• Physical Therapy Korea
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• v.6 no.3
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• pp.72-81
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• 1999

The purpose of this study was to identify the differences in pulmonary functioning after respiratory exercise with IPPB (Intermittent Positive Pressure Breather) in patients with progressive muscular dystrophy (PMD). The subjects were 46 patients with PMD who were admitted to the Rehabilitation Medicine Department of Youngdong Severance Hospital. The subjects were assigned into one of 2 groups. The control group received comprehensive treatments such as ROM exercise, deep breathing exercise, moist hot packs, and ultrasound twice a day while admitted at the Rehabilitation Medicine Department. Unlike the control group, the subjects at the experimental group received respiratory exercise treatment with IPPB. The subjects were admitted for 10~19 days, and the average length of hospital stay was 12.2 days. Pulmonary functioning was evaluated at admission and discharge by SENSOR MEDICS. The data were analyzed by a paired t-test and a independent t-test. The results were as follows: 1) The change of each parameter of pulmonary function tests were significantly improved in all groups after respiratory exercise treatment during admission (p<0.05). 2) By comparing the change of each parameter of pulmonary function tests between the experimental group and control group, the parameters of vital capacity (VC), forced vital capacity, forced vital capacity predicted (FVCP) and forced expiratory volume in 1 second (FEV1) were significantly improved in the experimental group which had received the pulmonary exercise treatment with IPPB (p<0.05). In conclusion, this study suggests that the pulmonary exercise treatments with IPPB facilitated improvement in the pulmonary functioning for the PMD patients during their hospital stay.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.539-547
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• 2019

Anoctamin 5 (ANO5)/TMEM16E belongs to a member of the ANO/TMEM16 family member of anion channels. However, it is a matter of debate whether ANO5 functions as a genuine plasma membrane chloride channel. It has been recognized that mutations in the ANO5 gene cause many skeletal muscle diseases such as limb girdle muscular dystrophy type 2L (LGMD2L) and Miyoshi muscular dystrophy type 3 (MMD3) in human. However, the molecular mechanisms of the skeletal myopathies caused by ANO5 defects are poorly understood. To understand the role of ANO5 in skeletal muscle development and function, we silenced the ANO5 gene in C2C12 myoblasts and evaluated whether it impairs myogenesis and myotube function. ANO5 knockdown (ANO5-KD) by shRNA resulted in clustered or aggregated nuclei at the body of myotubes without affecting differentiation or myotube formation. Nuclear positioning defect of ANO5-KD myotubes was accompanied with reduced expression of Kif5b protein, a kinesin-related motor protein that controls nuclear transport during myogenesis. ANO5-KD impaired depolarization-induced $[Ca2^{+}]_i$ transient and reduced sarcoplasmic reticulum (SR) $Ca^{2+}$ storage. ANO5-KD resulted in reduced protein expression of the dihydropyridine receptor (DHPR) and SR $Ca^{2+}-ATPase$ subtype 1. In addition, ANO5-KD compromised co-localization between DHPR and ryanodine receptor subtype 1. It is concluded that ANO5-KD causes nuclear positioning defect by reduction of Kif5b expression, and compromises $Ca^{2+}$ signaling by downregulating the expression of DHPR and SERCA proteins.

• Journal of Life Science
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• v.31 no.10
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• pp.913-921
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• 2021

Limb-girdle muscular dystrophy (LGMD) which is characterized by progressive muscle weakening of the hip and shoulder shows both dominant and recessive inheritances with many pathogenic genes including TTN. This study performed to identify genetic causes of a male patient with late onset (45 years old) autosomal recessive LGMD and atrial flutter. By application of the whole exome sequencing, we identified bi-allelic variants of TTN gene in the patient. One allele had a single missense variant of [c.24124G>T (p.V8042F)], while the other allele consisted of three missense variants of [c.29222G>C (p.R9741P) + c.67490A>G (p.H22497R) + c.75376C>T (p.R25126C)]. The p.V8042F allele was transmitted from his mother, while the other haplotype allele was putatively transmitted from his father. His two unaffected sons had only the p.R9741P. These variants have been not reported or rarely reported in the public human genome databases (1,000 Genome, gnomAD, and KRGDB). Most variants were located in the highly conserved immunoglobulin or fibronectin domains and were predicted to be pathogenic by the in silico analyses. The TTN giant protein plays a key role in muscle assembly, force transmission at the Z-line, and maintenance of resting tension in the I-band. In conclusion, we think that these bi-allelic compound heterozygous mutations may play a role as the genetic causes of the LGMD phenotype.

• Journal of Genetic Medicine
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• v.1 no.1
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• pp.33-37
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• 1997

Spinal muscular atrophy (SMA) is the second most common fatal disease of childhood with autosomal dominant mode of inheritance, and in its less severe form the third most common neuromuscular disease of childhood after Duchenne muscular dystrophy. The genetic defect was found to be on the long arm of chromosome 5 (5q11.2-q13.3) where many genes and microsatellite markers were missing. One of the most important genes is the Survival Motor Neuron (SMN) gene which is homozygously missing in 90% of SMA patients. Another important gene, the Neuronal Apoptosis Inhibitory Protein (NAIP) gene was found to be defective in 67% of SMA type I patients. Studies so far suggest SMA occurs when the genes on the long arm of chromosome 5 are mutated or deleted. Recently our hospital encountered 2 SMA patients of type I and II respectively. These patients both had homozygously defective SMN genes but intact NAIP genes. We are reporting these cases with bibliographic review and discussion. Korean SMA patients presumably have defects in SMN genes similar to those found in European patients, although the significance of NAIP genes remains to be established. SMN gene defects can be easily diagnosed using PCR and restriction enzymes, and this method could be applied towards convenient prenatal diagnosis and towards screening for family members at risk.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.48-54
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• 2017

