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Biomedical subjects

K Arahata

Publications and source records attributed to K Arahata.

At least 127 records · Page 7Linked to original sources
PubMed1991

Immunocytochemical analysis of dystrophin in congenital muscular dystrophy.

Using immunocytochemical methods, we examined the intensity and distribution of dystrophin and spectrin immunostaining of skeletal muscles from 51 congenital muscular dystrophy (CMD) patients including 36 Fukuyama congenital muscular dystrophy (FCMD) and 15 non-FCMD (other CMD). 17 age-matched spinal muscular atrophy (SMA) and 5 Duchenne muscular dystrophy (DMD) patient biopsies were studied as controls. All 15 non-FCMD and SMA patients showed normal localization of dystrophin at the surface membrane of each muscle fiber which was undetectable in DMD. In contrast, 34 of 36 FCMD patients exhibited an unusual immunostaining pattern with occasional (17-43%; mean = 28) negative or abnormally immunoreacted (partially deficient, fluffy or intense) fibers for dystrophin. Dystrophin was absent in 2 of 36 patients having a clinical diagnosis of FCMD, and intragenic deletion of the DMD gene was detected in one. Spectrin, a membrane cytoskeletal protein related to dystrophin, also showed an increased number of abnormally immunostained fibers in FCMD (25%), but not so high in age-matched DMD (9%) or SMA patient muscle (0%). Thus, our results suggested the presence of intrinsic factor(s) that produce abnormality of the plasma membrane of FCMD muscle.

Adolescent↗
PubMed1991

Apolipoprotein B is a major perforin inhibitor protein in human serum.

We purified the high-molecular-weight perforin inhibitor protein from normal human serum using DEAE-cellulose, HPLC-gel filtration and hydroxylapatite chromatography. This protein was shown to be identical to the serum apolipoprotein B-100 in terms of amino acid composition and the sequence of the digested peptides. This inhibitor protein not only inhibits the membrane binding activity of perforin but also the pore insertion activity of membrane-bound perforin.

Amino Acid Sequence↗
PubMed1991

Dystrophin abnormality in progressive muscular dystrophy--a review article.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder of muscle in children, with an incidence of approximately 1 in 3,300 male births. In about a third of affected boys, the disease is due to a new mutation, and most patients die in their early 20s. Over the last few years, the genetic, biochemical and histopathological basis of DMD has been elucidated greatly. In particular, the discovery of "dystrophin," the protein product of the DMD gene is truly an epoch-making success in the history of muscular dystrophy research. Dystrophin is now thought to be a cytoskeletal protein underlying the plasma membrane (known in muscle as the sarcolemma) of normal muscle fiber, and is undetectable or greatly reduced in DMD. In this review article, dystrophin in normal skeletal muscle and various neuromuscular diseases including DMD/BMD (Becker muscular dystrophy), and its carrier is discussed.

Child↗
PubMed1991

Epidemiology of progressive muscular dystrophy in Okinawa, Japan. Classification with molecular biological techniques.

We studied the prevalence of various types of progressive muscular dystrophy (PMD) in Okinawa, Japan on December 31, 1989 and the incidence of Duchenne muscular dystrophy (DMD) in 5-year periods from 1957 to 1985. We classified patients with PMD clinically, electrophysiologically, molecular biologically and immunohistochemically with antidystrophin antibody, especially for sporadic cases of DMD, Becker muscular dystrophy (BMD) and limb-girdle muscular dystrophy (LG). The prevalence for all PMD in Okinawa was 7.13 X 10(-5) for DMD, 1.82 X 10(-5) for BMD in the male population, 1.55 X 10(-5) for LG, 1.14 X 10(-5) for congenital muscular dystrophy, 2.03 X 10(-5) for facioscapulohumeral muscular dystrophy (FSH), and 9.13 X 10(-5) for myotonic dystrophy (MD) in the total population. The incidence of DMD in the period 1957-1985 was 15.41 X 10(-5) live-born males (LBM) and 3.21 X 10(-5) LBM for BMD. The incidence has apparently declined in Okinawa since 1975. The prevalence of BMD, FSH and MD was rather high in Okinawa compared with previous reports. Molecular biological techniques for classifying patients were indispensable for the epidemiological study of PMD.

