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Biomedical subjects

I Nonaka

Publications and source records attributed to I Nonaka.

At least 181 records · Page 10Linked to original sources
PubMed1997

[Molecular pathology of muscle diseases].

The most significant pathologic finding in muscular dystrophy(MD) is muscle fiber necrosis followed by regeneration. A membrane hypothesis to explain fiber necrosis seems to be confirmed by the discovery of dystrophin and dystrophin-associated glycoprotein (DAG); both are located along the muscle surface membrane. However the mechanism of muscle fiber degeneration cannot be fully explained by the membrane theory itself, because the gene product of Emery-Dreifuss MD is present in the nuclear membrane. Heterogeneous clinical expressions of mitochondrial diseases are also puzzling and have been explained by "tissue specificity" due to different population of wild and mutant mitochondrial DNA from tissue to tissue. The tissue with higher percentage of mutant mitochondrial DNA may not function in an "all-or-none" manner.

Cytoskeletal Proteins↗
PubMed1997

[Non-Fukuyama type congenital muscular dystrophy--merosin deficient and positive forms].

The classical form of congenital muscular dystrophy (CMD) is now classified into merosin-deficient and -positive forms. The merosin (laminin alpha 2) is one of three subunits of a muscle basement membrane protein, laminin. Patients with the merosin-deficient form have generalized muscle weakness and hypotonia from early infancy as seen in FCMD but with no significant central nervous system involvement. The serum creatine kinase (CK) is markedly elevated. Strikingly all patients examined by a CT/ MRI have diffuse white matter abnormalities mimicking leukodystrophy. The gene has been mapped to chromosome 6q2 in the coding region for merosin. Since the responsible gene and protein have not been identified in the merosin-positive form, this CMD is probably a group of heterogeneous diseases. The overall symptoms are mild, approximately 90% of patients learned to walk alone.

Animals↗
PubMed1996

Neural BC1 RNA in mouse skeletal muscle is a denervation-induced RNA whose expression is developmentally regulated.

We detected neural BC1 RNA in mouse skeletal muscle. The level of BC1 RNA was high in the fetus, but it declined progressively to the adult level as development proceeded. These observations suggest that this RNA is involved in the prenatal development and differentiation of muscles. Although its developmental expression correlates with the fetal period of polyneuronal innervation, BC1 RNA does not seem to play a direct role(s) in synaptogenesis, since its expression was not restricted to the neuromuscular junction. We also demonstrated that the BC1 RNA level in adult muscle was elevated after denervation, suggesting that changes in the activity of muscles or neural factors caused by axotomy, or both may result in BC1 RNA upregulation.

Actins↗
PubMed1996

Cerebral oxygen and glucose metabolism in glycogen storage disease with normal acid maltase: case report.

A 26-year-old male with cardiomyopathy, cervical muscle weakness and mental retardation was diagnosed as having glycogen storage disease with normal acid maltase on the basis of his clinical, pathological and biochemical findings. Positron emission tomography showed that cerebral oxygen metabolism was normal, while cerebral glucose metabolism was decreased in the cerebral cortexes. The decrease of the glucose metabolic rate may reflect an abnormality of cerebral glucose metabolism in this disorder and may be related to mental retardation, which is one of the characteristic symptoms.

Adult↗
PubMed1996

A novel mutation in the mitochondrial tRNA(Thr) gene associated with a mitochondrial encephalomyopathy.

A novel G-to-A transition at nucleotide 15915 in mtDNA is described. The patient showed a combination of muscle weakness, hearing loss, mental retardation, and seizures. Muscle biopsy showed RRFs and focal COX deficiency. We sequenced all mtDNA, and found 5 novel nucleotide substitutions. Three of them were synonymous mutations, one was a missense mutation in cytochrome b gene (A-->G at nt 15422), and the last one was the 15915 mutation in tRNA(Thr) gene. We screened for the 15422 and the 15915 mutations with mismatch primers and found that one of 104 normal individuals carried the former one and none of 175 had the latter one. The 15422 mutation existed in homoplasmic states both in the patient and the normal individual, suggesting that this is a polymorphism. In contrast the 15915 mutation resided in heteroplasmic states in muscle, skin fibroblast and blood. The nucleotide substitution at nt 15915 disrupts a highly conserved base pair in anticodon stem of the tRNA(Thr). Our data suggest that the 15915 mutation is an additional mtDNA mutation responsible for mitochondrial encephalomyopathies.

