Germinal centers are associated with postthymectomy myasthenia gravis in patients with thymoma.

BACKGROUND AND PURPOSE: Germinal centers (GCs) can be observed in the thymic tissues of patients with thymoma-associated myasthenia gravis (MG). Although an association between thymic GCs and MG has been suggested, it is unknown whether the presence of GCs could predict the development of MG after the resection of thymoma, known as postthymectomy MG. METHODS: We conducted a retrospective analysis of previously nonmyasthenic patients who underwent surgical removal of the thymoma. All available thymic tissue slides were rereviewed by a pathologist to assess for GCs. Patients were classified into GC-positive and GC-negative groups based on the presence of GCs. The incidence of postthymectomy MG was compared between the two groups, and the risk factors for postthymectomy MG were assessed. RESULTS: Of the 196 previously nonmyasthenic patients who underwent thymoma resection, 21 were GC-positive, whereas 175 were GC-negative. Postthymectomy MG developed in 11 (5.6%) patients and showed a higher incidence in the GC-positive group than in the GC-negative group (33.3% vs. 2.3%, p < 0.001). No postoperative radiotherapy and the presence of GCs were risk factors for postthymectomy MG in the univariate analysis. In multivariate analysis, invasive thymoma (hazard ratio [HR] = 9.835, 95% confidence interval [CI] = 1.358-105.372), postoperative radiotherapy (HR = 0.160, 95% CI = 0.029-0.893), and presence of GCs (HR = 15.834, 95% CI = 3.742-67.000) were significantly associated with postthymectomy MG. CONCLUSIONS: Thymic GCs may be a significant risk factor for postthymectomy MG. Even in patients with thymoma who do not show clinical symptoms of MG, postthymectomy MG should be considered, especially if thymic GCs are observed.

Anti-titin antibodies are associated with myocarditis in patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) can affect cardiac muscles with variable presentations. Myocarditis is a rare but potentially serious cardiac manifestation of MG. Although thymomas and anti-titin antibodies have been suggested as risk factors for myocarditis in patients with MG, their independent influence on myocarditis has rarely been assessed. METHODS: A retrospective chart review was conducted on 247 patients diagnosed with MG who were tested for anti-titin antibodies. Myocarditis was diagnosed on the basis of the European Society of Cardiology 2013 Task Force criteria for clinically suspected myocarditis. Patients were classified into myocarditis-positive and myocarditis-negative groups. Multivariate analysis was performed to analyze the risk factors for myocarditis. RESULTS: Of the 247 patients, 25 (10.1%) were myocarditis-positive and 222 (89.9%) were myocarditis-negative. Anti-titin antibody positivity was higher in the myocarditis-positive group than in the myocarditis-negative group (68.0% vs. 28.4%, p < 0.001). A history of MG crisis was more frequent in the myocarditis-positive group than in the myocarditis-negative group (64.0% vs. 10.4%, p < 0.001). The presence of anti-titin antibodies (odds ratio [OR] 7.906; confidence interval [CI] 2.460-25.401) and MG crisis (OR 24.807; CI 7.476-82.311) was significantly associated with myocarditis. The Cox regression model showed that the anti-titin antibody levels (hazard ratio [HR] 3.639; 95% CI 1.557-8.505) and MG crisis (HR 6.137; 95% CI 2.639-14.272) were significant risk factors for the development of myocarditis. CONCLUSION: The presence of anti-titin antibody was associated with myocarditis in patients with MG, whereas thymoma was not. Although rare, early suspicion of myocarditis could be required, especially in patients with MG having anti-titin antibodies.

Clinical Features and Brain MRI Findings in Korean Patients with AGel Amyloidosis.

