Publications by authors named "Hideo Honda"

31 Publications

Hyperactive/impulsive symptoms and autistic trait in institutionalized children with maltreatment experience.

New Dir Child Adolesc Dev 2021 Sep 9;2021(179):29-39. Epub 2021 Dec 9.

Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.

The present study examined how maltreatment experience was associated with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) symptoms in children under institutional care. The key caregivers of children and adolescents aged 6 to 18 years who were under institutional care in Nagano prefecture, Japan were asked to answer the background questionnaire, ADHD-Rating Scale, and the Japanese children's version of the Autism-Spectrum Quotient. A total of 378 valid responses were obtained, of which 222 reported maltreatment experience prior to institutionalization. Both hyperactive/impulsive and inattentive scores were significantly higher in the maltreated group. Maltreatment experience was significantly associated with the presence of hyperactive/impulsive symptoms (p = 0.003) and inattentive symptoms (p = 0.027). Particularly, those who had experienced physical abuse were significantly more likely to have hyperactive/impulsive symptoms (p = 0.012) and autistic trait (p = 0.002). Thorough assessment of neurodevelopmental symptoms should be performed when placing children with maltreatment experience into institutional care.
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http://dx.doi.org/10.1002/cad.20445DOI Listing
September 2021

Prevalence of clinical-level emotional/behavioral problems in schoolchildren during the coronavirus disease 2019 pandemic in Japan: A prospective cohort study.

JCPP Adv 2021 Apr 28;1(1):e12007. Epub 2021 Apr 28.

Department of Child and Adolescent Developmental Psychiatry Shinshu University School of Medicine Matsumoto Japan.

Background: Several empirical studies have investigated negative mental health outcomes related to the spread of infectious diseases, including coronavirus disease 2019 (COVID-19). However, little is known about children's emotional/behavioral problems, especially externalizing problems, during such situations. This prospective cohort study aimed to investigate pandemic-related emotional/behavioral problems and their risk factors among schoolchildren in Japan.

Methods: A total of 4800 parents with children in grades 1-12 participated in a two-wave longitudinal survey. Wave 1 and Wave 2 were conducted on March 4-8 and May 15-18, 2020, respectively. Survey items included demographic information, parental depression, children's diagnoses of neurodevelopmental disorders, the total length of school closure, and emotional/behavioral problems. Children's emotional/behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ), which has cutoff points to differentiate clinical-level problems, which were the primary focus of this study.

Results: The proportions of clinical-level problems were higher at Wave 2 (emotional symptoms = 24.8%, conduct problems = 22.7%, hyperactivity/inattention = 36.8%, peer relationship problems = 36.2%, and lack of prosocial behavior = 23.5%) compared to Wave 1. Lower grade-level and lower annual family income predicted the increased proportions of children's clinical-level emotional symptoms, hyperactivity/inattention, and prosocial behavior at Wave 2. The total length of school closure was not a significant predictor of subsequent emotional/behavioral problems. The highest proportion of clinical-level problems at Wave 2 for the four SDQ subscales was observed in children with neurodevelopmental disorders.

Conclusions: The number of schoolchildren with severe emotional/behavioral problems increased during the COVID-19 pandemic. Appropriate prevention and early intervention programs should be provided, especially for children who are in lower grade levels, have low family incomes, or have neurodevelopmental disorders.
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http://dx.doi.org/10.1111/jcv2.12007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206658PMC
April 2021

Trends in Autism Spectrum Disorder Diagnoses in Japan, 2009 to 2019.

JAMA Netw Open 2021 05 3;4(5):e219234. Epub 2021 May 3.

Department of Child and Adolescent Developmental Psychiatry, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.9234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097493PMC
May 2021

Possible utilization of salivary IFN-γ/IL-4 ratio as a marker of chronic stress in healthy individuals.

Neuropsychopharmacol Rep 2021 03 19;41(1):65-72. Epub 2021 Jan 19.

Mental Health Clinic for Children, Shinshu University Hospital, Matsumoto, Japan.

Introduction: Several studies show that psychological stress reduces Th1/Th2 ratio in blood samples. However, evidence is scarce regarding the cytokine alterations during stress in saliva. We investigated the influence of chronic stress on Th1/Th2 ratio and cytokine profiles in the saliva of healthy individuals. Further, we examined the associations of the salivary cytokine levels with sleep and attention problems, which are closely related with psychological stress.

Methods: Salivary levels of 27 cytokines were measured by multiplex bead array assays in 31 healthy young individuals (health science students and hospital staff consisting of 11 men and 20 women, mean age [standard deviation] =21.5 [0.8] years). The Kessler Psychological Distress scale (K10) and Athens Insomnia Scale (AIS) were administered to assess subjective chronic psychological stress and sleep problems. Further, participants were asked to wear Actigraph GT3X accelerometers for 3 days to assess the total sleep time. Attention problems were assessed by administering the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT).

Results: Thirteen cytokines with >80% detectable results were included in the main analyses. The IFN-γ/IL-4 ratio, which is a commonly used index for Th1/Th2 ratio, showed significant negative correlations with the K10 and AIS scores. None of the cytokines were significantly associated with sex, body mass index, sleep index measured by Actigraph, or IVA-CPT scores.

