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N-acetylaspartate (NAA) levels and serum brain-derived neurotrophic factor (BDNF) levels in patients with first-episode schizophrenia psychosis and age- and sex-matched healthy control subjects were investigated. In addition, plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared between the two groups.
Eighteen patients (nine males, nine females; age range: 13–52 years) were enrolled in the study, and 18 volunteers (nine males, nine females; age range: 15–49 years) with no current or past psychiatric history were also studied by magnetic resonance spectroscopy (MRS) as sex- and age-matched controls.
Levels of NAA/Cr in the left basal ganglia (p = 0.0065) and parieto-occipital lobe (p = 0.00498), but not in the frontal lobe, were significantly lower in patients with first-episode schizophrenia psychosis than in control subjects. No difference was observed between the serum BDNF levels of patients with first-episode schizophrenia psychosis and control subjects. In regard to the plasma levels of catecholamine metabolites, plasma MHPG, but not HVA, was significantly lower in the patients with first-episode psychosis than in control subjects. In addition, a significantly positive correlation was observed between the levels of NAA/Cr of the left basal ganglia and plasma MHPG in all subjects.
These results suggest that brain NAA levels in the left basal ganglia and plasma MHPG levels were significantly reduced at the first episode of schizophrenia psychosis, indicating that neurodegeneration via noradrenergic neurons might be associated with the initial progression of the disease.
Previous studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. FK506-binding protein 51 (FKBP51 or FKBP5) is a co-chaperone of heat-shock protein 90, and plays an important role in the negative feedback regulation of HPA axis function. It has been reported that a C/T single nucleotide polymorphism in the intron 2 of FKBP5 gene (rs1360780) affects FKBP5 protein levels and cortisol response to dexamethasone and psychological stress tests. Therefore, it is hypothesized that the FKBP5 polymorphism affects personality traits. In the present study, we studied the association between this polymorphism and personality traits in healthy subjects.
Subjects were 826 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the FKBP5 genotype was detected by a real-time PCR and cycling probe technology for SNP typing.
In total subjects, the group with the T allele predictive of impaired negative feedback regulation of the HPA axis had higher scores of harm avoidance (p = 0.043) and lower scores of cooperativeness (p = 0.019) compared to that without the T allele. The T allele was associated with higher scores of harm avoidance in females (p = 0.020) and lower scores of cooperativeness in males (p = 0.015).
The present study thus suggests that the FKBP5 polymorphism affects harm avoidance and cooperativeness in healthy subjects, with gender specificity.
Previous studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. Glucocorticoid receptor (GR) is the most important regulator of the HPA axis negative feedback system, and several polymorphisms of the GR gene are associated with altered glucocorticoid sensitivity. In the present study, we examined the associations between the GR polymorphisms and personality traits in healthy subjects.
Subjects were 880 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory (TCI). Two polymorphisms of the GR gene, i.e., G/C SNP in the intron 2 (BcII polymorphism, rs41423247) and A/G SNP in the exon 9β (9β polymorphism, rs6198), were detected by a real-time PCR and cycling probe technology for SNP typing.
The genotype distributions were G/G = 614, G/C = 240, and C/C = 26 for the BcII polymorphism, and A/A = 879 and A/G = 1 for the 9β polymorphism, respectively. There were no significant associations between the BcII genotype groups in any TCI dimension score.
The present study suggests that these two GR polymorphisms (BcII and 9β polymorphism) are not involved in the characterization of personality traits in healthy subjects.
There is a growing body of data suggesting the gene-environment interaction in the characterization of personality traits, but variation in ordinary parental rearing among environmental factors has not been focused yet. We examined the effects of the interaction between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and parental rearing on personality traits.
Subjects were 710 Japanese healthy volunteers. Perceived parental rearing was assessed by the Parental Bonding Instrument (PBI), which consists of the care and protection factors. Personality assessment was performed by the Temperament and Character Inventory (TCI), which has 7 dimensions, i.e., novelty seeking, harm avoidance, reward dependence, persistence, self-directedness, cooperativeness, and self-transcendence. The BDNF Val66Met polymorphism was detected by the PCR-RFLP method.
Parental rearing has significant main effects on all TCI dimensions except novelty seeking, while no significant main effects of the BDNF genotype on the TCI scores were found. The interaction between the BDNF genotype and maternal care of the PBI had significant effects on harm avoidance and self-directedness of the TCI. Post-hoc analyses showed that decreased maternal care was correlated with increased harm avoidance and decreased self-directedness in most of the genotype groups, and for both personality traits the correlation was highest in the Met/Met genotype and lowest in the Val/Val genotype and that for the Val/Met genotype was in between the two values.
