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.

N-acetyl endorphin in rat spermatogonia and primary spermatocytes.

In previous reports modest levels of beta-endorphin have been found by radioimmunoassay in rat testis, and localized by immunofluorescence to the interstitial cells. We have confirmed these previous reports and extended them by showing that the majority of testicular endorphins are acetylated forms, N-acetyl gamma-endorphin, N-acetyl alpha-endorphin, and N-acetyl beta-endorphin1-27. In addition, N-acetylated endorphins are not found in interstitial cells, but are confined to spermatogonia and primary spermatocytes.

Two-year carcinogenicity study of sodium fluoride in rats.

To determine the carcinogenic potential of sodium fluoride (NaF), we fed Sprague-Dawley rats a diet containing NaF for up to 99 weeks. Rats receiving NaF at a dose of 4, 10, or 25 mg/kg per day added to a low-fluoride diet were compared with controls receiving either a low-fluoride diet or laboratory chow. Each treatment group consisted of 70 rats of each sex. A 30% decrement in weight gain occurred at an NaF dose of 25 mg/kg per day. Evidence of fluoride toxicity was seen in the teeth, bones, and stomach, and the incidence and severity of these changes were related to the dose of NaF and the duration of exposure. Despite clear evidence of toxicity, NaF did not alter the incidence of preneoplastic and neoplastic lesions at any site in rats of either sex. Results from this study indicate that NaF is not carcinogenic in Sprague-Dawley rats.

Beta-endorphin and its congeners in rat pituitary and thyroid: effects of propylthiouracil and thyroid hormone administration.

Immunoreactive beta-endorphin (ir-beta EP) and immunoreactive N-acetyl-endorphin (ir-NacEP) have been demonstrated in the rat thyroid by specific RIA and characterized by reverse phase HPLC. In addition, pituitary and thyroid ir-beta EP and ir-NacEP levels have been determined after manipulation of the pituitary-thyroid axis by chronic (21 days) treatment with 1) propylthiouracil (PTU), 2) L-T4, 3) L-T3, or 4) T3 plus PTU. No difference in anterior pituitary or neurointermediate lobe ir-beta EP was seen between controls and treated groups (n = 8/group). In contrast, levels of ir-NacEP were markedly lower (P less than 0.01) in both hypo- and hyperthyroid groups than in controls, in both anterior pituitary and neurointermediate lobe. In the thyroid, levels of both ir-beta EP and ir-NacEP were profoundly depressed (P less than 0.01) in all treated groups, with no change in calcitonin levels, suggesting that the thyroid effect of PTU and T3/T4 may be specific for the synthesis, processing, and/or release of pro-opiomelanocortin derived peptides. The findings in this study suggest 1) that acetylation of pituitary and thyroid beta EP is similarly sensitive to PTU and thyroid hormone administration and 2) that in the thyroid, but not in the pituitary, both PTU and thyroid hormones markedly lower levels of pro-opiomelanocortin-derived peptides.

The identification and characterization of alpha-N-acetylated beta-endorphin in the human pituitary gland.

By using a radioimmunoassay specific for alpha-N-acetyl beta-endorphin and its C-terminally shortened forms, we have established the presence of immunoreactive alpha-N-acetyl endorphin (irNacEP) in extracts of five postmortem human pituitary glands (2.27 +/- 0.64 ng/gland). This immunoreactivity has been further characterized by subjecting these extracts to reverse-phase high-performance liquid chromatography (RP-HPLC). In all cases the major peaks of irNacEP co-migrated with synthetic human standard alpha-N-acetyl alpha-endorphin (Nac alpha EP), alpha-N-acetyl gamma-endorphin (Nac gamma EP) and Nac beta EP. These studies thus represent the initial demonstration that alpha-N-acetylation of beta-endorphin and its shorter molecular forms occurs in the human pituitary gland.

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.

New aromatic diamidines with central alpha-oxyalkane or alpha, omega-dioxyalkane chains. Structure-activity relationships for the inhibition of trypsin, pancreatic kallikrein, and thrombin and for the inhibition of the overall coagulation process.

A series of omega-amidinophenylalkyl amidinophenyl ethers was synthesized and examined for inhibitory activity against trypsin, pancreatic kallikrein, and thrombin. Modifications of the compounds included lengthening of the alkane chain, variation in the position of the amidino groups, and substitution of halogen on the benzene rings. The compounds act as competitive reversible inhibitors, and many of them possess considerable potency. An outstanding trypsin inhibitor was found in 4-amidinophenylethyl 4 amidino-2-bromophenyl ether (compound 7) with a Ki value of 7.3 x 10(-8) M (pH 8.1, 37 degrees). A number of aromatic diamidines with a central dioxyalkane chain were similarly studied. Here, 1-(4-amidino-2-iodophenoxy)-5-(3-amidinophenoxy)pentane (compound 32) was a highly effective inhibitor of bovine thrombin (Ki = 1.1 x 10(-6) M), of human thrombin, and of the overall clotting process of human plasma.