Conclusion: Chronic stress may be associated with alterations of the Th1/Th2 balance in salivary cytokine production. IFN-γ/IL-4 ratio in saliva may serve as a potential biomarker of chronic stress in healthy individuals.
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http://dx.doi.org/10.1002/npr2.12157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182956PMC
March 2021

Brief Report: Cumulative Incidence of Autism Spectrum Disorder Before School Entry in a Thoroughly Screened Population.

J Autism Dev Disord 2021 Apr;51(4):1400-1405

Child and Adolescent Developmental Psychiatry, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, Japan.

The present study aimed to identify the cumulative incidence of autism spectrum disorder (ASD) in a thoroughly screened population and to examine the behavioral and motor characteristics observed in children with ASD at the age of 18 months. Subjects were 1067 children who underwent a screening assessment for ASD at the routine 18-months health checkup. By the age of 6 years, 3.1% (4.3% of boys and 2.0% of girls) were diagnosed as having ASD by their attending pediatricians. Higher rate of difficulties in motor skills and social and communication skills had been reported in children with ASD at 18 months of age. This study showed that careful community-based screening system may be helpful in detecting ASD at early age.
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http://dx.doi.org/10.1007/s10803-020-04619-9DOI Listing
April 2021

Negative Correlation between Serum Cytokine Levels and Cognitive Abilities in Children with Autism Spectrum Disorder.

J Intell 2017 May 8;5(2). Epub 2017 May 8.

Mental Health Clinic for Children, Shinshu University Hospital, Matsumoto 390-8621, Japan.

Evidence suggests that cytokines may be one of the major factors influencing cognitive development in those with autism spectrum disorder (ASD). To shed light on the neural and cognitive mechanisms of ASD, we investigated the association between peripheral cytokine levels and cognitive profiles in children with ASD. The serum levels of 10 cytokines (granulocyte macrophage colony-stimulating factor, interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-α) were examined in 14 children with ASD using the Human Ultrasensitive Cytokine Magnetic 10-Plex Panel for the Luminex platform. The Wechsler Intelligence Scale for Children (WISC) was administered to each subject, and the relationships between WISC scores and serum levels of the cytokines were examined. The full-scale intelligence quotient (IQ) was significantly negatively correlated with the levels of IL-6 (Spearman's rank, < 0.0001, false discovery rate < 0.01). The levels of IL-6 and IFN-γ showed significant negative correlations with the verbal comprehension index ( < 0.001, < 0.01) and working memory index ( < 0.01, < 0.05), respectively. No other cytokines were significantly correlated with full-scale IQ or with any of the subscale scores of the WISC. The present results suggest negative correlations of IL-6 and IFN-γ levels with cognitive development of children with ASD. Our preliminary findings add to the evidence that cytokines may play a role in the neural development in ASD.
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http://dx.doi.org/10.3390/jintelligence5020019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526410PMC
May 2017

Effective Treatment of Night Terrors and Sleepwalking with Ramelteon.

J Child Adolesc Psychopharmacol 2016 12 20;26(10):948. Epub 2016 Jun 20.

1 Mental Health Clinic for Children, Shinshu University Hospital , Matsumoto, Japan .

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http://dx.doi.org/10.1089/cap.2016.0088DOI Listing
December 2016

[Developmental disorders in adulthood: concept, differential diagnosis, and treatment].

Authors:
Hideo Honda

Seishin Shinkeigaku Zasshi 2014 ;116(6):513-8

The number of cases diagnosed with developmental disorders is rapidly increasing among those consulting psychiatry clinics for the first time in their adulthood. The author presents the concept of developmental disorders, discusses how they can be differentiated from other psychiatric disorders, and proposes some treatments. From now on, all psychiatrists should know the difference between developmental disorders and other psychiatric disorders, and diagnose them multi-axially, including the dimension of development. They should always keep in mind how developmental disorders lead to difficulties in everyday life, and treat developmental disorders in conjunction with adequate environmental modifications along with the treatment of other comorbid psychiatric disorders.
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September 2014

[Effect of developmental disorders on personality and personality disorders].

Authors:
Hideo Honda

Seishin Shinkeigaku Zasshi 2013 ;115(6):635-41

Yamanashi Prefectural Center for Psychological Development.

Developmental disorders (DD) are now so common that it is even more necessary to investigate the relationship between DD and personality disorders (PD). Despite the lack of studies, DD and PD have much in common. For research on personality and its disorders, direct, real-time observation by researchers themselves on the "black box" of temperament and its interaction with the environment is needed. For research on DD, especially in those with mild DD symptoms, how developmental characteristics and their interaction with the environment affect the personality in adulthood should be investigated.
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November 2013

How can epidemiological studies contribute to understanding autism spectrum disorders?

Authors:
Hideo Honda

Brain Dev 2013 Feb 4;35(2):102-5. Epub 2012 Jul 4.

Yamanashi Prefectural Center for Psychological Development, 1-2-12 Kitashin, Kofu, Japan.