The present study suggests that the BDNF Val66Met polymorphism moderates the effects of parenting rearing, especially maternal care, on harm avoidance and self-directedness in healthy subjects.
It has been shown that certain personality traits are related to mortality and disease morbidity, but the biological mechanism linking them remains unclear. Telomeres are tandem repeat DNA sequences located at the ends of chromosomes, and shorter telomere length is a predictor of mortality and late-life disease morbidity. Thus, it is possible that personality traits influence telomere length. In the present study, we examined the relationship of leukocyte telomere length with personality traits in healthy subjects.
Subjects and methods:
The subjects were 209 unrelated healthy Japanese who were recruited from medical students at 4th–5th grade. Assessment of personality traits was performed by the Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI). Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene.
In the stepwise multiple regression analysis, shorter telomere length was related to lower scores of neuroticism (P < 0.01) and conscientiousness (P < 0.05) of the NEO-PI-R, and lower scores of harm avoidance (P < 0.05) and reward dependence (P < 0.05) of the TCI.
The present study suggests that leukocyte telomere length is associated with some personality traits, and this association may be implicated in the relationship between personality traits and mortality.
Research has shown that ADHD symptoms and functional impairment often persist beyond childhood into adulthood. Thus an effective therapy that can be tolerated over long-term use in adults is needed. This is the first long term safety and tolerability study of an adult ADHD medication in Asia.
Assess long-term safety, tolerability, and efficacy of atomoxetine (ATX) in adult Japanese ADHD patients.
Demonstrate the safety and tolerability of long-term ATX.
ATX (40-120 mg/day) was evaluated based on integrated analyses of a 10 week double-blind (DB) study and a 48 week open-label long term (LT) extension study. Long-term safety and tolerability were assessed by adverse events, discontinuation rate, and vital-signs. Efficacy measures included change from baseline in Conners’ Adult ADHD Rating Scale- Investigator Rated (CAARS-Inv:SV) total symptoms score, behavior Rating Inventory of Executive Function (BRIEF-A), and Adult ADHD/QoL Measure (AAQoL).
233 patients took ATX (LT mean final prescribed dose: 108.3 mg/day). AEs leading to discontinuations were seen in 37 (15.9%) patients, the most common being nausea in 10 (4.3%) patients. Statistically significant baseline-to-endpoint reductions in mean CAARS-Inv:SV total symptoms score during in the DB study continued throughout the LT study. Similar reductions were seen in BRIEF-A Self Report scores. These findings along with AAQoL results indicated that patients perceived improvements in both QoL and Executive Function.
Long-term ATX treatment was shown to be generally safe and tolerable in Japanese adult ADHD patients. Results also suggested ATX improved ADHD core symptoms, QoL and Executive Functions.
Meiotic maturation of oocytes requires a variety of ATP-dependent reactions, such as germinal vesicle breakdown, spindle formation, and rearrangement of plasma membrane structure, which is required for fertilization. Mitochondria are accordingly expected be localized to subcellular sites of energy utilization. Although microtubule-dependent cellular traffic for mitochondria has been studied extensively in cultured neuronal (and some other somatic) cells, the molecular mechanism of their dynamics in mammalian oocytes at different stages of maturation remains obscure. The present work describes dynamic aspects of mitochondria in porcine oocytes at the germinal vesicle stage. After incubation of oocytes with MitoTracker Orange followed by centrifugation, mitochondria-enriched ooplasm was obtained using a glass needle and transferred into a recipient oocyte. The intracellular distribution of the fluorescent mitochondria was then observed over time using a laser scanning confocal microscopy equipped with an incubator. Kinetic analysis revealed that fluorescent mitochondria moved from central to subcortical areas of oocytes and were dispersed along plasma membranes. Such movement of mitochondria was inhibited by either cytochalasin B or cytochalasin D but not by colcemid, suggesting the involvement of microfilaments. This method of visualizing mitochondrial dynamics in live cells permits study of the pathophysiology of cytoskeleton-dependent intracellular traffic of mitochondria and associated energy metabolism during meiotic maturation of oocytes.
We present the first reported case of primary small cell carcinoma of the lacrimal sac.
