Expression of protein kinase C-delta (PKC delta) is up-regulated by apoptosis-inducing stimuli. However, very little is known about the signaling pathways that control PKC delta gene transcription. In the present study, we demonstrate that JNK stimulates PKC delta gene expression via c-Jun and ATF2 in response to the anticancer agent doxorubicin (DXR) in mouse lymphocytic leukemia L1210 cells. Luciferase reporter assays showed that DXR-induced activation of the PKC delta promoter was enhanced by ectopic expression of JNK1, c-Jun, or ATF2, whereas it was strongly reduced by expression of dominant negative JNK1 or by treatment with the JNK inhibitor SP600125. Furthermore, point mutations in the core sequence of the c-Jun/ATF2 binding site suppressed DXR-induced activation of the PKC delta promoter. Our results suggest an additional role for a JNK signaling cascade in DXR-induced PKC delta gene expression.
Activating Transcription Factor 2/*physiology ; Animals ; Anthracenes/pharmacology ; Antibiotics, Antineoplastic/*pharmacology ; Apoptosis ; Cell Line, Tumor ; Doxorubicin/*pharmacology ; Mice ; Mitogen-Activated Protein Kinase 8/*physiology ; Mutation ; Promoter Regions, Genetic ; Protein Kinase C-delta/genetics/*metabolism ; Proto-Oncogene Proteins c-jun/antagonists & inhibitors/*physiology ; Signal Transduction/physiology ; Transcription, Genetic

There were many cases to apply artificial intelligence to medicine. Neural networks are nonparametric pattern recognition techniques that can be used to model complex relationships. In this paper, we present the analysis of the risk factors of the noninsulin-dependent diabetes mellitus using the artificial neural network and the logistic regression model. First, we developed five prediction models using artificial neural networks and a logistic regression model with the data of Yonchon study of diabetes mellitus. Next, we measured each area under the ROC(Receiver-Operating Characteristic) plots for the performance, and results re followings; multilayer perceptron with seventeen variables(MLP17) was 0.7608, multilayer perceptron with seven variables(MLP7) was 0.7664, radial basis function network with seventeen variables(RBF17) was 0.7919, radial basis function network with seven variables(RBF7) was 0.7715 and logistic regression model(REG7) was 0.8343. All of the variables used are seventeen, and seven variables for neural networks(MLP7 and RBF7) were selected by logistic regression model. The order of higher risk variables in the neural networks(slope) did not completely agree with that in the logistic regression model(odds ratio). However, all of the four higher risk variables that were significant in the statistic model(0.05) also had large slopes(0.3) in the neural network model. And our neural network model also display the influence of another variables in development of the noninsulin-dependent diabetes mellitus.
Artificial Intelligence ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Logistic Models ; Neural Networks (Computer) ; Risk Factors*

No abstract available.
Stomach Neoplasms*

PURPOSE: To explore a 3D conformal radiotherapy technique for a posterior fossa boost, and the potential advantages of a prone position for such radiotherapy. MATERIALS AND METHODS: A CT simulator and 3D conformal radiotherapy planning system was used for the posterior fossa boost treatment of a 13-year-old medulloblastoma patient. He was placed in the prone position and immobilized with an aquaplast mask and immobilization mold. CT scans were obtained of the brain from the top of the skull to the lower neck, with IV contrast enhancement. The target volume and normal structures were delineated on each slice, with treatment planning performed using non-coplanar conformal beams. RESULTS: The CT scans, and treatment in the prone position, were performed successfully. In the prone position, the definition of the target volume was made easier due to the well enhanced tentorium. In addition, the posterior fossa was located anteriorly, and with the greater choice of beam arrangements, more accurate treatment planning was possible as the primary beams were not obstructed by the treatment table. CONCLUSION: A posterior fossa boost, in the prone position, is feasible in cooperating patients, but further evaluation is needed to define the optimal and most comfortable treatment positions.
Adolescent ; Brain ; Carboxymethylcellulose Sodium ; Fungi ; Head* ; Humans ; Immobilization ; Masks ; Medulloblastoma ; Neck* ; Prone Position ; Radiotherapy ; Radiotherapy, Conformal ; Skull ; Tomography, X-Ray Computed

A case of Mycobacterium avium arthritis in a 39-year-old female patient with mixed connective tissue disease (MCTD) was reported. An extra-articular abscess had formed outside the knee joint and extended down the calf. A culture was taken of the abscess and synovial fluid disclosed Mycobacteriun avium. This was resistant to most anti-tuberculosis agents. A combination of anti-tuberculosis drugs followed a total resection of the abscess. We concluded that M avium septic arthritis could insidiously develop into an extra-articular abscess. A combination of anti-tuberculosis drugs with a total resection of the abscess was an effective treatment.
Adult ; Antitubercular Agents/therapeutic use ; Arthritis, Infectious/*microbiology/therapy ; Female ; Human ; Knee Joint/*microbiology/surgery ; Mixed Connective Tissue Disease/*complications ; Mycobacterium avium/drug effects/*isolation & purification ; Mycobacterium avium-intracellulare Infection/*complications/therapy

