Search PubMed⌕ Search

Biomedical subjects

I Nonaka

Publications and source records attributed to I Nonaka.

At least 307 records · Page 17Linked to original sources
PubMed1991

Progressive muscular dystrophy with particular reference to muscle regeneration.

In various progressive muscular dystrophies (PMD), there were a number of fibers with histological and histochemical characteristics of regenerating fibers. With a morphometric analysis in diseased muscles, an identification of type 2C fiber on ATPase stain was the most simple and reliable method for fiber type evaluation. The type 2C fiber comprised 16.5% in Duchenne and 27.5% in Fukuyama type congenital MD, suggesting an active regenerating process taking place in both diseases. Regenerative capacity of muscle fibers after experimental damage to dystrophic chicken and mdx mouse muscles was similar to those seen in nondystrophic control muscles. From the above results, we speculate that a certain environmental factor such as interstitial fibrosis seems to play a major role in delaying regeneration in dystrophic muscles.

Animals↗
PubMed1991

Simple detection of tRNA(Lys) mutation in myoclonus epilepsy associated with ragged-red fibers (MERRF) by polymerase chain reaction with a mismatched primer.

We developed a simple method for the detection of a tRNA(Lys) mutation in myoclonus epilepsy associated with ragged-red fibers (MERRF) by polymerase chain reaction with use of a mismatched primer. Although the tRNA(Lys) mutation does not alter recognition sequences for commercially available restriction enzymes, we have successfully changed two nucleotides flanking the A to G mutation at nucleotide position 8344 in a tRNA(Lys) gene of a mitochondrial genome. As a result, the mutation can be detected as a Nae I restriction fragment length polymorphism. With this method, all eight MERRF patients and an asymptomatic mother of a MERRF patient, from six independent families, had the same tRNA(Lys) mutation. Our method is simple and should also be useful for the quantitation of heteroplasmies.

Base Sequence↗
PubMed1991

The frequency of patients with dystrophin abnormalities in a limb-girdle patient population.

Of the 3,048 diagnostic muscle biopsies processed by the National Institute of Neuroscience, Tokyo, over 12 years, 41 cases carried the clinical diagnosis of limb-girdle muscular dystrophy. We have analyzed all 41 cases for dystrophin content in muscle by both immunofluorescence and immunoblot. We identified five male patients with an abnormal dystrophin pattern diagnostic of Becker muscular dystrophy, and two female patients with dystrophin patterns consistent with a manifesting carrier of Duchenne muscular dystrophy diagnosis. Thus, 17% of our limb-girdle patients showed a dystrophinopathy, indicating that they in fact had a disorder related to Duchenne/Becker muscular dystrophy. Misclassification of isolated male limb-girdle patients was 31% (4/13), while misclassification of isolated female limb-girdle patients was 13% (2/15). Using multiplex polymerase chain reaction analyses of small amounts of muscle biopsy DNA confirmed a dystrophin gene deletion in all five male Becker dystrophy patients identified. This study emphasizes the clinical overlap between limb-girdle muscular dystrophy and dystrophinopathies, and reinforces the necessity of dystrophin protein and gene studies for the accurate clinical diagnosis of isolated cases of muscular dystrophy.

Adolescent↗
PubMed1991

[MELAS without ragged-red fibers: a case report].

A female patient who had clinical characteristics of MELAS but with no apparent muscle symptoms was reported. She was in good health until 12 years and 5 months of age when she began to have afebrile generalized tonic-clonic convulsions. Thereafter, she had repeated stroke-like episodes, including headache, vomiting, convulsions, hemiparesis and left ehemianopsia. She had neither muscle weakness, fatigability nor atrophy. Laboratory examinations disclosed elevated lactate and pyruvate levels in the serum and cerebrospinal fluids, transient focal low density areas on brain CT and right sensorineural deafness by audiometry. No ragged-red fibers (RRF) were found in the first biopsy at 13 years and 6 months of age, and two RRF-like fibers containing red granular materials in the subsarcolemnal regions in the second at 15 years and 3 months of age. A biochemical assay on the two biopsied muscles demonstrated normal enzyme activities in the mitochondrial electron transport system. She was diagnosed as having MELAS because of remarkable mitochondrial abnormalities in smooth muscle cells in the intramuscular arterioles which were clearly demonstrated by succinic dehydrogenase (SDH) stain and on electron microscopy. It was suggested that the stroke-like episodes in this patient were induced by a preferential damage to the mitochondria in the blood vessel walls. Thus, we conclude that a simple method of identifying the strongly SDH-reactive blood vessels (SSV) in frozen sections is critical in supporting or making diagnosis of MELAS.