Cross-Cultural Comparison↗
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

[A rare case of adult-onset Becker muscular dystrophy diagnosed by dystrophin staining].

Different diagnosis of Becker muscular dystrophy (MD) from limb-girdle MD mainly depends on the differences of heredity form and age at onset. However, sporadic cases with either type of MD often occur, and occasionally Becker MD can occur in adult age when limb-girdle MD commonly occurs. We reported the male sporadic case of Becker MD with the onset at 30 year old who was diagnosed by dystrophin staining. At the age of 30, he noticed mild difficulty to stand up and instability when hurrying up stairs. His weakness of lower limb-girdle gradually progressed, but he is able to walk without any support at the present age of 54, and he never showed weakness in upper limbs. Neurological and laboratory examination revealed that severe atrophy of lower limb-girdle, mild calf hypertrophy and moderate elevate of serum CK level. These history and symptoms hardly distinguish between Becker and limb-girdle MD. Immunostaining of biopsy muscle from the patient using the antiserum against synthetic peptide fragment of dystrophin revealed faint and patchy pattern, and immunoblot revealed 380 kd of abnormal size dystrophin. These dystrophin testing confirmed that this case was a rare case of Becker MD with adult-onset and mild clinical course.

Dystrophin↗
PubMed1991

Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies.

Becker muscular dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein. To address potential structure-function relationships for the various domains of dystrophin, we examined both the dystrophin gene and protein in 68 patients with abnormal dystrophin. Eighty-six percent of BMD patients with dystrophin of altered size have deletions or duplications, and the observed sizes of dystrophin fit well with predictions based on DNA data. Deletions within the amino-terminal domain I tended to result in low levels of dystrophin and a more severe phenotype. The phenotypes of patients with deletions or duplications in the central rod domain were more variable. This region can be divided into three portions based on differences in clinical presentations of patients. Deletions around exons 4553 were most common and generally caused typical BMD; however, phenotypic variability among patients with similar mutations suggests that epigenetic and/or environmental factors play an important role in determining the clinical progression. In contrast, deletions or duplications in the proximal portion of this domain tended to cause severe cramps and myalgia. Finally, loss of the middle of this region probably causes a very mild phenotype, as only one such patient was found and his only symptom was elevated serum creatine phosphokinase levels.

Adolescent↗
PubMed1990

Detection of a fast isoform of C-protein with an antiserum directed against the N-terminal portion of dystrophin.

An antiserum raised against the N-terminal actin-binding portion of dystrophin cross-reacted with a 130-kDa protein in fast skeletal muscle. The results of purification and two-dimensional gel electrophoresis and its immunological properties demonstrated that this protein is identical to a 130-kDa basic isoform of fast-C-protein. These results suggest that the actin-binding domain of dystrophin shares one or more antigenic determinants with those of C-protein.

Antibodies↗
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

"Quadriceps myopathy": a clinical variant form of Becker muscular dystrophy.

A 26-year-old male with "quadriceps myopathy" is presented. He had a family history and only the bilateral quadriceps were wasted, without symptomatic weakness. The specimen of the muscle biopsy showed typical myopathic features without inflammatory reactions. The patchy defect of muscular dystrophin was proved by immunohistochemical study. Dystrophin analysis revealed abnormal 380 kDa dystrophin. Gene deletion was proved at exon 45-48 of Xp21 without frameshift. This case was considered to be a clinical variant form of Becker muscular dystrophy.

Adult↗
PubMed1990

A manifesting carrier of Duchenne muscular dystrophy with severe myocardial symptoms.

