The relation between immunologic variables and symptom factors in patients with major depressive disorder.

BACKGROUND: The associations between depression and immunity were investigated by measuring the scores of Hamilton Rating Scale for Depression (HRSD) and peripheral lymphocyte parameters in patients with major depressive disorder (MDD). METHODS: Forty-nine patients with MDD were recruited and their clinical symptoms are evaluated with 17-item HRSD which was factorized using the confirmatory factor analysis (i.e., depression factor, insomnia factor, and anxiety factor). Basic immunologic variables such as CD4, CD8, and CD56-positive cell numbers were measured by flow cytometry. Natural killer cell activity (NKCA) was also assessed by ELISA method using K-562 cells as target cells. All patients were treated for 4 weeks with selective serotonin reuptake inhibitors. Immunologic and clinical variables were measured both at baseline and after medication. RESULTS: CD8-positive cell number was increased (p < .05) and CD4/CD8 ratio was decreased (p < .01) after medication. NKCA showed a significant positive correlation with anxiety factor scores of HRSD (p < .05) at baseline. However, except NKCA, there was no correlation between other immunologic measures and symptom factors. CONCLUSION: These results suggest that immunologic measure such as NKCA may be an important variable for symptom of MDD such as anxiety during acute depressive state.

Complex formation of a 4-α-glucanotransferase using starch as a biocatalyst for starch modification.

A 4-α-glucanotransferases from Thermus thermophilus (TTαGT) possesses an extra substrate binding site, leading to facile purification of the intact enzyme using amylose as an insoluble binding matrix. Due to the cost of amylose and low recovery yield, starch was replaced for amylose as an alternative capturer in this study. Using gelatinized corn starch at pH 9 with 36-h incubation in the presence of 1 M ammonium sulfate increased the TTαGT-starch complex formation yield from 2 to 56%. In preparative-scale production, TTαGT produced in Bacillus subtilis was recovered by 42.1% with the same specific activity as that of purified TTαGT. Structural and rheological analyses of the enzymatically modified starches revealed that the starch complex exhibited catalytic performance comparable to soluble TTαGT, suggesting that the starch complex can be used as a biocatalyst for modified starch production without elution of the enzyme from the complex.

Natural killer cell activity in patients with major depressive disorder treated with escitalopram.

BACKGROUND: An association between depression and altered immunity has been suggested by many studies, although the findings are not fully consistent. The present investigation examined the effects of escitalopram on cellular immunity in patients with major depressive disorder (MDD). METHODS: Fifty-one patients with MDD were evaluated with the Hamilton Rating Scale for Depression and Montgomery-Åsberg Depression Rating Scale. The patients were grouped into responders (n=32) and non-responders (n=19). Adrenocorticotropic hormone, cortisol, CD4, CD8, CD19, and natural killer cells were measured at baseline and after a 4 week treatment with escitalopram. Plasma hormones and immune parameters were compared between groups. RESULTS: Responders showed increased activity, but not number, of natural killer cells after a 4 week treatment with escitalopram. There were no differences in plasma hormones and other immune parameters between groups, even though cortisol was decreased and CD19 was increased across both groups compared to baseline. CONCLUSIONS: The results suggest that natural killer cells play an important role in improving the symptoms of depressive patients responding to selective serotonin inhibitors. To deepen our understanding of the pathogenesis of depression, interactions between serotonin and the immune system should be further explored.

Auditory and visual P300 reflecting cognitive improvement in patients with schizophrenia with quetiapine: a pilot study.

We recorded event-related potentials (ERPs) in patients with schizophrenia before and after treatment with quetiapine, to investigate this drug's effects on cognitive function. Auditory and visual oddball stimulus discrimination paradigms were presented to patients with schizophrenia (N=20) before and after 3months' treatment with quetiapine. The 2-stimulus auditory oddball paradigm used a standard tone (1000Hz, 75dB, 80%) and a target tone (2000Hz, 75dB, 20%). The 2-stimulus visual oddball paradigm used a standard stimulus (small circle, 80%) and a target stimulus (large circle, 20%). Patients' severity of psychopathology was initially evaluated with the Positive and Negative Syndrome Scale (PANSS) and was likewise re-evaluated after treatment. After treatment with quetiapine, patients' P300 amplitudes increased over baseline for both tasks (auditory stimuli, P<0.01; visual stimuli, P<0.01) and their P300 latencies for both target stimuli decreased significantly (auditory stimuli, P<0.001; visual stimuli, P<0.01). Visual P300 amplitude was negatively correlated with the severity of positive symptoms at the Fz electrode before the treatment (r=-0.45, P<0.05). After treatment with quetiapine, there were no significant correlations between severity of positive or negative symptoms and visual P300 amplitudes for midline electrodes. These findings suggest that the reduced and delayed P300 may be a state marker for schizophrenia, which may in turn be modulated by positive symptoms, and also suggest that the amplitude and latency for both auditory and visual tasks may be decreased by quetiapine treatment. Based on these results, we suggest that the atypical antipsychotic quetiapine may improve some aspects of cognitive domains in patients with schizophrenia.

Methods of effective team-based learning administration and expected effects on medical education.