More and more studies on the frequency of autism spectrum disorders (ASD) have been published recently, most of which show the increase in prevalence data. In this review, the author pointed out factors and parameters to be considered in analyzing frequency data, i.e., the enlargement of the concept of autism, prevalence and incidence, accuracy and precision in the initial screening, and the effect of the "vaccine debate". The proportion of high-functioning ASD has been growing higher and higher due to better recognition in the last few years, and the apparent increase might still be the tip of an iceberg. Future epidemiological studies should include themes on diversity of the longitudinal course and re-conceptualization of ASD by dimensional diagnosis.
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http://dx.doi.org/10.1016/j.braindev.2012.06.003DOI Listing
February 2013

Novel monoclonal antibodies recognizing the active conformation of epidermal growth factor receptor.

Biochem Biophys Res Commun 2010 Apr 11;394(3):685-90. Epub 2010 Mar 11.

Biotechnology Research Group, Fundamental Research Department, Fujirebio Inc., Tokyo 192-0031, Japan.

The precise regulation of epidermal growth factor receptor (EGFR) is crucial for its function in cellular growth control. Although many antibodies against EGFR have been developed and used to analyze its regulation and function, it is not yet easy to analyze activated EGFR specifically. Activated EGFR has been mainly detected by its phosphorylation state using anti-phospho-EGFR and anti-phosphotyrosine antibodies. In the present study, we have established novel monoclonal antibodies which recognize the activated EGFR independently of its phosphorylation. Our antibodies detected active state of EGFR in immunoprecipitation and immunofluorescence, by recognizing the epitopes which are exposed through the conformational change induced by ligand-binding. Furthermore, we found that our antibodies preferentially detected the conformation of constitutively active EGFR mutants found in lung cancer cell lines. These results indicate that our antibodies may become novel research and diagnostic tools for detecting and analyzing the conformation of active EGFR in various cells and tissues.
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http://dx.doi.org/10.1016/j.bbrc.2010.03.052DOI Listing
April 2010

Extraction and Refinement Strategy for detection of autism in 18-month-olds: a guarantee of higher sensitivity and specificity in the process of mass screening.

J Child Psychol Psychiatry 2009 Aug 27;50(8):972-81. Epub 2009 Feb 27.

Yokohama Rehabilitation Center, Kohoku-ku, Yokohama, Japan.

Background: For early detection of autism, it is difficult to maintain an efficient level of sensitivity and specificity based on observational data from a single screening. The Extraction and Refinement (E&R) Strategy utilizes a public children's health surveillance program to produce maximum efficacy in early detection of autism. In the extraction stage, all cases at risk of childhood problems, including developmental abnormality, are identified; in the refinement stage, cases without problems are excluded, leaving only cases with conclusive diagnoses.

Methods: The city of Yokohama, Japan, conducts a routine child health surveillance program for children at 18 months in which specialized public health nurses administer YACHT-18 (Young Autism and other developmental disorders CHeckup Tool), a screening instrument to identify children at risk for developmental disorders. Children who screen positive undergo further observation, and those without disorders are subsequently excluded. To study the efficacy of early detection procedures for developmental disorders, including autism, 2,814 children born in 1988, examined at 18 months of age, and not already receiving treatment for diseases or disorders were selected.

Results: In the extraction stage, 402 (14.3%) children were identified for follow-up. In the refinement stage, 19 (.7%) of these were referred to the Yokohama Rehabilitation Center and diagnosed with developmental disorders. The extraction stage produced four false negatives, bringing total diagnoses of developmental disorders to 23 (.8%) - including 5 with autistic disorder and 9 with pervasive developmental disorder - not otherwise specified (PDDNOS). Sensitivity was 60% for autistic disorder and 82.6% for developmental disorders. Specificity for developmental disorders rose to 100% with the E&R Strategy. Picture cards used in YACHT-18 provided a finer screen that excluded some false positive cases.

Conclusions: An extraction and refinement methodology utilizing child health surveillance programs achieve high efficacy for early detection of autism.
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http://dx.doi.org/10.1111/j.1469-7610.2009.02055.xDOI Listing
August 2009

Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists.

J Agric Food Chem 2007 Mar 24;55(6):2276-81. Epub 2007 Feb 24.

Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA.

The insect muscarinic acetylcholine receptor (mAChR) is evaluated as a potential target for insecticide action. The mammalian M2/M4-selective antagonist radioligand [3H]AF-DX 384 (a pirenzepine analogue) binds to Drosophila mAChR at a single high-affinity site identical to that for the nonselective antagonist [3H]quinuclidinyl benzilate (QNB) and with a pharmacological profile distinct from that of all mammalian mAChR subtypes. Three nonselective antagonists (QNB, scopolamine, and atropine) show the highest affinity (Ki=0.5-2.4 nM) at the Drosophila target, and AF-DX 384 and M3-selective 4-DAMP (dimethyl-4-(diphenylacetoxy)piperidinium iodide) rank next in potency (Ki=5-18 nM). Eleven muscarinic antagonists generally exhibit higher affinity than eight agonists. On injection into houseflies, the antagonists 4-DAMP and (S)-(+)-dimethindene produce suppressed movement, the agonist (methyloxadiazolyl)quinuclidine causes knockdown and tremors, and all of them inhibit [3H]QNB binding ex vivo, indicating possible mAChR-mediated intoxication. The insect mAChR warrants continuing study in lead generation to discover novel insecticides.
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http://dx.doi.org/10.1021/jf0631934DOI Listing
March 2007

High-level production of yeast (Schwanniomyces occidentalis) phytase in transgenic rice plants by a combination of signal sequence and codon modification of the phytase gene.

