Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma

PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.

A Network Analysis of 15O-H2O PET Reveals Deep Brain Stimulation Effects on Brain Network of Parkinson's Disease

PURPOSE: As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. MATERIALS AND METHODS: We obtained [15O]H2O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. RESULTS: ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. CONCLUSION: Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

Prognostic Significance of Volume-Based FDG PET/CT Parameters in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation Therapy

PURPOSE: We investigated the prognostic role of volume-based parameters measured on 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scans in patients with locally advanced pancreatic cancer (LAPC) treated with chemoradiation therapy (CRT). MATERIALS AND METHODS: We enrolled 60 patients with LAPC who underwent FDG PET/CT before CRT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary pancreatic cancers were measured on FDG PET/CT scans. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to determine independent prognostic factors. RESULTS: The progression-free survival (PFS), locoregional progression-free survival (LRFPS), and overall survival (OS) for this population were 6.2, 10.9, and 13.2 months, respectively. The overall treatment response rate was 16.7% at 4 weeks after CRT, and the disease control rate (DCR) was 80.0%. DCR was significantly higher in patients with low SUVmax, MTV, or TLG, and showed strong correlation with longer survival times. On univariate analysis, MTV and TLG were significant prognostic factors for PFS, LRPFS, and OS, together with pre-CRT and post-CRT CA19-9 levels. Multivariate analyses demonstrated that MTV together with the pre-CRT CA19-9 level were independent prognostic factors for PFS, LRPFS, and OS, as was TLG for LRPFS and OS. CONCLUSION: MTV and the pre-CRT CA19-9 level provided independent prognostic information in patients with LAPC treated with CRT. Volume-based PET/CT parameters may be useful in identifying which subgroup of patients would benefit from radiation therapy as a part of CRT.

Quantitative Analysis of Simultaneous EEG Features during PET Studies for Childhood Partial Epilepsy

PURPOSE: To demonstrate the significance of simultaneous electroencephalography (EEG) recording during 2-deoxy-2-[18F] fluoro-D-glucose (FDG)-positron emission tomography (PET) in childhood partial epilepsy. MATERIALS AND METHODS: We included 46 children with partial epilepsy who underwent simultaneous EEG during PET. We compared the epileptogenic area of several EEG features including epileptiform discharges, focal polymorphic slow waves, and electrographic seizures, with the abnormal metabolic region on PET. We also compared the epileptogenic area of simultaneous EEG and PET with findings on magnetic resonance imaging (MRI) and video/EEG, as well as the histopathological diagnosis of the resected cortical area, in eight patients who underwent surgical resection of the epileptogenic area. RESULTS: Hypometabolic regions on interictal PET were concordant with epileptogenic areas of epileptiform discharges and focal polymorphic slow waves, according to their frequency and/or severity, with odds ratios of 1.35 and 1.81, respectively (p<0.05). Hypermetabolic PET was also concordant with epileptogenic areas of ictal events longer than 20 seconds during the period of FDG uptake. Among the eight patients who underwent surgical resection, six patients, including two with non-lesional MRI, had concordant EEG and PET findings, were confirmed pathologically, and became seizure-free after surgery. CONCLUSION: Simultaneous EEG is useful in identifying epileptogenic areas due to a high concordance with abnormal PET metabolic areas. Moreover, simultaneous EEG may also prevent false lateralization of PET from postictal and mixed metabolism during ictal events, as well as abnormal hypermetabolism, during frequent interictal epileptiform discharges.

Analysis of 18F-fluorodeoxyglucose positron emission tomography findings in patients with pituitary lesions