Adolescent↗
PubMed1996

Detection of DNA fragments encompassing the deletion junction of mitochondrial genome.

Deletions and occasional duplications in mitochondrial DNA have been known to be present in mitochondrial diseases and in aged tissues. The junctional sequences of the rearrangements must be determined for detecting duplication, but its procedures seem laborious for routine examination. The joint method of long polymerase chain reaction plus digestion by three restriction enzymes provides a simple method to detect and map the deletion sites of mitochondrial DNA.

Base Sequence↗
PubMed1996

Basement membrane abnormality in merosin-negative congenital muscular dystrophy.

In muscle biopsy specimens from three patients with merosin-negative congenital muscular dystrophy (CMD), there was marked variation in fiber size with evidence of necrotic and regenerating processes and with marked interstitial fibrosis. No muscle fibers or intramuscular nerves stained with merosin antibody. On electron microscopy, the basement membrane of all the muscle fibers was very poorly discernible and there were occasional disruptions, while the basement membrane of the Schwann cells was well preserved. On the other hand, the sarcolemmal basement membrane in merosin-positive CMD was well preserved even in patient with severe interstitial fibrosis. It remains to be determined how the defective basement membrane in merosin-negative CMD induces defective sarcolemma and eventual fiber necrosis.

Basement Membrane↗
PubMed1996

Activation of Ras and protection from apoptotic cell death by BDNF in PC12 cells expressing TrkB.

A clonal deoxyribonucleic acid (cDNA) clone of mouse trkB was expressed in cells of the rat PC12 pheochromocytoma cell line. The transformants followed apoptotic death upon serum deprivation. The addition of brain-derived neurotrophic factor (BDNF) to the culture medium supported the survival and neurite extension of the transformants in a serum-free condition. A Trk-family-specific protein kinase inhibitor, K-252a, inhibited the survival and neurite extension of the transformants in the presence of BDNF. BDNF activated autophosphorylation of trkB and caused the accumulation of a guanosine triphosphate (GTP)-bound form of Ras, both of which effects were also inhibited by K-252a. These results suggested that BDNF-triggered Ras activation is important for the survival and neuronal differentiation of PC12 cells in a serum-free condition.

Animals↗
PubMed1996

Nondystrophinopathic muscular dystrophies including myotonic dystrophy.

The spectacular progress concerning dystrophin and its pathology, the dystrophinopathies, has led to a somewhat arbitrarily separated heterogeneous group of nondystrophinopathic muscular dystrophies that currently comprise the Emery-Dreifuss type, the nosologically heterogeneous autosomal-recessive limb-girdle muscular dystrophy, the severe childhood autosomal-recessive muscular dystrophy, the merosin-positive and -negative congenital muscular dystrophies, the autosomal-recessive distal muscular dystrophy of Miyoshi, the facio-scapulo-humeral muscular dystrophy, and myotonic dystrophy, both the adult and neonatal variants. Deficiencies of adhalin in a particular form of limb-girdle muscular dystrophy, and of merosin in a particular form of congenital muscular dystrophy as well as the newly discovered principle of abnormal tri-nucleotide repeats in myotonic dystrophy are evidence of progress that has also amplified the notion of the dystrophinopathies that the protein-deficient muscular dystrophies can now be considered examples of contributions of the dystrophin-glycoprotein complex across the muscle fiber plasma membrane.

Adolescent↗
PubMed1996

Hypoparathyroidism and insulin-dependent diabetes mellitus in a patient with Kearns-Sayre syndrome harbouring a mitochondrial DNA deletion.

