Transcriptome analysis of skeletal muscle in dermatomyositis, polymyositis, and dysferlinopathy, using a bioinformatics approach

BackgroundPolymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies. Dysferlinopathy, caused by a dysferlin gene mutation, usually presents in late adolescence with muscle weakness, degenerative muscle changes are often accompanied by inflammatory infiltrates, often resulting in a misdiagnosis as polymyositis.ObjectiveTo identify differential biological pathways and hub genes related to polymyositis, dermatomyositis and dysferlinopathy using bioinformatics analysis for understanding the pathomechanisms and providing guidance for therapy development.MethodsWe analyzed intramuscular ribonucleic acid (RNA) sequencing data from seven dermatomyositis, eight polymyositis, eight dysferlinopathy and five control subjects. Differentially expressed genes (DEGs) were identified by using DESeq2. Enrichment analyses were performed to understand the functions and enriched pathways of DEGs. A protein–protein interaction (PPI) network was constructed, and clarified the gene cluster using the molecular complex detection tool (MCODE) analysis to identify hub genes.ResultsA total of 1,048, 179 and 3,807 DEGs were detected in DM, PM and dysferlinopathy, respectively. Enrichment analyses revealed that upregulated DEGs were involved in type 1 interferon (IFN1) signaling pathway in DM, antigen processing and presentation of peptide antigen in PM, and cellular response to stimuli in dysferlinopathy. The PPI network and MCODE cluster identified 23 genes related to type 1 interferon signaling pathway in DM, 4 genes (PDIA3, HLA-C, B2M, and TAP1) related to MHC class 1 formation and quality control in PM, and 7 genes (HSPA9, RPTOR, MTOR, LAMTOR1, LAMTOR5, ATP6V0D1, and ATP6V0B) related to cellular response to stress in dysferliniopathy.ConclusionOverexpression of genes related to the IFN1 signaling pathway and major histocompatibility complex (MHC) class I formation was identified in DM and PM, respectively. In dysferlinopathy, overexpression of HSPA9 and the mTORC1 signaling pathway genes was detected

Clinical and Pathological Characteristics of Four Korean Patients with Limb-Girdle Muscular Dystrophy type 2B

Limb-girdle muscular dystrophy type 2B (LGMD2B), a subtype of autosomal recessive limb-girdle muscular dystrophy (ARLGMD), is characterized by a relatively late onset and slow progressive course. LGMD2B is known to be caused by the loss of the dysferlin protein at sarcolemma in muscle fibers. In this study, the clinical and pathological characteristics of Korean LGMD2B patients were investigated. Seventeen patients with ARLGMD underwent muscle biopsy and the histochemical examination was performed. For the immunocytochemistry, a set of antibodies against dystrophin, α, β, γ, δ-sarcoglycans, dysferlin, caveolin-3, and β-dystroglycan was used. Four patients (24%) showed selective loss of immunoreactivity against dysferlin at the sarcolemma on the muscle specimens. Therefore, they were classified into the LGMD2B category. The age at the onset of disease ranged from 9 yr to 33 yr, and none of the patients was wheelchair bound at the neurological examination. The serum creatine kinase (CK) was high in all the patients (4010-5310 IU/L). The pathologic examination showed mild to moderate dystrophic features. These are the first Korean LGMD2B cases with a dysferlin deficiency confirmed by immunocytochemistry. The clinical, pathological, and immunocytochemical findings of the patients with LGMD2B in this study were in accordance with those of other previous reports

Artificial External Glottic Device for Passive Lung Insufflation

PURPOSE: For patients with neuromuscular disease, air stacking, which inflates the lungs to deep volumes, is important for many reasons. However, neuromuscular patients with severe glottic dysfunction or indwelling tracheostomy tubes cannot air stack effectively. For these patients, we developed a device that permits deep lung insufflations substituting for glottic function. MATERIALS AND METHODS: Thirty- seven patients with bulbar-innervated muscle weakness and/or tracheostomies were recruited. Twenty-three had amyotrophic lateral sclerosis, and 14 were tetraplegic patients due to cervical spinal cord injury. An artificial external glottic device (AEGD) was used to permit passive deep lung insufflation. In order to confirm the utility of AEGD, vital capacity, maximum insufflation capacity (MIC), and lung insufflation capacity (LIC) with AEGD (LICA) were measured. RESULTS: For 30 patients, MICs were initially zero. However, with the use of the AEGD, LICA was measurable for all patients. The mean LICA was 1,622.7±526.8 mL. Although MIC was measurable for the remaining 7 patients without utilizing the AEGD, it was significantly less than LICA, which was 1,084.3±259.9 mL and 1,862.9±248 mL, respectively (p<0.05). CONCLUSION: The AEGD permits lung insufflation by providing deeper lung volumes than possible by air stacking.ope

The Effect of Welding Residual Stress for Making Artificial Stress Corrosion Crack in the STS 304 Pipe