PURPOSE: To analyze the radioresponse of hepatocellular carcinomas (HCC), using accurate measurements of the tumor size in extrahepatic lymph node metastasis, and to obtain information for the future treatment of primary intrahepatic lesions. MATERIALS AND METHODS: Fifty-one extrahepatic lymph node metastases from primary HCCs, which could be treated by external radiotherapy alone, were included in this study. The radiation dose ranged from 30 to 51 Gy with fraction sizes of 2.0~3.0 Gy. Responses were determined by measuring the areas on CT scans 0, 1 and 3 months after the completion of radiotherapy. The median follow-up period of the surviving patients was 10 months. RESULTS: The overall response rate was 76%, and the important factors were; total dose of radiation, time dose fractionation (TDF) value and the biologically effective dose (BED). A dose of 45 Gy or higher showed an objective response rate of 93%, and if the TDF value was higher than 90, a similar result was observed. In about half (47%) of the patients the maximum response was observed at 3 months or later. The response duration was observable in 14 patients surviving 12 months or longer. Regrowth of irradiated lesions were observed in 4 (66.7%) patients among those who received less than 45 Gy, and in 4 (50%) among those who were treated with 45 Gy or more. There was a statistically significant difference in the survivals between the responders and non-responders (p=0.008). Gastrointestinal bleeding or ulceration was observed in 8 patients, including 3 with NCI common toxicity criteria grade III or higher. CONCLUSION: Radiotherapy was an effective palliative modality for extrahepatic metastasis in HCCs. A radiation dose of 45 Gy or higher (or a TDF value > or =90), was required for a major response.
Carcinoma, Hepatocellular ; Dose Fractionation ; Follow-Up Studies ; Hemorrhage ; Humans ; Lymph Nodes* ; Neoplasm Metastasis* ; Radiotherapy ; Tomography, X-Ray Computed ; Ulcer

PURPOSE: To establish and verify the proper and the practical IMRT (Intensity-modulated radiation therapy) patient QA (Quality Assurance). MATERIALS AND METHODS: An IMRT QA which consists of 3 steps and 16 items were designed and examined the validity of the program by applying to 9 patients, 12 IMRT cases of various sites. The three step QA program consists of RTP related QA, treatment information flow QA, and a treatment delivery QA procedure. The evaluation of organ constraints, the validity of the point dose, and the dose distribution are major issues in the RTP related QA procedure. The leaf sequence file generation, the evaluation of the MLC control file, the comparison of the dry run film, and the IMRT field simulate image were included in the treatment information flow procedure QA. The patient setup QA, the verification of the IMRT treatment fields to the patients, and the examination of the data in the Record & Verify system make up the treatment delivery QA procedure. RESULTS: The point dose measurement results of 10 cases showed good agreement with the RTP calculation within 3%. One case showed more than a 3% difference and the other case showed more than 5%, which was out side the tolerance level. We could not find any differences of more than 2 mm between the RTP leaf sequence and the dry run film. Film dosimetry and the dose distribution from the phantom plan showed the same tendency, but quantitative analysis was not possible because of the film dosimetry nature. No error had been found from the MLC control file and one mis-registration case was found before treatment. CONCLUSION: This study shows the usefulness and the necessity of the IMRT patient QA program. The whole procedure of this program should be performed, especially by institutions that have just started to accumulate experience. But, the program is too complex and time consuming. Therefore, we propose practical and essential QA items for institutions in which the IMRT is performed as a routine procedure.
Film Dosimetry ; Humans

Background/Aims: Biofeedback therapy is widely used to treat patients with chronic constipation, especially those with dyssynergic defecation. Yet, the utility of high-resolution manometry with novel parameters in the prediction of biofeedback response has not been reported. Thus, we constructed a model for predicting biofeedback therapy responders by applying the concept of integrated pressurized volume in patients undergoing high-resolution anorectal manometry. Methods: Seventy-one female patients (age: 48-68 years) with dyssynergic defecation who underwent initial high-resolution anorectal manometry and subsequent biofeedback therapy were enrolled. The manometry profiles were used to calculate the 3-dimensional integrated pressurized volumes by multiplying the distance, time, and amplitude during simulated evacuation. Partial least squares regression was performed to generate a predictive model for responders to biofeedback therapy by using the integrated pressurized volume parameters. Results: Fifty-five (77.5%) patients responded to biofeedback therapy. The responders and non-responders did not show significant differences in the conventional manometric parameters. The partial least squares regression model used a linear combination of eight integrated pressurized volume parameters and generated an area under the curve of 0.84 (95% confidence interval: 0.76-0.95, P < 0.01), with 85.5% sensitivity and 62.1% specificity. Conclusions Integrated pressurized volume parameters were better than conventional parameters in predicting the responsiveness to biofeedback therapy, and the combination of these parameters and partial least squares regression was particularly promising. Integrated pressurized volume parameters can more effectively explain the physiology of the anorectal canal compared with conventional parameters.

