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1.
J Intellect Disabil Res ; 60(10): 969-81, 2016 10.
Article in English | MEDLINE | ID: mdl-27476718

ABSTRACT

BACKGROUND: Individuals with Williams syndrome (WS) exhibit atypical attentional characteristics when viewing faces. Although atypical configural processing of faces has been reported in WS, the relative strengths of configural and local feature information to capture visual attention in WS remains unclear. We previously demonstrated that attentional capture by target-unrelated upright faces differs depending on what response is measured. Whereas eye movements reflected subtle atypical attentional properties at the late stage of visual search, manual responses could not capture the atypical attentional profiles towards target-unrelated upright faces in individuals with WS. Here we used the same experimental paradigm to assess whether sensitivity to configural facial information is necessary for capturing attention in WS. METHODS: We measured both eye movements and manual responses from 17 individuals with WS and 34 typically developing children and adults while they were actively involved in a visual search task with an inverted face distractor. Task measures (reaction time and performance accuracy) and gaze behaviour (initial direction of attention and fixation duration) were analysed for each stimulus. RESULTS: When the target and the inverted face were displayed in the same search array, reaction times and accuracies in individuals with WS showed similar tendencies as typical controls. Analysis of task and gaze measures revealed that attentional orienting towards inverted faces was not atypical. CONCLUSION: Although individuals with WS exhibited atypical gaze behaviour towards upright faces in our previous study, this unusual behaviour disappears if the faces are upside down. These findings suggest that local feature information alone (e.g. eyes) does not contribute to the heightened attention to faces, but configural information appears necessary for drawing attention to faces in individuals with WS, at least in the current experimental paradigm.


Subject(s)
Attention/physiology , Facial Recognition/physiology , Fixation, Ocular/physiology , Orientation/physiology , Psychomotor Performance/physiology , Williams Syndrome/physiopathology , Adolescent , Adult , Eye Movement Measurements , Female , Humans , Male , Young Adult
2.
Br J Cancer ; 100(1): 181-4, 2009 Jan 13.
Article in English | MEDLINE | ID: mdl-19127270

ABSTRACT

In a population-based prospective study of 19,998 Japanese individuals, consumption of vegetables, green-yellow and green leafy vegetables was inversely associated with the risk of hepatocellular carcinoma (101 cases), with multivariable hazard ratios for the highest vs lowest tertile of 0.61 (95% confidence interval (CI)=0.36-1.03, P(trend)=0.07), 0.65 (95% CI=0.39-1.08, P(trend)=0.06) and 0.59 (95% CI=0.35-1.01, P(trend)=0.04), respectively.


Subject(s)
Antioxidants/administration & dosage , Carcinoma, Hepatocellular/prevention & control , Fruit , Liver Neoplasms/prevention & control , Vegetables , Adult , Aged , Ascorbic Acid/administration & dosage , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Risk
3.
Struct Dyn ; 2(3): 034901, 2015 May.
Article in English | MEDLINE | ID: mdl-26798796

ABSTRACT

Time-resolved X-ray absorption spectroscopy was performed for aqueous ammonium iron(III) oxalate trihydrate solutions using an X-ray free electron laser and a synchronized ultraviolet laser. The spectral and time resolutions of the experiment were 1.3 eV and 200 fs, respectively. A femtosecond 268 nm pulse was employed to excite [Fe(III)(C2O4)3](3-) in solution from the high-spin ground electronic state to ligand-to-metal charge transfer state(s), and the subsequent dynamics were studied by observing the time-evolution of the X-ray absorption spectrum near the Fe K-edge. Upon 268 nm photoexcitation, the Fe K-edge underwent a red-shift by more than 4 eV within 140 fs; however, the magnitude of the redshift subsequently diminished within 3 ps. The Fe K-edge of the photoproduct remained lower in energy than that of [Fe(III)(C2O4)3](3-). The observed red-shift of the Fe K-edge and the spectral feature of the product indicate that Fe(III) is upon excitation immediately photoreduced to Fe(II), followed by ligand dissociation from Fe(II). Based on a comparison of the X-ray absorption spectra with density functional theory calculations, we propose that the dissociation proceeds in two steps, forming first [(CO2 (•))Fe(II)(C2O4)2](3-) and subsequently [Fe(II)(C2O4)2](2-).

