensory papillae (aciliated round-swellings) were observed on the anterior and posterior parts of the lip, respectively. On the lip of the ventral sucker, one pair of type II sensory papillae was distributed only on its posterior part. Sperms were seen emerging from or entering into the genital apparatus. The results showed that the surface ultrastructure of P. summa was unique among the heterophyid trematodes, especially in digitation of tegumental spines and in distribution of sensory papillae on oral and ventral suckers.
Animals ; Dogs ; Heterophyidae/*ultrastructure ; Microscopy, Electron, Scanning

PURPOSE: The measurement of radiation absorbed dose is useful to predict the response after I-131 labeled metaiodobenzylguanidine (MIBG) therapy and determine therapy dose in patients with unresectable or malignant pheochromocytoma. We estimated the absorbed dose in tumor tissue after high dose I-131 MIBG in a patient with pheochromocytoma using a gamma camera and Medical Internal Radiation Dose (MIRD) formula. MATERIALS AND METHODS: A 64-year old female patient with pheochromocytoma who had multiple metastases of mediastinum, right kidney and periaortic lymph nodes, received 74 GBq (200 mCi) of I-131 MIBG. We obtained anterior and posterior images at 0.5, 16, 24, 64 and 145 hours after treatment. Two standard sources of 37 and 74 MBq of I-131 were imaged simultaneously. Cummulated I-131 MIBG uptake in tumor tissue was calculated after the correction of background activity, attenuation, system sensitivity and count loss at a high count rate. RESULTS: The calculated absorbed radiation dose was 32-63 Gy/ 74 GBq, which was lower than the known dose for tumor remission (150-200 Gy). Follow-up studies at 1 month showed minimally reduced tumor size on computed tomography, and mildly reduced I-131 MIBG uptake. CONCLUSION: We estimated radiation absorbed dose after therapeutic I-131 MIBG using a gamma camera and MIRD formula, which can be peformed in a clinical nuclear medicine laboratory. Our RESULTS suggest that the measurement of radiation absorbed dose in I-131 MIBG therapy is feasible as a routine clinical practice that can guide further treatment plan. The accuracy of dose measurement and correlation with clinical outcome should be evaluated further.
3-Iodobenzylguanidine ; Female ; Follow-Up Studies ; Gamma Cameras ; Humans ; Kidney ; Lymph Nodes ; Mediastinum ; Middle Aged ; Neoplasm Metastasis ; Nuclear Medicine ; Pheochromocytoma

PURPOSE: The purpose of this study was to evaluate the diagnostic accuracy of [18F]FDG PET in the diagnosis of recurrent head and neck cancer after the completion of surgery and radiotherapy in patients with head and neck cancers. MATERIALS AND METHODS: In fifty-nine patients with head and neck cancers, whole body [18F]FDG PET studies were performed. According to the different therapeutic modalities, patients were divided into four groups (Group I; pre-treatment, Group II; surgery, Group III; radiotherapy, Group IV; both surgery and radiotherapy). [18F]FDG PET images were compared with clinical, CT and histopathologic findings. RESULTS: For detection of metastatic lymph nodes in 14 patients of pre-treatment group (group I), the sensitivity and specificity of PET were 100% (10/10) and 75% (3/4), and those of CT were 80% (8/10) and 100% (4/4). For detection of recurrence in 45 patients of post-treatment group, overall sensitivity and specificity of PET were 96.2% (25/26) and 78.9% (15/19) [(100% and 75% in group II, 80% and 50% in group III, and 100% and 100% in group IV)] without significant difference from pre-treatment group (p>0.1). In detecting recurrence, the sensitivity and specificity of [18F]FDG PET were 90.9% (10/11) and 20% (1/5) in 16 patients who underwent [18F]FDG PET within 2 months after the completion of treatment. The specificity of these patients was significantly lower than that of 29 patients (100% of sensitivity and specificity) who underwent [18F]FDG PET 2 months after treatment (p<0.05). CONCLUSION: [18F]FDG PET is an accurate diagnostic modality for the detection of recurrence in head and neck cancer. Post-therapy [18F]FDG PET should be obtained at least 2 months after the completion of surgery or radiotherapy.
Diagnosis ; Head and Neck Neoplasms ; Head* ; Humans ; Lymph Nodes ; Neck* ; Radiotherapy* ; Recurrence ; Sensitivity and Specificity

