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Kazuma Sugie

Publications and source records attributed to Kazuma Sugie.

13 recordsLinked to original sources
PubMed2006

Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia.

We showed that humanin (HN), an endogenous peptide against Alzheimer disease-related insults, was expressed in muscles of patients with chronic progressive external ophthalmoplegia (CPEO), a major mitochondrial disease. Because HN was recently found to block proapoptotic Bax function and exert its versatile cytoprotective effects in association with an increase in ATP levels, HN expression may thus reflect a physiological response against degenerative changes in the muscles of patients with CPEO. We found HN expression in all four patients examined, each of whom had different mitochondrial DNA mutations including two different single DNA deletions, multiple deletions, and no major mutations detected. We also found that HN expression was not linked to focal cytochrome c deficiency, strongly associated with the subtype of CPEO with single deletions. These results suggest that HN expression is more closely related to degenerative changes in all types of CPEO. Notably, HN was also expressed in non-degenerative muscle fibers of patients with CPEO or Leigh syndrome, who had the 8993T>G mutation in the mitochondrial ATPase 6 gene known to be associated with impaired ATP synthesis. Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities.

Adolescent↗
PubMed2005

Novel representation of astasia associated with posterior cingulate infarction.

BACKGROUND AND PURPOSE: The representation elicited in the cingulate motor area has been demonstrated in animals, but remains unclear in humans. In particular, the representation and pathogenic mechanisms of the posterior cingulate cortex are poorly understood, especially in humans. We describe a case of posterior cingulate infarction associated with contralateral astasia. CASE DESCRIPTION: A 67-year-old right-handed man with a 10-year history of hypertension suddenly presented with right-sided pulsion on attempting to stand or sit. On the following day, he could not maintain a sitting position. The patient immediately fell to the floor because of instability, characterized by marked right-sided pulsion despite no muscle weakness, sensorial deficits, or cerebellar ataxia. Magnetic resolution imaging of the brain showed abnormal intensity in the posterior parts of the cingulate, with no other clinically significant lesions. CONCLUSIONS: Because the cingulate motor area is connected to the vestibulocerebellar system through the thalamic nuclei, disruption of this connection by posterior cingulate infarction may result in astasia.

Aged↗
PubMed2005

Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent.

Humanin (HN) was originally identified as an endogenous peptide that protects neuronal cells from apoptosis induced by various types of Alzheimer's disease-related insults. We have previously indicated that HN increases cellular ATP levels and speculated that this peptide may rescue energy-deficient cells in mitochondrial disorders. Here, we report, for the first time, increased HN expression in skeletal muscles from patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). HN was strongly positive in all ragged-red fibers (RRFs) and some non-RRFs, and most of them were type 1 fibers generally requiring higher energy than type 2 fibers. HN in these fibers was localized in mitochondria. HN expression was also increased in small arteries that strongly reacted for succinate dehydrogenase. Our experiments on muscular TE671 cells indicated the possibility that synthesized HN increases cellular ATP levels by directly acting on mitochondria. From these in vivo and in vitro findings, we propose that HN expression might be induced in response to the energy crisis within affected fibers and vessels in MELAS muscles and further be a possible therapeutic candidate for MELAS.

Adenosine Triphosphatases↗
PubMed2005

Autophagic vacuoles with sarcolemmal features delineate Danon disease and related myopathies.

Among the autophagic vacuolar myopathies (AVMs), a subgroup is characterized pathologically by unusual autophagic vacuoles with sarcolemmal features (AVSF) and includes Danon disease and X-linked myopathy with excessive autophagy. The diagnostic importance and detailed morphologic features of AVSF in different AVMs have not been well established, and the mechanism of AVSF formation is not known. To address these issues, we have performed detailed histologic studies of myopathies with AVSF and other AVMs. In Danon disease and related AVMs, at the light microscopic level, autophagic vacuoles appeared to be accumulations of lysosomes, which, by electron microscopy consisted of clusters of autophagic vacuoles, indicative of autolysosomes. Some autolysosomes were surrounded by membranes with sarcolemmal proteins, acetylcholinesterase activity, and basal lamina. In Danon disease, the number of fibers with AVSF increased linearly with age while the number with autolysosomal accumulations decreased slightly, suggesting that AVSF are produced secondarily in response to autolysosomes. Most of the AVSF form enclosed spaces, indicating that the vacuolar membranes may be formed in situ rather than through sarcolemmal indentation. This unique intracytoplasmic membrane structure was not found in other AVMs. In conclusion, AVSF with acetylcholinesterase activity are autolysosomes surrounded by secondarily generated intracytoplasmic sarcolemma-like structure and delineates a subgroup of AVMs.

Acetylcholinesterase↗
PubMed2004

Two novel CAV3 gene mutations in Japanese families.

Caveolin-3 deficiency is a rare, autosomal dominant, muscle disorder caused by caveolin-3 gene (CAV3) mutations and consists of four clinical phenotypes: limb-girdle muscular dystrophy type 1C (LGMD-1C), rippling muscle disease, distal myopathy, and familial hyperCKemia. So far, only 13 mutations have been reported. We here report two novel heterozygous mutations, 96C>G (N32K) and 128T>A (V43E), in the CAV3 gene in two unrelated Japanese families with LGMD-1C. Both probands presented with elevated serum CK level with calf muscle hypertrophy in their childhood but without apparent muscle weakness. However, their mothers showed mild limb-girdle weakness in addition to high CK level. Caveolin-3 was deficient and caveolae were lacking in muscles from both patients. Our data confirm that caveolin-3 deficiency causes LGMD-1C and expand the variability in CAV3 gene mutations.

Adult↗
PubMed2004

Subcellular localization of fukutin and fukutin-related protein in muscle cells.