Plant Biotechnol J 2005 Jan;3(1):43-55

Functional Chemicals Laboratory, Mitsui Chemicals, Inc., Togo 1144, Mobara 297-0017 Japan.

This study was designed to produce yeast (Schwanniomyces occidentalis) phytase in rice with a view to future applications in the animal feed industry. To achieve high-level production, chimeric genes with the secretory signal sequence of the rice chitinase-3 gene were constructed using either the original full-length or N-truncated yeast phytase gene, or a modified gene whose codon usage was changed to be more similar to that of rice, and then introduced into rice (Oryza sativa L.). When the original phytase genes were used, the phytase activity in the leaves of transgenic rice was of the same level as in wild-type plants, whose mean value was 0.039 U/g fresh weight (g-FW) (1 U of activity was defined as 1 micromol P released per min at 37 degrees C). In contrast, the enzyme activity was increased markedly when codon-modified phytase genes were introduced: up to 4.6 U/g-FW of leaves for full-length codon-modified phytase, and 10.6 U/g-FW for truncated codon-modified phytase. A decrease in the optimum temperature and thermal stability was observed in the truncated heterologous enzyme, suggesting that the N-terminal region plays an important role in enzymatic properties. In contrast, the optimum temperature and pH of full-length heterologous phytase were indistinguishable from those of the benchmark yeast phytase, although the heterologous enzyme was less glycosylated. Full-length heterologous phytase in leaf extract showed extreme stability. These results indicate that codon modification, combined with the use of a secretory signal sequence, can be used to produce substantial amounts of yeast phytase, and possibly any phytases from various organisms, in an active and stable form.
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http://dx.doi.org/10.1111/j.1467-7652.2004.00098.xDOI Listing
January 2005

Comparison of endothelial function in the carotid artery between normal and short-term hypercholesterolemic rabbits.

Comp Biochem Physiol C Toxicol Pharmacol 2006 Oct 3;144(2):197-203. Epub 2006 Sep 3.

Second Department of Physiology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo, 142-8555, Japan.

The present study was undertaken to investigate and compare the vascular function in carotid arteries isolated from normal short-term hypercholesterolemic rabbits. Rabbits were fed normal or 0.5% cholesterol chow for 5 weeks. The tension of isolated carotid artery rings was measured isometrically. Serum lipid levels were measured and morphometric analysis was performed. And content of nitrate/nitrite in the carotid artery was also determined. In the carotid artery precontracted by phenylephrine, the cholesterol chow diet administered for 5 weeks decreased acetylcholine-induced relaxation at only middle concentrations, though it significantly increased the content of nitrate/nitrite, the sum of stable nitric oxide metabolites, in the carotid artery. Cholesterol chow for 5 weeks had no influence on sodium nitroprusside-induced relaxation in the carotid artery. The N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine was significantly decreased in rabbits receiving the cholesterol chow as compared to rabbits receiving the control diet. The resistant part of acetylcholine-induced relaxation was significantly inhibited when the carotid artery was treated with glibenclamide, a selective inhibitor of ATP-sensitive K(+) channels, 4-aminopyridine, an inhibitor of voltage-dependent K(+) channels, or charybdotoxin, an inhibitor of large and intermediate conductance Ca(2+)-activated K(+) channels, and it was significantly inhibited by tetraethylammonium, a non-selective inhibitor of Ca(2+)-activated K(+) channels and N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a nonselective cytochrome P-450 monooxygenase (CYP) inhibitor, or ketoconazole, a selective CYP3A inhibitor in only normal rabbits. These results suggest that short-term hypercholesterolemia decreased EDHF-induced relaxation mediated through K(+) channels in rabbit carotid artery and that it may be due partially to the inhibition of CYP3A system in the carotid artery at an early stage of hypercholesterolemia.
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http://dx.doi.org/10.1016/j.cbpc.2006.08.011DOI Listing
October 2006

Recombinant, rice-produced yeast phytase shows the ability to hydrolyze phytate derived from seed-based feed, and extreme stability during ensilage treatment.

Biosci Biotechnol Biochem 2006 Jun;70(6):1524-7

Functional Chemicals Laboratory, Mitsui Chemicals, Inc., Togo, Mobara.

When fresh rice leaves producing yeast Schwanniomyces occidentalis phytase were grounded and mixed with the whole extract of seed-based feed for pigs, the release of orthophosphate increased significantly. More specifically, phytate, a major source of phosphorus in the seeds, was hydrolyzed by heterologous phytase. Moreover, when transgenic rice plants were ensiled for up to 12 weeks, no decrease in the phytase activity of the heterologous enzyme was observed. This result strongly suggests that transgenic rice plants producing yeast phytase can be stored as silage without any loss of enzyme activity until usage as a feed additive.
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http://dx.doi.org/10.1271/bbb.60039DOI Listing
June 2006

Insect nicotinic acetylcholine receptors: neonicotinoid binding site specificity is usually but not always conserved with varied substituents and species.