BACKGROUND/AIMS: Although magnetic resonance imaging (MRI) is a good visual modality for the evaluation of pituitary lesions, it has limited value in the diagnosis of mixed nodules and some cystic lesions. We evaluated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) for patients with pituitary lesions. METHODS: 18F-FDG PET and MRI were performed simultaneously in 32 consecutive patients with pituitary lesions. The relationships between FDG uptake patterns in PET and MRI findings were analyzed. RESULTS: Of 24 patients with piuitary adenomas, 19 (79.2%) showed increased uptake of 18F-FDG in the pituitary gland on PET scans. All patients with pituitary macroadenomas showed increased 18F-FDG uptake on PET scans. Meanwhile, only five (50%) of the 10 patients with pituitary microadenomas showed positive PET scans. Interestingly, of two patients with no abnormal MRI findings, one showed increased 18F-FDG uptake on PET. For positive 18F-FDG uptake, maximum standardized uptake values (SUVmax) > 2.4 had 94.7% sensitivity and 100% specificity. In addition, SUVmax increased in proportion to the size of pituitary adenomas. Most cystic lesions did not show 18F-FDG uptake on PET scans. CONCLUSIONS: About 80% of pituitary adenomas showed positivity on PET scans, and SUVmax was related to the size of the adenomas. PET may be used as an ancillary tool for detection and differentiation of pituitary lesions.

Is the GABA System Related to the Social Competence Improvement Effect of Aripiprazole? An 18F-Fluoroflumazenil PET Study

OBJECTIVE: Patients with schizophrenia who are treated with aripiprazole experience some benefits including an improvement of social competence, but the underlying mechanism of this improvement has not been investigated yet. This study aimed to provide preliminary evidence that the GABA system may be involved in the effect of aripiprazole on social competence. METHODS: Seventeen outpatients with schizophrenia (9 taking aripiprazole and 8 taking risperidone) and 18 healthy controls underwent 18F-fluoroflumazenil PET, and GABAA receptor binding potential was compared between the three groups. RESULTS: Voxelwise one-way ANOVA showed that GABAA receptor binding potentials in the right medial prefrontal cortex (p=0.04) and right dorsolateral prefrontal cortex (p=0.02) were significantly lower in the aripiprazole group than the risperidone group, and those in the left frontopolar cortex (p=0.03) and right premotor cortex (p=0.02) were significantly lower in the aripiprazole group than the risperidone and control groups. CONCLUSION: Our results suggest that aripiprazole administration results in increased GABA transmission in the prefrontal regions, and that these increases may be a neural basis of aripiprazole's clinical benefits on an improvement of social competence.

A System for Concurrent TMS-fMRI and Evaluation of Imaging Effects

PURPOSE: The purpose of this study was to setup a concuurent transcranial magnetic stimulation (TMS)-functional MRI (fMRI) system for understanding causality of the functional brain network. MATERIALS AND METHODS: We manufactured a TMS coil holder using nonmagnetic polyether ether ketone (PEEK). We simulated magnetic field distributions in the MR scanner according to TMS coil positions and angles. To minimize image distortions caused by TMS application, we controlled fMRI acquisition and TMS sequences to trigger TMS during inter-volume intervals. RESULTS: Simulation showed that the magnetic field below the center of the coil was dramatically decreased with distance. Through the MR phantom study, we confirmed that TMS application around inter-volume acquisition time = 100 miliseconds reduced imaging distortion. Finally, the applicability of the concurrent TMS-fMRI was tested in preliminary studies with a healthy subject conducting a motor task within TMS-fMRI and passive motor movement induced by TMS in fMRI. CONCLUSION: In this study, we confirmed that the developed system allows use of TMS inside an fMRI system, which would contribute to the research of brain activation changes and causality in brain connectivity.

Prognostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients with Resectable Pancreatic Cancer

PURPOSE: We evaluated the prognostic value of 18F-2-fluoro-2-deoxyglucose positron emission tomography (FDG PET) in patients with resectable pancreatic cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of pancreatic cancer patients who underwent curative resection, which included 64 consecutive patients who had preoperative FDG PET scans. For statistical analysis, the maximal standardized uptake value (SUVmax) of primary pancreatic cancer was measured. Survival time was estimated by the Kaplan-Meier method, and Cox's proportional hazard model was used to determine whether SUVmax added new predictive information concerning survival together with known prognostic factors. p3.5) showed significantly shorter OS and DFS than the low SUVmax group. Multivariate analysis of OS and DFS showed that both high SUVmax and poor tumor differentiation were independent poor prognostic factors. CONCLUSION: Our study showed that degree of FDG uptake was an independent prognostic factor in pancreatic cancer patients who underwent curative resection.