We report a 17-year-old girl with short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, sensorineural hearing loss, and cardiac conduction defect (Kearns-Sayre syndrome). A large-scale deletion (6741 base pairs) in mitochondrial DNA was found in her muscle specimen. She also had insulin-dependent diabetes mellitus (IDDM). On admission, her plasma glucose level was elevated at 31.0mmol/l with mild ketoacidosis, and haemoglobinA1c elevated at 16.5%. After improvement of diabetic ketoacidosis, she was placed on insulin 24-30 units/day despite her small body weight of 25 kg. There was reduced excretion of urinary C-peptide at 3.97 nmol/day. In addition, she had idiopathic hypoparathyroidism with a serum calcium level of 2.15 mmol/l, phosphate 1.7 mmol/l, and intact PTH below 10 ng/l. Human leucocyte associated antigen typing showed A24, A26; B54, B61; CW1, CW3; DR8, DR14; DQ1 and DQ3, suggesting that the presence of HLA-A24 and CW3 antigen contributed to the association of IDDM and hypoparathyroidism, similar to Japanese patients with polyglandular autoimmune syndrome, complicated by hypoparathyroidism and IDDM. We suggest that a genetic linkage, as well as mitochondrial dysfunction, may be responsible for the association of the two disease states. This is an extremely rare case of Kearns-Sayre syndrome, presenting in association with IDDM and idiopathic hypoparathyroidism.

Adolescent↗
PubMed1996

Congenital muscular dystrophy: Clinical and pathologic study of 50 patients with the classical (Occidental) merosin-positive form.

We studied 50 patients with the merosin-positive form of congenital muscular dystrophy (MP-CMD) clinically and pathologically. The frequency of MP-CMD in our laboratory was approximately one-half that of the Fukuyama type and one-sixth that of Duchenne muscular dystrophy. The early signs of MP-CMD included decreased fetal movement during pregnancy (14%) and poor suck (42%), floppiness (30%), and respiratory difficulty (16%) in early infancy. Eighty-six percent of the patients had delayed motor development. Ninety-two percent of the patients followed beyond age 4 years had learned to walk. The disease was relatively slowly progressive, except in six patients who rapidly lost ambulation. Almost all patients had normal IQ, except four who were mildly to moderately retarded. Of the patients examined by cranial CT/MRI, 24% showed cerebral atrophy and 11% had areas of white matter lucency. Muscle biopsy results in those younger than 5 years showed mild dystrophic changes consisting of variation in fiber size and scattered necrotic and regenerating fibers. In older children, there were additional chronic dystrophic changes, including fiber splitting (32%), moth-eaten appearance (32%), marked fatty replacement (46%), and abnormal fiber type distribution (59%). The manifestations of MP-CMD were generally milder and more slowly progressive than those of the Fukuyama type and merosin-negative form of congenital muscular dystrophy.

Adolescent↗
PubMed1996

Myotonia congenita with painful muscle cramps.

A sporadic Japanese case of myotonia congenita with painful muscle cramps is reported. Electromyographic examinations disclosed myotonic discharge with dive bomber sounds at insertion, and high-amplitude, high-frequency motor unit potentials during the muscle cramps. Biopsied muscle specimens and EMG findings showed non-specific mild myopathic changes. There was no abnormal expansion of CTG repeat within the myotonic dystrophy gene. This patient's disorder closely resembles Becker's myotonia congenita Type II though the family history of was non contributory.

Biopsy↗
PubMed1996

Mitochondrial encephalomyopathy with elderly onset of stroke-like episodes.

A 52-year-old woman with a history of a hearing disturbance since age 20 experienced visual hallucinations and convulsions, followed by right hemiparesis and aphasia. On the basis of a muscle biopsy and mitochondrial DNA analysis, she was diagnosed as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This case is unique in that the stroke-like episodes occurred 30 years after disease onset.

Age of Onset↗