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Biomedical subjects

I Nonaka

Publications and source records attributed to I Nonaka.

At least 253 records · Page 14Linked to original sources
PubMed1993

Haemopoietic activity associated with biglycan like proteoglycan.

One of the monocytic cell colony stimulating factors produced by thymic myoid cells, a 100 kDa factor, was purified by reversed phase HPLC and found to be homologous to the secreted form of proteoglycan 1 (biglycan) core protein. This biglycan associated colony stimulating factor did not carry an immunological motif of macrophage colony stimulating factor (M-CSF), but predominantly stimulated the proliferation and differentiation of monocytic lineage cells from bone marrow cells, nonadherent thymic cells and peritoneal exudate cells.

Amino Acid Sequence↗
PubMed1993

Myogenin gene disruption results in perinatal lethality because of severe muscle defect.

Myogenin is a member of the basic helix-loop-helix (bHLH) gene family and converts multipotential mesodermal cells to myoblasts. The four members of the myoD family show unique spatio-temporal expression patterns and therefore may have different functions during myogenesis. Here we inactivate the myogenin gene in order to understand its role in myogenesis. Homozygous mutations are lethal perinatally owing to the resulting major defects in skeletal muscle. The extent of disorganization of muscle tissue differs in three regions. In the latero-ventral body wall, most cells, including myogenic cells, disappear and there is rapid accretion of fluid. In the limbs, cells of the myogenic lineage exist, but they are severely disrupted, and some of them are mono-nucleate with properties of myoblasts. In contrast, there are many axial, intercostal and back muscle fibres to be seen, although fibres are mainly disorganized and Z-lines are not present in most myofibrils. These findings are evidence that myogenin is crucial for muscle development in utero and demonstrate that other members of the myogenic gene family cannot compensate for the defect.

Animals↗
PubMed1993

Inhibitory effects of enzymatic hydrolysates of collagen and collagen-related synthetic peptides on fibrinogen/thrombin clotting.

Inhibitory effects of some enzymatic hydrolysates of collagen and collagen-related synthetic peptides on fibrinogen/thrombin clotting were investigated. The hydrolysate of porcine skin collagen with thermolysin or bacterial collagenase inhibited fibrinogen/thrombin clotting, but did not inhibit the activity of thrombin. Although the activity was not pronounced, the hydrolysate of collagen with such proteinases as trypsin and pepsin also inhibited the clotting. Gly-Pro-Arg, which is a known inhibitor of fibrinogen/thrombin clotting, was isolated from the bacterial collagenase hydrolysate of porcine collagen by HPLC. Collagen-related synthetic peptides such as Gly-Pro-Arg-Gly, Gly-Pro-Arg-Gly-Pro, Gly-Pro-Arg-Gly-Pro-Ala, Gly-Pro-Arg-Gly-Pro-Pro, and Gly-Pro-Arg-Pro-Pro also inhibited the clotting, but did not inhibit the activity of thrombin. The inhibitory activity of Gly-Pro-Arg-Gly-Pro-Pro and Gly-Pro-Arg-Pro-Pro was more marked than that of Gly-Pro-Arg. However, Gly-Pro-Lys, Gly-Ala-Arg, Gly-Pro-Hyp, Ala-Gly-Pro-Arg and Gly-Pro-Ala-Gly-Pro-Arg had no inhibitory effect on the clotting.

Amino Acid Sequence↗
PubMed1993

Abnormal expression of dystrophin-associated proteins in Fukuyama-type congenital muscular dystrophy.

The absence of dystrophin causes Duchenne muscular dystrophy. Dystrophin is associated with a large complex of sarcolemmal glycoproteins which provides a linkage to the extracellular matrix component, laminin, and when dystrophin is absent all the dystrophin-associated proteins are much reduced. We report here that dystrophin-associated proteins have abnormally low expression in Fukuyama-type congenital muscular dystrophy (FCMD), despite near-normal expression of dystrophin. An abnormality of dystrophin-associated proteins in the sarcolemma seems to be a common denominator in the pathological processes leading to muscle cell necrosis in three forms of severe muscular dystrophy (Duchenne, Japanese Fukuyama-type, and north African Duchenne-like autosomal recessive).