Radiotechnologists and Radiation Exposure from PET and PET/CT Systems / 대한산업의학회지

OBJECTIVES: In this study, radiotechnologists who work performing PET and PET/CT methodologies were analyzed in order to find the cause for the differences in radiation exposure as they applied to general characteristics, work characteristics, knowledge, and exposure recognition or conduct. METHODS: From April 15th, 2010 to May 14th, 2010, we conducted a retrospective analysis on 80 radiotechnologists using data garnered from their individual general characteristics, work characteristics, knowledge, and exposure recognition or conduct. Their average annual radiation exposure dosages were measured using a thermoluminescence dosimeter. A multiple regression analysis was performed as a statistical tool. RESULTS: Regarding the general PET and PET/CT characteristics, when the work experience was short, the exposure dose was higher. The factors of age, marriage, work experience in nuclear medicine, PET, PET/CT, and sex were found to have statistically significant effects. The knowledge, recognition, and conduct factors for the radiotechnologists were affected by unsecure radiation exposure at the moment of carrying, unsecure radiation exposure at the moment of injection, the application of protection at the moment of injection, and the use of auto distributor. It was found that, the use of an auto distributor, efforts in reducing the radiation exposure, unsecure exposure when with a patient, and the application of protective procedures at the moment of injection affected the overall factor of radiotechnologists radiation exposure dose. CONCLUSIONS: We believe that if radiotechnologists would reduce their radiation exposure by using auto distributors, make efforts to reduce the chance of exposure, and be conscious of radiation, they would be able to reduce the radiation exposure dose even during unavoidable circumstances.

Immunotherapy of Malignant Melanoma with Tumor Lysate-Pulsed Autologous Monocyte-Derived Dendritic Cells

PURPOSE: Dendritic cell (DC) vaccination for melanoma was introduced because melanoma carries distinct tumor-associated antigens. The purpose of this study was to investigate the efficacy and safety of DC vaccination for melanoma in Korea. MATERIALS AND METHODS: Five patients with stage IV and one with stage II were enrolled. Autologous monocyte-derived DCs (MoDCs) were cultured and pulsed with tumor-lysate, keyhole limpet hemocyanin, and cytokine cocktail for mature antigen-loaded DC. DC vaccination was repeated four times at 2-week intervals and 2-4x107 DC were injected each time. RESULTS: Reduced tumor volume was observed by PET-CT in three patients after DC vaccination. Delayed type hypersensitivity responses against tumor antigen were induced in five patients. Tumor antigen-specific IFN-gamma-producing peripheral blood mononuclear cells were detected with enzyme-linked immunosorbent spot in two patients. However, the overall clinical outcome showed disease progression in all patients. CONCLUSION: In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.

Clinical Significance of Myocardial Uptake on F-18 FDG PET/CT Performed in Oncologic Patients / 핵의학분자영상

PURPOSE: F-18 fluorodeoxyglucose (FDG) uptake of myocardium is influenced by various factors. Increased glycolysis, and subsequent increased F-18 FDG uptake has been reported in ischemic cardiomyopathy. However, clinical significance of incidentally found myocardial F-18 FDG uptake has not been clarified. We retrospectively reviewed the degree and pattern of myocardial uptake in patients without history of ischemic heart disease who underwent torso F-18 FDG PET/CT for evaluation of neoplastic disease. MATERIALS AND METHODS: From January 2005 to June 2009, 77 patients who underwent F-18 FDG PET/CT and Tc-99m sestamibi stress/rest SPECT within 3 months were enrolled. RESULTS: Of 77 patients, 55 (71.4%) showed increased F-18 FDG uptake in the myocardium. In this population, 40 showed uniform uptake pattern, while 15 showed focal uptake. In patients with uniform uptake, 17 showed decreased uptake in the septum without perfusion defect on myocardial SPECT. Remaining 23 patients showed uniform uptake, with 1 reversible perfusion defect and 1 fixed perfusion defect. In 15 patients with focal uptake, 9 showed increased F-18 FDG uptake in the base, and only 1 of them showed reversible perfusion defect on myocardial SPECT. In the remaining 6 focal uptake group, 4 had reversible perfusion defect in the corresponding wall, and 1 had apical hypertrophy. CONCLUSION: We demonstrated that septal defect pattern and basal uptake pattern in the myocardium may represent normal variants. Focal myocardial uptake other than normal variants on oncologic torso F-18 FDG PET/CT with routine fasting protocol may suggest ischemic heart disease, thus further evaluation is warranted.