PURPOSE: The aim of the study was to evaluate the treatment outcomes of stereotactic radiosurgery (SRS) using a stereotactic body frame for primary or metastatic thoracic tumors. Methods and Materials: Between January 1998 and December 2003, 101 lesions from 91 patients with primary or metastatic thoracic tumors were treated. The eligible patients included 38 with primary lung cancers and 53 with metastatic tumors from the lung, liver, gastrointestinal and other organs. All patients were immobilized using a stereotactic body frame and permitted to breathe shallowly. The respiratory movement was restricted by a diaphragm controller when the tumor movement was greater than 5 mm. Recently, for further restriction of tumor movement, an active breathing control (ABC) apparatus was used in some trained patients whose tumors located in lower lobe. Three to eight coplanar or non-coplanar photon beams were used to adequately cover the planning target volume. A dose of 10~12 Gy per fraction was given three to four times over consecutive days, to a total dose of 30~48 Gy (median 40 Gy). Local control was assessed as complete or partial responses and by a stable disease, as measured by serial chest CT scans at 1 month, and then every 3-months, and/or 18FDG-PET scans 1 month after treatment. The median follow-up period was 14 months, ranging from 4 to 56 months. RESULTS: The overall response rate was 82%, with twenty (22%) complete and 55 (60%) partial responses. The rate of crude local control in all patients was 86% and the one- and two-year local progression free survival rates were 90 and 81%, respectively. The patients who received 48 Gy showed better local progression free survival than those that received 40 Gy or less (one-year; 100% vs. 86.7%), but this was not statistically significant. Of the 21 patients with primary lung cancer, local progression was observed in 3, at 12, 21 and 26 months after treatment, and the one- and two- year local progression free survival rates were 93 and 81%, respectively. The set-up error, as checked by CT-simulation and portal films, for every treatment was within 5 mm in all directions (X, Y and Z axis). No pulmonary complications greater than RTOG toxicity criteria grade 2 were observed. CONCLUSION: From our experience of the stereotactic body frame based radiosurgery it appears a safe and promising treatment modality for the local management of primary or metastatic lung tumors. The optimal total dose, fractionation schedule and treatment volume should be modified after a longer follow-up of these results. Further study related to the optimal evaluation tools is also necessary to differentiate local tumor progression from radiation-induced pulmonary injury
Appointments and Schedules ; Diaphragm ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Liver ; Lung ; Lung Injury ; Lung Neoplasms ; Radiosurgery* ; Respiration ; Tomography, X-Ray Computed

To evaluate the feasibility and treatment outcomes of stereotactic radiosurgery (SRS) using a stereotactic body frame (Precision TherapyTM), we prospectively reviewed 34 tumors of the 28 patients with primary or metastatic intrathoracic lung tumors. Eligible patients included were 9 with primary lung cancer and 19 with metastatic tumors from the lung, liver and many other organs. A single dose of 10 Gy to the clinical target volume (CTV) was delivered to a total dose of 30~40 Gy with 3~4 fractions. Four to 8 coplanar or non-coplanar static fields were generated to adequately cover the planning target volume (PTV) as well as to exclude the critical structures as much as possible. More than 90% of the PTV was delivered the prescribed dose in the majority of cases (average; 96%, range; 74%~100%). The mean PTV was 41.4 cc ranging from 4.4 to 230 cc. Set-up error was within 5 mm in all directions (X, Y, Z axis). The response was evaluated by using a chest CT and or 18FDG-PET scans after SRS treatment, 11 patients (39%) showed complete response, 12 (43%) partial response (decrease of more than 50% of the tumor volume), and 4 patients showed minimally decreased tumor volume or stable disease, but 1 patient showed progressive disease. With a median follow-up period of 18 months, a median local disease progression free interval was 18 months ranging from 7 to 35 months. Although all patients developed grade 1 radiation pneumonitis within 3 months, none had symptomatic or serious late complications after completing SRS treatment. Given these observations, it is concluded that the stereotactic body frame based SRS is a safe and effective treatment modality for the local management of primary or metastatic lung tumors. However, the optimum total dose and fractionation schedule used should be determined after the longer follow-up of these results.
Appointments and Schedules ; Disease Progression ; Follow-Up Studies ; Humans ; Liver ; Lung Neoplasms* ; Lung* ; Prospective Studies ; Radiation Pneumonitis ; Radiosurgery* ; Tomography, X-Ray Computed ; Tumor Burden