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Biomedical subjects

I Nonaka

Publications and source records attributed to I Nonaka.

At least 163 records · Page 9Linked to original sources
PubMed1997

Apoptotic nuclear degeneration in Marinesco-Sjögren syndrome.

In 12 patients with the clinical characteristics of Marinesco-Sjögren syndrome including an autosomal recessive inheritance, congenital cataracts, mental retardation, cerebellar ataxia and progressive muscle weakness, the most common pathological finding was rimmed vacuole formation comprising from 0.1% to 10% of fibers in their muscle biopsy samples. The nuclear changes varied from condensed chromatin granules to vacuolation with amorphous inclusions which were predominantly seen in younger patients with prominent rimmed vacuoles, suggesting a close relationship between nuclear change and rimmed vacuole formation. From the severe destructive changes in nuclei, we speculated that the nuclear changes in Marinesco-Sjögren syndrome play a primary role in muscle degeneration resulting in myofibrillar disorganization and rimmed vacuole formation. In 2 patients, the TUNEL method demonstrated scattered myonuclei with fragmented DNA, but "ladder formation" was not found, probably because of the small numbers of nuclei with fragmented DNA. Nuclear degeneration with focal myofibrillar degeneration seen in these muscle samples suggests that the apoptotic process may occur in muscle disorders, especially in diseases with rimmed vacuole formation.

Adult↗
PubMed1997

Granulomatous myositis: pathologic re-evaluation by immunohistochemical analysis of infiltrating mononuclear cells.

To characterize the non-caseating granuloma formation in granulomatous myositis, we analyzed infiltrating mononuclear cells in 7 patients including 2 sarcoid patients, using monoclonal antibodies with a modified immunoperoxidase method. All granulomas consisting of epithelioid, infiltrating mononuclear cells and multinucleated giant cells had markedly increased numbers of CD45Ro-positive cells. The infiltrating inflammatory cells were mostly T lymphocytes and macrophages. The majority of T lymphocytes behaved as T helper/inducer subtype, expressing CD4 positivity. Although the ratio of CD4- to CD8-positive cells in the granuloma in muscle biopsies was not significantly different from that in other organs seen in systemic sarcoidosis, T helper/inducer and T suppressor/cytotoxic cells showed some characteristic distributions: CD4-positive cells accumulated in the center of, and CD8-positive cells at the periphery of, the granuloma. The distribution of infiltrating cells did not differ between muscle biopsies from patients with and without systemic sarcoidosis, suggesting that both groups share the same pathogenetic mechanism in granuloma formation.

Aged↗
PubMed1997

Muscle histopathology in diabetes mellitus associated with mitochondrial tRNA(Leu(UUR)) mutation at position 3243.

Diabetes mellitus associated with 3243 mitochondrial tRNA(Leu(UUR)) mutation (DM-Mt3243) is a subtype of the mitochondrial multisystem syndromes, usually lacking myopathy. Muscle biopsies were obtained from 5 patients with diabetes and one patient with impaired glucose tolerance, all possessing the 3243 mutation without hallmarks of MELAS. The specimens were subjected to histochemical, biochemical, and genetic analysis. Ragged-red fibers were seen in 4 of the 6 patients (67%), and focal cytochrome c oxidase deficiency in 3 (50%). Strongly succinate dehydrogenase-reactive blood vessels was found in 5 patients (83%). The histochemical signs were present even when the mutant percentage was very low. The percentage of mutant DNA was almost always higher in muscles than in leukocytes. The combination of allele specific PCR amplification and PCR-RFLP method was useful to evaluate the mutant proportion. The mutant percentage in muscle was under 50% in 5 (83%) patients. Mitochondrial enzyme activity was deficient only in one patient. This study presents the detailed muscle histopathology in the DM-Mt3243 group. Abnormal histopathologic findings seemed similar to those noted in MELAS. However, mutant percentage in muscles was lower than that of MELAS, and respiratory chain enzyme activity was well preserved.

Acidosis, Lactic↗
PubMed1997

Recurrent pain attacks in a 3-year-old patient with myoclonus epilepsy associated with ragged-red fibers (MERRF): a single-photon emission computed tomographic (SPECT) and electrophysiological study.

