Correction: Cellular and molecular basis for stress-induced depression.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction: Elevation of p11 in lateral habenula mediates depression-like behavior.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Time series analysis of delta neutrophil index as the predictor of sepsis in patients with acute poisoning.

Delta neutrophil index (DNI), which reflects the fraction of immature granulocytes, is used to detect infection and sepsis from noninfectious conditions, but few studies have evaluated in the early stage of acute poisoning. This retrospective observational study was performed on acute poisoning patients who visited to the emergency department (ED) and were consecutively admitted in intensive care units over 18-month period. The serial DNI, conventional inflammatory biomarkers, and culture results were obtained in the ED and after admission. The outcomes were the identification of sepsis, bacteremia, and 30-day mortality. Of 166 patients (mean age, 56.0 years) in this cohort, 59 (35.5%) had sepsis and 29 (17.5%) had bacteremia. Initial and peak DNI fractions 24 h after ED admission were strong independent predictors of sepsis development. Analysis of the area under the curve according to multiple receiver operating characteristics showed that DNI had a higher capability to predict sepsis than other parameters (0.815 for DNI, 0.700 for procalcitonin, 0.681 for C-reactive protein, and 0.741 for white blood cell). Using multivariable logistic regression analysis, it was found that DNI was an independent predictor of sepsis (95% confidence interval (CI) of odds: 1.03-1.18) and bacteremia (95% CI: 1.01-1.14). Therefore, initial and serial measurement of DNI may serve as useful risk predictor for development of sepsis or bacteremia in acute poisoning.

Elevation of p11 in lateral habenula mediates depression-like behavior.

The lateral habenula (LHb) is a key brain region involved in the pathophysiology of depression. It is activated by stimuli associated with negative experiences and is involved in encoding aversive signals. Hyperactivity of LHb is found in both rodent models of depression and human patients with depression. However, little is known about the underlying molecular mechanisms. Here we show that in LHb neurons, p11, a multifunctional protein implicated in depression, is significantly upregulated by chronic restraint stress. Knockdown of p11 expression in LHb alleviates the stress-induced depression-like behaviors. Moreover, chronic restraint stress induces bursting action potentials in LHb neurons, which are abolished by p11 knockdown. Overexpression of p11 in dopamine D2 receptor-containing LHb neurons of control mice induces depression-like behaviors. These results have identified p11 in LHb as a key molecular determinant regulating negative emotions, which may help to understand the molecular and cellular basis of depression.

Cellular and molecular basis for stress-induced depression.

Chronic stress has a crucial role in the development of psychiatric diseases, such as anxiety and depression. Dysfunction of the medial prefrontal cortex (mPFC) has been linked to the cognitive and emotional deficits induced by stress. However, little is known about the molecular and cellular determinants in mPFC for stress-associated mental disorders. Here we show that chronic restraint stress induces the selective loss of p11 (also known as annexin II light chain, S100A10), a multifunctional protein binding to 5-HT receptors, in layer II/III neurons of the prelimbic cortex (PrL), as well as depression-like behaviors, both of which are reversed by selective serotonin reuptake inhibitors (SSRIs) and the tricyclic class of antidepressant (TCA) agents. In layer II/III of the PrL, p11 is highly concentrated in dopamine D2 receptor-expressing (D2+) glutamatergic neurons. Viral expression of p11 in D2+ PrL neurons alleviates the depression-like behaviors exhibited by genetically manipulated mice with D2+ neuron-specific or global deletion of p11. In stressed animals, overexpression of p11 in D2+ PrL neurons rescues depression-like behaviors by restoring glutamatergic transmission. Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, which provides a framework for the development of new strategies to treat stress-associated mental illnesses.

Pharmacokinetics of amoxicillin trihydrate in cultured olive flounder (Paralichthys olivaceus).