The value of Dedicated Tc-99m MIBI Scintimammography in the Evaluation of Patients with Palpable Breast Lesions in Comparison with Mammography: Preliminary Result / 핵의학분자영상

PURPOSE: There are few studies evaluating the usefulness of dedicated high-resolution scintimammography and no studies using delayed washout with this dedicated high resolution scintimammography for the evaluation of breast lesions. We underwent this study to evaluate the clinical usefulness of Tc-99m MIBI in evaluating patients with palpable breast lesions using dedicated high-resolution scintimammography. MATERIALS AND METHODS: This study included 19 patients with 23 palpable breast lesions who underwent mammography. Tc-99m MIBI was taken to further characterize these lesions. Scintimammography images were acquired with standard craniocaudal and mediolateral oblique views and delayed images were additionally taken. Final conclusions were based on histopathology, either by biopsy or mastectomy results. RESULTS: Eighteen lesions were malignant and five were benign. Mammography was indeterminate for thirteen lesions, nine of those were malignant. Mammography also categorized one lesion as benign in a dense breast, but scintimammography and pathology results showed malignancy. Of the five benign lesions, two were visible on scintimammography, but delayed images showed washout. CONCLUSION: Based on our preliminary results, dedicated high resolution scintimammography seems to be very useful in characterizing palpable lesions that were indeterminate or negative on mammography.

Imaging of Cancer Metabolism using Positron Emission Tomography

In the 1920's, Warburg reported an observation that cancer cells depend on glycolysis even in the presence of available oxygen likely due to impaired function of mitochondria. Since then, this Warburg s effect has been the most important hypothesis in cancer metabolism and is considered as a seventh hallmark of many human cancers. Aerobic glycolysis was originally attributable to increased bioenergetic needs in rapidly proliferating cancer cells. Recently, biosynthetic aspects of aerobic glycolysis, which reprograms cancer metabolism to synthesize macromolecules such as nucleotides, fatty acids, amino acids, etc., are under active investigation. Introduction of positron emission tomography (PET) and metabolic radiotracers including F-18 flurorodeoxyglucose (FDG) and C-11 acetate made it possible to image cancer metabolism in vivo and to renew the interests on this issue. Studies have found that cancer cells with highly glycolysis features are associated with resistance to many chemotherapeutic regimens and radiation treatment. Therefore, development of glycolytic inhibitors can have an incremental effect to conventional treatments. In addition, functional imaging with metabolic radiotracers will continuously play important roles in detecting cancers and monitoring therapeutic responses to novel anti-metabolic approaches to cancer cells.

Anhedonia and Ambivalence in Schizophrenic Patients with Fronto-Cerebellar Metabolic Abnormalities: A Fluoro-D-Glucose Positron Emission Tomography Study

OBJECTIVE: Prefrontal and cerebellar abnormalities have been associated with higher cognitive deficits in schizophrenia. The current study aimed to show whether or not schizophrenic patients with fronto-cerebellar functional abnormalities show more anhedonia or ambivalence. METHODS: Regional cerebral metabolic activity was measured using fluoro-D-glucose positron emission tomography and was compared between 24 patients with chronic schizophrenia and 22 healthy normal volunteers. The existence of regional prefrontal hypofunction and regional cerebellar hyperfunction was investigated in each patient. Demographic and clinical variables including the emotional self-report scales were compared between the subgroups of the patients categorized according to the existence and the absence of the regional dysfunctions. RESULTS: Comparisons between each patient and the total normal controls revealed that 14 of the total twenty-four patients had regional hypofrontal functions, whereas 11 patients had regional hypercerebellar functions. Patients with prefrontal hypofunction showed more severe anhedonia than those without prefrontal hypofunction, whereas patients with cerebellar hyperfunction compared to those without cerebellar hyperfunction had more severe ambivalence. CONCLUSION: It seems that fronto-cerebellar abnormalities may be associated with cardinal emotional features of schizophrenia, such as anhedonia and ambivalence.

