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Biomedical subjects

Ohiko Hashimoto

Publications and source records attributed to Ohiko Hashimoto.

11 recordsLinked to original sources
PubMed2005

Polyhistidine tract expansions in HOXA1 result in intranuclear aggregation and increased cell death.

HOXA1 gene is part of a cluster of homeotic selector genes that regulates the anteroposterior patterning of mammals during embryonic development. HOXA1 encodes two alternatively spliced mRNAs with two isoforms, A and B, the former contains the homeodomain and expressed in early embryonic development. HOXA1 contains a string of 10 histidine repeats. However, individuals heterozygous for 7, 9, 11, and 12 histidine repeat variants were present among the Japanese population, notably in some autism cases. To determine the biological implications of the different polyhistidine repeat lengths, we expressed these variants in COS-7 and a human neuroblastoma cell line (SK-N-SH). Expression of expanded variants of HOXA1 isoform A, containing 11 and 12 polyhistidine, resulted in early and great degree of protein aggregation in the nucleus. This aggregation resulted in accelerated cell death in cells expressing 11 and 12 expanded variants compared to those transfected with 7 and 10 polyhistidine variants. Furthermore, we showed that these aggregates were ubiquitinated and were inhibited by a histidine-modifying compound, DEPC. These data suggest that HOXA1 protein with polyhistidine tract expansions misfold, aggregate, and have a toxic effect on cell.

Animals↗
PubMed2005

Delayed automatic detection of change in speech sounds in adults with autism: a magnetoencephalographic study.

OBJECTIVE: Autism is a form of pervasive developmental disorder in which dysfunction in interpersonal relationships and communication is fundamental. This study evaluated neurophysiological abnormalities at the basic level of language processing, i.e. automatic change detection of speech and non-speech sounds, using magnetoencephalographic recording of mismatch response elicited by change in vowels and tones. METHODS: The auditory magnetic mismatch field (MMF) was evaluated in 9 adults with autism and 19 control subjects using whole-head magnetoencephalography. The MMF in response to the duration change of a pure tone or vowel /a/ and that in response to across-phoneme change between vowels /a/ and /o/, were recorded. RESULTS: The groups were not significantly different in MMF power under any conditions. However, the autism group showed a left-biased latency prolongation of the MMF particularly under the across-phoneme change condition, and this latency delay was significantly associated with greater symptom severity. CONCLUSIONS: These results suggest that adults with autism are associated with delayed processing for automatic change detection of speech sounds. These electrophysiological abnormalities at the earliest level of information processing may contribute to the basis for language deficits observed in autism. SIGNIFICANCE: These results provide the first evidence for delayed latency of phonetic MMF in adults with autism.

Acoustic Stimulation↗
PubMed2005

No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population.

Autism is a child-onset pervasive developmental disorder, with a significant role of genetic factors in its development. Genome-wide linkage studies have suggested a 7q region as a susceptibility locus for autism. We investigated several single nucleotide polymorphisms (SNPs) of Forkhead Box P2 (FOXP2) and Protein-Tyrosine Phosphatase, Receptor-type, Zeta-1 (PTPRZ1) at the 7q region in Japanese patients with autism and healthy controls. No significant difference was observed, after correction for the multiple testing, in allele, genotype or haplotype frequencies of the SNPs of FOXP2 or PTPRZ1 between patients and controls. No evidence was thus obtained for a major role of FOXP2 or PTPRZ1 in the development of autism.

Adolescent↗
PubMed2004

Association between the neurofibromatosis-1 (NF1) locus and autism in the Japanese population.

Autistic patients have a 100 to 190-fold increased risk of neurofibromatosis compared to the general population. This suggests that the two diseases may share a common etiological background. Recently, a new allele (or the six-repeat allele) of the (AAAT)(n) repeat polymorphism in an Alu sequence in the neurofibromatosis-1 (NF1) gene was observed exclusively in severe autistic patients, not in controls, in Caucasians of French ancestry. This suggests a role of the NF1 gene in the development of autism. We investigated three microsatellite polymorphisms within the intron-27b and intron-38 of the NF1 region, including the (AAAT)(n) and two (CA)n repeat polymorphisms, in Japanese subjects with autism (n = 74) and controls (n = 122). The six-repeat allele of the (AAAT)(n) polymorphism was not found either in patients or controls, possibly indicating an ethnic difference in the polymorphism. However, significant differences were observed in the allele distributions of the (AAAT)(n) and a (CA)(n), which were located at intron-27b, between patients and controls, although an association was not significant between autism and another polymorphism at intron-38. This may suggest an involvement of the NF1 locus in susceptibility to autism, although further investigations are recommended.