4.
J Med Chem ; 41(5): 658-67, 1998 Feb 26.
Article in English | MEDLINE | ID: mdl-9513593

ABSTRACT

To develop a novel antipsychotic agent which is an agonist of dopamine (DA) autoreceptors and an antagonist of postsynaptic DA receptors, a series of 7-[4-[4-(substituted phenyl)-1-piperazinyl]butoxy]-3,4-dihydro-2 (1H)-quinolinones was synthesized and their dual activities were examined. The postsynaptic DA receptor antagonistic activities of the compounds were evaluated by their ability to inhibit stereotypy induced by apomorphine in mice, and the autoreceptor agonist activities were determined by their effects on the gamma-butyrolactone (GBL)-induced increase in L-dihydroxyphenylalanine (DOPA) synthesis in the mouse brain. Many compounds inhibited the stereotypic behavior, and several compounds reversed the GBL-induced increase in the DOPA synthesis. Among them, 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butoxy]-3,4-dihydro-2 (1H)-quinolinone (28, aripiprazole, OPC-14597) was found to have these two activities. This compound reversed the GBL-induced DOPA synthesis (ED50 values of 5.1 mumol/kg p.o.) and inhibited the APO induced stereotypy (ED50 values of 0.6 mumol/kg p.o.). Compound 28 induced catalepsy at 10 times higher dose than that required for the antagonism of APO-induced stereotypy (ED50 value of 7.8 mumol/kg p.o.).


Subject(s)
Antipsychotic Agents/chemical synthesis , Piperazines/chemical synthesis , Quinolones/chemical synthesis , 4-Butyrolactone/pharmacology , Animals , Antipsychotic Agents/pharmacology , Apomorphine/pharmacology , Aripiprazole , Brain/drug effects , Brain/metabolism , Catalepsy/chemically induced , Dihydroxyphenylalanine/biosynthesis , Dopamine Agonists/pharmacology , Dopamine Antagonists/chemical synthesis , Dopamine Antagonists/pharmacology , GABA Modulators/pharmacology , Male , Mice , Mice, Inbred ICR , Molecular Structure , Piperazines/adverse effects , Piperazines/pharmacology , Quinolones/adverse effects , Quinolones/pharmacology , Rats , Stereotyped Behavior/drug effects , Structure-Activity Relationship
5.
J Med Chem ; 43(2): 177-89, 2000 Jan 27.
Article in English | MEDLINE | ID: mdl-10649973

ABSTRACT

To develop a novel antidepressant drug with central nervous system-stimulating activity, we prepared a series of 1-[omega-(4-substituted phenyl-1-piperazinyl)alkyl]-3, 4-dihydro-2(1H)-quinolinone derivatives and examined their activities by their effects at 30 and 100 mg/kg po on the sleeping time of mice anesthetized with halothane and on the time required for recovery from coma induced in mice by cerebral concussion. We examined their binding affinities for sigma receptors by evaluating their ability to inhibit [(3)H]-1,3-di(o-tolyl)guanidine ([(3)H]DTG) binding to the rat whole brain membrane in comparison with three putative sigma receptor agonists: 1,3-di(o-tolyl)guanidine (DTG, 66), (+)-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2, 6-methano-3-benzazecin-8-ol (SKF10,047, 67), and (+)-1,2,3,4,5, 6-hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl)-2, 6-methano-3-benzazecin-8-ol (pentazocine, 68). Among the series of derivatives, 1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-3, 4-dihydro-5-methoxy-2(1H)-quinolinone hydrochloride (34b) and its mesylate (34c), at a dose of 30 mg/kg po, reduced the sleeping time and the time for recovery from coma and they inhibited [(3)H]DTG binding for sigma receptors. The putative sigma receptor agonists reduced the sleeping time and the time for recovery from coma whereas two sigma receptor antagonists, alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol hydrochloride (BMY14802, 69) and cis-9-[3-(3, 5-dimethyl-1-piperazinyl)propyl]carbazole dihydrochloride (rimcazole, 70), were inactive in the two tests. Preadministration of the putative sigma receptor antagonists 69 (3 mg/kg po) and 70 (30 mg/kg po) completely antagonized the actions of 34b and the sigma receptor agonists in the test for recovery from coma. These results suggested that 34b and 34c are sigma receptor agonists. Furthermore, a single administration of 1 and 10 mg/kg po 34b and 34c showed antidepressant-like activity by reducing the immobility time in the forced-swimming test with mice, while a tricyclic antidepressant, 10, 11-dihydro-N,N-dimethyl-5H-dibenz[b,f]azepine-5-propanamine hydrochloride (imipramine, 1) (10 and 30 mg/kg po), did not reduce the time after a single administration. 1 reduced the time after repeated administration of 30 mg/kg po once a day for 4 days. The structure-activity relationship of the series of compounds is also discussed.