No abstract available.
Humans ; Stomach Neoplasms* ; Stomach*

PURPOSE: This treatment planning study was undertaken to evaluate the impact of beam angle configuration of intensity-modulated radiotherapy (IMRT) on the dose of the normal liver in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The computed tomography datasets of 25 patients treated with IMRT for HCC were selected. Two IMRT plans using five beams were made in each patient; beams with equidistance of 72degrees (Plan I), and beams with a 30degrees angle of separation entering the body near the tumor (Plan II). Both plans were generated using the same constraints in each patient. Conformity index (CI), homogeneity index (HI), gamma index, mean dose of the normal liver (Dmean_NL), Dmean_NL difference between the two plans, and percentage normal liver volumes receiving at least 10, 20, and 30 Gy (V10, V20, and V30) were evaluated and compared. RESULTS: Dmean_NL, V10, and V20 were significantly better for Plan II. The Dmean_NL was significantly lower for peripheral (p = 0.001) and central tumors (p = 0.034). Dmean_NL differences between the two plans increased in proportion to gross tumor volume to normal liver volume ratios (p = 0.002). CI, HI, and gamma indices were not significantly different for the two plans. CONCLUSION: The IMRT plan based on beams with narrow separations reduced the irradiated dose of the normal liver, which would allow radiation dose escalation for HCC.
Carcinoma, Hepatocellular ; Humans ; Liver ; Radiotherapy, Intensity-Modulated ; Tumor Burden

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*

PURPOSE: It is important to differentiate malignant from benign lesions of intraocular masses in choosing therapeutic plan. Biopsy of intraocular tumor is not recommended due to the risk of visual damage. We evaluated the usefulness of F-18-FDG PET imaging in diagnosing intraocular neoplasms. MATERIALS AND METHODS: F-l8-FDG PET scan was performed in 13 patients (15 lesions) suspected to have malignant intraocular tumors. There were 3 benign lesions (retinal detachment, choroidal effusion and hemorrhage) and 10 patients with 12 malignant lesions (3 melanomas, 7 retinoblastomas and 2 metastatic cancers). Regional eye images (256*256 and 128*128 matrices) were obtained with or without attenuation correction. Whole body scan was also performed in eight patients (3 benign and 6 malignant lesions). RESULTS: All malignant lesions were visualized while all benign lesions were not visualized. The mean peak standardized uptake value (SUV) of malignant lesions was 2.64+/-0.57 g/ml. There was no correlations between peak SUV and tumor volume. Two large malignant lesions (>1000 mm3 ) showed hot uptake on whole body scan. But two medium-sized lesions (100-l000 mm3) looked faint and two small (<100 mm3) lesions were not visualized. The images reconstructed with 256*256 matrix showed lesions more clearly than those with 128X128 matrix. CONCLUSION: F-18-FDG PET scan is highly sensitivity in detecting malignant intraocular tumor. For the evaluation of small-sized intraocular lesions, whole body scan is not appropriate because of low sensitivity. A regional scan with sufficient acquisition time is recommended for that purpose. Image reconstruction in matrix size of 256*256 produced clearer images than the ones in 128X128, but it does not affect the diagnostic sensitivity.
Biopsy ; Choroid ; Diagnosis* ; Humans ; Image Processing, Computer-Assisted ; Melanoma ; Orbital Neoplasms ; Positron-Emission Tomography ; Retinoblastoma ; Tumor Burden ; Whole Body Imaging

To determine how closely end- tidal PCO2 measured by capnometer(Datex, Finland), a kind of infrared gas analyzer, reflects arterial PCO2(measured by Corning 175: U.S.A.) during general anesthegia, peak- tidal PCO2 and arterial were measured simultaneously. Thirty patients ranging between the age of 18 and 49, having no apparent abnomalities and having physical status class I by American Society of Anesthesiologist's classification-were seleted for the study. The anesthesia was induced with 2.5% pentothal sodium 4~5 mg/kg, succinylcholine 1mg/kg and incubated. The anesthesia was maintained with each 2 L/min gas flow of nitrous oxide, oxygenand 1 halothne. The patients were ventilated br anesthetic ventilator with tidal volume 8~10 ml/kg and ramie of 15 Per minute. The measurement of CO2 gas tension was performed 20 minutes after the induction when the patient's anesthetic conditions were stabilized. The CO2 gas ganlples were taken from mouth piece inserted between endotracheal adapter and circle breathing circuit, The arterial blood tramples were taken from the radial artery. There was a significant correlation between the end-tidol PCO2 and the arterial PCO2 in this series. The mean arterial PCO2 was 37.57+/-4.59 mmHg and the mean end tidal PCO2 was 23.73+/-5.78 mmHg. The mean difference between the arterial and the end tidal PCO2 was 6.53+/-2.23 mmHg. The correlation index between the two measurement was 0.8. In conclusion, the measurement of the end-tidal PCO2 by Datex Capnometer reflected the blood PCO2 and is convenient method of clinical use for its non invasiveness and continuous measurement of ventilatory status of patients under general anesthesia.
Anesthesia ; Anesthesia, General* ; Boehmeria ; Carbon Dioxide* ; Carbon* ; Humans ; Mouth ; Nitrous Oxide ; Radial Artery ; Respiration ; Sodium ; Succinylcholine ; Thiopental ; Tidal Volume ; Ventilators, Mechanical ; Zea mays