Biomedical subjects

Jun Goto

Publications and source records attributed to Jun Goto.

32 records · Page 2Linked to original sources

PubMed2003

Physical map and haplotype analysis of 16q-linked autosomal dominant cerebellar ataxia (ADCA) type III in Japan.

Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. We previously mapped a gene locus for ADCA with pure cerebellar syndrome (ADCA type III) to a 3-cM region in chromosome 16q, and found a common haplotype among affected individuals. This region was exactly within the locus for another ADCA, spinocerebellar ataxia type 4 (SCA4). To identify the gene causing 16q-linked ADCA type III, we constructed a contig with 38 bacterial artificial chromosome clones between D16S3043 and D16S3095. The size of this contig was estimated to be 4.8 Mb. We found more than 500 nucleotide tandem repeats, including 9 CAG/CTG repeats in this candidate region, although none of the 94 tandem repeats analyzed were expanded in affected individuals. However, we found 11 new polymorphic markers, giving 22 markers spanning the candidate region. By typing these markers on eight Japanese families with ADCA type III, including two new families, we found that a common "founder" haplotype is seen in a more restricted 3.8-Mb region, spanning markers GGAA05 and D16S3095. We present here a newly refined critical interval of 16q-ADCA type III/SCA4. Data of 11 new DNA markers on 16q22.1 would also be useful for other research of genes mapped to this region.

Cerebellar Ataxia↗

PubMed2003

Human skeletal muscle calcium channel alpha1S is expressed in the basal ganglia: distinctive expression pattern among L-type Ca2+ channels.

Voltage-gated calcium channels (VGCCs) are essential molecules for neuronal function. VGCCs consist of five subunits, alpha1, alpha2, beta, gamma, and delta. Among the ten subtypes of the alpha1 subunit (alpha1A-I and S), expression of alpha1S was previously believed to be restricted to the skeletal muscle. We report here, however, that alpha1S is also expressed in human and rat central nervous system. First, we performed PCR screening for VGCC alpha1 subunits in human nervous system using degenerate primers, and identified alpha1S as well as all the eight alpha1 subunits with previously described expression. Intriguingly, alpha1S was selectively localized to the basal ganglia, particularly the caudate nucleus. In situ hybridization showed that alpha1S was expressed in medium-sized caudate neurons. Quantitative analysis using real time RT-PCR revealed a distinct pattern of alpha1S expression among L-type calcium channels. Furthermore, RT-PCR using laser-mediated manipulation of single cells suggested that human alpha1S was coexpressed with ryanodine receptors (RYRs) in GABAergic neurons. Our results suggest the potential relevance of alpha1S to dopaminergic signal transduction and calcium-induced calcium release in caudate neurons.

Animals↗

PubMed2003

The aging of human Meissner's corpuscles as evidenced by parallel sectioning.

We examined cross-sectional areas of Meissner's corpuscles to evaluate the changes in their morphology and density that occur during the aging process. Our study of 10 tissue specimens from the right index finger pulp of 10 males, showed that both the size and the number of Meissner's corpuscles decrease with age. We claim greater accuracy in our data thanks to the use of a new sectioning method, namely parallel sectioning of the skin.

Aged↗

PubMed2003

Differences in the axonal compositions of the human mandibular nerve between dentulous and edentulous jaws.

We examined the human mandibular nerve to find differences in the composition of nerve fiber axons between dentulous and edentulous jaws Using Goto's modification of Masson-Goldner's method. We discovered that the edentulous jaw did not contain any large size axons, compared with the dentulous jaw. This can be considered as evidence that the larger fibers innervating the periodontal ligament decreased degenerated after tooth loss.

Aged↗

PubMed2003

Age-related changes in nerve fibers of the human fasciculus gracilis.

Nerve fibers of the human fasciculus gracilis were studied on 10 male cadavers aged 41-97 years using a discriminative staining method and a microscopic image-analyzing system. Our data show that the transverse areas of axons in the human fasciculus gracilis significantly decrease with age, while no significant correlation was observed between the number of fibers and age.

Adult↗

PubMed2002

Ultrastructure of nuclear aggregates formed by expressing an expanded polyglutamine.

Intranuclear inclusions have been observed in the brains of patients affected with Huntington's disease (HD). Neuro 2A cells that transiently expressed HD exon 1 bearing 74 glutamine repeats linked to the green fluorescent protein (GFP) and the nuclear localization sequence (NLS) contained aggregates in nuclei. The aggregates were purified by fractionation with centrifugation followed by fluorescence-activated cell sorting (FACS). Heat treatment of the aggregate in an SDS sample buffer caused the dense aggregate cores to disappear and generated a basket-like structure composed of fibrils. Biochemical analysis of the aggregates revealed that the HD exon 1-GFP fusion protein was the major component. The heterogeneous nuclear ribonucleoproteins F and H, histones and ubiquitin were found to be associated with the aggregates. Our observations suggest that the N-terminal fragment of huntingtin may organize the skeletal structure of the aggregates and may disturb normal cellular functions by trapping other proteins within the aggregates.

Amino Acids↗

PubMed2002

Development of the human lateral cuneate nucleus: a morphometric evaluation.

The morphometric development of the human lateral cuneate nucleus was examined in nine fetuses and neonates at 18-40 weeks of gestation, a 2-month-old infant and a 63-year-old adult. The authors observed serial sections of the brain containing lateral cuneate nucleus and measured the volume of nuclear column and the number, cell body area and perimeter of neurons using a microscope with a drawing tube and an image-analyzing computer system. A morphometric evaluation revealed that a turning point in the development of the human lateral cuneate nucleus occurring at 30 WG, as this marks the beginning of a gradual increase in the average area and average perimeter; And it is the point at which the neuropil index suddenly increases sharply, to fall back down to lower levels afterwards. The establishment of a neuronal connection between the lateral cuneate nucleus and the cerebellum, which is necessary for proper performance of movements in the upper part of the body.