Subject(s)
Antidepressive Agents/chemical synthesis , Antidepressive Agents/pharmacology , Piperazines/chemical synthesis , Piperazines/pharmacology , Quinolones/chemical synthesis , Quinolones/pharmacology , Animals , Antidepressive Agents/therapeutic use , Brain Concussion/drug therapy , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred ICR , Piperazines/therapeutic use , Quinolones/therapeutic use , Rats , Rats, Wistar , Receptors, sigma/drug effects , Receptors, sigma/therapeutic use , Structure-Activity Relationship
6.
Oral Oncol ; 39(8): 821-8, 2003 Dec.
Article in English | MEDLINE | ID: mdl-13679205

ABSTRACT

The purpose of this study was to determine the frequency of human papillomavirus (HPV) infections in the normal oral cavity of children in Japan. Oral squamous cell specimens were collected from 77 children (44 boys and 33 girls), aged 3 and 5 years. Extracted DNA was evaluated for HPV infections by polymerase chain reaction (PCR) methods, using consensus primers for the L1 region, specific primers, and direct DNA sequencing analysis. Thirty-seven of 77 specimens (48.1%) were positive for HPV DNA. Positive rates of boys and girls in all specimens were 28.3 (22/77) and 19.5 (15/77)%, respectively. The positive rate in 3-year-old children was 45.2 (14/31)%, and positive rates in boys and girls were 52.6 (10/19) and 33.3 (4/12)%, respectively. The positive rate in 5-year-old children was 50.0 (23/46)%, and positive rates in boys and girls were 48.0 (12/25) and 52.4 (11/21)%, respectively. HPV types were determined by specific PCR and direct DNA sequencing analysis. Frequent HPV types in the specimens of all children were HPV-16 (11/37; 29.7%),-1 (6/37; 16.2%),-2 (6/37; 16.2%),-75 (6/37; 16.2%). The results of the present investigation indicate that many HPVs, including HPV-16 (a high-risk type for cancer), are present in the oral cavity of 3- and 5-year-old children. It is suggested, therefore, that the oral cavity is already a reservoir of HPVs in childhood where later HPV-associated diseases, such as oral cancer and other oral lesions, may develop.


Subject(s)
Mouth Diseases/epidemiology , Mouth Diseases/virology , Papillomaviridae , Papillomavirus Infections/epidemiology , Tumor Virus Infections/epidemiology , Age Distribution , Child, Preschool , DNA, Viral/analysis , Disease Reservoirs , Female , Humans , Japan/epidemiology , Male , Mouth Neoplasms/virology , Papillomaviridae/genetics , Polymerase Chain Reaction/methods , Prevalence , Risk Factors , Sequence Analysis, DNA , Sex Distribution
7.
Br J Cancer ; 94(5): 740-2, 2006 Mar 13.
Article in English | MEDLINE | ID: mdl-16465189

ABSTRACT

In a population-based prospective study of 49 850 Japanese men, body mass index and height were not significantly associated with risk of prostate cancer (311 cases), although small positive effects could not be ruled out in advanced cases (91 cases).