We reported a 3-year-old girl with myoclonus epilepsy associated with ragged-red fibers (MERRF) who was afflicted with recurrent pain attacks and allodynia on the right side of the body. Although magnetic resonance imaging showed normal intensity in the thalamus, single-photon emission computed tomography (SPECT) revealed hypoperfusion in the thalamus. Somatosensory evoked potentials showed delayed early cortical responses, particularly on right median nerve stimulation. The parenteral administration of cytochrome c with flavin mononucleotide and thiamine diphosphate abolished the intolerable pain. This clinical improvement was objectively supported by the results of SPECT and neurophysiological findings. These observations suggested that a dysfunction of the thalamus was responsible for her pain and that cytochrome c therapy was of benefit for this symptom.

Child, Preschool↗
PubMed1997

Congenital familial myopathy with type 2 fiber hypoplasia and type 1 fiber predominance.

A 12-month-old girl with delayed developmental milestones, due to muscle hypotonia and weakness from early infancy, exhibited type 2 fiber hypoplasia. A muscle biopsy specimen disclosed type 1 fiber predominance and type 2B fiber deficiency compatible with congenital myopathy. During the following 4 years, she continued to have mild muscle weakness, but no mental retardation. Her mother had similar symptoms from early infancy with minimal progression. Although type 2 fiber hypoplasia is a non-specific finding in various diseases, it may be a specific finding in a limited number of patients with hereditary congenital non-progressive myopathy.

Adult↗
PubMed1997

Treatment of mitochondrial encephalomyopathy with a combination of cytochrome C and vitamins B1 and B2.

The therapeutic efficacy of a regimen consisting of intravenous injection of Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine diphosphate for mitochondrial encephalomyopathy (MEM) was examined. This combined therapy was applied to nine patients with MEM, including four with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. For the standard regimen, Cardiocrome was first injected daily, usually for 4 weeks, and later by means of intermittent injections for maintenance treatment. Clinical improvement was obtained in eight of the patients. Improvement was observed in the muscle symptoms of easy fatigability, motor disability and severity of stroke-like episodes, as well as in various other symptoms such as phosphate, tinnitus, headache, corneal edema, chilblains, thalamic pain, respiratory failure, and nystagmus. This clinical improvement was maintained for more than 1 year by additional intermittent injections. In conclusion, this therapy was fairly effective for the management of patients with MEM.

Adolescent↗
PubMed1997

Respiratory failure in nemaline myopathy.

Four patients with nemaline myopathy, 1 with the severe infantile form and 3 with the benign congenital (classical) form, exhibited significant respiratory problems. In the patient with the severe infantile form, respiratory failure paralleled the generalized muscle weakness, whereas the 3 patients with the benign infantile form suddenly developed respiratory failure while still ambulant. Polysomnographic studies performed on 2 patients revealed that apnea or irregular thoracic movements occurred only during rapid eye movement sleep, when hypercapnia was also demonstrated on serial transcutaneous partial O2 and partial CO2 monitoring. A discrepancy between motor ability and respiratory involvement probably is not uncommon in patients with the moderate congenital form of nemaline myopathy. Clinicians must always be alert to respiratory failure when monitoring patients with nemaline myopathy.

Adolescent↗
PubMed1997

Electron microscopic examination of basal lamina in Fukuyama congenital muscular dystrophy.

By light microscopy we previously obtained immunocytochemical evidence for basal lamina (BL) abnormality of skeletal muscle in Fukuyama congenital muscular dystrophy (FCMD). To further elucidate the pathological involvement of the BL in FCMD, we examined by electron microscopy the skeletal muscle in 12 cases of FCMD, nine cases of age-matched neuromuscular diseases unrelated to FCMD, and a case of merosin-negative CMD (MCMD). We found that the BL of skeletal muscle fibres in all patients with FCMD and the MCMD patient had a thin, deranged and often disrupted appearance. These features were more prominent in large calibre (> 15 microns) fibres than in small calibre (approximately 8 microns) fibres. Replication of the BL was not observed in 11 of the 12 FCMD patients. Although the BL over the intact plasma membrane had occasional gaps, the plasma membrane under the disrupted BL was normal in some case. Our results indicate the presence of fragile BL which may precede plasma membrane damage in FCMD skeletal muscle.

