Jinyoung Park

Gene–Culture Interaction Oxytocin Receptor Polymorphism (OXTR) and Emotion Regulation

Research has demonstrated that certain genotypes are expressed phenotypically in different forms depending on the social environment. To examine sensitivity to cultural norms regarding emotion regulation, we explored the expression of the oxytocin receptor polymorphism (OXTR) rs53576, a gene previously related to socioemotional sensitivity, in conjunction with cultural norms. Emotional suppression is normative in East Asian cultures but not in American culture. Consequently, we predicted an interaction of Culture and OXTR in emotional suppression. Korean and American participants completed assessments of emotion regulation and were genotyped for OXTR. We found the predicted interaction: Among Americans, those with the GG genotype reported using emotional suppression less than those with the AA genotype, whereas Koreans showed the opposite pattern. These findings suggest that OXTR rs53576 is sensitive to input from cultural norms regarding emotion regulation. These findings also indicate that culture is a moderator that shapes behavioral outcomes associated with OXTR genotypes.

Overexpression of High-Mobility Group Box 2 Is Associated with Tumor Aggressiveness and Prognosis of Hepatocellular Carcinoma

Purpose: We investigated the expression of high-mobility group box 2 (HMGB2) in patients with hepatocellular carcinoma (HCC) and its clinical effects with underlying mechanisms. Experimental Design: HMGB2 mRNA levels were measured in 334 HCC patients by real-time reverse transcription-PCR and HMGB2 protein levels in 173 HCC patients by immunohistochemical studies. The HMGB2 expression level was measured by Western blotting for three HCC cell lines. To clarify the precise role of HMGB2 on cell proliferation, we did in vitro analysis with expression vectors and small interfering RNAs. Results: HMGB2 mRNA and protein expression were significantly higher in HCC than in noncancerous surrounding tissues (P < 0.0001) and showed a positive correlation (ρ = 0.35, P < 0.001). HMGB2 overexpression was significantly correlated with shorter overall survival time, both at mRNA (P = 0.0054) and protein level (P = 0.023). Moreover, HMGB2 mRNA level was an independent prognostic factor for overall survival in a multivariate analysis (P = 0.0037). HMGB2 knockdown by small interfering RNAs decreased cell proliferation, and overexpression of HMGB2 by expression vectors diminished cisplatin- and etoposide-induced cell death. Conclusions: Our clinical and in vitro data suggest that HMGB2 plays a significant role in tumor development and prognosis of HCC. These results can partly be explained by altered cell proliferations by HMGB2 associated with the antiapoptotic pathway. Clin Cancer Res; 16(22); 5511–21. ©2010 AACR.

The relationship between psychosocial functioning and resilience and negative symptoms in individuals at ultra-high risk for psychosis

Objective: Decline in psychosocial functioning seems to be a core feature in schizophrenia across various phases of the disorder. Little is known about the relationship between psychosocial functioning and protective factors or psychopathologies in individuals in the prodrome phase of psychosis. We aimed to investigate whether psychosocial functioning is impaired in individuals in the putative prodromal phase of schizophrenia, and, if so, to identify factors associated with compromised psychosocial functioning. Method: Sixty participants at ultra-high risk (UHR) for psychosis and 47 healthy controls were recruited. All subjects were assessed in terms of psychosocial functioning using the Quality of Life Scale. A clinical assessment of psychopathology and protective factors, including resilience and coping style, was also conducted. Results: Psychosocial functioning in UHR participants was found to be compromised; this dysfunction was associated with negative symptoms, adaptive coping, and resilience. In addition, baseline resilience was lower among those in the UHR group who converted to frank psychosis than among those who did not. Conclusions: These findings imply that treatment strategies for individuals at UHR for psychosis should be comprehensive, promoting resilience as well as targeting the reduction of positive and negative symptoms to foster social reintegration and recovery.

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas.