Adolescent↗
PubMed1993

Immunoblot analysis of dystrophin-related protein (DRP).

Polyclonal antibodies against the carboxy-terminal portion of dystrophin-related protein (DRP), the putative autosomal gene product which shares sequence homology with dystrophin, show the clear expression of DRP in mouse fetal muscle and in cultured human muscle cells, but not in mature mouse or human muscle. DRP has the same molecular mass as X-linked dystrophin and is recovered from the membrane fraction, but is associated with membranes more loosely than dystrophin.

Amino Acid Sequence↗
PubMed1993

Increased mitochondrial DNA in blood vessels and ragged-red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

Using in situ hybridization, we studied muscle biopsy specimens from 4 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Three of the 4 patients with MELAS had a mutation at position 3243 of mitochondrial DNA (mtDNA) in the transfer RNALeu(UUR) gene, and the other patient had a mutation at position 3271 in the same transfer RNALeu(UUR) gene. Quantitative analysis using Southern blot hybridization and polymerase chain reaction showed 80 to 90% mutant mtDNA in muscle. In situ hybridization analysis showed that total mtDNAs (both normal and mutant) were extremely increased in blood vessels with high succinate dehydrogenase activity (strongly succinate dehydrogenase-reactive blood vessels) and ragged-red fibers. Cytochrome c oxidase activity in most of these reactive blood vessels and ragged-red fibers was positive. The similar morphological behavior in these vessels and fibers suggests that an increase in mutant mtDNA is responsible for mitochondrial proliferation and dysfunction in both tissues where cytochrome c oxidase is not a primarily defective enzyme. The pattern of expression of genes for mtDNA-encoded ribosomal RNA and the protein-coding region cytochrome c oxidase subunit II were similar in muscle specimens of patients with MELAS, patients with chronic progressive external ophthalmoplegia, and normal control subjects, and also between the two MELAS mutations. These results do not support the hypothesis that impaired transcription termination is a molecular defect in MELAS.

Blood Vessels↗
PubMed1993

"All-or-none" cytochrome c oxidase positivity in mitochondria in chronic progressive external ophthalmoplegia: an ultrastructural--cytochemical study.

Teased single muscle fibers from 6 patients with chronic progressive external ophthalmoplegia (CPEO) showed a segmental defect in cytochrome c oxidase (COX) activity. On ultrastructural--cytochemical examination, the majority of mitochondria in COX-positive segments were COX-positive, whereas all mitochondria in COX-negative segments were COX-negative. This "all-or-none" COX positivity in mitochondria in CPEO with deleted mitochondrial DNA can be explained by the "threshold effect," which induces the tissue-specific involvement and clinical heterogeneity.

Electron Transport Complex IV↗
PubMed1993

Dystrophin-related protein in skeletal muscles in neuromuscular disorders: immunohistochemical study.

Thirty-four biopsied muscles of Duchenne, Becker and congenital muscular dystrophy, congenital myotonic dystrophy and amyotrophic lateral sclerosis were examined by an immunocytochemical method with an anti-dystrophin-related protein (DRP) antibody. Strongly positive immunoreaction to DRP at the neuromuscular junctions in all biopsied specimens and faint reaction on the surface membrane of atrophic fibers in amyotrophic lateral sclerosis suggest that DRP is an anchor protein of the acetylcholine receptor. Additionally, the surface membrane of muscle fibers of Duchenne muscular dystrophy was positively stained. DRP is, therefore, thought to be expressed to compensate for dystrophin deficiency in these muscle fibers.

Amino Acid Sequence↗
PubMed1993

Cytochrome c oxidase activity is deficient in blood vessels of patients with myoclonus epilepsy with ragged-red fibers.