Fukuyama-type congenital muscular dystrophy and congenital muscular dystrophy 1C are congenital muscular dystrophies that commonly display reduced levels of glycosylation of alpha-dystroglycan in skeletal muscle. The genes responsible for these disorders are fukutin and fukutin-related protein (FKRP), respectively. Both gene products are thought to be glycosyltransferases, but their functions have not been established. In this study, we determined their subcellular localizations in cultured skeletal myocytes. FKRP localizes in rough endoplasmic reticulum, while fukutin localizes in the cis-Golgi compartment. FKRP was also localized in rough endoplasmic reticulum in skeletal muscle biopsy sample. Our data suggest that fukutin and FKRP may be involved at different steps in O-mannosylglycan synthesis of alpha-dystroglycan, and FKRP is most likely involved in the initial step in this synthesis.

Adult↗
PubMed2004

[Immunohistochemical studies of a variant of congenital muscular dystrophy].

Three Japanese patients from 2 families had a phenotype indistinguishable from that of Fukuyama-type congenital muscular dystrophy (FCMD). A full mutational analysis of the fukutin gene, however, revealed neither a 3 kb insertion (the Japanese founder mutation) nor a point mutation. A RT-PCR analysis of one of the patients revealed a normal expression of the fukutin transcript, suggesting that they have a new variant of CMD. An immunohistochemical analysis of the muscle of one case showed that the immunoreaction to alpha-dystroglycan (DG) was barely detectable on the surface membranes of muscle fibers. Immunoreactions to beta-DG, dystrophin, laminin alpha-2 chain and sarcoglycan were normal. These findings raise the possibility that the abnormality of alpha-DG is integral to the pathology seen in this variant of CMD. Analysis of POMGnT1 gene, which is causative of muscle-eye-brain disease, revealed no mutation in this case.

Child, Preschool↗
PubMed2003

Characterization of Danon disease in a male patient and his affected mother.

Danon disease, primary lysosome-associated membrane protein-2 (LAMP-2) deficiency, is histologically characterized by unusual vacuoles bound by membranes with sarcolemmal features in skeletal muscle. We studied skeletal muscle specimens from a male patient with genetically confirmed Danon disease who had two muscle biopsies, at age 20 months and 16 years, and from his mother with cardiomyopathy but without clinically apparent skeletal myopathy. In the patient, the number of vacuoles increased over the 14-year interval between biopsies, suggesting that the number of vacuolated fibers increases with age, and correlates with the development of muscle symptoms. In contrast, in the muscle biopsy from the mother there were no vacuoles even though she had decreased LAMP-2.

Adolescent↗
PubMed2003

[Merosin-positive congenital muscular dystrophy with early orthopaedic problems in relation to Ullrich's disease].

We report three patients with sporadic merosin-positive congenital muscular dystrophy (CMD) with torticollis and/or developmental dislocation of the hip in early childhood. Diagnosis of merosin-positive CMD was based on their clinical and dystrophic muscle biopsy findings. At the age 13 months, patient 1 was found to have developmental dislocation of both hips, which was surgically treated at 5 years. Patient 2 had severe torticollis and contracture of both hip joints which had been present since the neonatal period, and underwent repair of the torticollis at 2 years. Patient 3 was found to have developmental dislocation of the left hip at one month of age. Although she had generalized muscle hypotonia she learned to walk at 23 months. She had no facial muscle involvement nor contracture of joints, but had hyperlaxity of distal joints. Her muscle biopsy showed complete collagen VI deficiency immunohistochemically. In contrast to merosin-deficient CMD, merosin-positive CMD appears to be a group of heterogeneous diseases. Since collagen VI was reported to be defective in Ullrich's disease, patient 3 may be diagnosed as having Ullrich's disease but had no typical clinical characteristics of the disease. Further study is needed to identify the pathogenetic mechanism of congenital muscular dystrophy with early joint abnormalities to determine whether there is a primary abnormality of the connective tissue including collagen VI.

Adolescent↗
PubMed2002

Expression of the costimulatory molecule BB-1 and its receptors in patients with scleroderma-polymyositis overlap syndrome.

We investigated expression of costimulatory molecules BB-1, B7-1 (CD80), B7-2 (CD86), and their counter-receptors CD28 and CTLA-4 (CD152) in muscle biopsy specimens of patients with scleroderma-polymyositis overlap syndrome (SSc-PM), primary polymyositis (PM), and other related diseases to examine whether the muscle fibers in patients with SSc-PM behave as antigen-presenting cells (APCs). The major histocompatibility (MHC) class II-positive muscle fibers of SSc-PM patients reacted with monoclonal antibodies (mAb) against BB-1 but not against B7-1 or B7-2. The CD4+ T cells expressed the counter-receptors CD28 and CTLA-4, and bound with the BB-1-positive muscle fibers in cell-to-cell contact. Our findings show that muscle fibers in patients with SSc-PM function as "professional" APCs in a way distinct from muscle fibers in patients with primary PM.

Abatacept↗
PubMed2002

Hereditary motor and sensory neuropathy with minifascicle formation in a patient with 46XY pure gonadal dysgenesis: a new clinical entity.

This case report is of a patient with 46XY pure gonadal dysgenesis, who presented with chronic progressive motor and sensory polyneuropathy. The sural nerve biopsy exhibited minifascicle formations accompanied by a marked decrease in myelinated fibers. This is the first report of polyneuropathy with minifascicle formations in 46XY pure gonadal dysgenesis. Because a similar polyneuropathy was recently reported in a case with 46XY partial gonadal dysgenesis, it is possible that these cases represent a new type of hereditary motor and sensory neuropathy associated with gonadal dysgenesis.

Biopsy↗