Novel bis(benzamidino) compounds with an aromatic central link. Inhibitors of thrombin, pancreatic kallikrein, trypsin, and complement.

A series of novel aromatic diamidines was synthesized and evaluated for antiproteolytic activity. The compounds were distignuished by inclusion of an aromatic ring structure--either benzene or bisbenzene or naphthalene--in the link between two amidinobenzene moieties. A highly potent inhibitor of bovine thrombin was discovered in alph, alph'-bis(4-amidino-2-iodophenoxy)-p-xylene with a Ki value of 1.1 X 10(-7) M (pH 8.1, 37 degrees), while alpha, alpha'-bis(4-amidino-2-iodophenoxy)-m-xylene was found to be an outstanding inhibitor of porcine pancreatic kallikrein (Ki = 3.1 X 10(-8) M). Several of the compounds investigated also demonstrated a considerable blocking effect on typsin and on the complement-dependent immune lysis of red cells.

N-acetylated endorphins in ovine anterior pituitary and neuro-intermediate lobe.

We have used an antiserum for immunohistochemistry and RIA/RP-HPLC which recognizes all fragments of N-acetylated endorphin (NacEP). In the rat neuro-intermediate lobe (N-IL), in addition to the N-acetylated forms of immunoreactive-beta-endorphin (ir-beta EP) already reported, we have demonstrated Nac beta EP as a minor component. In the sheep pituitary processing of beta EP is markedly different. In the anterior pituitary (AP), staining was indistinguishable with beta EP and NacEP antisera, in contrast with the rat where many fewer AP cells stained with the NacEP antiserum. Secondly, as in the rat, all N-IL cells stained with both antisera; on RP-HPLC, however, the major forms of NacEP in the sheep N-IL were Nac beta EP (approximately 40%), Nac beta EP (approximately 25%) and Nac beta EP (approximately 20%), with Nac beta EP (approximately 2%) as a minor component. A similar profile was seen on RP-HPLC of sheep AP. These data suggest that (1) patterns of processing in sheep AP are similar to those in N-IL, though the extent of acetylation is less and (2) in the sheep pituitary low molecular weight acetylated fragments predominate, in contrast with the rat.

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.

alpha-N-acetylated beta-endorphin is differentially processed in the normal and hypothalamo-pituitary-disconnected (HPD) ewe.

We have used specific radioimmunoassay and high-performance liquid chromatography (HPLC) to determine content and molecular forms of pituitary alpha-N-acetylated endorphin (NacEP) in the intact and hypothalamo-pituitary-disconnected (HPD) sheep. No significant differences were seen in anterior pituitary (AP) immunoreactive (ir-) NacEP levels (control = 4.34 +/- 0.45 ng/mg; HPD = 4.38 +/- 0.83 ng/mg; n = 4) or in HPLC profiles following pituitary disconnection. In contrast, levels of ir-NacEP in the HPD intermediate lobe (IL) (263 +/- 16.5 ng/mg; n = 4) were double those in the control (110 +/- 14 ng/mg; n = 4), accompanied by a marked change in the molecular profile. In the control IL, the major species were Nac alpha EP (30%), Nac gamma EP (30%) and Nac beta EP1-27 (35%); in HPD IL, Nac beta EP1-27 (65%) is the dominant molecular form, with Nac alpha EP (11%) and Nac gamma EP (9%) relatively minor components.

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.

Classification, pathogenicity, and drug susceptibility of hemolytic gram-negative bacteria isolated from sick or dead chickens.

Fifteen hemolytic gram-negative bacteria were isolated from the respiratory tracts of sick birds suffering from a long-lasting respiratory syndrome or from the bone marrow of dead birds distributed in the southern part of Taiwan. These were classified as Pseudomonas aeruginosa (10 isolates), Pseudomonas fluorescens (2 isolates), Pseudomonas stutzeri (1 isolate), Pasteurella haemolytica (1 isolate), and Proteus morganii (1 isolate). Each isolate was inoculated intraperitoneally into one group of ten 4-week-old male white leghorn chickens. Mortality and lesions were scored daily for 1 week. Three of the 10 isolates of Pseudomonas aeruginosa caused 100% mortality. Six other isolates of Pseudomonas aeruginosa and the one isolate of Proteus morganii caused 50% mortality. The remaining isolates induced less than 30% mortality. The sole nonpathogenic sample was one isolate of Pseudomonas fluorescens. When therapeutic levels of 22 antibiotics or sulfa drugs were evaluated for their inhibitory activity against the 15 isolates, the most effective were apramycin (15/15), gentamicin (15/15), spectinomycin (13/15), oxytetracycline (8/15), and sulfachloropyrazine (7/15). The least effective were ampicillin, cloxacillin, and tiamulin, which were not effective against any of the isolates. The 14 other drugs were of very low (> 4/15) effectiveness. Most of the isolates studied were virulent for chickens and very resistant to currently used drugs.

Psychological sequelae of sterilization in women in Singapore.

