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Biomedical subjects

Kayoko Saito

Publications and source records attributed to Kayoko Saito.

At least 19 recordsLinked to original sources
PubMed2006

TRH therapy in a patient with juvenile Alexander disease.

Alexander disease is a rare disorder of the central nervous system caused by a de novo mutation in the glial fibrillary acidic protein (GFAP) gene. Unlike the much more common infantile form, the juvenile form is slowly progressive with bulbar, pyramidal and cerebellar signs. Herein, we report a 9-year old Japanese girl suffering from frequent vomiting, slurred speech and truncal ataxia. Juvenile Alexander disease was diagnosed by genetic analysis, which detected a novel GFAP mutation, D360V. We also describe our clinical success in treating this patient with thyrotropin releasing hormone (TRH).

Alexander Disease↗
PubMed2006

Cardiac involvement in Fukuyama-type congenital muscular dystrophy.

BACKGROUND: Fukuyama-type congenital muscular dystrophy is an autosomal recessive disorder characterized by generalized skeletal muscle weakness and hypotonia from early infancy and by mental retardation. Little is known about cardiac involvement in patients with Fukuyama-type congenital muscular dystrophy. This study evaluated whether cardiac involvement exists in patients with Fukuyama-type congenital muscular dystrophy. METHODS AND RESULTS: We evaluated left ventricular function using M-mode and Doppler echocardiography in 34 patients with Fukuyama-type congenital muscular dystrophy. The age ranged from 6 months to 30 years (median: 6 years). A total of 64 recordings were analyzed. Left ventricular dimensions and parameters of systolic function measured included left ventricular end-diastolic dimension, left ventricular fractional shortening, left ventricular wall thickness, and the mean velocity of circumferential fiber shortening and end-systolic wall stress relationship. Left ventricular end-diastolic dimension z score >2 was observed in 2 patients (6%). Left ventricular fractional shortening <0.28 and/or reduced mean velocity of circumferential fiber shortening in the mean velocity of circumferential fiber shortening-end-systolic wall stress relationship were observed in 16 patients (47%). A significant correlation between age and left ventricular fractional shortening was observed, and left ventricular fractional shortening decreased with age. Of 12 patients >15 years of age, 10 (83%) showed decreased left ventricular systolic function. Left ventricular fractional shortening was normal in most patients <10 years of age, and it was reduced in most patients >15 years of age. Five patients died of heart failure or respiratory problems, and a histologic examination confirmed the presence of myocardial fibrosis. No patients showed increased left ventricular wall thickness or a conduction abnormality on electrocardiograms. CONCLUSION: Cardiac involvement exists in patients with Fukuyama-type congenital muscular dystrophy and becomes evident in older children in the second decade. A cardiac evaluation, including echocardiograms and subsequent follow-up, is important, especially in patients >10 years of age.

Adolescent↗
PubMed2006

The mildest known case of Fukuyama-type congenital muscular dystrophy.

We present a 14-year-old boy with Fukuyama-type congenital muscular dystrophy (FCMD) who shows the mildest muscle weakness ever reported with this affliction and exceptionally mild mental retardation, but who has intractable epilepsy. Magnetic resonance imaging showed the typical abnormalities of FCMD. Molecular genetic analyses revealed a 3 kb insertion mutation in the fukutin gene heterozygously. We could find no mutation in the coding region of the fukutin gene in the chromosome without a 3 kb insertion. The most probable mechanism of clinical manifestation in this patient could be either a mutation in the noncoding regions of the fukutin gene on the chromosome without the ancestral founder haplotype of FCMD, or an error in the process of transcription or translation. Another possibility is the abnormalities in other genes involved in the glycosylation of alpha-dystroglycan, such as Fukutin-related protein and LARGE genes.

Adolescent↗
PubMed2006

Unified method for Bayesian calculation of genetic risk.