J Agric Food Chem 2006 May;54(9):3365-71

Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA.

The diversity of neonicotinoid insecticides acting as insect nicotinic acetylcholine (ACh) receptor (nAChR) agonists is illustrated by imidacloprid (IMI) with chloropyridinylmethyl (CPM) and N-nitroimine substituents, dinotefuran (DIN) with tetrahydrofurylmethyl (TFM) and N-nitroimine moieties, and acetamiprid (ACE) with CPM and N-cyanoimine groups. These three neonicotinoids are used here as radioligands to test the hypothesis that they all bind to the same site in the same way in both fruit flies (Drosophila melanogaster) and a leafhopper pest (Homalodisca coagulata): that is, neonicotinoid binding site specificity is conserved in the insect nAChRs. Multiple approaches show that [3H]IMI and [3H]ACE interact with an identical site in both species. However, although [3H]DIN binds with high affinity in both insects, its pharmacological profile in Homalodisca is surprisingly unique, with high sensitivity to some TFM-containing compounds and ACh. The TFM moiety of DIN may bind in a different orientation compared to the CPM group of IMI and ACE.
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http://dx.doi.org/10.1021/jf0601517DOI Listing
May 2006

Neo-nicotinoid metabolic activation and inactivation established with coupled nicotinic receptor-CYP3A4 and -aldehyde oxidase systems.

Toxicol Lett 2006 Feb 8;161(2):108-14. Epub 2005 Sep 8.

Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720-3112, USA.

Two important enzymes in metabolism of the principal neo-nicotinoid insecticide imidacloprid are liver microsomal CYP3 A4 and cytosolic aldehyde oxidase (AOX). CYP3A4 oxidation at several molecular sites and AOX reduction at the nitro substituent result in either an increase (activation) or decrease (inactivation) of agonist potency at nicotinic acetylcholine receptors (nAChRs), both insect and vertebrate alpha 4beta 2. This study evaluates activation or inactivation of 11 neo-nicotinoids in a continuous two-step system coupling metabolism and receptor binding. For metabolism, the neo-nicotinoid is incubated with CYP3A4 and NADPH or AOX with the cosubstrate N-methyl-nicotinamide, terminating the reaction with ketoconazole or menadione, respectively, to inhibit further conversion. For receptor assay, either the Drosophila nAChR and [(3)H]imidacloprid or the alpha4 beta2 nicotinic receptor and [(3)H](-)-nicotine are added to determine changes in neo-nicotinoid potency. With the Drosophila nAChR assay, the N-methyl compounds N-methyl-imidacloprid and thiamethoxam are activated 4.5-29-fold by CYP3 A4 whereas nine other neo-nicotinoids are not changed in potency. With the vertebrate alpha4 beta2 nAChR, AOX enhances imidacloprid potency but CYP3 A4 does not. The AOX system coupled with the Drosophila receptor strongly inactivates clothianidin, dinotefuran, imidacloprid, desmethyl-thiamethoxam, and thiamethoxam with some inactivation of nitenpyram and nithiazine, and little or no effect on four other compounds.
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http://dx.doi.org/10.1016/j.toxlet.2005.08.004DOI Listing
February 2006

Alteration in endothelial function and modulation by treatment with pioglitazone in rabbit renal artery from short-term hypercholesterolemia.

Vascul Pharmacol 2005 Jun;43(1):47-55

Department of Internal Medicine, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku, Tokyo 160-0023, Japan.

The present study was undertaken to investigate endothelial function and epoxyeicosatrienoic acids (EETs), which is a cytochrome P-450 monooxygenase (CYP) metabolite and one of the candidates as an endothelium-derived hyperpolarizing factor (EDHF) in the renal artery isolated from short-term hypercholesterolemic rabbits, and also to characterize the effects of pioglitazone on it. Rabbits were fed normal, 0.5% cholesterol chow, or 0.5% cholesterol chow plus 300 ppm pioglitazone for 5 weeks. The tension of isolated renal artery rings was measured isometrically. Serum lipid levels were measured and morphometric analysis was performed. EET contents in the renal artery were also determined. The cholesterol chow diet for 5 weeks increased serum lipid levels, and pioglitazone had no influence on it. In the phenylephrine precontracted renal artery, the cholesterol chow did not affect acetylcholine-induced relaxation. The N(G)-nitro-l-arginine- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine was significantly enhanced in rabbits receiving the cholesterol chow as compared to rabbits receiving the control diet, and pioglitazone normalized it. The resistant part of acetylcholine-induced relaxation was significantly inhibited when the renal artery was treated with charybdotoxin, an inhibitor of large- and intermediate-conductance Ca(2+)-activated K(+) channels, or N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a nonselective CYP inhibitor, and it was significantly inhibited by sulfaphenazole, a selective CYP2C9 inhibitor in rabbits receiving only the cholesterol chow. In KCl-precontracted renal artery, the cholesterol chow inhibited acetylcholine-induced relaxation and pioglitazone normalized it. The cholesterol chow increased the production of EETs and reduced nitrate/nitrite contents in the renal artery, and pioglitazone strongly suppressed them. These results suggest that the EETs may be one of the EDHFs in the rabbit renal artery and beneficial effects of pioglitazone on alterations in endothelial function induced by cholesterol feeding are due, in part, to the protective action on the nitric oxide system and/or the suppression of increased production of EETs.
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http://dx.doi.org/10.1016/j.vph.2005.03.005DOI Listing
June 2005

No effect of MMR withdrawal on the incidence of autism: a total population study.