Acidosis, Lactic↗
PubMed1991

[A case of mitochondrial encephalomyopathy with schizophrenic psychosis, dementia and neuroleptic malignant syndrome].

A 37-year-old male with an 8-year-history of schizophrenic psychosis and dementia developed hyperpyrexia and cataleptic rigidity during haloperidol administration. He was transferred to our hospital where he was noticed to have generalized muscle weakness and atrophy. In his muscle biopsy, there were numerous ragged-red fibers and focal cytochrome c oxidase deficiency. In addition, the presence of strongly SDH-reactive blood vessels (SSV) in his muscle biopsy suggests that the similar systemic vascular abnormality as seen in MELAS plays a certain role for inducing the central nervous system symptoms. He discontinued haloperidol, and was placed on coenzyme Q and idebenone which were effective for his psychic problems. Several months later, his schizophrenic symptom disappeared and mental status improved from IQ of 60 to 68. We would emphasize that mitochondrial encephalomyopathies must be taken into account for differential diagnosis for psychiatric patients with mental deterioration.

Adult↗
PubMed1991

[A case with MELAS associated with epilepsia partialis continua].

We report a 14-year-old boy with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) who presented repeated episodes of abdominal pain and vomiting since the age of 8 years. In addition, he developed strokelike episodes with myoclonic seizures and transient hemiplegia on three occasions. At the age of 14-1/12-years, he also developed epilepsia partialis continua persisting for 10 days, which was associated with myoclonic seizures synchronized with spike discharges at the right central area. Laboratory examination disclosed increased levels of lactate and pyruvate in serum and CSF and low density areas in the bilateral temporal regions on CT scan. Muscle biopsy showed scattered ragged-red fibers. The enzyme activities (pyruvate dehydrogenase complex, pyruvate carboxylase, phosphoenol pyruvate carboxykinase, and cytochrome c oxidase) and the rates of decarboxylation of [3-14C]pyruvate in cultured skin fibroblasts were within normal ranges.

Acidosis, Lactic↗
PubMed1991

[A case of facioscapulohumeral muscular dystrophy with infantile spasms, sensorineural deafness and retinal vessel abnormality].

We report an 18-year-old female with facioscapulohumeral dystrophy (FSHD), who had sensorineural deafness, retinal vessel abnormality, mental retardation, and epilepsy. She had infantile spasms at 6 months of age. Muscle atrophy and weakness of facial muscles were first noticed at 3 years of age. From 10 years of age, she had rapidly progressive generalized muscle weakness especially of facial, neck and truncal muscles with marked lordosis. Although mental retardation is commonly complicated with FSHD, infantile spasms or epilepsy has never been reported. Not only mental retardation but epilepsy may be one of the central nervous system symptoms in a systemic disorder, FSHD.

Adolescent↗
PubMed1991

[Carnitine palmitoyltransferase deficiency in a patient with severe psychomotor retardation].

A 13-year-old girl who had severe brain damage due to unknown prenatal cause presented rhabdomyolysis triggered by a mild viral infection. Her muscle biopsy revealed mild variation in fiber size and type 2 fiber atrophy without excess lipid storage. Biochemical analysis of the biopsied material showed decreased carnitine palmitoyltransferase (CPT) activity (15% of the control). Serum and urinary carnitine levels were normal. Skeletal muscle CT scanning showed multiple low density spots. The patient was diagnosed as having CPT deficiency. She recovered from rhabdomyolysis without renal failure after a month with conservative therapy. CPT deficiency is usually found in young healthy persons. This is the first case report of CPT deficiency which presented severe psychomotor retardation since neonatal period.