Bayesian inference has been used for genetic risk calculation. In this traditional method, inheritance events are divided into a number of cases under the inheritance model, and some elements of the inheritance model are usually disregarded. We developed a genetic risk calculation program, GRISK, which contains an improved Bayesian risk calculation algorithm to express the outcome of inheritance events with inheritance vectors, a set of ordered genotypes of founders, and mutation vectors, which represent a new idea for description of mutations in a pedigree. GRISK can calculate genetic risk in a common format that allows users to execute the same operation in every case, whereas the traditional risk calculation method requires construction of a calculation table in which the inheritance events are variously divided in each respective case. In addition, GRISK does not disregard any possible events in inheritance. This program was developed as a Japanese macro for Excel to run on Windows.

Algorithms↗
PubMed2006

Altered glycosylation of alpha-dystroglycan in neurons of Fukuyama congenital muscular dystrophy brains.

To test the hypothesis that the disruption of fukutin protein produces the brain pathology through hypoglycosylation of alpha-dystroglycan (alpha-DG), we immunostained Fukuyama congenital muscular dystrophy (FCMD) brains with an antibody that recognizes the polysaccharide epitope of alpha-DG. Immunoreactivity of the glia-limitans along the cortical surface, as well as that of the glial endfeet around vessel walls, was preserved in the FCMD cerebrum. However, fragmentation of the immunostained glia-limitans was noted in association with parenchymal protrusion and gyral fusion. In the FCMD cerebellum, this fragmentation of alpha-DG labeling was limited to the area of micropolygyria, and immunostaining at the glia-limitans and vessel walls was comparable to that of the control brains, in structurally normal areas. In the hippocampus, neurons of the dentate gyrus and corpus ammonis were immunopositive for alpha-DG in control subjects, but this staining was markedly decreased in FCMD brains. In contrast, immunolabeling of blood vessels and the glia-limitans was preserved in this region. Fukutin antisera clearly labeled hippocampal neurons in control brains, while this labeling was decreased in FCMD brains. Thus, hypoglycosylation of alpha-DG was evident in neurons, but not in the glial cell population of FCMD brains. This suggests that the mechanism of alpha-DG glycosylation may differ between neurons and glial cells, and that a fukutin gene defect may result in functional disruption through hypoglycosylation of both neuronal and glial alpha-DG.

Adolescent↗
PubMed2006

Prenatal diagnosis of Fukuyama congenital muscular dystrophy.

Fukuyama congenital muscular dystrophy (FCMD) is characterized by infantile hypotonia, symmetrical generalized muscle weakness, and neuronal migration disturbances that result in changes consistent with cobblestone lissencephaly with cerebral and cerebellar cortical dysplasia. FCMD is recognized as an autosomal recessive genetic defect. Genetic counselling is recommended for parents at risk of having a child with FCMD. Given the high risk and overwhelming prospect of having another child with this incurable devastating condition leads many couples to consider prenatal diagnosis. In Japanese families, haplotype analysis using microsatellite markers is available. In non-Japanese families, DNA sequence analysis is available. Both disease-causing alleles of an affected family member must be identified before prenatal testing can be performed.

Female↗
PubMed2006

Beta-blocker therapy for cardiac dysfunction in patients with muscular dystrophy.

BACKGROUND: In muscular dystrophy, cardiac function deteriorates with time and heart failure is one of the major causes of death. Although the combination of angiotensin-converting enzyme inhibitors (ACEI) and beta-blockers improves cardiac function in adults, little is known about the efficacy of those drugs in patients with muscular dystrophy. METHODS AND RESULTS: The effect of the beta-blocker, carvedilol, and/or ACEI on ventricular function in patients with muscular dystrophy was studied. Carvedilol and an ACEI were given to 13 patients (ACEI group; mean age 18 years, range 7-27 years), and an ACEI only to 15 patients (carvedilol group; mean age 15 years, range 8-29 years). Diagnoses included Duchenne muscular dystrophy (n=25), Fukuyama muscular dystrophy (n=2), and Emery-Dreifuss muscular dystrophy (n=1). Echocardiographic parameters of the left ventricle were measured during the 2-3 years of follow-up. In the carvedilol group, combination therapy of carvedilol and an ACEI for 2 years resulted in a significant increase in left ventricular fractional shortening (LVFS). In the ACEI group, there was no significant change in LVFS. Left ventricular end-diastolic dimension increased in the ACEI group, but not in the carvedilol group. CONCLUSION: Carvedilol plus an ACEI improves left ventricular systolic function in patients with muscular dystrophy.