Subject(s)
Body Height , Body Mass Index , Prostatic Neoplasms/etiology , Adult , Aged , Cohort Studies , Humans , Japan/epidemiology , Male , Middle Aged , Prostatic Neoplasms/epidemiology , Risk Factors
8.
Mol Hum Reprod ; 11(2): 93-8, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15579657

ABSTRACT

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It has been demonstrated that the CYP1A1 metabolizes not only environmental chemicals but also estrogens, and glutathione-S-transferases (GSTs) are detoxification enzymes that protect cells from toxicants by conjugation with glutathione. In this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1 polymorphisms with hypospadias, a case-control study of 31 case mothers who had boys with hypospadias and 64 control mothers was performed in Japan. These polymorphisms were investigated by PCR-based methods using DNA from peripheral lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and homozygous CYP1A1 were less frequent in the case mothers than in the control mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74, OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal smoking on the hypospadias risks among the gene polymorphisms. The results suggest that mothers with the CYP1A1 MspI variant allele may have a decreased risk for hypospadias.


Subject(s)
Cytochrome P-450 CYP1A1/genetics , Genetic Predisposition to Disease , Hypospadias/genetics , Polymorphism, Restriction Fragment Length , Adult , Case-Control Studies , Child , Female , Gene Frequency , Glutathione Transferase/genetics , Humans , Japan , Male , Risk Factors , Smoking , Surveys and Questionnaires
9.
Phys Rev Lett ; 91(14): 147202, 2003 Oct 03.
Article in English | MEDLINE | ID: mdl-14611550

ABSTRACT

Magnetic phase transitions in coupled magnetic sandwiches of Cu/Co/Cu/Ni/Cu(100) and Cu/Co/Fe/Ni/Cu(100) are investigated by photoemission electron microscopy. Element-specific magnetic domains are taken at room temperature to reveal the critical thickness at which the magnetic phase transition occurs. The results show that a coupled magnetic sandwich undergoes three types of magnetic phase transitions depending on the two ferromagnetic films' thickness. A phase diagram is constructed and explained in the process of constructing Monte Carlo simulations, which corroborate the experimental results.

10.
Int Arch Occup Environ Health ; 77(7): 461-70, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15558298

ABSTRACT

OBJECTIVES: As the airtightness of dwellings has recently increased, problems associated with indoor air pollution and dampness have become important environmental health issues. The aim of this study was to clarify whether symptoms in residents living in newly built dwellings were related to chemicals and dampness. METHODS: Symptoms of 317 residents were surveyed by standardized questionnaires, and the concentrations of formaldehyde, acetaldehyde, and 17 volatile organic compounds (VOCs) in their homes were measured. Dampness (condensation on window panes and/or walls, and mold growth) was identified by questionnaires given to the householders or their partners. RESULTS: Some VOCs (toluene, butyl acetate, ethylbenzene, alpha-pinene, p-dichlorobenzene, nonanal, and xylene) were significantly related to the symptoms, and the sum of all VOCs (all identified VOCs) was significantly related to throat and respiratory symptoms [odds ratio (OR) for eye symptoms =2.4; 95% confidence interval (CI) 1.0-5.5], although the concentrations of VOCs were relatively low. As for the dampness index, condensation on window panes and/or walls was related to all symptoms, and mold growth was related to all symptoms except skin, throat and respiratory and general symptoms. As the number of dampness signs increased, the ORs increased for the symptoms except general symptoms (OR for nose symptoms = 4.4, 95% CI 1.6-11.9). CONCLUSION: Both VOCs and dampness were significantly related to symptoms. We should take measures to reduce the concentrations of VOCs, dampness and microbial growth in dwellings.


Subject(s)
Air Pollution, Indoor/analysis , Hazardous Substances/analysis , Humidity , Sick Building Syndrome/epidemiology , Acetaldehyde/analysis , Adult , Female , Formaldehyde/analysis , Humans , Japan/epidemiology , Logistic Models , Male , Middle Aged , Organic Chemicals/analysis , Prevalence , Sick Building Syndrome/physiopathology
11.
West J Med ; 146(4): 489, 1987 Apr.
Article in English | MEDLINE | ID: mdl-18750212
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