PURPOSE: The aim of this study was to analyze the results of quantitative and qualitative student evaluations of team-based learning (TBL) and student achievement evaluations during TBL. METHODS: Questionnaires that evaluated medical student perception and self-assessment of the TBL experience included 38 questions on the TBL process. Also, we used scores from the TBL session to investigate student academic achievement. RESULTS: Our results showed that the more proper the educational environments were, the more focused students were on team learning. According to the distribution period for preliminary assignments, there was a difference in self-directed learning. In addition, team members had the opportunity to learn new knowledge by interacting with each other, and when they had the experience of feedback, they understood the instruction topics through team learning better. With regard to peer evaluation, the students who recognized the importance of assessment studied more sincerely and honestly. By experiencing the TBL process, every team showed a high significance in the group readiness assurance test score compared with the individual readiness assurance test score, and student satisfaction with the TBL and expectation levels about capacity strengthening increased as well. CONCLUSION: TBL is an effective teaching and learning method and has positive impacts on student academic achievement. A study on student academic achievement and perception of TBL is expected to provide medical educators with suggestions on planning teaching strategies for effective TBL administration.

Effects of chromosomal variations on pharmacokinetic activity of zolpidem in healthy volunteers: an array-based comparative genomic hybridization study.

Zolpidem has been known as a very safe and effective hypnotic drug used to treat a variety of patients with insomnia. Even though the same dose of the medicine is administered to each patient, the blood level of zolpidem and the time required to obtain peak concentration are not consistent among different people. We evaluated the relationship between the peak concentrations of zolpidem and chromosomal imbalances using a high-resolution genome-wide array-based comparative genomic hybridization (CGH) in 16 healthy volunteers in order to detect the genetic factors underlying the variations. The present study showed that chromosomal losses were detected in the 4q35.2, 9p13.1 and 9p12 regions, and those gains were indicated in the 2p14, 11q13.4 and 15q11.2 regions. The abnormal regions were confirmed by fluorescence in situ hybridization (FISH) and real-time PCR. It is suggested that array-CGH analysis may be used as a measure for pharmacogenomic applications in the patients with insomnia and for further exploration of candidate genomic regions implicated in sleep disturbances.

Natural Killer T cells in patients with major depressive disorder.

CD56 (Natural Killer T) cells showed a significant negative correlation with depressive symptom scale scores in acute and unmedicated patients with major depressive disorder. Decreased CD56 cells may reflect the severity of depressive symptoms but not the severity of anxiety symptoms in major depression.

Identification of DNA copy-number aberrations by array-comparative genomic hybridization in patients with schizophrenia.

Chromosomal abnormalities are implicated as important markers for the pathogenesis in patients with schizophrenia. In this study, with using bacterial artificial chromosome (BAC) array-based comparative genomic hybridization (CGH), we analyzed DNA copy-number changes among 30 patients with schizophrenia. The most frequent changes were partial gain of Xq23 (52%) and loss of 3q13.12 (32%). Other frequent gains were found in: 1p, 6q, 10p, 11p, 11q, 14p, and 15q regions, and frequent losses were found in: 2p, 9q, 10q, 14q, 20q, and 22q regions. The set of abnormal regions was confirmed by real-time PCR (9q12, 9q34.2, 11p15.4, 14q32.33, 15q15.1, 22q11.21, and Xq23). All real-time PCR results were consistent with the array-CGH results. Therefore, it is suggested that array-CGH and real-time PCR analysis could be used as powerful tools in screening for schizophrenia-related genes. Our results might be useful for further exploration of candidate genomic regions in the pathogenesis of schizophrenia.

MAP, a protein interacting with a tumor suppressor, merlin, through the run domain.

Merlin (or schwannomin) is a tumor suppressor encoded by the neurofibromatosis type 2 gene. Many studies have suggested that merlin is involved in the regulation of cell growth and proliferation through interactions with various cellular proteins. To better understand the function of merlin, we tried to identify the proteins that bind to merlin using the yeast two-hybrid screening. Characterization of the positive clones revealed a protein of 749 amino acids named merlin-associated protein (MAP), which showed wide tissue distribution in Northern blot analysis. Sequence analysis revealed that MAP is a potential homologue of a yeast check-point protein, BUB2, and contains TBC, SH3, and RUN domains, thereby implicating its role in the Ras-like GTPase signal pathways. MAP and merlin were directly associated in vitro and in vivo, and colocalized in NIH3T3 cells. The RUN domain of MAP and the C-terminus of merlin appeared to be responsible for their interaction. MAP decreased the AP-1-dependent promoter activity additively with merlin in NIH3T3 cells. In addition, merlin and MAP synergistically reduced the colony formation of NIH3T3 cells. These results suggest that MAP may play a cooperative role in the merlin-mediated growth suppression of cells.

A naturalistic study of risperidone treatment in seven affiliated university hospitals in Korea.

This retrospective naturalistic study, conducted on patients with schizophrenia, was undertaken to examine the differences in the clinical characteristics of subjects who were treated with risperidone, but who were discontinued soon after administration, and those who were maintained on the drug for a long-term period. Data on 210 of 580 inpatients with schizophrenia who were treated with risperidone and whose complete medical records were available, were analyzed. Patients maintained on risperidone for at least 2 years were assigned to a 'long-term maintenance' (LTM) group and those who were discontinued within 6 months of risperidone administration were assigned to an 'early drop-out' (ED) group. The parameters used for comparisons included the patients' demographic characteristics, the presence/absence of physical or psychiatric comorbidities, the severity of the psychopathology, the typology of the schizophrenia, the nature and subjects' responses to previous antipsychotic treatments (if any) and dosages of risperidone treatment. Of the 210 subjects, 67 (31.9%) belonged to the ED group, whereas 143 (68.1%) were maintained on risperidone at 2 years. There were no significant differences in the demographics, nor in the severity of the psychopathology, nor were there significant differences in the starting or maximal dosages of risperidone administered between the two groups. Exposure to any previous antipsychotic and the longest maintained final dosage of risperidone were significantly different in the two groups. We believed that a multicenter-based retrospective naturalistic study would provide useful information about the efficacy and other practical aspects of antipsychotic administration.