J Child Psychol Psychiatry 2005 Jun;46(6):572-9

Yokohama Rehabilitation Center, Yokohama, Japan.

Background: A causal relationship between the measles, mumps, and rubella (MMR) vaccine and occurrence of autism spectrum disorders (ASD) has been claimed, based on an increase in ASD in the USA and the UK after introduction of the MMR vaccine. However, the possibility that this increase is coincidental has not been eliminated. The unique circumstances of a Japanese MMR vaccination program provide an opportunity for comparison of ASD incidence before and after termination of the program.

Methods: This study examined cumulative incidence of ASD up to age seven for children born from 1988 to 1996 in Kohoku Ward (population approximately 300,000), Yokohama, Japan. ASD cases included all cases of pervasive developmental disorders according to ICD-10 guidelines.

Results: The MMR vaccination rate in the city of Yokohama declined significantly in the birth cohorts of years 1988 through 1992, and not a single vaccination was administered in 1993 or thereafter. In contrast, cumulative incidence of ASD up to age seven increased significantly in the birth cohorts of years 1988 through 1996 and most notably rose dramatically beginning with the birth cohort of 1993.

Conclusions: The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD.
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http://dx.doi.org/10.1111/j.1469-7610.2005.01425.xDOI Listing
June 2005

Rapid and simple determination of epoxyeicosatrienoic acids in rabbit renal artery by reversed-phase HPLC with fluorescence detection.

Vascul Pharmacol 2005 Mar;42(4):163-9

Department of Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

A liquid chromatographic method with fluorescence detection coupled with a solid-phase extraction was applied to the rapid determination of epoxyeicosatrienoic acids (EETs) in the rabbit renal artery. The EETs were extracted with an acetonitrile from renal artery homogenate and concentrated by a solid-phase extraction method. The concentrated EETs were reacted directly with a 6, 7-dimethoxy-1-methyl-2 (1H)-quinoxalinone-3-propionyl-carboxylic acid (DMEQ) hydrazide and separated by a reversed-phase HPLC with eluting a combination of a step-wise and a gradient of a mixture of methanol and water. The content of EETs in the renal arteries was significantly greater in the 0.5% cholesterol fed rabbits than in control rabbits. It is suggested that hyperchlesterolemia increases the production of EETs in the rabbit renal artery.
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http://dx.doi.org/10.1016/j.vph.2004.12.003DOI Listing
March 2005

Cumulative incidence of childhood autism: a total population study of better accuracy and precision.

Dev Med Child Neurol 2005 Jan;47(1):10-8

Developmental Psychiatry Unit, Yokohama Rehabilitation Center, 1770 Toriyama-cho, Kohoku-ku, Yokohama, 222-0035, Japan.

Most studies on the frequency of autism have had methodological problems. Most notable of these have been differences in diagnostic criteria between studies, degree of cases overlooked by the initial screening, and type of measurement. This study aimed to replicate the first report on childhood autism to address cumulative incidence as well as prevalence, as defined in the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) Diagnostic Criteria for Research. Here, the same methodological accuracy (exactness of a measurement to the true value) as the first study was used, but population size was four times larger to achieve greater precision (reduction of random error). A community-oriented system of early detection and early intervention for developmental disorders was established in the northern part of Yokohama, Japan. The city's routine health checkup for 18-month-old children served as the initial mass screening, and all facilities that provided child care services aimed to detect all cases of childhood autism and refer them to the Yokohama Rehabilitation Center. Cumulative incidence up to age 5 years was calculated for childhood autism among a birth cohort from four successive years (1988 to 1991). Cumulative incidence of childhood autism was 27.2 per 10000. Cumulative incidences by sex were 38.4 per 10000 in males, and 15.5 per 10000 in females. The male:female ratio was 2.5:1. The proportions of children with high-functioning autism who had Binet IQs of 70 and over and those with Binet IQs of 85 and over were 25.3% and 13.7% respectively. Data on cumulative incidence of childhood autism derived from this study are the first to be drawn from an accurate, as well as precise, screening methodology.
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http://dx.doi.org/10.1017/s0012162205000034DOI Listing
January 2005

Hypothyroidism changes adrenoceptor- and muscarinic receptor-mediated blood pressure responses.

Eur J Pharmacol 2005 Jan 23;507(1-3):311-6. Epub 2004 Nov 23.

Second Department of Physiology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, Japan.