Adolescent↗
PubMed1991

[Congenital neuromuscular disease with uniform type 1 fibers : a case report].

A 3-year-old boy was seen because of delayed developmental milestones, waddling gait, nonprogressive proximal muscle weakness and hyporeflexia. Serum creatine kinase levels were normal and EMG was non-diagnostic. Muscle biopsy revealed complete absence of type 2 A and 2 B fibers in addition to a moderate variation in fiber size. Diagnostic findings for congenital nonprogressive myopathies were not present such as nemaline bodies, cores, targetoid structure, central nuclei or selective type 1 fiber atrophy. This was the first case of a distinct form of non-progressive congenital myopathy, "congenital neuromuscular disease (myopathy) with uniform type 1 fibers", accompanied with mental retardation in Japan.

Child, Preschool↗
PubMed1990

A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies.

Mitochondrial encephalomyopathies are usually divided into three distinct clinical subgroups: (1) mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS); (2) myoclonus epilepsy associated with ragged-red fibres (MERRF); and (3) chronic progressive external ophthalmoplegia (CPEO) including Kearns-Sayre syndrome. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNA(Leu)(UUR) that is specific to patients with MELAS. Because this mutation creates an ApaI restriction site, we could perform a simple molecular diagnostic test for the disease. The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested. Southern blot analysis confirmed that the mutant DNA always coexists with the wild-type DNA (heteroplasmy).

Base Sequence↗
PubMed1990

Quadriceps myopathy: forme fruste of Becker muscular dystrophy.

We examined dystrophin, the protein product of the Duchenne muscular dystrophy gene, in muscle biopsy specimens from 4 male patients with quadriceps myopathy, all of whom showed a mild and slowly progressive myopathy confined to the quadriceps muscles. All 4 patients had clear abnormalities of dystrophin, and were diagnosed as having Becker muscular dystrophy by both immunofluorescence and immunoblot examinations; that is, dystrophin of an abnormal molecular mass was visualized in muscle cryosections as "patchy" or discontinuous immunostaining at the surface membrane of the muscle fibers. One patient had a brother who showed widespread myopathic changes consistent with typical Becker muscular dystrophy. We conclude that the syndrome called quadriceps myopathy includes a group of forme fruste Becker muscular dystrophy.

Adult↗
PubMed1990

Myopathy in Marinesco-Sjögren syndrome: an ultrastructural study.

Seven muscle biopsies from patients with the clinical characteristics of Marinesco-Sjögren syndrome (MSS) revealed myopathic changes of two types; muscle fiber necrosis followed by regeneration and focal myofibrillar degeneration inducing autophagocytosis with rimmed vacuole formation. In two young patients, massive muscle fiber necrosis with phagocytic invasion was the predominant feature and autophagic phenomenon was minimal, resembling the findings in progressive muscular dystrophy. Myofibrillar degeneration with autophagic phenomenon was prominent in five adult patients. The coexistence of these two degenerative processes and the secondarily induced reactive changes of muscle fiber hypertrophy, interstitial fibrosis, occasional ragged-red fibers and type 1 fiber predominance, are responsible for the wide spectrum of muscle pathology in MSS. The dense double-membrane structure surrounding myonuclei, previously reported as being specific to MSS, was present in only one biopsy.

Adult↗
PubMed1990

Chronic progressive external ophthalmoplegia: a correlative study of mitochondrial DNA deletions and their phenotypic expression in muscle biopsies.

