High-resolution copy number variation analysis of schizophrenia in Japan.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Serological comparison of antibodies to avian influenza viruses, subtypes H5N2, H6N1, H7N3 and H7N9 between poultry workers and non-poultry workers in Taiwan in 2012.

In Taiwan, avian influenza virus (AIV) subtypes H5N2, H6N1 and H7N3 have been identified in domestic poultry, and several strains of these subtypes have become endemic in poultry. To evaluate the potential of avian-to-human transmission due to occupational exposure, an exploratory analysis of AIV antibody status in poultry workers was conducted. We enrolled 670 poultry workers, including 335 live poultry vendors (LPVs), 335 poultry farmers (PFs), and 577 non-poultry workers (NPWs). Serum antibody titres against various subtypes of viruses were analysed and compared. The overall seropositivity rates in LPVs and PFs were 2·99% (10/335) and 1·79% (6/335), respectively, against H5N2; and 0·6% (2/335) and 1·19% (4/335), respectively, for H7N3 virus. Of NPWs, 0·35% (2/577) and 0·17% (1/577) were seropositive for H5N2 and H7N3, respectively. Geographical analysis revealed that poultry workers whose workplaces were near locations where H5N2 outbreaks in poultry have been reported face greater risks of being exposed to viruses that result in elevated H5N2 antibody titres. H6N1 antibodies were detected in only one PF, and no H7N9 antibodies were found in the study subjects. Subclinical infections caused by H5N2, H6N1 and H7N3 viruses were thus identified in poultry workers in Taiwan. Occupational exposure is associated with a high risk of AIV infection, and the seroprevalence of particular avian influenza strains in humans reflects the endemic strains in poultry in this region.

Avian influenza monitoring in migrating birds in Taiwan during 1998-2007.

Avian influenza virus (AIV) monitoring in migratory birds has been performed in Taiwan since 1998. From 1998 to 2007, 29,287 samples were collected from wild ducks, shorebirds, and other wild birds in the four wetlands around Taiwan and at two outside islets, Penghu and Kinmen. Virus isolation was performed for all collected samples by inoculating chicken embryos. The AIV in the allantoic fluid was identified using hemagglutination and reverse transcription PCR. The AIV prevalence from those samples was 0.81% (237/29,287). The peak prevalence reached 1.06% (186/17,493) from September to December, during which time migrating ducks came from the North. The prevalence from January to April was 0.51%. However, no virus was isolated from May to August. The partial HA genes of 28 H4 AIVs were sequenced and analyzed. The phylogenetic tree showed that a correlation existed between the isolation years and the evolutional distances. The pathogenicity of the isolated H5 and H7 AIVs was determined by intravenous pathogenicity index (IVPI) testing in specific-pathogen-free chickens and by HA cleavage sequencing. Using the IVPI test and the HA cleavage sequences, all of the H5 or H7 AIVs isolated were determined to be low pathogenicity AIVs.

Simultaneous quantification of three isoflavonoid glycosides in rabbit plasma after oral administration of Astragalus mongholicus extract by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

A selective and sensitive liquid chromatography coupled with triple stage quadruple tandem mass spectrometry (HPLC/TSQ-MS/MS) was developed and validated for simultaneous quantification of calycosin-7-O-beta-D-glycoside (CCSG), formononetin-7-O-beta-D-glycoside (Ononin) and (6R,10R)-9,10-dimethoxypterocarpan-3-O-beta-D-glycoside (DPG) in rabbit plasma. Plasma samples were extracted with solid-phase extraction (SPE), separated on an Inertsil ODS-3 column and detected by tandem mass spectrometry with electrospray ionization (ESI) interface in positive selective reaction monitoring (SRM) mode. 3,7,8-Trimethoxy-xanthone-1-O-primaverose was used as internal standard (IS) for quantitative measurement. For each analyte, one major product ion was chosen and used for screening of it. Calibration curves were generated over the range of 2-1000 ng mL(-1) with the correlation coefficients greater than 0.99 by using a weighted (1/chi) least squares linear regression. The method had the lower limit quantification of 0.15, 0.21 and 0.19 for CCSG, Ononin and DPG, respectively, with precision less than 20%. The intra- and inter-day precisions ranged from 2.48 to 6.38% and 4.81 to 11.78% (R.S.D.%), respectively. This assay is suitable for determining the above three trace glycosides in rabbit plasma simultaneously and thus investigating the pharmacokinetics of glycosides from Astragalus mongholicus extract in rabbits.

