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Tetsuo Ashizawa

Publications and source records attributed to Tetsuo Ashizawa.

28 records · Page 2Linked to original sources
PubMed2003

[Recent changes in the neurology residency program in the United States].

Residency in the United States has been known as one of the most organized systems for postgraduate medical education in the world. However, recent changes in the social, ethical and economic environment in the healthcare have brought new demands to the residency education. This review focuses on the new changes introduced by the Accreditation Council for Graduate Medical Education and Residency Review Committees, especially the changes directly relevant to neurology. These include changes in evaluation of residents and programs, work hours of residents and training curriculum. Additionally, residency program directors are facing new challenges of protecting healthcare private information, managed care, underrepresented minorities and visa acquisition by international medical graduates. Consequently, the workload of residency program directors has become more demanding.

Accreditation↗
PubMed2002

The GAA triplet-repeat sequence in Friedreich ataxia shows a high level of somatic instability in vivo, with a significant predilection for large contractions.

Friedreich ataxia is commonly caused by large expansions of a GAA triplet-repeat (GAA-TR) sequence in the first intron of the FRDA gene. We used small-pool PCR to analyze somatic variability among 7190 individual FRDA molecules from peripheral blood DNA of subjects carrying 12 different expanded alleles, ranging in size from 241 to 1105 triplets. Expanded alleles showed a length-dependent increase in somatic variability, with mutation loads ranging from 47% to 78%. We noted a strong contraction bias among long alleles (>500 triplets), which showed a 4-fold higher frequency of large contractions versus expansions. Some contractions were very large; of all somatic mutations scored, approximately 5% involved contractions of >50% of the original allele length, and 0.29% involved complete reversion to the normal/premutation length (< or =60 triplets). These observations contrast sharply with the strong expansion bias seen in expanded CTG triplet repeats in myotonic dystrophy. No somatic variability was detected in >6000 individual FRDA molecules analyzed from 15 normal alleles (8-25 triplets). A premutation allele with 44 uninterrupted GAA repeats was found to be unstable, ranging in size from 6 to 113 triplets, thus establishing the threshold for somatic instability between 26 and 44 GAA triplets. Analysis of an additional 7850 FRDA molecules from serially passaged lymphoblastoid cell lines carrying nine expanded alleles (132-933 triplets) showed very low mutation loads, ranging from 0% to 6.2%. Our data indicate that expanded GAA-TR alleles in Friedreich ataxia are highly mutable and have a natural tendency to contract in vivo, and that these properties depend on multiple factors, including DNA sequence, triplet-repeat length and unknown cell-type-specific factors.

DNA↗
PubMed2002

Clinical features and ATTCT repeat expansion in spinocerebellar ataxia type 10.

BACKGROUND: Spinocerebellar ataxia type 10, an autosomal dominant disease characterized by ataxia and seizures, is caused by a large expansion of an unstable ATTCT pentanucleotide repeat. OBJECTIVES: To characterize the phenotypic expression of spinocerebellar ataxia type 10 and to examine the genotype-phenotype correlations in 2 large families. DESIGN: Clinical characterization and genotype-phenotype correlation. SETTING: Studies at 2 medical schools with private practice referral. PATIENTS: Twenty-two affected individuals from 2 large Mexican American pedigrees. RESULTS: Of the 22 individuals, ataxia was the initial symptom in 21; seizure disorders developed in 11, mostly within several years following the onset of ataxia. The seizure frequency was different in the 2 families: 3 (25%) of 12 had seizures in family 1, and 8 (80%) of 10 had seizures in family 2 (P =.01). A brain magnetic resonance imaging or computed tomographic scan showed cerebellar atrophy in all patients examined. An electroencephalogram demonstrated epileptiform discharges in 4 of 8 patients studied. Although anticipation was apparent in both families, only family 1 showed a strong inverse correlation between age of onset and repeat number (r(2) = 0.79, P =.001). In family 1, 8 transmissions, of which 7 were paternal, resulted in an average gain of 1940 repeats. In contrast, despite anticipation, 2 affected male subjects transmitted their expanded alleles to 8 progenies, with an average loss of 755 repeats, in family 2. CONCLUSIONS: Seizure is an integral part of the spinocerebellar ataxia type 10 phenotype, with documented morbidity and mortality. Family-dependent factors may alter the frequency of the seizure phenotype and the pattern of intergenerational repeat size changes, making the genotype-phenotype correlation complex.

Adult↗
PubMed2002

Instability of a premutation allele in homozygous patients with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is caused by the expansion of an unstable CTG repeat in the DMPK gene on chromosome 19q13.3. We present two siblings with DM1 who each inherited a premutation allele, (CTG)43, stably transmitted from the mother and a full-mutation allele, either (CTG)500 or (CTG)180, derived from a paternal protomutation allele, (CTG)52. Small-pool polymerase chain reaction analysis showed that the (CTG)52 repeat allele was relatively stable in somatic tissues but was highly unstable in the male germline and extremely biased toward further expansion, consistent with the high levels of anticipation observed in DM1 families. The (CTG)43 allele showed subtle somatic instability in the mother, with maximum additions of two repeats and deletions of one repeat. Conversely, in the younger affected siblings the (CTG)43 allele showed a high degree of somatic instability (approximately 70% mutation load), resulting in deletions reverting to the high end of the normal range (down to [CTG]33) and additions up to the proto-mutation range (up to [CTG]64). The difference in the somatic stability of the (CTG)43 allele between the mother and her offspring suggests that interallelic interactions or other mechanisms in trans regulate the stability of the (CTG)43 premutation allele.

Adult↗
PubMed2002

Genetic ataxia.

Advances in molecular genetics have led to identification of an increasing number of genes responsible for inherited ataxic disorders. Consequently, DNA testing has become a powerful method to unambiguously establish the diagnosis in some of these disorders; however, there are limitations in this approach. Furthermore, the ethical, social, legal and psychological implications of the genetic test results are complex, necessitating appropriate counseling. This article intends to help the practicing neurologist clinically differentiate these disorders, choose appropriate genetic tests, and recognize the importance of counseling.

Chromosome Aberrations↗
PubMed2002

Vaccination with a MHC class II peptide attenuates cellular and humoral responses against tAChR and suppresses clinical EAMG.

An animal model of myasthenia gravis (MG), termed experimental autoimmune MG (EAMG), can be induced in C57BL/6 (B6, H-2b) mice by immunization with Torpedo californica acetylcholine receptor (tAChR). We have investigated the effect of vaccination with MHC class II peptide I-A beta(b)62-76 on clinical EAMG and on T cell and antibody (Ab) responses against tAChR. B6 mice were vaccinated with the peptide (25 microg/mouse) four times prior to two injections with tAChR. The incidence of clinical EAMG in vaccinated mice was 14% (3 out of 22 mice) compared to 48% (17 out of 35 mice) in control non-vaccinated or PBS-immunized mice. The T cells of the vaccinated group showed lower proliferative responses to tAChR and to T-cell epitope-containing tAChR alpha-chain peptides than the T cells of controls. In addition, the Ab responses in the vaccinated group was also lower against tAChR and some of the B-cell epitope-containing tAChR alpha-chain peptides.

Amino Acid Sequence↗