AKT1 signaling pathway is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. In this study, we explored the prognostic significance of AKT1 pathway in intrahepatic cholangiocarcinomas. We investigated the status of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphorylated (p) AKT1 (p-AKT1), p-mammalian target of rapamycin (p-MTOR), p-p70 ribosomal protein S6 kinase (p-RPS6KB2) and p-eukaryotic initiation factor 4E-binding protein-1 (p-EIF4EBP1) in 101 intrahepatic cholangiocarcinomas by immunohistochemistry. Western blot analysis was performed to verify the expression levels of p-AKT1 and p-MTOR. The relationship of protein expression with clinicopathological data and the correlations of protein expression levels were explored. The overexpression of p-AKT1, p-MTOR, and PTEN was associated with a better survival in patients with intrahepatic cholangiocarcinoma (P=0.0137, 0.0194, and 0.0337, respectively). In a multivariate analysis, PTEN was an independent prognostic factor, and p-AKT1 showed tendency (P=0.032 and 0.051, respectively). The overexpression of p-MTOR was correlated with well-to-moderately differentiated tumors (P<0.001) and tumors without metastasis (P=0.046). Expression levels of the AKT1 signaling pathway proteins in this study showed positive correlations with each other, except for PTEN. Aberrant expressions of p-AKT1 and p-MTOR in intrahepatic cholangiocarcinoma were associated with a favorable prognosis, possibly in a PTEN-independent manner. Our results indicate that dysregulation of the AKT1 pathway may have an important role in the development of intrahepatic cholangiocarcinoma, but not necessarily in the progression of the disease.

Epithelial–mesenchymal transition gene signature to predict clinical outcome of hepatocellular carcinoma

Hepatocellular carcinoma is one of the most lethal cancers worldwide. More accurate stratification of patients at risk is necessary to improve its clinical management. As epithelial–mesenchymal transition is critical for the invasiveness and metastasis of human cancers, we investigated expression profiles of 12 genes related to epithelial–mesenchymal transition through a real‐time polymerase chain reaction. From a univariate Cox analysis for a training cohort of 128 hepatocellular carcinoma patients, four candidate genes (E‐cadherin [CDH1], inhibitor of DNA binding 2 [ID2], matrix metalloproteinase 9 [MMP9], and transcription factor 3 [TCF3]) with significant prognostic values were selected to develop a risk score of patient survival. Patients with high risk scores calculated from the four‐gene signature showed significantly shorter overall survival times. Moreover, the multivariate Cox analysis revealed that four‐gene signature (P = 0.0026) and tumor stage (P = 0.0023) were independent prognostic factors for overall survival. Subsequently, the four‐gene signature was validated in an independent cohort of 231 patients from three institutions, in which high risk score was significantly correlated with shorter overall survival (P = 0.00011) and disease‐free survival (P = 0.00038). When the risk score was entered in a multivariate Cox analysis with tumor stage only, both the risk score (P = 0.0046) and tumor stage (P = 2.6 × 10−9) emerged as independent prognostic factors. In conclusion, we suggest that the proposed gene signature may improve the prediction accuracy for survival of hepatocellular carcinoma patients, and complement prognostic assessment based on important clinicopathologic parameters such as tumor stage. (Cancer Sci 2010)

Quantification of thalamocortical tracts in schizophrenia on probabilistic maps.

Diffusion properties of the thalamocortical pathways were compared between 30 schizophrenic patients and 22 healthy age-matched and sex-matched volunteers. T1-weighted and diffusion tensor images were used for cortical parcellation and probabilistic tractography to generate population-based thalamocortical pathway maps. The weighted fractional anisotropy and the longitudinal and transversal diffusivity of each pathway were calculated for individual participants. Patients with schizophrenia demonstrated decreased anisotropy and increased longitudinal and transversal diffusivity within the pathways from the mediodorsal nucleus and the pulvinar to the orbitofrontal and parietal-occipital-temporal lobes. Anisotropy decreases and diffusivity increases were correlated with positive and negative syndrome scale scores. Alterations in global diffusion properties within the thalamocortical pathways imply the disruption of brain circuitry in schizophrenic patients.

Theta-gamma coupling during a working memory task as compared to a simple vigilance task

Theta-gamma coupling (TGC) is known to reflect working memory processes, but it is unclear whether TGC as measured by scalp electroencephalography (EEG) reflects working memory processes or nonspecific attentional processes. In this study, we examined the degree of TGC during a visuo-spatial working memory task (2-back task) vs. a simple vigilance task in 13 young participants. During the working memory task, TGC increased in the frontal area at approximately 40 Hz. In addition, TGC was also significantly different at high-gamma frequency despite no differences in gamma power between the two tasks, and a correlation between TGC only during the working memory task and hit rate was observed. These results suggest that TGC reflects working memory processes and may be a useful bio-physiological marker of working memory.