Afferent Pathways↗

PubMed2002

Enhanced SUMOylation in polyglutamine diseases.

Small ubiquitin-like modifiers (SUMOs) are proteins homologous to ubiquitin that possibly regulate intranuclear protein localization, nuclear transport, and ubiquitination. We examined patients of DRPLA, SCA1, MJD, and Huntington's disease and found that neurons in affected regions of the brain react strongly to SUMO-1, a family member of SUMOs. Western blot with a transgenic mouse expressing mutant ataxin-1 showed the increase of SUMOylated proteins in the cerebellar cortex, which we named ESCA1 and ESCA2. These results indicated activation of SUMO-1 system in polyglutamine diseases and predicted its involvement in the pathology.

Animals↗

PubMed2002

Unstable transmission of the RS447 human megasatellite tandem repetitive sequence that contains the USP17 deubiquitinating enzyme gene.

The RS447 megasatellite DNA, which maps to human chromosome 4p16.1, is a highly polymorphic conserved tandem repetitive sequence containing a functional deubiquitinating enzyme gene, USP17. To characterize the hypervariability seen in RS447 fully, we have conducted a pedigree analysis of RS447 transmission by high-resolution pulsed-field gel electrophoresis. We have identified 44 distinct alleles in 74 unrelated chromosomes containing 20-103 copies of the 4.7-kb RS447 unit. Five of 60 parent-to-offspring transmissions clearly show changes in copy number, indicating a high frequency (approximately 8.3%) of meiotic instability. Evidence for somatic mosaicism has also been observed. Searches of the database have revealed the presence of minor RS447 sequences mapping to chromosome 8p23, raising the possibility of a rearrangement or transposition of RS447 within the human genome. These results suggest that the unstable nature of RS447 megasatellite DNA gives rise to its hypervariability and may contribute to the structural dynamics of this repetitive DNA in the genome.

Cell Line↗

PubMed2002

Identification of CAG repeat-containing genes expressed in human brain as candidate genes for autosomal dominant spinocerebellar ataxias and other neurodegenerative diseases.

To obtain novel candidate genes for autosomal dominant spinocerebellar ataxia and other neurodegenerative disorders in which gene mutations remain unidentified, we screened a human fetal brain cDNA library using (CAG)(10) repeat probes. Sixteen cDNAs were isolated and mapped to chromosomes 1, 2, 3, 6, 9, 13, 15, 16, 22, and X. Although we failed to detect abnormal CAG repeat expansion within these genes in Japanese patients with inherited neurodegenerative diseases, these genes remain potential candidate genes for neurodegenerative diseases that feature anticipation.

Brain↗

PubMed2002

Heme oxygenase-1 reduces murine monocrotaline-induced pulmonary inflammatory responses and resultant right ventricular overload.

Monocrotaline (MT), a pyrrolizidine alkaloid, causes pulmonary hypertension (PH) in rats and is widely utilized to analyze the pathophysiology of PH. However, a murine PH model with which transgenic animals may be used has not been established. To establish a murine MT-induced PH model, we administered different amounts of MT and determined the extent of right ventricular (RV) overload and PH. We also examined the expression of heme oxygenase-1 (HO-1), a potential antistress protein in MT-treated animals, and evaluated the functional role of HO-1 by administering an HO-1 inhibitor. Significant pulmonary inflammation and RV hypertrophy were observed when mice were given 600 mg/kg weight of MT weekly for 8 weeks. In addition, elevated RV pressure and induction of HO-1 in lung and RV were observed with this dose of MT. Interestingly, inhibition of HO activity promoted inflammatory changes in the lung and the resultant RV hypertrophy. HO-1 may play defensive roles against murine MT-induced pulmonary inflammation and the resultant RV overload.

Animals↗

PubMed2002

Morphometric nerve fiber analysis of the human inferior alveolar nerve: lateral asymmetry.

We studied morphometric nerve fiber analysis and the lateral asymmetry of the inferior alveolar nerve (IAN). Human IANs were resected at the mandibular foramen. The preparation of sections involved fixation, washing, dehydration, embedding, sectioning and staining as described in our previous reports. We estimated the average total number of myelinated axons in the right IAN to be 22,808, with an average transverse area of 37.6 microm2, an average perimeter of 23.0 microm, and average circularity ratio of 0.85, with the same measurements in the left IAN being 24,289, 33.9 microm2, 21.6 microm, and 0.86, respectively. Morphological differences between the right and left side were analyzed by applying parametric tests (unpaired t-test) to all measured items. According to these results, the IAN did not demonstrate notable lateral asymmetry in any measured item. We considered that these results were caused by using subjects with the same dentulous condition in both sides.

Aged↗

PubMed2002

Distributions of lesions in hanging suicide brains.

We found a morphological similarity in the distribution of vascular lesions in five hanging suicide brains. The overall findings on the lesions remind us of the venous origin but not of the arterial origin of the blood supply. Morphometric evaluations did not reveal any valuable conclusion. The results of this pathological research may be of clinical importance for the treatment of hanging patients.

Airway Obstruction↗

PubMed2002

Morphometric analysis of the human femoral nerve and its ageing process.

We analysed the sizes of nerve fibres in the human femoral nerve which innervates the quadriceps femoris muscles. The material was taken from 14 cadavers aged from 61 to 97 years. A linear regression analysis disclosed a significant age-related decrease of the mean transverse area of axons. Such decrease with age may be an indication of motoneuron atrophy. Our results could help in the understanding of the correlation between morphology and function during the ageing process.

Aged↗