The stress corrosion crack is one of the fracture phenomena for the major structure components in nuclear power plant. During the operation of a power plant, stress corrosion cracks are initiated and grown especially in dissimilar weldment of primary loop components. In particular, stress corrosion crack usually occurs when the following three factors exist at the same time: susceptible material, corrosive environment, and tensile stress (residual stress included). Thus, residual stress becomes a critical factor for stress corrosion crack when it is difficult to improve the material corrosivity of the components and their environment under operating conditions. In this study, stress corrosion cracks were artificially produced on STS 304 pipe itself by control of welding residual stress. We used the instrumented indentation technique and 3D FEM analysis (using ANSYS 12) to evaluate the residual stress values in the GTAW area. We used the custom-made device for fabricating the stress corrosion crack in the inner STS 304 pipe wall. As the result of both FEM analysis and experiment, the stress corrosion crack was quickly generated and could be reproduced, and it could be controlled by welding residual stress

Assisted Cough and Pulmonary Compliance in Patients with Duchenne Muscular Dystrophy

The aim of this study was to investigate the factors affecting cough ability, and to compare the assisted cough methods in patients with Duchenne muscular dystrophy (DMD). A total seventy-one male patients with DMD were included in the study. The vital capacity (VC) and maximum insufflation capacity (MIC) were measured. The unassisted peak cough flow (UPCF) and three different techniques of assisted peak cough flow were evaluated. UPCF measurements were possible for all 71 subjects. But when performing the three different assisted cough techniques, peak cough flows (PCFs) could be obtained from only 51 subjects. The mean value of MICs (1801 ± 780 cc) was higher than that of VCs (1502 ± 765 cc) (p < 0.01). All three assisted cough methods showed a significantly higher value than the unassisted method (F=80.92, p < 0.01). The manual assisted PCF under MIC (MPCFmic) significantly exceeded those produced by manual assisted PCF (MPCF) or PCF under MIC (PCFmic). The positive correlation between the MIC, VC difference (MIC-VC), and the difference between PCFmic and UPCF (PCFmic-UPCF) was seen (r=0.572, p < 0.01). The preservation of pulmonary compliance is important for the development of an effective cough as well as assisting the compression and expulsive phases. Thus, the clinical importance of the inspiratory phase and pulmonary compliance in assisting a cough should be emphasized

Estrogen Antagonist and Development of Macular Hole

To describe the clinical and optical coherence tomography (OCT) features of a macular hole (MH) or its precursor lesion in patients treated with systemic antiestrogen agents. We reviewed the medical history of the patient, ophthalmic examination, and both fundus and OCT findings. Three female patients receiving antiestrogen therapy sought treatment for visual disturbance. All of the patients showed foveal cystic changes with outer retinal defect upon OCT. Visual improvement was achieved through surgery for the treatment of MH in two patients. Antiestrogen therapy may result in MH or its precursor lesion, in addition to perifoveal refractile deposits. OCT examination would be helpful for early detection in such cases

How Respiratory Muscle Strength Correlates with Cough Capacity in Patients with Respiratory Muscle Weakness

PURPOSE: The purpose of this study is to investigate how respiratory muscle strength correlates to cough capacity in patients with respiratory muscle weakness. MATERIALS AND METHODS: Forty-five patients with amyotrophic lateral sclerosis (ALS), 43 with cervical spinal cord injury (SCI), and 42 with Duchenne muscular dystrophy (DMD) were recruited. Pulmonary function tests including forced vital capacity (FVC) and respiratory muscle strength (maximal expiratory pressure, MEP; maximal inspiratory pressure, MIP) were performed. The correlation between respiratory muscle strength and cough capacity was analyzed. RESULTS: In the SCI group, FVC in a supine position (2,597 +/- 648 mL) was significantly higher than FVC in a sitting position (2,304 +/- 564 mL, p < 0.01). Conversely, in the ALS group, FVC sitting (1,370 +/- 604 mL) was significantly higher than in supine (1,168 +/- 599 mL, p < 0.01). In the DMD group, there was no statistically significant difference between FVC while sitting (1,342 +/- 506 mL) and FVC while supine (1,304 +/- 500 mL). In addition, the MEP and MIP of all three groups showed a significant correlation with peak cough flow (PCF) (p < 0.01, Pearson's correlation analysis). In the SCI group, MIP was more closely correlated with PCF, while in the ALS and DMD groups, MEP was more closely correlated with PCF (p < 0.01, multiple regression analysis). CONCLUSION: To generate cough flow, inspiratory muscle strength is significantly more important for SCI patients, while expiratory muscle function is significantly more important for ALS and DMD patients.ope

A Case of Duodenal Anisakiasis with Duodenal Ulcer

Humans can be incidentally parasitized by third-stage larvae of Anisakis species following the ingestion of raw or undercooked seafood. Acute gastric anisakiasis is one of the most frequently encountered complaints in Korea. However, duodenal anisakiasis with duodenal ulcer had not been reported in Korea, despite the habit of eating raw fish. In this case, a 47-year-old man was hospitalized because of sharp epigastric pain and repeated vomiting after eating raw fish 3 days previously. On admission, esophagogastroduodenoscopic examination revealed an active duodenal bulb ulcer. At 5 mm away from the ulcer margin, a whitish linear worm was found with half of its body penetrating the duodenal mucosa. Herein, we report this case of duodenal anisakiasis accompanied by duodenal ulcer