Analysis on the association between EEG and 2-deoxy-2-18F-D-glucose (FDG)-PET findings in children with epilepsy / 소아과

PURPOSE: We performed EEG and PET on children with epilepsy concomitantly in order to evaluate the effects of epileptiform and non-epileptiform discharge of EEG on glucose metabolism. METHODS: Seventy three children with epilepsy who had PET and EEG simultaneously were included in our study. The subjects were classified in two ways: (1) based on the frequency of epileptiform discharge and (2) the severity of non- epileptiform discharge. We evaluated the clinical aspects of their seizures, the severity of focal slow waves during the interictal period with the frequency of spikes or sharp waves in order to compare with the PET results. RESULTS: The subjects were divided by the frequency of epileptiform discharge, with 13 in the no/rare group, 7 in the occasional group, and 53 children in the frequent group. The concordant rates with PET in each group were 0%, 42.9%, and 67.9%, respectively, showing high correlations with the frequency of epileptiform discharge (P<0.05, r=0.491). The subjects as divided by the severity of non-epileptiform discharge were 15 in the no group, 25 in the infrequent group, 17 in the intermediate group, and 16 in the continuous group. The concurrence rates with PET for each group were 13.3%, 52.0%, 64.7%, and 68.8%, respectively, also showing a high correlation with the severity of non-epileptiform discharge (P<0.05, r= 0.365). CONCLUSION: Epileptiform discharge and non-epileptiform discharge in EEG showed a certain association with hypometabolism in PET. We recommend EEG to reduce false lateralization and to localize lesions in cases of high frequency and severity.

Imaging of Viral Thymidine Kinase Gene Expression by Replicating Oncolytic Adenovirus and Prediction of Therapeutic Efficacy

PURPOSE: We have used a genetically attenuated adenoviral vector which expresses HSVtk to assess the possible additive role of suicidal gene therapy for enhanced oncolytic effect of the virus. Expression of TK was measured using a radiotracer-based molecular counting and imaging system. MATERIALS AND METHODS: Replication-competent recombinant adenoviral vector (Ad-deltaE1B19/55) was used in this study, whereas replication-incompetent adenovirus (Ad-deltaE1A) was generated as a control. Both Ad-deltaE1B19/55-TK and Ad-deltaE1A-TK comprise the HSVtk gene inserted into the E3 region of the viruses. YCC-2 cells were infected with the viruses and incubated with 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (I-131 FIAU) to measure amount of radioactivity. The cytotoxicity of the viruses was determined, and gamma ray imaging of HSVtk gene was performed. MTT assay was also performed after GCV treatment. RESULTS: On gamma counter-analyses, counts/minute (cpm)/microgram of protein showed MOIs dependency with deltaE1B19/55-TK infection. On MTT assay, Ad-deltaE1B19/55-TK led to more efficient cell killing than Ad-deltaE1A-TK. On plate imaging by gamma camera, both Ad-deltaE1B19/55-TK and Ad-deltaE1A-TK infected cells showed increased I-131 FIAU uptake in a MOI dependent pattern, and with GCV treatment, cell viability of deltaE1B19/55-TK infection was remarkably reduced compared to that of Ad-deltaE1A-TK infection. CONCLUSION: Replicating Ad-deltaE1B19/55-TK showed more efficient TK expression even in the presence of higher-cancer cell killing effects compared to non-replicating Ad-deltaE1A-TK. Therefore, GCV treatment still possessed an additive role to oncolytic effect of Ad-deltaE1B19/55-TK. The expression of TK by oncolytic viruses could rapidly be screened using a radiotracer-based counting and imaging technique.