Performance of large-size superconducting coil in 0.21T MRI system.

A high-temperature superconductor (HTS) was used on magnetic resonance imaging (MRI) receiver coils to improve image quality because of its intrinsic low electrical resistivity. Typical HTS coils are surface coils made of HTS thin-film wafers. Their applications are severely limited by the field of view (FOV) of the surface coil configuration, and the improvement in image quality by HTS coil is also reduced as the ratio of sample noise to coil noise increases. Therefore, previous HTS coils are usually used to image small in vitro samples, small animals, or peripheral human anatomies. We used large-size HTS coils (2.5-, 3.5-, and 5.5-in mean diameter) to enhance the FOV and we evaluated their performance through phantom and human MR images. Comparisons were made among HTS surface coils, copper surface coils, and cool copper surface coils in terms of the signal-to-noise ratio (SNR) and sensitivity profile of the images. A theoretical model prediction was also used to compare against the experimental result. We then selected several human body parts, including the wrist, feet, and head, to illustrate the advantage of HTS coil over copper coil when used in human imaging. The results show an SNR gain of 200% for 5.5-in HTS coil versus same size copper coils, while for 2.5- and 3.5-in coils it is 250%. We also address the various factors that affect the performance of large size HTS coils, including the coil-to-sample spacing due to cryogenic probe and the coil-loading effect.

Identification and subtyping of avian influenza viruses by reverse transcription-PCR.

Avian influenza viruses have 15 different hemagglutinin (HA) subtypes (H1-H15). We report a procedure for the identification and HA-subtyping of avian influenza virus by reverse transcription-PCR (RT-PCR). The avian influenza virus is identified by RT-PCR using a set of primers specific to the nucleoprotein (NP) gene of avian influenza virus. The HA-subtypes of avian influenza virus were determined by running simultaneously 15 RT-PCR reactions, each using a set of primers specific to one HA-subtype. For a single virus strain or isolate, only one of the 15 RT-PCR reactions will give a product of expected size, and thus the HA-subtype of the virus is determined. The result of HA-subtyping was then confirmed by sequence analysis of the PCR product. A total of 80 strains or isolates of avian influenza viruses were subtyped by this RT-PCR procedure, and the result of RT-PCR gave an excellent (100%) correlation with the result of the conventional serological method. The RT-PCR procedure we developed is rapid and sensitive, and could be used for the identification and HA-subtyping of avian influenza virus in organ homogenates.

Measurement of one-bond 1H-13C, couplings in backbone-labelled proteins.

NMR dipole-dipole couplings between protein backbone nuclei (1H(alpha), 13C(alpha), 15N, 1H(N), 13C') offer enormous scope for the rapid determination of protein global folds. Here, we show that measurement of one-bond splittings in the protein backbone is facilitated by use of protein that is selectively isotopically enriched only in the backbone atoms. In particular, 1H(alpha)-13C(alpha) couplings can be measured simply and with high sensitivity by use of conventional heteronuclear single quantum correlation (HSQC) techniques.

[The location of new porcine microsatellites by means of PRINS and somatic cell hybrid panel].

In this study, two new microsatellites HAU02 and HAU06, which are screened and cloned. HUA02 and HAU06 are repectively mapped in lq23-27 and 6q11-21 by means of PRINS (primed in situ labeling) and somatic cell hybrid (SCH) panel techniques, we discussed their advantage and disadvantage in gene mapping. These two means provide us more techniques in gene mapping, and the locations of these new microsatellites accumulate more resource for Porcine Physical Map.

[Establishment of rabbit model for peritoneal dialysis related peritonits].