A 67-year-old Japanese woman was referred to our department with a two-month history of left medial canthal swelling, epiphora and occasional nasal bleeding. Nasal endoscopy revealed a readily bleeding tumour in the left inferior meatus. Computed tomography and magnetic resonance imaging scans demonstrated that the tumour was mainly located in the left lacrimal sac. Histopathological studies of a biopsy specimen revealed small cell carcinoma. The patient was treated with four cycles of chemotherapy consisting of cisplatin and etoposide, in combination with radiotherapy. There was no evidence of recurrence or metastasis for five years.
Small cell carcinoma originating in the head and neck region has been reported to be highly aggressive and to have a poor prognosis. We report a case of primary small cell carcinoma of the lacrimal sac successfully treated with chemo-radiotherapy.
A total of 571 swine sera collected at an abattoir in the city of Obihiro, Hokkaido during the period February–November 1984 were tested for antibody against human (H1N1) influenza virus strains. A high prevalence of antibody was observed for only 3 months from April to June in that year, in 81/180 sera (45·0%) to A/USSR/92/77 strain and in 50/180 sera (27·8%) to a current epidemic strain (A/Hokkaido/1/84). Some cross-reactions were observed between the A/USSR/92/77 and A/Hokkaido/1/84 antibodies (r = 0·75). Only minor relationships were noted between the A/New Jersey/8/76 (swine type H1N1) and A/USSR/92/77 (r = 0·35) or A/Hokkaido/1/84 (r = 0·51) antibodies. Absorption of sera positive for antibody to the A/Hokkaido/1/84 strain with the homologous virus strain removed all detectable antibodies, while the absorption of the sera with the A/New Jersey/8/76 strain produced incomplete absorption in one half of the sera tested. These resultsstrongly suggest that the swine became infected with a human H1N1 virus as piglets during an epidemic of influenza which occurred in the human population during January and February 1984.
A total of 6346 swine sera collected at an abattoir in the city of Obihiro, Hokkaido during the years 1978–87 were tested for the presence of antibodies to swine and human influenza viruses. A high incidence of antibody to A/New Jersey/8/76 (swine type H1N1) virus was observed throughout the 10 years except for the occasional month and a single long period of 15 months. Antibodies to human H3N2 virus in swine appeared to be related to the epidemics of human influenza which occurred in the study area during the years 1980–3, but unrelated to the epidemics during the years 1984–7. A large number of swine were found to be antibody positive to a human H1N1 virus during the period April to June 1964, and a smaller number, during the period November 1986 to June 1987. Both were in relation to human influenza epidemics. However, there were long periods where human H1N1 antibodies in swine could not be found.
The first occurrence of swine influenza in Japan was recognized in 1977, when it was presumed that the disease was introduced via imported swine (Shibata elal. 1978). Further outbreaks of swine influenza and a high prevalence of antibody to the virus in Japanese swine populations have been reported by several workers (Yamane, Sukeno & Ishida, 1978; Sugimura elal. 1981; Ogawa elal. 1983). An outbreak of influenza virus infection due to an H3N2 strain was previously seen in a herd of swine in Osaka, Japan (Sugimura etal. 1975). Later the co-existence of swine (H1N1) and human (H3N2) influenza viruses was confirmed by serological and virological studies on Japanese swine populations (Onta et al. 1978; Sugimura et al. 1980; Arikawa et al. 1982). In a previous report (Miwa et al. 1986), we suggested that the swine became infected with a human H1N1 virus as piglets during an epidemic of influenza which occurred in the human population at the same time. The present study was undertaken to evaluate the changes in the prevalence of antibodies against swine and human influenza viruses in Japanese swine during the past 10 years.
There are few data on circulatory pro-inflammatory cytokine levels and cytokine gene polymorphisms in H. pylori-positive patients. A cross-sectional study was conducted to examine the effects of H. pylori infection, gastric atrophy, and the IL-8 T-251A polymorphism on plasma IL-8 levels in 98 Japanese adults. Seventy-one subjects were positive for H. pylori infection. The geometric mean of plasma IL-8 concentration was significantly higher in subjects with H. pylori infection than in those without (P=0·001). The development of atrophy was negatively associated with IL-8 levels in the H. pylori-positive subjects, although not significantly. Plasma IL-8 levels in the T/T genotype were associated with H. pylori infection and atrophy status (P=0·016). Our findings suggested that circulating IL-8 levels were associated with H. pylori infection. The effect of H. pylori infection on plasma IL-8 levels was not clearly modified by the IL-8 T-251A polymorphism.
