Efficacy and Tolerability of Aripiprazole: A 26-Week Switching Study from Oral Antipsychotics

Objective To determine if the maintenance effectiveness and tolerability of aripiprazole demonstrated in a 12-week study were maintained in an extension phase (up to 26 weeks). Methods This study was the extension of our switching study from other antipsychotics to aripiprazole in symptomatically stable patients with schizophrenia or schizoaffective disorder. All the patients were randomly assigned to the aripiprazole group or the non-aripiprazole group. The effectiveness analysis consisted of the comparison of the upper bound of the 95% confidence interval (CI) of the mean Clinical Global Impression-Improvement (CGI-I) score to 4 (no change) at the end of the study. Results At the baseline, the aripiprazole group (n=135) and the non-aripiprazole group (n=31) were comparable with respect to their mean ages, gender distribution, baseline Positive and Negative Syndrome Scale scores, and Clinical Global Impression-Severity (CGI-S) scores. The study showed that the mean CGI-I score was 2.92 (95% CI: 2.72-3.12) in the aripiprazole group and 2.81 (95% CI: 2.35-3.26) in the non-aripiprazole group at 26 weeks. In the aripiprazole group, the remission rates at 12 and 26 weeks were 74.8% and 72.6%, respectively, and 80.2% of the patients with remission at 12 weeks maintained their remission state until the end of the study. About one-fourth of the patients in the aripiprazole group reported one or more spontaneous treatment-emergent adverse events, such as insomnia, headache, and nausea. Conclusion This study suggested that most clinically stable outpatients with schizophrenia maintain their remission states after being switched to aripiprazole, without serious symptom aggravation and adverse events over a course of 26 weeks. Psychiatry Investig 2010;7:189-195This study was supported by Korea Otsuka Pharmaceuticals (KOP 010402).Kim CY, 2009, INT CLIN PSYCHOPHARM, V24, P181, DOI 10.1097/YIC.0b013e32832c25d7Kolotkin RL, 2008, EUR PSYCHIAT, V23, P561, DOI 10.1016/j.eurpsy.2008.01.1421Findling RL, 2008, AM J PSYCHIAT, V165, P1432, DOI 10.1176/appi.ajp.2008.07061035Tandon R, 2008, SCHIZOPHR RES, V100, P20, DOI 10.1016/j.schres.2007.11.033Wolf J, 2007, CURR MED RES OPIN, V23, P2313, DOI 10.1185/030079907X225448Moeller KE, 2006, J CLIN PSYCHIAT, V67, P1942Chrzanowski WK, 2006, PSYCHOPHARMACOLOGY, V189, P259, DOI 10.1007/s00213-006-0564-3Tandon R, 2006, SCHIZOPHR RES, V84, P77, DOI 10.1016/j.schres.2005.12.857Lieberman JA, 2005, NEW ENGL J MED, V353, P1209Kim CY, 2005, J CLIN PSYCHIAT, V66, P887Kasper S, 2003, INT J NEUROPSYCHOPH, V6, P325, DOI 10.1017/S1461145703003651Pigott TA, 2003, J CLIN PSYCHIAT, V64, P1048Potkin SG, 2003, ARCH GEN PSYCHIAT, V60, P681Marder SR, 2003, SCHIZOPHR RES, V61, P123, DOI 10.1016/S0920-9964(03)00050-1Kane JM, 2002, J CLIN PSYCHIAT, V63, P763WEIDEN PJ, 1995, SCHIZOPHRENIA BULL, V21, P419

Small-scale, semi-automated purification of eukaryotic proteins for structure determination