Basement Membrane↗
PubMed1997

The association between haematological manifestation and mtDNA deletions in Pearson syndrome.

We studied the proportion of deleted mitochondrial DNA in blood cells from patients with Pearson syndrome. Patient 1 is a 17-year-old female with Kearns-Sayre syndrome who survived Pearson syndrome. Patient 2 is a 5-year-old boy with Pearson syndrome who recovered from refractory anaemia but continues to have thrombocytopenia and neutropenia. Patient 3 is a female neonate who died with severe acidosis and pancytopenia at 14 days of age. Southern blot analysis was performed with total DNA from three patients' blood cells and two samples of bone marrow cells from one patient. In peripheral blood, patients with a higher proportion of deleted mitochondrial DNA had lower blood cell counts. In patient 2, the percentage of mutant mitochondrial DNA in bone marrow cells decreased as anaemia improved. This indicates that the proportion of deleted mitochondrial DNA in peripheral blood and in bone marrow has a tendency to correlate to the severity of haematological manifestation.

Adolescent↗
PubMed1997

Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of beta-dystroglycan in the outer plexiform layer of the retina.

Dp260 is a C-terminal isoform of dystrophin and is expressed specifically in the retina. Abnormal electroretinograms (ERG) in some Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients are likely linked to a disruption of Dp260. To clarify the importance of Dp260 in the retina, we examined dystrophin exon 52 knock-out mice, whose expression of Dp260 is impaired. We also confirmed the localization of Dp260 in the outer plexiform layer (OPL) of the retina. Disruption of Dp260 causes a change in the localization of beta-dystroglycan, which is normally found in the OPL of the retina. This suggests a requirement for Dp260 for normal formation of the dystrophin-dystroglycan complex in the retina. Dp71, also expressed in the retina, was, however, not detected in the OPL. The difference in localization of Dp260 and Dp71 implies that the two isoforms have different functions. The dystrophin exon 52 knock-out mice had a prolonged implicit time of the b-wave in ERG, although no significant change was observed in amplitude. These ERG findings differed from those of DMD and BMD patients, especially with regard to amplitude of the b-wave, but make it clear that Dp260 is required for normal electrophysiology.

Animals↗
PubMed1997

Altered expression of the alpha7beta1 integrin in human and murine muscular dystrophies.

The alpha7beta1 integrin is the primary laminin receptor on skeletal myoblasts and adult myofibers. It has distinct functions during muscle development and contributes to muscle structural integrity. We have studied this integrin in cases where expression of dystrophin or laminin are compromised. Immunofluorescence demonstrates an increase in alpha7beta1 in patients with Duchenne muscular dystrophy and in mdx mice that lack dystrophin. Analysis of RNA from mdx mice and from patients with Duchenne and Becker muscular dystrophies indicates that the increase in the alpha7beta1 integrin is regulated at the level of alpha7 gene transcription. In contrast, the levels of alpha7beta1 integrin are severely diminished in patients with laminin alpha2 chain congenital dystrophy muscular dystrophy and in dy/dy mice that also do not make the alpha2 laminin chain. Analysis of RNA from the hindlimbs of dy/dy mice demonstrated that in the absence of laminin alpha7 gene transcription is inhibited and limited to specific alternatively spliced isoforms. We suggest that the increased expression of alpha7beta1 integrin in the absence of dystrophin compensates for the reduced dystrophin-mediated linkage of fibers with the basal lamina and modulates the development of pathology associated with these diseases. The decrease in alpha7beta1 integrin and its transcripts in the absence of laminin likely contributes to the severe myopathy that results from laminin alpha2 chain deficiency and suggests that laminin-2 regulates expression of the alpha7 integrin gene. The role of the alpha7beta1 integrin in muscle integrity also suggests that compromised expression of this receptor may underlie as yet undefined myopathies.

Adult↗
PubMed1997

A comparative freeze-fracture study of plasma membrane of dystrophic skeletal muscles in dy/dy mice with merosin (laminin 2) deficiency and mdx mice with dystrophin deficiency.