More than half of the intramuscular blood vessels in muscle biopsies from five patients with myoclonus epilepsy with ragged-fibers (MERRF) who had a point mutation in mitochondrial DNA at the tRNALys region were darkly stained with succinate dehydrogenase (SDH) stain, showing the morphologic characteristics of strongly SDH-reactive blood vessels (SSV), but they had no cytochrome c oxidase (CCO) activity. By electron cytochemistry, the mitochondria in the smooth muscle cells of SSV had no CCO activity. On the other hand, SSV in muscle biopsies from patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) had normal CCO activity as shown by light and electron microscopy. The defect in CCO activity in the arteriolar smooth muscle cells and in muscle fibers suggests that CCO deficiency is related to the pathophysiology of MERRF.

Adolescent↗
PubMed1993

Reciprocal expression of dystrophin and utrophin in muscles of Duchenne muscular dystrophy patients, female DMD-carriers and control subjects.

We examined muscle biopsies from patients with Duchenne muscular dystrophy (DMD: 39 patients) and Becker muscular dystrophy (BMD: 11 patients), female DMD-carriers (4 patients), and control subjects (26 persons) for the expression of dystrophin and utrophin. Control subjects showed all fibers to be dystrophin-positive, while utrophin staining was negative or weak. On the other hand, muscles from DMD patients showed the inverse staining patterns: dystrophin was negative and utrophin staining strong. Thus, there was a reciprocal pattern of expression between dystrophin and utrophin. This reciprocal relationship was confirmed to some extent at the single-fiber level in female carriers of DMD showing a mosaic immunostaining of dystrophin. We consider that utrophin may have a function similar to that of dystrophin, and compensate to some extent for dystrophin deficiency in DMD.

Adolescent↗
PubMed1993

Abnormal localization of laminin subunits in muscular dystrophies.

To address potential involvement of muscle basal lamina and membrane cytoskeleton proteins in the etiology of non-dystrophinopathy muscular dystrophies, we examined the immunostaining intensity and distribution of laminin subunits (A, B1, B2 and M), type IV collagen, dystrophin and spectrin in skeletal muscle biopsies from 64 myopathic patients (17 Fukuyama congenital muscular dystrophy: FCMD, 13 congenital muscular dystrophy unrelated to FCMD: other CMD, 16 Duchenne muscular dystrophy: DMD, and 18 other neuromuscular diseases. In FCMD muscle, we found a significant reduction of laminin M (merosin; a striated muscle specific basal lamina-associated protein) with approximately 26% of levels seen in controls by quantitative immunofluorescence. Other CMD and DMD muscles showed less dramatic reductions (78%, 80%, respectively). The localization of laminin M was also abnormal in FCMD muscle. Laminin B1 and B2 showed abnormalities similar to those observed with laminin M, but were less marked. Laminin A was only detected in rare regenerating fibers in control biopsies, whereas it was seen around most muscle fibers in FCMD patients, and in dystrophin deficient muscle fibers from DMD patients and its carrier. Staining intensity of type IV collagen in FCMD muscle was not significantly different from the other diseases. These findings may implicate a primary or central role for the basal lamina in FCMD muscle.

Adolescent↗
PubMed1993

Mitochondrial DNA mutations at nucleotide positions 3243 and 3271 in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a comparative study.

Of 50 patients with the clinical characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), 38 had a point mutation at nucleotide position (nt) 3243 in the tRNA(Leu(UUR)) region in mitochondrial DNA and 6 at nt 3271 in the same tRNA(Leu(UUR)) gene. Except for the later onset of the disease in the patients with the 3271 mutation, there were no clinical, biochemical and pathological differences between the two groups. Since the nt 3271 region is not located in the binding site for mitochondrial transcription termination (mTERM) factor, which has been proposed to be defective in the 3243 mutation, a functional defect in tRNA itself might be responsible for the enzyme defects in MELAS patients; however the mechanism by which the defective tRNA(Leu(UUR)) induces the stroke-like episodes remains to be clarified.

Adolescent↗
PubMed1993

Monomelic muscle atrophy.