The study was aimed at investigating the pharmacokinetics of amoxicillin trihydrate (AMOX) in olive flounder (Paralichthys olivaceus) following oral, intramuscular, and intravenous administration, using high-performance liquid chromatography following. The maximum plasma concentration (Cmax ), following oral administration of 40 and 80 mg/kg body weight (b.w.), AMOX was 1.14 (Tmax , 1.7 h) and 0.76 µg/mL (Tmax , 1.6 h), respectively. Intramuscular administration of 30 and 60 mg/kg of AMOX resulted in Cmax values of 4 and 4.3 µg/mL, respectively, with the corresponding Tmax values of 29 and 38 h. Intravenous administration of 6 mg/kg AMOX resulted in a Cmax of 9 µg/mL 2 h after administration. Following oral administration of 40 and 80 mg/kg AMOX, area under the curve (AUC) values were 52.257 and 41.219 µg/mL·h, respectively. Intramuscular 30 and 60 mg/kg doses resulted in AUC values of 370.274 and 453.655 µg/mL·h, respectively, while the AUC following intravenous administration was 86.274 µg/mL·h. AMOX bioavailability was calculated to be 9% and 3.6% following oral administration of 40 and 80 mg/kg, respectively, and the corresponding values following intramuscular administration were 86% and 53%. In conclusion, this study demonstrated high bioavailability of AMOX following oral administration in olive flounder.

Novel fusion transcripts in human gastric cancer revealed by transcriptome analysis.

Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.

Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia.

Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.

Characteristics of responders and non-responders to risperidone monotherapy or placebo in co-occurring bipolar disorder and anxiety disorder.

Clinical characteristics predicting response and remission to psychopharmacological treatment of bipolar disorder (BD) and co-occurring anxiety disorders have been understudied. We hypothesized that non-response to risperidone or placebo in individuals with co-occurring BD and anxiety symptoms would be associated with a more severe clinical course of BD, and certain demographic variables. This study was a secondary analysis of a randomized, double-blind, parallel, 8-week study comparing risperidone monotherapy and placebo in individuals with BD plus current panic disorder, current generalized anxiety disorder (GAD), or lifetime panic disorder (n=111) [31]. We compared clinical characteristics of responders (50% improvement on the Hamilton Anxiety Scale [HAM-A]) and non-responders as well as remitters (HAM-A<7) and non-remitters in risperidone treatment (n=54) and placebo (n=57) groups. For non-responders in the risperidone group, co-occurring lifetime panic disorder was significantly more common than for non-responders in the placebo group. Apart from this, no significant differences in course of illness or demographics were found either between or across groups for patients with BD and co-occurring anxiety symptoms receiving risperidone or placebo in this acute phase study.

Effect of wrist position on the measurement of carpal indices on the lateral radiograph.

The purpose of this study was to find out whether the carpal indices measured on lateral radiographs with a slightly malpositioned wrist are the same as those measured in the true neutral position. Lateral radiographic views of 25 wrists were taken with 5° intervals from 20° of flexion to 20° of extension. Most carpal indices measured in the flexed or extended position were significantly different from the wrist in zero flexion-extension, except scapholunate angle at 5° of extension and scaphocapitate angle at 5° and 10° of flexion. Starting from the flexed position, there was an average of -4.0° change in radioscaphoid angle, -1.0° in scapholunate angle, -1.0° in scaphocapitate angle, +3.0° in radiolunate angle, and +2.0° in lunocapitate angle for each 5° of extension with linear trends. The results from this study suggest that even minimal degrees of flexion-extension can affect the measurements of carpal indices on lateral radiographs.

Transthoracic fine-needle aspiration biopsy of the lungs using a C-arm cone-beam CT system: diagnostic accuracy and post-procedural complications.

OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of transthoracic fine-needle aspiration biopsy (TFNAB) using a C-arm cone-beam CT (CBCT) system and to assess risk factors for immediate post-procedural complications in patients with lung lesions. METHODS: From October 2007 to April 2009, 94 TFNAB procedures using a C-arm system were studied in 91 patients with pulmonary lesions a chest CT scans. We retrospectively reviewed the patients' radiological and histopathological findings. We evaluated the lesion size, lesion abutted to pleura and presence or absence of emphysema along the needle path, lesion depth, visibility of target lesion and patient's position. Pneumothorax and pulmonary haemorrhage were assessed after TFNAB. Overall diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analysed. RESULTS: In 94 TFNAB procedures, 58 lesions were malignant and 36 were benign. The sensitivity, specificity, PPV, NPV and overall diagnostic accuracy rate of TFNAB were 93.1%, 100%, 100%, 90% and 97.9%, respectively. Pneumothorax was developed in 24 procedures. None of the parameters showed significant impact on the frequency of the pneumothorax. Overall haemorrhage occurred in 43 procedures. The incidence of overall haemorrhage was higher in patients with smaller lesions, longer pleural distance and pleural abutted lesions (p<0.05). Differences in visibility at projection radiographs were statistically significant between patients with or without perilesional haemorrhage (p<0.05). CONCLUSION: Transthoracic fine-needle aspiration biopsy using a C-arm CBCT system is feasible for imaging guidance of lung lesion and early detection of the procedural-related complications.