Hypothyroidism was induced by the administration of 0.03% methimazole to drinking water for 1, 2 or 6 weeks to study whether there is a change in adrenoceptor- and muscarinic receptor-mediated blood pressure responses in hypothyroid rats. After 1, 2 and 6 weeks of treatment, the pressor response to norepinephrine was progressively suppressed, and after 6 weeks a significant suppression was observed as compared to control. The depressor response induced by isoprenaline, acetylcholine or sodium nitroprusside was not significantly different between control and hypothyroid rats at any time. The pressor response induced by N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide (NO) synthase, was significantly reduced in hypothyroid rats after 1, 2 or 6 weeks of treatment, and the magnitude of the reduction was almost the same for three groups. These results indicated that hypothyroidism causes a time-dependent decrease in pressor responses mediated by alpha-adrenoceptors, but a time-independent decrease in those induced by L-NOARG, and suggest that a progressive decrease in alpha-adrenoceptor-mediated pressor responses occurs in hypothyroidism; however, the decrease in basal NO production and/or release in the peripheral vasculature already occurs in hypothyroid rats at an early stage of the disease.
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http://dx.doi.org/10.1016/j.ejphar.2004.11.002DOI Listing
January 2005

Characterization of endothelium-dependent relaxation and modulation by treatment with pioglitazone in the hypercholesterolemic rabbit renal artery.

Eur J Pharmacol 2004 Aug;497(3):317-25

Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

The present study was undertaken to investigate vascular function in hypercholesterolemic rabbits and also to characterize the effects of pioglitazone on it. Rabbits were fed normal, 0.5% cholesterol chow, or 0.5% cholesterol chow plus 300 ppm pioglitazone for 5 or 10 weeks. The tension of isolated renal artery rings was measured isometrically, and morphometric analysis was performed. The cholesterol chow diet administered for 5 weeks did not affect acetylcholine-induced relaxation in the renal artery but that for 10 weeks decreased it. The N(G)-nitro-L-arginine (L-NOARG)- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine in the renal artery was enhanced in rabbits receiving the cholesterol chow for 5 or 10 weeks, as compared to rabbits receiving the control diet, and the percentage of plaque area formation was increased in the renal artery by the cholesterol chow for 10 weeks. Pioglitazone normalized them without lowering serum lipid levels. The resistant parts of acetylcholine-induced relaxation was significantly inhibited when the renal artery was treated with charybdotoxin, an inhibitor of large and intermediate conductance Ca(2+)-activated K(+) channels, or N,N-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a cytochrome P-450 monooxygenase inhibitor. Results indicate that hypercholesterolemia enhances endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in the rabbit renal artery and pioglitazon normalizes it without lowering serum lipid levels, and suggest that the maintenance of endothelial function by pioglitazon is related to the mechanisms for its anti-atheromatous activity.
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http://dx.doi.org/10.1016/j.ejphar.2004.06.062DOI Listing
August 2004

Production of lupin acid phosphatase in transgenic rice for use as a phytate-hydrolyzing enzyme in animal feed.

Biosci Biotechnol Biochem 2004 Jul;68(7):1611-6

Functional Chemicals Laboratory, Mitsui Chemicals, Inc, Togo 1144, Mobara 297-0017, Japan.

The acid phosphatase gene from lupin was expressed in transgenic rice plants under the control of the maize ubiquitin promoter or rice chlorophyll a/b binding protein (Cab) promoter. Transgenic rice leaves exhibited up to an 18-fold increase in phytate-hydrolyzing activity. Based on the phytate-hydrolyzing activity at pH 5.5, more than 85% this activity was retained after heat-treatment at 80 degrees C for 15 min, and the heterologous enzyme in leaf sections and leaf extracts was relatively stable during storage. A distinct increase in released phosphate was observed when the heterologous enzyme was mixed with the feed extract. These results suggest that the heterologous enzyme in rice plants may maintain its desired characteristics as a phytate-hydrolyzing enzyme when added to animal feed.
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http://dx.doi.org/10.1271/bbb.68.1611DOI Listing
July 2004

Acute hyperthyroidism alters adrenoceptor- and muscarinic receptor-mediated responses in isolated rat renal and femoral arteries.

Eur J Pharmacol 2004 Jun;493(1-3):191-9

Second Department of Physiology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawa, Tokyo, 142-8555, Japan.

The effects of acute hyperthyroidism on the vasorelaxing responses to isoprenaline and acetylcholine were investigated in isolated rat renal and femoral arteries. In the renal artery, isoprenaline- and acetylcholine-induced relaxations were significantly greater in hyperthyroid rats than in control rats. In the femoral artery, only the acetylcholine-induced relaxation was significantly greater in hyperthyroid rats than in control rats. In the renal artery, NG-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide (NO) synthase, reduced isoprenaline- and acetylcholine-induced relaxations in both hyperthyroid and control rats and the isoprenaline-induced relaxation was still greater in hyperthyroid rats than in control rats, but no difference in the acetylcholine-induced relaxation was seen between the two groups of rats since L-NOARG almost abolished the acetylcholine-induced relaxation. In the femoral artery, L-NOAGR reduced the isoprenaline-induced relaxation in control rats but not in hyperthyroid rats, while it almost abolished the acetylcholine-induced relaxation in both groups of rats. 17-Octadecynoic acid (17-ODYA), a cytochrome P-450 monooxygenase inhibitor, reduced the isoprenaline-induced relaxation in renal and femoral arteries from hyperthyroid and control rats, but it did not change the acetylcholine-induced relaxation in both arteries. These results indicate that acute hyperthyroidism significantly enhances beta-adrenoceptor-mediated relaxation of the renal artery and muscarinic receptor-mediated relaxation of both renal and femoral arteries, suggesting that these effects may be due to an alteration in the NO and cytochrome P-450 systems of the artery.
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http://dx.doi.org/10.1016/j.ejphar.2004.04.033DOI Listing
June 2004

Differences in the mechanisms for relaxation of aorta induced by 17beta-estradiol or progesterone between normotensive and hypertensive rats.