Adolescent↗
PubMed2005

[Muscular dystrophy].

The muscular dystrophies are a genetically heterogeneous group of progressive disorders that lead to the breakdown of the integrity of skeletal muscle. Numerous recent advances made in research into the molecular genetics of muscular dystrophy have highlighted the diversity of this family of disorders. Muscle biopsy allows the immunohistochemical analysis of various muscle specific proteins, and can provide important data enabling definitive diagnosis. Muscle biopsy is not always necessary, such as in the case of Duchenne or Fukuyama type dystrophies, which are relatively easy to diagnose by genetic testing; in such cases, however, consideration must given to the ethical implications of testing. The future promises the development of new therapeutic approaches and clinical applications based on genetic diagnostic data.

Genetic Techniques↗
PubMed2004

Fukutin expression in mouse non-muscle somatic organs: its relationship to the hypoglycosylation of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy.

Recent studies suggest that hypoglycosylation of alpha-dystroglycan (alpha-DG) may play an essential role in the pathogenesis of Fukuyama-type congenital muscular dystrophy (FCMD), which is caused by defects in the fukutin gene and characterized by dystrophic changes in the skeletal muscles and dysplastic lesions in the central nervous system. alpha-DG is expressed in many organs in addition to muscle and brain, although these organs are not affected in FCMD. To elucidate whether or not fukutin protein is involved in the glycosylation of alpha-DG in non-muscle somatic organs, we examined the distribution pattern of fukutin in developing and adult mouse tissues. The fukutin antisera labeled the acinar cells of the pancreas, the renal glomerular and tubular cells, and the epithelium of the bronchi, salivary gland, alimentary tract and skin in both fetal and adult mice. This distribution pattern was also confirmed by in situ hybridization. Antisera against alpha-DG and beta-DG labeled the same cellular populations in each organ, especially along the cell surface membrane. We also examined the glycosylation status of alpha-DG in autopsied FCMD cases (n = 5) and found evidence of hypoglycosylation in the kidney, lung, skin and intestine. These results suggest that fukutin protein is involved in the glycosylation process of alpha-DG in non-muscle somatic organs both during development and in the adult. It is unclear why muscle and brain symptoms predominate in FCMD, however re-evaluation of the functions of alpha-DG and fukutin protein in non-muscle somatic organs may provide valuable insight.

Adolescent↗
PubMed2004

Cloning of cDNA encoding a regeneration-associated muscle protease whose expression is attenuated in cell lines derived from Duchenne muscular dystrophy patients.

In the dystrophin-mutant mdx mouse, an animal model for Duchenne muscular dystrophy (DMD), damaged skeletal muscles are efficiently regenerated and thus the animals thrive. The phenotypic differences between DMD patients and the mdx mice suggest the existence of factors that modulate the muscle wasting in the mdx mice. To identify these factors, we searched for mRNAs affected by the mdx mutation by using cDNA microarrays with newly established skeletal muscle cell lines from mdx and normal mice. We found that in the mdx muscle cell line, 12 genes, including L-arginine:glycine amidinotransferase and thymosin beta4, are up-regulated, whereas 7 genes, including selenoprotein P and a novel regeneration-associated muscle protease (RAMP), are down-regulated. Northern blot analysis and in situ hybridization revealed that RAMP mRNA is predominantly expressed in normal skeletal muscle and brain, and its production is enhanced in the regenerating area of injured skeletal muscle in mice. RAMP expression was much lower in individual muscle cell lines derived from biopsies of six DMD patients compared to a normal muscle cell line. These results suggest that RAMP may play a role in the regeneration of skeletal muscle and that its down-regulation could be involved in the progression of DMD in humans.

Amino Acid Sequence↗
PubMed2004

Thalamic lesions in a long-surviving child with spinal muscular atrophy type I: MRI and EEG findings.