Determination of low (137)Cs concentration in seawater using ammonium 12-molybdophosphate adsorption and chemical separation method.

A new method has been developed for analyzing (137)Cs in a small volume of seawater. Ammonium 12-molybdophosphate (AMP) was used two times during pretreatment procedure. The first step was to adsorb (137)Cs in seawater samples into AMP in order to reduce sample volume, and the second was to remove (87)Rb, interference nuclide for beta counting. The AMP adsorbing (137)Cs was dissolved by sodium hydroxide solution, and then (137)Cs was finally formed to be cesium chloroplatinate precipitate by adding 10% hexachloroplatinic acid. The beta rays emitted from (137)Cs were measured with a low background gas-proportional alpha/beta counter. This method was applied to several seawater samples taken in the East Sea of Korea. Compared to the routinely used gamma-spectrometry method, this new AMP method was reliable and suitable for analyzing (137)Cs in deep seawater.

Nationwide survey on the natural radionuclides in industrial raw minerals in South Korea.

A Nationwide survey on the natural radioactivity in industrial raw mineral commodities (17 kinds of domestic and 18 kinds of imported) that are representative minerals used in production and consumption in South Korea was conducted. The target industrial minerals can be categorized into two groups. The first group covers non-metallic and metallic raw minerals with low levels of radioactivity such as clay, silica sand, carbonates, bituminous and anthracite coal, iron ores, ilmenite, rutile, and phosphate ore. The other group comprises minerals with high levels of radioactivity including zircon and monazite. One hundred and sixty-four domestic and imported samples were analysed by gamma-ray spectroscopy using an HPGe detector. The (40)K content ranges from <0.00131 to 2.69Bq g(-1), and (226)Ra and (232)Th range over <0.0006 to 0.630 and <0.0008 to 0.474Bq g(-1), respectively. There was no anthropogenic radioactive signal in any of the samples.

Cell cycle arrest and lytic induction of EBV-transformed B lymphoblastoid cells by a histone deacetylase inhibitor, Trichostatin A.

Latent infection of the Epstein-Barr virus (EBV) is strongly associated with the pathogenesis of several human tumor types. The restricted expression of the latent EBV antigens is critical for EBV-associated tumors to escape from immune surveillance. EBV lytic replication can be triggered by various treatments and the induced lytic genes cause strong cytotoxic T lymphocyte (CTL) responses. Histone acetylation or deacetylation is associated with chromatin remodeling and regulates gene expression. Histone deacetylase (HDAC) inhibitors affect cell cycle progression as well as gene expression in a wide variety of transformed cells. We examined whether an HDAC inhibitor, TSA, can affect cell cycle progression and induce EBV lytic replication in EBV-transformed lymphoblastoid cell lines (LCLs). TSA caused cell cycle arrest at low concentrations and induced apoptosis at higher (>300 nM) concentrations in the LCLs and EBV negative BJAB cells. To clarify the underlying mechanism of TSA-induced cell cycle arrest, expression of cell cycle regulatory factors was examined by RNase protection assay and Western blot analysis. Following TSA treatment, a reduced expression of cyclin D2 and an induction of p21 may have played an essential role for G1 arrest in LCLs, while p21 induction might have arrested BJAB cells in G1 phase. A Cdk inhibitor, p57, was increased by 300 nM TSA in both LCLs and BJAB cells, indicating its role in apoptosis. Moreover, immunofluorescene assay and Western blotting showed that TSA induced EBV lytic replication in LCL cells. These results suggest that TSA may exert an enhanced anti-tumor effect for EBV-associated tumors not only by inducing a cell cycle arrest and apoptosis, but also by triggering an EBV lytic cycle.

Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis.

Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

Influence of VEGF gene polymorphisms on the severity of ankylosing spondylitis.