Adolescent↗
PubMed2004

Gastrin-releasing peptide receptor (GRPR) locus in Japanese subjects with autism.

Gastrin-releasing peptide receptor (GRPR) gene is considered a candidate locus for infantile autism for several reasons. The present study investigated two polymorphic sites (C/450/T and C/661/T) in the second exon of the GRPR gene in Japanese patients with autism (DSM-IV) and healthy subjects. The two polymorphic sites were at high linkage disequilirium, consistent with a previous study in a North American population. The C450-C661 allele, which was observed in one-third of the chromosomes from the North American subjects, was less frequent (6-7%) in the Japanese subjects, suggesting a large ethnic difference in the frequency of the polymorphism. The allele frequencies and genotype distributions were not significantly different between the patients and controls. However, further studies are required to exclude the GRPR locus as a candidate locus for autism, considering the low frequency of the polymorphism in the Japanese subjects.

Adolescent↗
PubMed2004

[Support for the family from infancy].

A rising tendency has been reported for child abuse in our country in recent years, and the need to provide support for child-care capabilities in the home has been raised. In this context, attention has turned to the mother-child relationship and the mother's mental health from early on, in pregnancy and the antenatal period. In particular, it has become clear that the incidence of post-partum maternity blues and puerperal depression is higher than hitherto believed, drawing focus upon the effects of the mother's depression on the mother-child relationship. This report outlines the research and clinical intervention we have been undertaking for the mother's depression in pregnancy and the puerperium in relation to maternal attachment. 1) Results from studies in the puerperium on a group of mothers with children admitted to the NICU and a control group of mothers, and a 1-year follow-up study on the control group of mothers have revealed a relationship between a mother's depression and maternal attachment in the puerperium with depression and maternal attachment after 1 year, indicating the importance of focusing on the mother's depression and maternal attachment from the puerperium in thinking about maternal mental health and the mother-child relationship. 2) We have been attempting clinical intervention for the mother's psychological problems through the obstetric clinic, obstetric ward, and NICU, since 1998. The number of subjects, interviews, interview content, and other such data are reported. 3) A borderline personality disorder case we have been involved with clinically from age 19 is presented, for discussion of problems arising in the mother-child relationship from pregnancy through the child-rearing years.

Adult↗
PubMed2003

Antenatal depression and maternal-fetal attachment.

BACKGROUND: In recent years, attention has been turned to maternal mental health in relation to the mother-child relationship accompanying a widening in focus, i.e. taking into account not only the puerperium, but also the stage of pregnancy. This applies to studies that have revealed a connection between depression and maternal attachment in the postpartum period and late pregnancy. This study, however, was designed to evaluate the maternal-fetal relationship in the first and second trimesters, being the first one to address this issue in these early stages. SAMPLING AND METHODS: Zung's Self-Rating Depression Scale (ZSDS), the original Antenatal Maternal Attachment Scale (AMAS), and a questionnaire addressing peripheral factors were given to 216 pregnant women (3-6 months of gestation) who visited the Nagoya University Hospital between September 1998 and June 2001. RESULTS: Contrary to reports on the latter stages of pregnancy, no direct association was observed between depression in mothers and maternal-fetal attachment before fetal movement was perceived. CONCLUSION: However, education, form of employment, planning of pregnancy, and premenstrual mood changes were found to be associated with the ZSDS score (mean: 41.9), while form of employment, feelings regarding pregnancy, and sources of support were extracted as factors associated with the AMAS, which are of interest in terms of the subsequent association between depression and maternal-fetal attachment in the peri- and postnatal periods.

Adult↗