Brain magnetic resonance imaging was conducted in a girl with genetically confirmed spinal muscular atrophy (SMA) type I. This patient has survived 6 years, to date, under mechanical ventilation. T2-weighted and fluid-attenuated inversion recovery images revealed high signal intensity lesions in the anterolateral portions of the bilateral thalami. Electroencephalography disclosed diffuse beta activity upon awakening and during light sleep. In addition, fast and prolonged spindles were observed. Although mild neuronal changes in the lateral nucleus of the thalamus have been described in several autopsied cases, this is the first study to demonstrate neuroradiologically and neurophysiologically the thalamic lesions in genetically confirmed SMA type I.

Child↗
PubMed2004

Benign familial infantile convulsions: linkage to chromosome 16p12-q12 in 14 families.

PURPOSE: Benign familial infantile convulsions (BFIC) is a form of idiopathic epilepsy. It is characterized by clusters of afebrile seizures occurring around the sixth month of life. The disease has a benign course with a normal development and rare seizures in adulthood. Previous linkage analyses defined three susceptibility loci on chromosomes 19q12-q13.11, 16p12-q12, and 2q23-31. However, a responsible gene has not been identified. We studied linkage in 16 further BFIC families. METHODS: We collected 16 BFIC families, without an additional paroxysmal movement disorder, of German, Turkish, or Japanese origin with two to eight affected individuals. Standard two-point linkage analysis was performed. RESULTS: The clinical picture included a large variety of seizure semiologies ranging from paleness and cyanosis with altered consciousness to generalized tonic-clonic seizures. Interictal EEGs showed focal epileptiform discharges in six patients, and three ictal EEGs in three distinct patients revealed a focal seizure onset in different brain regions. In all analyzed families, we found no evidence for linkage to the BFIC loci on chromosomes 19q and 2q, as well as to the known loci for benign familial neonatal convulsions on chromosomes 8q and 20q. In 14 of the families, the chromosome 16 locus could be confirmed with a cumulative maximum two-point lod score of 6.1 at marker D16S411, and the known region for BFIC could be narrowed to 22.5 Mbp between markers D16S690 and D16S3136. CONCLUSIONS: Our data confirm the importance of the chromosome 16 locus for BFIC and may narrow the relevant interval.

Adolescent↗
PubMed2003

Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease.

Muscle-eye-brain disease (MEB), an autosomal recessive disorder prevalent in Finland, is characterized by congenital muscular dystrophy, brain malformation and ocular abnormalities. Since the MEB phenotype overlaps substantially with those of Fukuyama-type congenital muscular dystrophy (FCMD) and Walker-Warburg syndrome (WWS), these three diseases are thought to result from a similar pathomechanism. Recently, we showed that MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) gene. We describe here the identification of seven novel disease-causing mutations in six of not only non-Finnish Caucasian but also Japanese and Korean patients with suspected MEB, severe FCMD or WWS. Including six previously reported mutations, the 13 disease-causing mutations we have found thus far are dispersed throughout the entire POMGnT1 gene. We also observed a slight correlation between the location of the mutation and clinical severity in the brain: patients with mutations near the 5' terminus of the POMGnT1 coding region show relatively severe brain symptoms such as hydrocephalus, while patients with mutations near the 3' terminus have milder phenotypes. Our results indicate that MEB may exist in population groups outside of Finland, with a worldwide distribution beyond our expectations, and that the clinical spectrum of MEB is broader than recognized previously. These findings emphasize the importance of considering MEB and searching for POMGnT1 mutations in WWS or other congenital muscular dystrophy patients worldwide.

Adult↗
PubMed2003

A 1-year-old infant with McArdle disease associated with hyper-creatine kinase-emia during febrile episodes.

A 14-month-old girl was hospitalized due to repeated hyper-creatine kinase (CK)-emia during pyrexia. Mild hypotonia was observed, but other physical and neurological findings were unremarkable. The serum CK level was normal at rest or normothermia. Open muscle biopsy was performed on the rectus femoris, and showed glycogen storage and complete lack of phosphorylase activity histochemically and biochemically, establishing the diagnosis of McArdle disease. The diagnosis of McArdle disease in early infancy is uncommon. Until this study there have been no reports of clinical symptoms or muscle biopsy findings for McArdle disease in early childhood. This disease must be considered when transient hyper-CKemia is observed in infants, even if glycogen storage is unremarkable as compared with adult cases.

Biopsy↗