The intramembranous particle (IMP), orthogonal array (OA) and orthogonal array subunit particle (OASP) densities of skeletal muscle plasma membranes of merosin deficient dy/dy mice and their control mice at 7, 14 and 28 days after birth were analysed by freeze-fracture electron microscopy. Similar studies were performed on dystrophin-deficient mdx mice with mild muscle weakness at 28 days after birth for the comparison with those of dy/dy mice with severe muscle weakness at the same age. In the pre-clinical stage of dy/dy mice at 14 days after birth, the membranes showed a significantly decreased density of OAs (P<0.01 by Wilcoxon rank-sum test) as compared with control mice, while those in the clinical stage of dy/dy mice at 28 days after birth showed normal IMP density but a marked depletion of OA density (P<0.01). Moreover, at 28 days after birth, the reduction of OAs in the plasma membranes of dy/dy mice was more marked than that of mdx mice (P<0.05 by Wilcoxon rank-sum test). These results provided us with the information that the OA density was affected more severely with merosin deficiency than with dystrophin deficiency, and again supported our previously proposed concept that the clinical severity in muscular dystrophies correlated with the OA density.

Animals↗
PubMed1997

In vitro and in vivo anti-platelet effects of enzymatic hydrolysates of collagen and collagen-related peptides.

Collagen-related peptides, Gly-Pro-Arg and its analogues, were examined for their inhibitory effects on platelet aggregation induced by the addition of ADP. Human platelet aggregation was suppressed by more than 50% with each of Gly-Pro-Arg and such Gly-Pro-Arg-containing peptides as Gly-Pro-Arg-Gly, Gly-Pro-Arg-Gly-Pro, Gly-Pro-Arg-Pro-Pro, and Gly-Pro-Arg-Pro-Pro-Pro at a concentration of 0.3 mM. The inhibitory effects of these peptides were about 10 times higher in human PRP than in rat PRP. Other Gly-Pro-Arg analogues such as Sar-Pro-Arg, Gly-Pro-Lys, Gly-Ala-Arg, and Ala-Gly-Pro-Arg had no inhibitory effect at a concentration from 0.1 to 0.8 mM even in human PRP. Intravenous and oral administrations of Gly-Pro-Arg and enzymatic hydrolysates of collagen suppressed the decrease in platelet count for endotoxin-induced DIC in rats. Collagen itself has been regarded as a potent inducer of platelet aggregation, but these findings suggest that collagen-related peptides and enzymatic hydrolysates of collagen prevent platelet aggregation.

Animals↗
PubMed1997

[Cousins with X-linked recessive myotubular myopathy].

We describe two cousins with severe infantile form of myotubular myopathy. In Japan this disease has previously been reported in only three families. Case 1. The propositus, a 2-year-5-month-old boy, had been on a respirator since birth. He had a history of severe neonatal asphyxia and sequential hypotonia with dyspnea. Findings diagnostic of congenital myotubular myopathy, such as central nuclei and peripheral halo of muscle fibers, were demonstrated in his biopsied muscle. Case 2. A male the cousin of case 1 had congenital myopathy and died at 3 months of age due to respiratory failure. His muscle biopsy disclosed the identical findings as had been seen in case 1. These two cases were born to twin mothers, suggesting X-linked recessive inheritance. Early diagnosis and proper treatment of myotubular myopathy are important, because this condition may be erroneously-interpreted as the sequelae of neonatal asphyxia.

Child, Preschool↗
PubMed1997

[A case of congenital hypomyelination neuropathy with type I Chiari malformation and mental retardation].

A four-year old boy with congenital hypomyelination neuropathy (CHMN) had mental retardation and a tic disorder, the latter commencing at 2 years of age. The diagnosis of CHMN was confirmed by electron microscopy of his biopsied sural nerve which showed loss of large myelinated fibers, decreased density of myelinated fibers, many naked axons and atypical onion bulb formation. MR imaging showed type I Chiari malformation in the absence of clinical signs attributable to it. Auditory brainstem response (ABR) showed delayed wave I peak latency, prolonged I--III interpeak latency, broad wave II duration and normal III--V interpeak latency, suggesting abnormal peripheral and normal central myelination. The association of CHMN with mental retardation. Chiari malformation and tic disorder has never been reported, the significance of which remained unclear.

Arnold-Chiari Malformation↗