A 42-year-old so-called manifesting carrier of Duchenne muscular dystrophy (DMD), whose first complaints were severe myocardial symptoms, is described. Immunohistochemical study using anti-dystrophin anti-serum and analysis of cloned segments of X chromosome DNA were performed. Her two sons and one of her brothers appear to have had the same disease. She was admitted to the hospital complaining of dyspnoea, back pain and palpitations and was first diagnosed as having myocardial infarction. However, this diagnosis was excluded. The echocardiogram showed diffuse abnormalities of myocardial function. Serum enzymes were increased. Minimal weakness and decreased deep tendon reflexes were detected in her left lower extremity. Muscle biopsy revealed a small number of necrotic fibres. Immunohistochemical study using anti-dystrophin antiserum showed a mosaic pattern of the surface membrane. Analysis of cloned segments of X chromosome DNA from the patient and her son showed the XmnI(Asp) alleles of pERT 87-15 and the TaqI alleles of pERT 87-8 in both patients.

Adult↗
PubMed1990

Calcium is essential for both the membrane binding and lytic activity of pore-forming protein (perforin) from cytotoxic T-lymphocyte.

The influence of Ca on the membrane binding and lytic activity of lymphocyte pore-forming protein (perforin) was studied. In the absence of Ca, perforin did not bind to the target membranes and did not support lysis of the target cells. In contrast, in the presence of Ca perforin was able to bind to the cell membrane (Km greater than 0.2 mM). Almost all the perforin molecules bind to the membrane within 1 min at 0 degrees C. The addition of EDTA abolished the binding, indicating that the effects of Ca on the membrane binding are reversible. On the other hand, the perforin-mediated lysis of target cells was temp-dependent and also required the presence of Ca in the reaction mixture (Km = 0.05 mM). The difference between the Km values for the membrane binding and lytic activity suggests the presence of two distinct Ca-requiring steps in perforin-mediated target cell lysis.

Animals↗
PubMed1990

Antibody against the C-terminal portion of dystrophin crossreacts with the 400 kDa protein in the pia mater of dystrophin-deficient mdx mouse brain.

The mdx mouse is an animal model for X-linked Duchenne muscular dystrophy. A polyclonal antibody against a synthetic peptide IV equivalent to the C-terminal portion (amino acids 3495-3544) of dystrophin crossreacted with a 400 kDa protein in the brain and the spinal cord of mdx mouse, as well as in the control B10 mouse. However, the protein did not crossreact with the polyclonal antibody raised against the N-terminal portion of dystrophin peptide I (amino acids 215-264). Immunofluorescent micrography revealed that the outside of the small arteries and the pia mater of the brain strongly reacted with the anti-peptide IV antibody. These results strongly suggest the presence of a crossreactive protein other than dystrophin, possibly a dystrophin-related autosomal gene product, in the pia mater.

Animals↗
PubMed1990

[A case of Becker muscular dystrophy with schizophrenic symptoms].

A 23-year-old male patient with Becker muscular dystrophy (BMD) who showed schizophrenic symptoms was reported. He tumbled easily and was poor at running since age at 8 years. He had difficulty in climbing stairs and was idle away all day long since age at 21 years. Although his premorbid personality was not schizoid, he showed auditory hallucinations and delusions without any psychogenetic moment at the age of 23. At first, he seemed to be schizophrenic, but after the treatment with antipsychotics, he always had an insight into his disease and exhibited natural emotional communication. He showed no autism and character changes. According to the Wechsler Adult Intelligence Scale (WAIS), intellectual impairment was notified (total IQ58). Neurological examinations revealed weakness and atrophy of muscles in the proximal part of his lower extremities, and pseudohypertrophy of calves. In the serum enzyme, serum creatine kinase (CK) level was elevated (700 U/L). Abnormal Q waves appeared in the leads, II, III, aVF, V5, V6 on the electrocardiogram (ECG), and the finding of the echocardiography suggested dilated cardiomyopathy. The electroencephalogram (EEG) revealed the basic rhythm of 9-10 Hz with 0 activities of 6-7 Hz which were predominant in frontparietal and central leads. The electromyogram (EMG) revealed a myopathic pattern with low voltage and short duration. A muscle biopsy from right biceps brachii disclosed the abnormal immunofluorescent staining pattern of dystrophin which is consistent with BMD patient, i.e., "patchy," discontinuous and faint immunoreaction at surface membrane of the fiber. Both molecular weight (380 kd: n = 400) and amount (30%; n = 100) of dystrophin were reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Immune effector mechanisms in inflammatory myopathies.