OBJECTIVE: To establish a rabbit model corresponding with clinical characteristics of peritoneal dialysis related peritonitis. METHODS: Twelve New Zealand rabbits were randomly divided into peritonitis group and control group. They were infused standard living Staphylococcus aureus 3 x 10(9) colony forming unit (cfu) (peritonitis group) or 0.9% NaCl 1 ml (control group). After 48 hours, Laboratory rabbits in acute uremic model underwent regular dialysis for 6 hours. At different points of time, the concentration of glucose in dialysate and the dialysate/plasma (D/P) ratio of the concentration creatinine (Cr), total protein(TP), album(Alb) and IgG, the counts of leukocyte in dialysate and water ultrafiltrate were determined. RESULTS: D/D0 were significantly lower in the peritonitis group than that in the control group (P < 0.05). The counts of leukocyte and D/P ratio of Cr, TP, Alb and IgG were significantly increased in the peritonitis group (all P < 0.05). The drained volume was lower in the peritonitis group than that in the control group (but P > 0.05). CONCLUSION: In the rabbit model infused intraperoneally staphylococcus aureus, (1) transport peritoneum of low and large molecular weight solutes is increased, (2) the volume of ultrafiltrate is decreased, (3) the counts of leukocyte in dialysate is increased. These change in this model is basic all correspond with the clinical feature of patients of peritoneal dialysis related peritonitis. So this rabbit model of peritoneal dialysis related peritonitis is a successful experimental infection model.

[Urinary RBP and glucocorticoid hormone therapy sensibility in adult primary nephrotic syndrome].

OBJECTIVE: To clarify the relationship between the renal tubular function and the efficacy of glucocorticoid, in adult patients with primary nephrotic syndrome. METHODS: Pro- and post-therapy urinary RBP and NAG were determined double antibodies sandwich ELISA and color comparimetry with p-nitrate reductase, respectively, in eighty adult patients with primary nephritic syndrome, according to the concentrations of urinary protein, these patients were divided into three no remission group, partial remission group and fully remission group, fifty-one normal persons as control group. Renal tubular function parameters among groups were compared before and after therapy, and the results were analysed when those parameters were used to predict the sensibility of glucocorticoid therapy. RESULTS: 1. There were no significant differences in urinary RBP, NAG and protein levels before treatment among patient groups (P > 0.05); 2. There were significant decreases in urinary RBP and NAG following glucocorticoid therapy in those response to glucocorticoid (P < 0.01); 3. There were significant differences in urinary protein, RBP and NAG among three groups of patients with primary nephrotic syndrome after treatment. CONCLUSION: Determination of urinary RBP may predict the sensibility of the therapy in the adult patients with primary nephrotic syndrome and its diagnostic efficiency is better than urinary NAG.

Oral care for children with leukaemia.

OBJECTIVES: To review the oral care regimens for children with acute leukaemia, and to present an easy-to-follow oral care protocol for those affected children. DATA SOURCES: Medline and non-Medline search of the literature; local data; and personal experience. STUDY SELECTION: Articles containing supportive scientific evidence were selected. DATA EXTRACTION: Data were extracted and reviewed independently by the authors. DATA SYNTHESIS: Cancer is an uncommon disease in children, yet it is second only to accidents as a cause of death for children in many countries. Acute leukaemia is the most common type of malignancy encountered in children. The disease and its treatment can directly or indirectly affect the child's oral health and dental development. Any existing lesions that might have normally been dormant can also flare up and become life-threatening once the child is immunosuppressed. Proper oral care before, during, and after cancer therapy has been found to be effective in preventing and controlling such oral complications. CONCLUSION: Proper oral care for children with leukaemia is critical. Long-term follow-up of these children is also necessary to monitor their dental and orofacial growth.

Evaluation of absorbed radiation dose to working staff during cardiac catheterization procedures.

BACKGROUND: Cardiac catheterization has been used frequently for the evaluation and treatment of patients with heart diseases. The working staff, particularly cardiologists who perform these procedures, have the highest potential risk of receiving high radiation doses due to close contact with patients. The purpose of this study was to measure and evaluate the accumulated radiation dosage of the cardiologists while they were performing clinical procedures in the cardiac catheterization laboratory. The working environment of the catheterization laboratory was also monitored for radiation. METHODS: Thermoluminescent dosimeters (TLDs) with very high sensitivity were employed for dose evaluations. They were taped to various parts of the body of the cardiologists during catheterization procedures. For environmental monitoring, TLDs were also distributed at several sites of the catheterization rooms for a period of 2 to 4 weeks. RESULTS: The study showed that the left wrist of the cardiologists received the highest radiation dose (338 microsieverts [microSv]/procedure) and the left lens received the second highest dose (149 microSv/procedure) during the procedures. The dose to the knees was unexpectedly high (92 microSv/procedure), partly due to radiation leakage from the lead curtain shielding under the patient couch. On average, the effective radiation dose per year was 37 mSv/y for a cardiologist who performs 10 catheterization procedures per week. Compare this to the occupational exposure limit of 50 mSv/y. The estimated accumulated equivalent dose to the lens was 152 mSv/y, which exceeded the regulatory limit for occupational exposure. CONCLUSIONS: Using proper lead shielding and increasing the distance from the radiation source are good strategies for reducing the radiation dose in medical staff. The work area outside the catheterization room was considered safe because the radiation level was essentially equivalent to the background radiation level.