Two patients with slowly progressive muscle atrophy limited to only one leg are reported. They had pes equinovarus deformity and muscle weakness in the affected leg but no symptom in the other limbs. Muscle biopsies from the affected leg showed dystrophic changes consisting of variation in muscle fiber size, endomysial fibrosis, and necrotic and regenerating fibers. Dystrophin was normally expressed at the surface membrane of the muscle fibers. These two patients possibly had a variant of distal muscular dystrophy, though a neural influence could not be completely excluded.

Biopsy↗
PubMed1993

Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33.

Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. Twenty-one FCMD families, 13 of them with consanguineous marriages, were analysed by genetic linkage analyses with polymorphic microsatellite markers to map the FCMD gene. Significant lod scores were obtained with the markers D9S58 (Zmax = 5.81 at theta = 0.06), D9S59 (Zmax = 4.33 at theta = 0.02), and HXB (Zmax = 3.28 at theta = 0.09) on chromosome 9q31-33. Multipoint analysis placed FCMD between D9S58 and D9S59, with a maximum lod score of 16.93. These markers will be useful for presymptomatic, prenatal and carrier diagnosis of family members carrying FCMD, and they represent important resources for the identification of a gene responsible for FCMD.

Chromosome Mapping↗
PubMed1993

A dystrophin-associated glycoprotein, A3a (one of 43DAG doublets), is retained in Duchenne muscular dystrophy muscle.

We determined several internal amino acid sequences of dystrophin-associated glycoprotein, A3a (one of the 43DAG doublets), of rabbit skeletal muscle. All the sequences of A3a determined were found in the C-terminal region of dystroglycan, which is the region assumed to be the cytoplasmic domain of 43DAG [Ibraghimov-Beskrovnaya et al. (1992) Nature 355, 696-702]. Therefore, A3a is identical with 43DAG. We raised an antibody (PA3a) against a synthetic polypeptide equivalent to one of the internal amino acid sequences of A3a. The antibody specifically reacted with A3a of rabbit skeletal muscle. PA3a, however, did not react with A3b, the other 43DAG doublet, suggesting that the 43DAG doublets are different proteins from each other. When the human control muscles were examined, PA3a immunohistochemically stained the cell surface membranes and exclusively reacted with a single protein similar to A3a in the SDS extracts. The protein was also detected in the SDS extract of the Duchenne muscular dystrophy (DMD) muscle devoid of dystrophin. When the muscle specimens from 30 DMD patients were immunohistochemically examined with the antibody, the cell surface membranes were consistently stained. Therefore, we conclude that the dystrophin-associated protein, A3a, is retained in DMD muscles.

Amino Acid Sequence↗
PubMed1993

A T-to-G mutation at nucleotide pair 8993 in mitochondrial DNA in a patient with Leigh's syndrome.

We studied a patient with Leigh's syndrome using neurophysiologic, radiologic, enzymatic, biochemical, and molecular analysis. Her clinical course had started with acute encephalopathic symptoms at 7 months of age. With repeated remission and exacerbation, she developed hypotonia and symptoms of brainstem dysfunction, such as irregular respiration and swallowing difficulty. These symptoms were followed by epileptic seizures, including simple partial seizures and tonic spasms. Both serum lactate and serum pyruvate levels were elevated, and deficient activity was detected in cytochrome c oxidase in her quadriceps femoris muscle. From the early stages, we noted an abnormality in the auditory brainstem response and visual evoked potentials, and an abnormal symmetrical low-density area in the basal ganglia on the computed tomographic scan. We found a mitochondrial DNA point mutation at 8993 in blood samples from both the patient and her mother using a simple polymerase chain reaction method. The ratio of wild and mutant mitochondrial DNA calculated densitometrically on polymerase chain reaction products was 56.6% in the patient's blood cells and 8.4% in her mother's. This patient's disorder was thought to be maternally inherited Leigh's syndrome. Her brother had died of the identical clinical features at 1 year 9 months of age.

Base Composition↗