Association of Lifestyle-related Comorbidities With Periodontitis: A Nationwide Cohort Study in Korea

Abstract The aim of this study was to determine the association of periodontitis with lifestyle-related comorbidities (LCs) using data in the Korean National Health Insurance Cohort Database from 2002 to 2013. This was a retrospective study involving a large national cohort with patient samples (representing 2% of the total Korean population) stratified on the basis of sociodemographic information. Using this precisely extracted database, the correlations between LCs (cerebral infarction, angina pectoris, myocardial infarction, hypertension, diabetes mellitus, rheumatoid arthritis, erectile dysfunction, osteoporosis, and obesity) and periodontitis were investigated while adjusting for confounding bias. Univariate and multiple logistic regression analyses were used to evaluate differences in variable factors. Among a total of 1,025,340 samples, 321,103 (31.3%) cases were diagnosed with periodontitis. Statistically significant associations were found between all LCs except myocardial infarction and periodontitis (P < 0.005). Periodontitis is significantly and positively correlated with LCs (except for myocardial infarction) after adjusting for confounding bias. In particular, lifestyle-related diseases, erectile dysfunction, and osteoporosis seem to be intimately related to periodontitis.

Efficacy of US-guided Percutaneous Cholecystocholangiography for the Early Exclusion and Type Determination of Biliary Atresia

PURPOSE To evaluate the efficacy of ultrasonographically (US)-guided percutaneous cholecystocholangiography (PCC) for early diagnosis and characterization of biliary atresia in infants with cholestatic liver disease. MATERIALS AND METHODS Institutional review board approval was obtained for this study. Parental informed written consent was obtained. From October 2003 to August 2010, 22 infants (12 male, 10 female; age range, 1-138 days) were referred to the radiology department for PCC. Indications for PCC were suspected biliary atresia at 24-hour delayed technetium 99m-diisopropyl-phenylcarbamoylmethyl-iminodiacetic acid (DISIDA) scintigraphy because no excretion was observed in the small bowel (n = 17) or when the results of the scan or liver biopsy could not be obtained within 3 days because of a delay in schedule (n = 5). A diagnosis of biliary atresia was excluded when there was contrast material visualized in the gallbladder, biliary system, and passage to the duodenum. Patients with biliary atresia underwent surgery as the reference standard. RESULTS Among the 18 patients who underwent successful PCC, biliary atresia was excluded in 13, with diagnoses as follows: total parenteral nutrition-associated cholestasis (TPNAC) (n = 6), neonatal hepatitis (n = 4), congenital syphilis (n = 1), neonatal lupus (n = 1), and congenital cytomegalovirus hepatitis (n = 1). Biliary atresia was diagnosed in five patients (four with type IIIb and one with type IIIa) and was confirmed at surgery. In four infants in whom US-guided gallbladder puncture had failed, biliary atresia (n = 2) and TPNAC (n = 2) were diagnosed. CONCLUSION PCC is a safe and useful technique for early exclusion when biliary atresia cannot be ruled out after traditional screening tests; in addition, it may be useful for preoperative type determination of biliary atresia.

Prestimulus EEG alpha activity reflects temporal expectancy

Since prestimulus EEG alpha activity has recently been considered to convey prestimulus top-down processing, we investigated whether prestimulus alpha activity reflects temporal expectancy of upcoming stimulation even under the non-classical contingent negative variation (CNV) paradigm. EEG was recorded from 16 subjects performing a color and a shape discrimination task manipulated with constant and variable inter-stimulus interval (ISI) conditions. The power of oscillatory activity was investigated by convolving the EEG signals with Morlet wavelets. The constant ISI condition yielded significantly shorter reaction times than the variable ISI condition, indicating more efficient preparation for upcoming stimuli during the constant ISI. We found significantly higher prestimulus alpha activity in the constant ISI condition than in the variable ISI condition, but no significant CNV even in the constant ISI condition. Such a reflection of temporal expectancy in the prestimulus alpha activity corroborates that the prestimulus top-down mental state for preparing upcoming task-performance is considerably reflected in the prestimulus ongoing alpha activity.