Deleted mitochondrial DNA (mtDNA) has been shown to coexist with normal mtDNA (heteroplasmy) in muscles from chronic progressive external ophthalmoplegia, including Kearns-Sayre syndrome. In this study, we correlated heteroplasmic mtDNA abnormality with clinical, biochemical and histological findings with the following results: (1) large deletions ranging from 1.8 to 8.8 kb in 22 muscle specimens from 28 patients who had ophthalmoplegia clinically and focal cytochrome c oxidase (CCO) deficiency by histochemistry, (2) no difference in clinical and biochemical findings between patients with and without mtDNA deletions, (3) no relationship between the size, site or populations of deleted mtDNA and respiratory chain enzyme activities in muscles, (4) positive correlation between the number of CCO-deficient fibers and the populations of deleted mtDNA, and (5) higher incidence of CCO-negative fibers in patients with deleted mtDNA than in those with no deletion of mtDNA. These results suggest that deleted mtDNA is, at least in part, responsible for focal CCO deficiency as a phenotypic expression and that the investigation on pathogenetic mechanism of focal CCO deficiency may provide a clue to understanding the underlying pathophysiology in this disorder.

Chromosome Deletion↗
PubMed1990

Progressive cytochrome c oxidase deficiency in a case of Leigh's encephalomyelopathy.

We report the morphological, biochemical, immunological, and genetic findings in a patient with the clinical characteristics of Leigh's disease due to multisystemic cytochrome c oxidase (CCO) deficiency. Muscle biopsy at 2 years and 5 months of age showed markedly decreased CCO and cytochrome a + a3, moderately decreased NADH-cytochrome c reductase to 46.3%, and generalized loss of immunologically detectable CCO subunits, but other respiratory chain enzyme proteins were normal. All the tissues examined at autopsy showed decreased activity of all respiratory chain enzymes except complex II. The decrease in cytochromes b and a + a3 were in harmony with decreased enzyme activities in complex III and IV (CCO), respectively. All immunologically detectable subunits of CCO in immunoprecipitation were uniformly decreased in the cardiac and skeletal muscles, but subunits 1 and 4 were selectively decreased in other organs except liver. No large deletion could be detected in the cardiac muscle mtDNA after digestion with restriction enzymes. These results suggest that the respiratory chain enzymes are variable in their activity and the amount of enzyme proteins decreases as the disease progresses.

Brain↗
PubMed1990

1-[11C]pyruvate turnover in brain and muscle of patients with mitochondrial encephalomyopathy. A study with positron emission tomography (PET).

We examined pyruvate turnover using 1-[11C]pyruvate in the brain and epicranial muscle of 6 patients with mitochondrial encephalomyopathy (MEM), diagnosed by muscle biopsy and mitochondrial enzyme assay. The radioactivity was measured by positron emission tomography (PET). The time-activity curve for 11C in both brain and muscle generated after i.v. injection of 1-[11C]pyruvate consisted of 2 components in normal subjects and patients, i.e. a fast and a slow component which were assumed to represent the aerobic (mitochondrial) and anaerobic (glycolytic) metabolism of pyruvate, respectively. In the brain and muscle of patients, the aerobic component was smaller and the anaerobic larger than in normals. The extent of this abnormality seemed to reflect the severity of the disease. The same slight abnormality for [11C]pyruvate turnover was also observed in the brain of MEM patients who were without cerebral symptoms. Cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) of most patients were lower than those of normals, and the oxygen extraction fraction (OEF) was decreased in many patients.

Adult↗
PubMed1990

Degradation of connectin (titin) in Fukuyama type congenital muscular dystrophy: immunochemical study with monoclonal antibodies.

Connectin (also called titin) is a myofibrillar elastic filament which links a thick filament to a neighbouring Z line in a sarcomere and thus contributes significantly to the elasticity of myofibrils. In a previous study, we demonstrated by Western blot analysis of the biopsied skeletal muscles using an anti-connectin monoclonal antibody that connectin was degraded extensively after 5 years of age in Duchenne muscular dystrophy (DMD), while it was degraded mildly in Becker muscular dystrophy and only minimally in myotonic dystrophy, limb girdle dystrophy, amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. In the present study, we investigated the degradation state of connectin in Fukuyama type congenital muscular dystrophy (FCMD) by a similar method using 2 distinct anti-connectin monoclonal antibodies. In FCMD, connectin degradation began much earlier than in DMD: Definite degradation was already observed in 5-8-month-old patients. It was presumed that connectin degradation would play an important role in the myofibrillar degeneration in the early stage of FCMD.

Antibodies, Monoclonal↗