Biomedical subjects

Yu-ichi Goto

Publications and source records attributed to Yu-ichi Goto.

At least 19 recordsLinked to original sources

PubMed2003

Blockade of bombesin-like peptide receptors impairs inhibitory avoidance learning in mice.

Several studies reported that peripheral administration of bombesin (BN) and gastrin-releasing peptide (GRP) improved some forms of memory performance. In the present study, we examined the role of endogenous BN-like peptide(s) for the acquisition of inhibitory avoidance learning in mice using BN-like peptide receptor antagonists. An administration of [Leu(13)-(psi-CH(2)NH)-Leu(14)]BN (antagonizes GRP-R>neuromedin B receptor (NMB-R)) impaired the performance of inhibitory avoidance learning in all doses (16, 32, 64 nmol/kg). While the effect was somewhat lesser than [Leu(13)-(psi-CH(2)NH)-Leu(14)]BN, BIM23127 (antagonizes NMB-R>GRP-R) also impaired performance in a moderate dose (32 nmol/kg). These results showed that endogenous BN-like peptides have some role(s) for the modulation of learning and memory, and suggest that NMB/NMB-R pathway may also be involved in the memory acquisition and modulation as well as GRP/GRP-R pathway.

Animals↗

PubMed2003

A double mutation (G11778A and G12192A) in mitochondrial DNA associated with Leber's hereditary optic neuropathy and cardiomyopathy.

We report a male patient with Leber's hereditary optic neuropathy (LHON) and hypertrophic cardiomyopathy. Besides a G11778A mutation in the ND4 gene of the mitochondrial DNA (mtDNA), one of the most common mutations in LHON patients, sequencing of total mtDNA revealed a G12192A mutation in the tRNA (His) gene that was recently noted to be a risk factor for cardiomyopathy. Because no case of LHON presenting with cardiomyopathy has been reported, the present finding suggests that the G12192A mutation caused cardiomyopathy as an additional symptom. In the present case, the double pathogenic mtDNA mutations may be associated either synergistically or concomitantly with two different clinical manifestations.

Cardiomyopathies↗

PubMed2003

Expression of ARPP-16/19 in rat denervated skeletal muscle.

It is known that denervation of rat skeletal muscle causes atrophy and this is often adopted as a model for human muscle atrophy. To understand the molecular changes that occur, it is important to identify the profiles of differential gene expression. In the present study, we investigated differentially expressed genes in denervated muscle using DNA microarrays with printed genes preferentially expressed in skeletal muscle. We found that several genes are differentially expressed. Of these genes, ARPP-16/19 (cAMP-regulated phosphoprotein 16/19) is selectively enhanced after denervation. The expression of ARPP-16/19 in denervated muscles starts to increase from two days after denervation surgery. On the other hand, the expression of ARPP-16/19 does not change in hind-limb suspended muscles, such as EDL and soleus muscles. These results suggest that the increase in ARPP-16/19 mRNA expression is regulated by unknown factor(s) secreted from nerves, and not by electrical muscle activity.

Animals↗

PubMed2003

Direct evidence for two distinct forms of the flavoprotein subunit of human mitochondrial complex II (succinate-ubiquinone reductase).

Succinate-ubiquinone reductase (complex II) is an important enzyme complex in both the tricarboxylic acid cycle and aerobic respiration. A recent study showed that defects in human complex II are associated with cancers as well as mitochondrial diseases. Mutations in the four subunits of human complex II are associated with a wide spectrum of clinical presentations. Such tissue-specific clinical symptoms suggest the presence of multiple isoforms of the subunits, but subunit isoforms have not been previously reported. In the present study, we identified two distinct cDNAs for the human flavoprotein subunit (Fp) from a single individual, and demonstrated expression of these two isoforms in skeletal muscle, liver, brain, heart and kidney. Interestingly, one of the Fp isoforms was encoded as an intronless gene.

Adolescent↗

PubMed2002

Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome.

The gene encoding the beta-site amyloid precursor protein cleaving enzyme 2 (BACE2) has been determined to be located on the long arm of chromosome 21 at 21q22.3. BACE2 cleaves the amyloid precursor protein at the beta-secretase site and is thought to contribute to amyloid beta protein production. In the present study, changes in the expression of BACE2 were investigated immunohistochemically in the frontal cortex of patients with Down syndrome (DS). The immunoreactivity for BACE2 was detected in neurofibrillary tangle-bearing neurons from the elderly DS brains with Alzheimer-type neuropathology, but were not detected in those of DS brains without Alzheimer-type neuropathology or of control brains of any age. This suggests the possibility that the elevated expression of BACE2 is involved in the Alzheimer-type neuropathology of DS.

Adolescent↗

PubMed2002

A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions.

Autosomal dominant progressive external ophthalmoplegia is a mitochondrial disorder characterized by multiple large deletions of mitochondrial DNA. A recent study showed pathogenic heterozygous missense mutations in the heart/skeletal muscle isoform of the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients. In one Japanese autosomal dominant progressive external ophthalmoplegia family, we found a novel A-to-G heterozygous mutation at nucleotide 311 of the adenine nucleotide translocator 1 gene, which segregated with affected individuals and could not be detected in the genomic DNA sequence of 120 normal controls. This mutation converted a highly conserved aspartic acid into a glycine at codon 104. Polymerase chain reaction analysis of single muscle fibers showed the presence of one type of deletion in each fiber, suggesting clonal expansion of mitochondrial DNA with deletions. These findings support the pathogenesis of the adenine nucleotide translocator 1 gene mutation in human disease.

Adult↗

PubMed2002

Germline mosaicism of a novel mutation in lysosome-associated membrane protein-2 deficiency (Danon disease).

We identified a family with lysosome-associated membrane protein-2 deficiency (Danon disease) associated with a novel 883 ins-T mutation in the lysosome-associated membrane protein-2 gene located at Xq24. Although the affected son and daughter carried the same mutation, it was not detected in their mother's peripheral blood or buccal cells; this indicated germline mosaicism. This is the first molecular evidence for germline mosaicism in Danon disease and has important implications for genetic counseling.

Adult↗

PubMed2002

A point mutation of mitochondrial ATPase 6 gene in Leigh syndrome.

A T-to-G transition at nucleotide 9176 (T9176G) in the mitochondrial adenosine triphosphate 6 gene (MTATP6) was detected in two siblings with Leigh syndrome. Heteroplasmy was observed in the mother's leukocytes. The T9176G mutation changes a highly conserved leucine residue to an arginine in subunit 6 of ATPase and is maternally inherited like mutations in the other mitochondrial genes. Another mutation in the same codon (T9176C) has been previously reported in Leigh syndrome. This gives strong support to the relevance of MTATP6 dysfunction in Leigh syndrome and the importance of leucine at that position.

Child↗

PubMed2002