GABA Receptor Imaging / 핵의학분자영상

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABAA-receptor that allows chloride to pass through a ligand gated ion channel and GABAB-receptor that uses G-proteins for signaling. The GABAA-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABAA-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18F-fluoroflumazenil (FFMZ) has been developed to overcome 11C's short half-life. 18F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using 11C-FMZ PET instead of 18F-FDG PET, restrict the foci better and may also help find lesions better than high resolution MR. GABAA receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

Empathy and Mood Awareness Reflected in the Resting-State Brain Metabolic Activity in the Patients with Schizophrenia and Normal Subjects

OBJECTIVES: Empathy has been conceptualized as the ability of emotional resonance and perspective-taking. Emotional awareness has been proposed as the basis of empathy. In this study we examined the relationship between empathy and mood awareness and their neural correlates in resting-state activity in normal controls and patients with schizophrenia. METHODS: Empathy and mood awareness scale scores were compared between 29 patients with schizophrenia and 21 normal controls by voxel-based t-tests and voxel-based correlation analyses of resting-state 18F-FDG PET images. RESULTS: Empathy and mood labeling scale scores were significantly decreased in schizophrenic patients. Mood monitoring was positively correlated with empathy score in normal controls, but not in schizophrenic patients. In normal controls, empathy was positively correlated with resting-state activities in the intraparietal sulcus and mood monitoring was positively correlated with the temporal pole, frontopolar cortex, inferior temporal gyrus, entorhinal cortex and the subgenual prefrontal cortex resting activities. The orbitofrontal cortex resting activity was positively correlated with mood monitoring-related subgenual prefrontal cortex activity in the normal controls. Patients with schizophrenia showed decreased orbitofrontal resting activity and loss of its correlations with mood monitoring-related regional activities. CONCLUSION: This study showed that alteration in the resting-state activity in schizophrenia may reflect dysfunctional empathy and distorted characteristic of emotional awareness. However, the resting-state activity may not reflect the relationship between emotional awareness and empathy.

Developmental Disability Animal Model Based on Neonatal Lipopolysaccharide with Altered 5-HT Function

Developmental disability shows life-long behavioral abnormality with no significant physical malformation. This study was undertaken to develop an animal model for developmental disability by using two-factor approach. Lipopolysaccharide (LPS), a bacterial toxin, and NAN-190, a 5-HT1A receptor antagonist, were administered to Sprague-Dawley rats on postnatal day (PND) 5 to induce inflammation and an altered 5-HT system, respectively. Long-term alteration of behavior occurred in the drug-treated groups. The LPS-treated group showed impaired motor coordination in the Rota-rod test. The LPS- treated or both LPS and NAN-190-treated groups showed impaired fore-paw muscle power in the wire maneuver test. These groups also showed decreased white matter volume and increased serotonergic fibers. The LPS and NAN-190-treated group also exhibited neurologic deficit in the placing reaction test and impaired equilibrium function in the tilt table test. The results showed that a variety of altered behaviors can be generated by two factor model, and suggested that combination of important etiologic factors and possible underlying defects is a promising strategy of establishing an animal model for developmental disabilities.

Effects of Antioxidants on the Gamma-Radiation Damage of the Cultured Vascular Smooth Mucle Cells of Rat Aorta

To study the protective effects of antioxidants on the radiation damages of the cells, vascular smooth muscle cells (VSMC) from thoracic aorta of Sprague-Dawley rats were cultured and irradiated with gamma-ray. Cell viability was measured by direct cell counting and MTT assay, and flow cytometry was performed to measure fractional distributions of the cells. Gamma-ray irradiation inhibited cell proliferations accompanied with decreased G1 phase and increased S- and G2/M phases, and the maximum effects were observed at 1500 or 2000 cGy. Submaximal concentrations of antioxidants, such as allopurinol, vitamin C, N-acetylcycteine (NAC), lipoic acid, dihydrolipoic acid and rebamipide tended to increase the cell viability suppressed by low dose of radiation (500 cGy), and enalapril and vitamin E increased it significantly. Allopurinol, vitamin E, NAC, lipoic acid, captopril and enalapril significantly increased G1 phase. Allopurinol and vitamin E tended to increase c-Myc expression, detected by Western blot, that was reduced by the radiation, and enalapril increased it significantly. The cell viability and c-Myc expression were highly correlated (r=0.97) with each other. These results suggest that antioxidants, especially enalapril and vitamin E, recover the viability of VSMC from gamma-radiation injury, through a mechanism which includes increase of c-Myc protein expression.