Eur J Pharmacol 2003 Jul;472(1-2):119-26

Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, Tokyo 193-0392, Japan.

The tension in isolated ring preparations of the thoracic aorta from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was measured isometrically to study if there are any differences in the mechanisms of 17beta-estradiol- or progesterone-induced relaxation between WKY and SHR aortic rings. 17beta-Estradiol and progesterone caused dose-dependent vascular relaxation of the thoracic aorta precontracted with norepinephrine in both WKY and SHR, and the relaxation induced by 17beta-estradiol was greater in SHR than WKY. However, no difference was observed in progesterone-induced relaxation between SHR and WKY. With the exception of tetraethylammonium, an inhibitor of Ca(2+)-activated K(+) channels, glibenclamide, a selective inhibitor of ATP-sensitive K(+) channels, or 4-aminopyridine, a selective inhibitor of voltage-dependent K(+) channels, significantly reduced 17beta-estradiol-induced relaxation only in SHR, but not in WKY. Both 17beta-estradiol and progesterone inhibited Ca(2+)-induced vasocontraction of the thoracic aorta in K(+) depolarization medium in WKY and SHR. These results suggest that the mechanisms of 17beta-estradiol-induced relaxation in SHR aorta are at least partially mediated via ATP-sensitive and voltage-sensitive K(+) channels in addition to the inhibition of Ca(2+) channels, although those of progesterone-induced relaxation in both WKY and SHR are mainly concerned with the inhibition of Ca(2+) channels rather than the operation of K(+) channels. Moreover, a difference in 17beta-estradiol-induced relaxation between WKY and SHR aorta suggests a possibility that vascular response in SHR is modified by hypertension.
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http://dx.doi.org/10.1016/s0014-2999(03)01858-2DOI Listing
July 2003

A fluctuation in adrenocepter- and muscarinic receptor-mediated blood pressure responses in acute hyperthyroid rats.

Vascul Pharmacol 2003 Jan;40(1):1-6

Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Japan.

Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (T(4), 0.5 mg/kg/day) for 3 days, 1 week, or 2 weeks to study whether there is a fluctuation in adrenoceptor- and muscarinic receptor-mediated blood pressure responses at a hyperthyroid stage. T(4) treatment for 3 days or 1 week significantly suppressed the pressor response induced by norepinephrine (NE). The depressor responses induced by isoprenaline or acetylcholine (ACh) were increased by T(4) treatment for only 3 days. The pressor response induced by N(G)-nitro-L-arginine (L-NA) was increased by T(4) treatment for only 3 days. Results suggest that adrenoceptor- and muscarinic receptor-mediated blood pressure responses fluctuate in hyperthyroidism caused by T(4) in rats, that the basal nitric oxide (NO) production and/or release are increased in hyperthyroid rats at an early stage of the disease.
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http://dx.doi.org/10.1016/s1537-1891(02)00310-5DOI Listing
January 2003

Effect of hypothyroidism on beta-adrenoceptor-mediated relaxation in the rat thoracic aortae. A time-dependent study.

Vascul Pharmacol 2002 Mar;38(3):149-55

Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 193-0392, Japan.

We investigated the time dependency of hypothyroid-induced changes in beta-adrenoceptor-mediated relaxation of vascular smooth muscle. Methimazole (0.03%) was administered to male Wistar-Imamichi rats for 3 days, 1, 2 or 6 weeks. This treatment led to significant increases in thyroid weight while inhibiting growth rate. Tension in isolated rings of thoracic aortae from control and hypothyroid rats was measured isometrically. Responses of aortic rings to cumulative doses of acetylcholine (ACh) and sodium nitroprusside (SNP) were not significantly different between control and hypothyroid groups. After 3 days and 1 week of treatment, isoprenaline (ISO)-induced relaxation was unchanged, but after 2 and 6 weeks, a marked increase was observed as compared to controls. Removal of the endothelium and pretreatment with NG-nitro-L-arginine (L-NOARG) inhibited the ISO-induced relaxation in both groups; but whereas this degree of inhibition was the same for both groups after 3 days and 1 week, it was significantly less pronounced in hypothyroid rats after 2 and 6 weeks as compared to their controls. These results suggest that hypothyroidism has a time-dependent influence on beta-adrenoceptor-mediated relaxation in the rat thoracic aortae and that the enhancement after 2 and 6 weeks of methimazole treatment may be due to a hypothyroid-induced alteration in arterial smooth muscle function.
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http://dx.doi.org/10.1016/s1537-1891(02)00166-0DOI Listing
March 2002
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