OBJECTIVES: To investigate the role of polymorphisms of the vascular endothelial growth factor (VEGF) gene in susceptibility to ankylosing spondylitis (AS), and their relationship to clinical features and radiographic severity. METHODS: This study included 157 patients with AS and 140 healthy unrelated controls. Polymorphisms of the VEGF gene were analysed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism assay and amplification refractory mutation system-PCR. Haplotypes were reconstructed using the Bayesian algorithm. Radiographic severity was assessed by the Bath Ankylosing Spondylitis Radiological Index (BASRI). RESULTS: The genotype frequencies of the polymorphisms were in Hardy-Weinberg equilibrium. The distributions of genotypes and alleles did not differ between AS patients and controls. Among the six haplotypes reconstructed based on the tight linkage disequilibrium at positions -2578, -1154 and -634 (pairwise linkage disequilibrium coefficient, r = 0.361-0.706), no haplotype was associated with susceptibility to AS. Clinical features were analysed for the four haplotypes (CGC, CGG, AAG, AGG) which were prevalent. In carriers of the AGG haplotype, the frequency of cervical spine involvement was significantly higher (P = 0.002, P(corr) = 0.036) and that of patients showing a BASRI score >6 was also higher (P = 0.025, P(corr) = 0.45). CONCLUSIONS: This study demonstrates that polymorphisms of the VEGF gene may contribute to disease severity in AS.

VEGF gene polymorphisms and susceptibility to rheumatoid arthritis.

OBJECTIVES: To investigate polymorphisms of the VEGF gene in patients with rheumatoid arthritis (RA), their relationship to clinical features and the radiographic progression of joint disease. METHODS: One hundred and forty patients with RA and 149 healthy unrelated controls were recruited. We examined four polymorphisms of the VEGF gene which are reported to be associated with production of vascular endothelial growth factor (VEGF), using polymerase chain reaction (PCR) restriction fragment length polymorphism assay and amplification refractory mutation system (ARMS) PCR. Haplotypes were predicted by Bayesian algorithm using the Phase program. RESULTS: All four polymorphisms were in Hardy-Weinberg equilibrium in both patients and controls. The frequency of the 936 T allele, which has been associated with lower production of VEGF, was significantly increased in RA patients compared with controls (22.7 vs 13.4%, P = 0.002). The frequencies of two haplotypes (CGCT and AAGT) which were predicted using the Phase program were significantly increased in RA patients compared with controls [33 vs 14%, odds ratio (OR) 2.636, 95% confidence interval (CI) 1.38-5.04 for CGCT; 17 vs 6%, OR 3.08, 95% CI 1.20-7.92 for AAGT]. The carriers of the susceptible haplotypes in RA patients had a younger age at disease onset but did not show a difference in the progression rate of radiographic joint destruction. CONCLUSIONS: Our data suggest that the VEGF gene may play a role in the development of RA

Comparative analysis of superfamilies of NBS-encoding disease resistance gene analogs in cultivated and wild apple species.

Eleven distinct families of resistance gene analogs (RGAs) with the characteristic nucleotide-binding sequence (NBS) were identified in two wild apple species, Malus prunifolia and M. baccata, and two cultivated apple cultivars, M. domestica cv. Fuji and M. domestica cv. Hong-ok, using PCR approaches with degenerate primers based on two conserved motifs of known NBS-LRR resistance genes. These RGA families were found to be represented in all the apple species tested, including wild and cultivated species. However, their sequences are very divergent from each other. Furthermore, the low level of recombination detected within their RGA families supports the idea that the evolution of NBS-encoding sequences in apple species involves the gradual accumulation of mutations. Despite the high diversity of the RGA families found in all apple species, the apparent lack of differentiation between wild and cultivated forms suggests that other factors, such as the capacity to tolerate pathogens, might play an important role in the survival of wild-type species.

Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women.

A case-control study was performed to assess the potential influence of CYP19 Arg(264)Cys and CYP1B1 Leu(432)Val polymorphisms on breast cancer risk in a series of Korean breast cancer patients and controls. The results suggest that the CYP19 Arg(264)Cys polymorphism modifies breast cancer risk (OR=1.5, 95% CI=1.1-2.2), especially in association with alcohol consumption (P for interaction=0.04), whereas the CYP1B1 Leu(432)Val polymorphism appears to play no role here.