A simple approach that allows cost-effective automated purification of recombinant proteins in levels sufficient for functional characterization or structural studies is described. Studies with four human stem cell proteins, an engineered version of green fluorescent protein, and other proteins are included. The method combines an expression vector (pVP62K) that provides in vivo cleavage of an initial fusion protein, a factorial designed auto-induction medium that improves the performance of small-scale production, and rapid, automated metal affinity purification of His8-tagged proteins. For initial small-scale production screening, single colony transformants were grown overnight in 0.4 ml of auto-induction medium, produced proteins were purified using the Promega Maxwell 16, and purification results were analyzed by Caliper LC90 capillary electrophoresis. The yield of purified [U-15N]-His8-Tcl-1 was 7.5 μg/ml of culture medium, of purified [U-15N]-His8-GFP was 68 μg/ml, and of purified selenomethione-labeled AIA–GFP (His8 removed by treatment with TEV protease) was 172 μg/ml. The yield information obtained from a successful automated purification from 0.4 ml was used to inform the decision to scale-up for a second meso-scale (10–50 ml) cell growth and automated purification. 1H–15N NMR HSQC spectra of His8-Tcl-1 and of His8-GFP prepared from 50 ml cultures showed excellent chemical shift dispersion, consistent with well folded states in solution suitable for structure determination. Moreover, AIA–GFP obtained by proteolytic removal of the His8 tag was subjected to crystallization screening, and yielded crystals under several conditions. Single crystals were subsequently produced and optimized by the hanging drop method. The structure was solved by molecular replacement at a resolution of 1.7 Å. This approach provides an efficient way to carry out several key target screening steps that are essential for successful operation of proteomics pipelines with eukaryotic proteins: examination of total expression, determination of proteolysis of fusion tags, quantification of the yield of purified protein, and suitability for structure determination

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

Genome-Wide Association Study of Lung Adenocarcinoma in East Asia and Comparison With a European Population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

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

Abstract 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

HOX gene analysis in the osteogenic differentiation of human mesenchymal stem cells

Human bone marrow-derived mesenchymal stem cells (hMSCs) have the capacity to differentiate into osteoblasts during osteogenesis. Several studies attempted to identify osteogenesis-related genes in hMSCs. Although HOX genes are known to play a pivotal role in skeletogenesis, their function in the osteogenesis of hMSCs has not yet been investigated in detail. Our aim was to characterize the expression of 37 HOX genes by multiplex RT-PCR to identify the ones most probably involved in osteogenic differentiation. The results showed that the expression patterns of four HOX genes were altered during this process. In particular, the expression levels of HOXC13 and HOXD13 were dramatically changed. Real-time PCR and Western blot analysis were performed in order to further analyze the expression of HOXC13 and HOXD13 . The qRT-PCR results showed that transcription of HOXC13 was up-regulated by up to forty times, whereas that of HOXD13 was down-regulated by approximately five times after osteogenic differentiation. The Western blot results for the HOXC13 and HOXD13 proteins also corresponded well with the real-time PCR result. These findings suggest that HOXC13 and HOXD13 might be involved in the osteogenic differentiation of hMSCs

Effects of Corticosteroids on Expression of Interleukin-18 in the Airway Mucosa of a Mouse Model of Allergic Rhinitis

OBJECTIVES: In this study, we aimed to investigate the release and response of interleukin (IL)-18 to steroid treatment in a mouse model of allergic rhinitis. METHODS: BALB/c mice were sensitized systemically by intraperitoneal injection of ovalbumin and locally by ovalbumin inhalation. Dexamethasone sodium phosphate was given by intraperitoneal injection in the steroid treatment group. Symptom scores, eosinophil counts, and IL-18 concentrations in the nasal and lung lavage fluids were analyzed. RESULTS: The symptom scores and eosinophil counts of the negative control and steroid treatment groups were significantly lower than those of the positive control group (p < .01). The mean IL-18 concentrations in the nasal lavage fluid were not significantly different among the three groups (56.68 +/- 9.57,63.39 +/- 8.93, and 64.47 +/- 6.83 pg/mL, respectively). The IL-18 concentrations in the lung lavage fluid were significantly different between the positive control group and the steroid treatment group (430.75 +/- 154.54 and 69.94 +/- 14.26 pg/mL, respectively, p = .028). CONCLUSIONS: The IL-18 concentration was found to be increased in the lung lavage fluid, but not in the nasal lavage fluid, in a mouse model of allergic rhinitis. Increased IL-18 concentrations returned toward the previous concentrations after steroid treatment. These results suggest that the roles of IL-18 may be different in the pathogenesis of allergic rhinitis and the pathogenesis of asthma