Purpose: Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal-recessive disorder characterized by early-onset hypotonia associated with brain malformations in dystroglycanopathy. Although the wide spectrum of congenital muscular dystrophies causes difficulty in diagnosis, correlating the genotype with the clinical phenotype can help diagnose FCMD. Here, we evaluated the correlation of targeted molecular genetic analysis of FKTN gene mutation with the FCMD phenotype. Methods: This study was conducted retrospectively with 9 subjects. Inclusion criteria included clinical symptoms characterized by early-onset hypotonia with magnetic resonance imaging (MRI) featuring brain malformations. FKTN gene-alteration analysis was performed using various FKTN gene-analysis methods, including sequencing. Results: Among the 9 subjects studied, 4 (44.4%) were male and 5 (55.6%) were female. The median age of onset of the first symptom was 3.1 months. The first symptom was a delayed milestone in 6 cases (66.7%). All 9 subjects (100%) presented with early-onset hypotonia and global delayed development. All subjects presented with cortical malformation in their brain MRIs. Of the 9 subjects, 6 subjects had previously undergone muscle biopsy and 4 cases (4/6; 66.7%) showed dystrophic or myopathic features. Pathogenic mutations causing FCMD were identified in 3 cases. Conclusions: In this study, all 3 subjects with FKTN mutations showed important MRI findings (pachygyria and cerebellar dysplasia). These data suggest that patients with characteristic phenotypes who show pachygyria and cerebellar abnormalities in brain MRIs may have a high probability of being diagnosed with FCMD.

• BMB Reports
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• v.51 no.7
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• pp.327-337
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• 2018

Lamin A and its alternative splicing product Lamin C are the key intermediate filaments (IFs) of the inner nuclear membrane intermediate filament. Lamin A/C forms the inner nuclear mesh with Lamin B and works as a frame with a nuclear shape. In addition to supporting the function of nucleus, nuclear lamins perform important roles such as holding the nuclear pore complex and chromatin. However, mutations on the Lamin A or Lamin B related proteins induce various types of human genetic disorders and diseases including premature aging syndromes, muscular dystrophy, lipodystrophy and neuropathy. In this review, we briefly overview the relevance of genetic mutations of Lamin A, human disorders and laminopathies. We also discuss a mouse model for genetic diseases. Finally, we describe the current treatment for laminopathies.

• BMB Reports
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• v.49 no.8
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• pp.414-423
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• 2016

MG53 is a member of the TRIM-family protein that acts as a key component of the cell membrane repair machinery. MG53 is also an E3-ligase that ubiquinates insulin receptor substrate-1 and controls insulin signaling in skeletal muscle cells. Since its discovery in 2009, research efforts have been devoted to translate this basic discovery into clinical applications in human degenerative and metabolic diseases. This review article highlights the dual function of MG53 in cell membrane repair and insulin signaling, the mechanism that underlies the control of MG53 function, and the therapeutic value of targeting MG53 function in regenerative medicine.

• 대한생식의학회:학술대회논문집
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• 2003.12a
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• pp.82-83
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• 2003

• Journal of Chest Surgery
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• v.55 no.1
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• pp.88-90
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• 2022

Tracheo-innominate artery fistula (TIF) is a rare, life-threatening complication of tracheostomy that makes it difficult to secure the airway due to massive bleeding, constituting a medical emergency. Therefore, most successful surgical treatments include innominate artery debridement and tracheal fistula repair. Herein, we report a case of successful surgical treatment of a TIF while maintaining cerebral blood flow through an artificial vascular graft.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.1-8
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• 2005

Myotonic Dystrophies type 1 and 2 (DM1/2) are neuromuscular disorders which belong to a group of genetic diseases caused by unstable CTG triplet repeat (DM1) and CCTG tetranucleotide repeat (DM2) expansions. In DM1, CTG repeats are located within the 3' untranslated region of myotonin protein kinase (DMPK) gene on chromosome 19q. DM2 is caused by expansion of CCTG repeats located in the first intron of a gene coding for zinc finger factor 9 on chromosome 3q. The CTG and CCTG expansions are located in untranslated regions and are expressed as pre-mRNAs in nuclei (DM1 and DM2) and as mRNA in cytoplasm (DM1). Investigations of molecular alterations in DM1 discovered a new molecular mechanism responsible for this disease. Expansion of un-translated CUG repeats in the mutant DMPK mRNA disrupts biological functions of two CUG-binding proteins, CUGBP and MNBL. These proteins regulate translation and splicing of mRNAs coding for proteins which play a key role in skeletal muscle function. Expansion of CUG repeats alters these two stages of RNA metabolism in DM1 by titrating CUGBP1 and MNBL into mutant DMPK mRNA-protein complexes. Mouse models, in which levels of CUGBP1 and MNBL were modulated to mimic DM1, showed several symptoms of DM1 disease including muscular dystrophy, cataracts and myotonia. Mis-regulated levels of CUGBP1 in newborn mice cause a delay of muscle development mimicking muscle symptoms of congenital form of DM1 disease. Since expansion of CCTG repeats in DM2 is also located in untranslated region, it is predicted that DM2 mechanisms might be similar to those observed in DM1. However, differences in clinical phenotypes of DM1 and DM2 suggest some specific features in molecular pathways in both diseases. Recent publications suggest that number of pathways affected by RNA CUG and CCUG repeats could be larger than initially thought. Detailed studies of these pathways will help in developing therapy for patients affected with DM1 and DM2.