The Chinese in Singapore erroneously believe that there is an association between sterilization and castration. This belief has led to deep-seated fears that sterilization may result in obesity, physical weakness, and impairment of sexual function. Beginning in 1969, Singapore authorities introduced increasingly stronger social policies to help reduce family size. Subsequently, there was a large increase in the number of tubal ligations. It was initially thought that this might result in a high incidence of psychological sequelae. A study of 150 women who had had culdoscopic ligations showed that 6.3 percent were dissatisfied at the end of 2 years. Women with fewer than 4 children and those with fewer than 2 sons tended to be more dissatisfied with sterilization.

[Dento-facial structural characteristics in Angle Class II malocclusion associated with abnormal facial divergency].

Lateral cephalometric radiographs of 60 adult patients with Angle class 11 malocclusion associated with abnormal facial divergency were collected from the Orthodontic Department of the National Taiwan University Hospital. They were divided into a hyperdivergent group (35 cases) and a hypodivergent group (25 case), according to mandibular plane angle (SN-MP). The 19 landmarks on each cephalometric tracing were digitized into a computer, then computer-aided cephalometric analysis was performed to calculate the 17 skeletal measurements and 13 dentoalveolar measurements. The dento-facial structural characteristics of the hyperdivergent and hypodivergent groups were compared. It was found that the subjects of the hyperdivergent group revealed a greater tendency of divergency in the anterior cranial base plane, Frank-fort horizontal plane, palatal plane, occlusal plane, and mandibular plane. Hyperdivergent facial type, supposedly indicating an open bite or a tendency toward an open bite, has a longer lower anterior facial height, shorter posterior facial height, longer upper anterior and posterior dental height. While, the majority of dentofacial characteristics of the hypodivergent facial type observed in is study were directly opposite to those of the hyperdivergent facial type. The relationships of incisor overbite depth and other skeletal and dentoalveolar parameters were illustrated by Pearson's correlation coefficient and stepwise multiple regression analysis by means of the SPSS/PC statistic program. With the incisor overbite depth as the dependent variable, the independent variables included on the regression analysis were the 10 items of skeletal and dentoalveolar parameters. The compared parameters showed a statistically significant correlation with the incisor overbite depth (P < 0.001). By the stepwise method, the variables included on the regression equation were (1) N-Go-Gn, (2) A-Gn-Ar, (3) N-Ans/ans-Me, and (4) U1L1. The value of R square (R2) in the regression analysis was 0.543. It demonstrated that only a 54.3% variation in incisor overbite depth can be explained by variations in those skeletal and dentoalveolar variables.

Seroepidemiological survey of feline retrovirus infections in cats in Taiwan in 1993 and 1994.

In order to investigate the prevalence of infections with three feline retroviruses feline immunodeficiency virus (FIV), feline leukemia virus (FeLV) and feline syncytial virus (FSV) in Taiwan, we collected a total of 75 blood samples from cats from veterinary hospitals, a breeding cattery and a homeless shelter in 1993 and 1994. We examined the presences of anti-FIV and FSV antibodies and FeLV-p27 antigen in these samples by the indirect immunofluorescence and/or enzyme-linked immunosorbent assays. All of the serum samples positive for FIV were obtained from homeless cats and the overall FIV positive rate was 4%. The overall positive rates of FSV and FeLV were 28% and 1.3%, respectively. From these results, together with previous seroepidemiological surveys by others, it was revealed that the prevalence of FIV and FeLV infections appeared to be lower in Taiwan than in the United States or Japan. In contrast, the prevalence of FSV infection in Taiwan was as high as that in Japan.

High dose rate (HDR) brachytherapy technique: for carcinoma of uterine cervix using Nucletron applicators.

This study describes our existing treatment method for high dose rate (HDR) brachytherapy of carcinoma of uterine cervix using Nucletron applicators. Based on our clinical experience with low dose rate (LDR) brachytherapy since 1986, we deliver 40-45Gy by external and 30Gy by internal radiation therapy. The change in regimen using HDR brachytherapy is that internal radiation dose is given in 5 fractions at weekly intervals following external radiotherapy. We have analyzed the dosimetry of 20 patients; total of 100 treatments done at our center using ring-tandem (R-T) and ovoid-tandem (O-T) applicator combinations. Since O-T applicator has more flexibility of using desired tandem length and reduced rectum and bladder dose due to internal shielding inside the ovoids, we have made the transition from R-T to O-T combination of applicator. The dose volume histogram of the isodose curve indicates that there is an increase in isodose volume with the O-T applicator by as much as 1.5 times as compared to R-T applicator. In majority of the treatments, rectum and bladder doses are less than 70% of target dose, however in very few treatments, the bladder dose has increased to more than the target dose, in which case, the applicators were reseated and added more packing or reduced the dose per fraction, for better tolerance of late responding normal tissues. All our dose calculations are checked with an independent calculation method and agreement was obtained with in 5-7% discrepancy.(ABSTRACT TRUNCATED AT 250 WORDS)