A total of 1799 swine sera collected in Toyama prefecture in the central part of Japan during the years 1978–82 were tested for antibody against swine influenza virus (SIV), A/New Jersey/8/76 (H1N1). A high prevalence of antibody was observed in the years after the severe epizootic of SI, 34·5% in 1979 and 51·7% in 1982. In other years, the percentages of positive sera were low and ranged from 1·7 to 12·4%. Regional variations were seen in relation to a small scale epizootic. No antibody to SIV was detected in any of the sera collected during the warm season. In the following dry and cold winter, however, a severe epizootic occurred among the swine populations.
Alveolar echinococcosis (AE) is endemic to Hokkaido, Japan. For the past 20 years, detection of AE among inhabitants has involved serological screening using an enzyme-linked immunosorbent assay (ELISA) followed by Western blotting (WB). Between the years 1987 and 2000, antigens targeted on 66, 55 and 30–35 kDa bands were routinely used in the WB step of AE diagnosis. However, since 2001 diagnosis has been dependent on three smaller molecular weight antigens (26–28, 18 and 7–8 kDa). Due to its higher sensitivity, this improved WB approach has been used as a confirmation step in the screening process and also for the testing of suspected AE cases in hospital outpatients. Using the improved WB technique, a total of 1745 serum samples were examined in 2001–2006 with 81 patients detected and registered with AE. Interestingly, sera from 76 of the 81 diagnosed AE patients (93.8%) demonstrated reactivity with all three antigens. However, sera from the remaining five patients (6.2%) demonstrated no reactivity with the 18 kDa antigen, even though they exhibited clearly detectable levels of reactivity with the 26–28 and 7–8 kDa bands. These results suggest that medical practitioners need to pay particular attention to the specific reactions to some different diagnostic antigens to minimize the risk of misdiagnosing AE patients. In turn, these results may also provide important diagnostic information for cystic echinococcosis (CE).
A neutral beam injection (NBI) into a field-reversed configuration (FRC) is simulated by the electron-fluid and ion-particle method. The neutral beam particle is injected tangentially to the field-null circle, and the simulation is done on a two-dimensional cross section of the FRC. An initial equilibrium state is obtained from the Grad–Shafranov equation including the beam current term. It is found that the start of radial ion flow is delayed by the NBI.
A nationwide study was undertaken to determine the susceptibility to penicillin and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated from 114 adult patients with community-acquired pneumonia over 22 months at 20 hospitals and medical centres in different regions in Japan. All but five isolates were from sputum. Forty-eight isolates (42·1%) were susceptible, 40 (35·1%) showed intermediate resistance (MIC, 0·12–1·0 μg/ml) and 26 (22·8%) were resistant (MIC, [ges ]2·0 μg/ml) to penicillin G. All isolates were susceptible to ceftriaxone (breakpoint 1 μg/ml), imipenem (4 μg/ml) and vancomycin (4 μg/ml). Most were resistant to erythromycin, clarithromycin and azithromycin; only two were resistant to levofloxacin. Differences were found in the distribution of serotypes among isolates showing susceptibility to penicillin (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and 23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25 strains of serotype 19F had a single DNA profile, pattern A, a pattern closely similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A strains were not susceptible to penicillin but carried the macrolide resistance gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous but six were highly similar (pattern b) yet distinct from the Spanish multidrug-resistant 23F clone although possibly related to the Taiwan multidrug-resistant 23F clone. The pattern b strains were not susceptible to penicillin and also harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the pandemic multidrug-resistant serotypes should be intensified.
This paper describes film characterization of Ultra Low-k (ULK) dielectrics modified by UV curing with different wavelength bands. We have demonstrated UV hardening of ULK-SiOC (k=2.65) with two types of UV bulbs (UV-X and UV-Y) and the UV modifications of ULK-SiOC film properties are characterized by using FT-IR spectroscopy, 29Si Solid-state NMR spectroscopy and Raman spectroscopy. FT-IR and NMR analyses reveal that UV-Y curing is preferable for UV curing modification of ULK-SiOC. UV-Y curing increases Q mode peak in NMR, resulting in the enhanced Si-O crosslinking, while UV-X curing increases TH mode and TOR mode peaks. Spin lattice relaxation time T1 for 29Si is decreased with UV curing. This result indicates that UV curing enhances molecular motion in Si-O network. Raman analysis shows that UV curing increases amorphous carbon groups, which corresponds to the enhanced molecular motion in Si-O network.