Controlled acid hydrolysis of colominic acid under microwave irradiation.

The hydrolysis of colominic acid under microwave irradiation was studied and compared with traditional heating methods. The microwave irradiation has several advantages over the heating method in the hydrolysis of colominic acid: (a) products with higher degrees of polymerization are obtained, (b) less lactone byproducts are observed, and (c) the hydrolytic rate is much faster. These advantages are probably due to the microwave effect. Oligosialic acids as the products of the acid hydrolysis of polysialic acid with conventional heating methods were fully lactonized, especially under the conditions of higher temperature and stronger acid.

High-performance capillary electrophoretic characterization of different types of oligo- and polysialic acid chains.

We have carried out comparative structural analysis of novel oligo- and polysialic acid chains from diverse sources. Controlled acid hydrolysates of (a) colominic acid, alpha2-->8-linked homopolymer of N-acetylneuraminic acid (Neu5Ac), (b) alpha2-->8-linked oligo/polyNeu5Gc chains present in rainbow trout egg polysialoglycoprotein, and (c) alpha2-->8-linked oligomers of deaminoneuraminic acid (KDN) residues of KDN-rich glycoprotein derived from rainbow trout vitelline envelope were analyzed by high-performance capillary electrophoresis (HPCE). The results showed that three different types of alpha2-->8-linked oligosialic acids having same degree of polymerization can be separated by HPCE. A partial hydrolysate of colominic acid with mild acid was shown by CE to form intramolecular esters during the controlled hydrolysis and the subsequent workup procedure. In contrast, lactonization of (-->5-Oglycolyl-Neu5Gcalpha2-->)n, alpha2-->5-Oglycolyl-linked homopolymer of N-glycolylneuraminic acid (Neu5Gc) present in the egg jelly coat of sea urchin, did not take place as readily as in (-->8Neu5Acalpha2-->)n.

Novel cytotoxic diterpenes, excavatolides A-E, isolated from the Formosan gorgonian Briareum excavatum.

The chemistry of Briareum excavatum, a Formosan gorgonian coral, was investigated. This study has led to the isolation of five novel marine natural products, excavatolides A-E (1-5), together with brianolide (6). The structures of the above compounds were established by spectral and chemical methods. The relative configuration of excavatolide B (2) was further confirmed by a single-crystal X-ray structure analysis. Cytotoxicity of these compounds toward various cancer cell lines also is described.

HDR source calibration methods and discrepancies.

PURPOSE: To report the calibration discrepancies observed in HDR sources and our methods of calibration of a new source. METHODS AND MATERIALS: 21 sources have been calibrated since March 1991 to February 1996 and discrepancies are reported in comparison to the certificate value. The calibration methodology used for two different systems: the NEL Farmer system and reentrant well chamber (HDR-1000) are described. A lead shield insert developed for use with the well chamber for timer linearity measurement is described. RESULTS: Eleven sources had discrepancy from 0 to 1%, 7 sources had discrepancy from 1 to 5%, and 3 sources had discrepancy from 5 to 10%. The maximum discrepancy observed was -8.04 % for one source. Our procedure of dealing with situations when discrepancy exceeds the range of +/-5% value is discussed. CONCLUSION: (a) The discrepancies that we observed in our study are compared with other users and found to be within the range of values observed. (b) Due to the easy set up procedure, less prone to error in the use of well chamber and with the use of a new lead insert, we conclude in our case that, the well system can be used for monthly calibration of HDR source and timer linearity measurements. (c) Because the Farmer system has a first generation calibration factor, obtained by interpolation of two calibration energies from ADCL, we prefer to use the Farmer system for determining the activity of the new HDR source.