PM, IBM, and DM represent the commonly occurring inflammatory myopathies. In DM, the effector response appears to be predominantly humoral and directed against intramuscular blood vessels; a local humoral response may occur in muscle itself. Capillary lysis precedes other pathologic changes, suggesting that the capillary endothelium is an early and possibly primary target of the immune response. Questions remain about the role of immune complexes versus circulating antibodies, whether the muscle fiber injury can be explained by ischemia alone, and the possible role of endomysial CD8+ T cells. In PM and IBM, there is evidence for T-cell mediated cytotoxicity against the muscle fibers; however, muscle fiber destruction also could result from antibody-dependent complement-mediated lysis of the sarcolemma. Questions remain about the identity of the muscle fiber surface antigen(s) recognized by T cells and the molecular mechanisms of T-cell-mediated muscle fiber destruction.

Antigen-Antibody Complex↗
PubMed1990

[A manifesting carrier of Duchenne muscular dystrophy presenting mosaic distribution of dystrophin negative and positive muscle fibers].

A 25-year-old female patient with an approximate 10-year-history of slowly progressive muscle weakness was diagnosed as a manifesting carrier of Duchenne muscular dystrophy (DMD) because her muscle biopsy showed scattered fibers with no dystrophin on immunohistochemical staining. She had no family history of neuromuscular disorders. She was in good health until about 14 years of age, when she developed muscle weakness and atrophy of the extremities with slow aggravation. On admission at the age of 25 years, she had asymmetrical muscle atrophy in the lower extremities; the left femur, right femur, left crus, and right crus measured 36.0, 40.5, 31.5, and 35.5 cm in circumference, respectively. However, the muscle weakness of the extremities was symmetrical with no laterality, and the proximal muscles in the lower extremities were predominantly affected to 3+/5 MMT test. She walked with a mild wadding manner and stood up with Gower' maneuver. Deep tendon reflexes of the extremities were almost normoactive with no pathologic reflexes. As to laboratory findings, serum enzymes of muscular origin were elevated; GOT was 44 IU/l, GPT 60 IU/l, LDH 829 IU/l, CK 4238 IU/l, and aldolase 31 SL units. The electromyogram showed myopathic changes mixed with some neurogenic components. Peripheral nerve conduction velocity was normal. A computed tomography of the skeletal muscles showed more marked atrophy and lower density in the left lower extremity than in the right. The biopsied left gastrocnemius muscle demonstrated a marked variation in fiber size with some necrotic and regenerating fibers. On immunohistochemical stain with anti-dystrophin antibody, the dystrophin negative fibers were scattered among positive fibers in a mosaic distribution.

Adult↗
PubMed1990

[A case of Becker muscular dystrophy presenting cardiac failure as an initial symptom].

Was reported a 23-year-old man with Becker muscular dystrophy (BMD), manifesting heart failure as an initial symptom. He had admitted to a hospital because of his sudden exertional dyspnea due to dilated cardiomyopathy. Because of elevated serum CK level, he had admitted to our hospital for further clinical evaluation. His uncle and male cousin were affected by a mild progressive muscle weakness since second decades. Physically, his intelligence was slightly below the average (WAIS total IQ 71). There was a slight weakness in his pelvic and shoulder girdle muscles. Pseudohypertrophy was observed in calves and tongue. Serum CK level was markedly elevated to ten times of the upper normal limits. Both EMG and muscle biopsy examinations revealed mild myopathic changes. Electrocardiogram showed tall R waves in leads V1 and V2, abnormal Q waves in I, aVL, V5 and V6 and flattened T waves in V5 and V6. On immunostaining of the biopsied skeletal muscle, patchy appearance of dystrophin on the surface membrane of the fiber was detected, which is consistent with BMD. Myocardiac damages in BMD are not always related either to the duration or the severity of the skeletal muscle weakness, as shown in our present case. The possibility that subclinical BMD is one of causes for dilated cardiomyopathy always must be considered.

Adult↗