PURPOSE: AGel amyloidosis is systemic amyloidosis caused by pathogenic variants in the GSN gene. In this study, we sought to characterize the clinical and brain magnetic resonance image (MRI) features of Korean patients with AGel amyloidosis. MATERIALS AND METHODS: We examined 13 patients with AGel amyloidosis from three unrelated families. Brain MRIs were performed in eight patients and eight age- and sex-matched healthy controls. Therein, we analyzed gray and white matter content using voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and FreeSurfer. RESULTS: The median age at examination was 73 (interquartile range: 64-76) years. The median age at onset of cutis laxa was 20 (interquartile range: 15-30) years. All patients over that age of 60 years had dysarthria, cutis laxa, dysphagia, and facial palsy. Two patients in their 30s had only mild cutis laxa. The median age at dysarthria onset was 66 (interquartile range: 63.5-70) years. Ophthalmoparesis was observed in three patients. No patient presented with muscle weakness of the limbs. Axial fluid-attenuated inversion recovery images of the brain showed no significant differences between the patient and control groups. Also, analysis of VBM, TBSS, and FreeSurfer revealed no significant differences in cortical thickness between patients and healthy controls at the corrected significance level. CONCLUSION: Our study outlines the clinical manifestations of prominent bulbar palsy and early-onset cutis laxa in 13 Korean patients with AGel amyloidosis and confirms that AGel amyloidosis mainly affects the peripheral nervous system rather than the central nervous system.

Nogo-A Is Critical for Pro-Inflammatory Gene Regulation in Myocytes and Macrophages.

Nogo-A (Rtn 4A), a member of the reticulon 4 (Rtn4) protein family, is a neurite outgrowth inhibitor protein that is primarily expressed in the central nervous system (CNS). However, previous studies revealed that Nogo-A was upregulated in skeletal muscles of Amyotrophic lateral sclerosis (ALS) patients. Additionally, experiments showed that endoplasmic reticulum (ER) stress marker, C/EBP homologous protein (CHOP), was upregulated in gastrocnemius muscle of a murine model of ALS. We therefore hypothesized that Nogo-A might relate to skeletal muscle diseases. According to our knocking down and overexpression results in muscle cell line (C2C12), we have found that upregulation of Nogo-A resulted in upregulation of CHOP, pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while downregulation of Nogo-A led to downregulation of CHOP, IL-6 and TNF-α. Immunofluorescence results showed that Nogo-A and CHOP were expressed by myofibers as well as tissue macrophages. Since resident macrophages share similar functions as bone marrow-derived macrophages (BMDM), we therefore, isolated macrophages from bone marrow to study the role of Nogo-A in activation of these cells. Lipopolysaccharide (LPS)-stimulated BMDM in Nogo-KO mice showed low mRNA expression of CHOP, IL-6 and TNF-α compared to BMDM in wild type (WT) mice. Interestingly, Nogo knockout (KO) BMDM exhibited lower migratory activity and phagocytic ability compared with WT BMDM after LPS treatment. In addition, mice experiments data revealed that upregulation of Nogo-A in notexin- and tunicamycin-treated muscles was associated with upregulation of CHOP, IL-6 and TNF-α in WT group, while in Nogo-KO group resulted in low expression level of CHOP, IL-6 and TNF-α. Furthermore, upregulation of Nogo-A in dystrophin-deficient (mdx) murine model, myopathy and Duchenne muscle dystrophy (DMD) clinical biopsies was associated with upregulation of CHOP, IL-6 and TNF-α. To the best of our knowledge, this is the first study to demonstrate Nogo-A as a regulator of inflammation in diseased muscle and bone marrow macrophages and that deletion of Nogo-A alleviates muscle inflammation and it can be utilized as a therapeutic target for improving muscle diseases.

Long Noncoding RNA Expression Profiling Reveals Upregulation of Uroplakin 1A and Uroplakin 1A Antisense RNA 1 under Hypoxic Conditions in Lung Cancer Cells.

Hypoxia plays important roles in cancer progression by inducing angiogenesis, metastasis, and drug resistance. However, the effects of hypoxia on long noncoding RNA (lncRNA) expression have not been clarified. Herein, we evaluated alterations in lncRNA expression in lung cancer cells under hypoxic conditions using lncRNA microarray analyses. Among 40,173 lncRNAs, 211 and 113 lncRNAs were up- and downregulated, respectively, in both A549 and NCI-H460 cells. Uroplakin 1A (UPK1A) and UPK1A-antisense RNA 1 (AS1), which showed the highest upregulation under hypoxic conditions, were selected to investigate the effects of UPK1AAS1 on the expression of UPK1A and the mechanisms of hypoxia-inducible expression. Following transfection of cells with small interfering RNA (siRNA) targeting hypoxiainducible factor 1α (HIF-1α), the hypoxia-induced expression of UPK1A and UPK1A-AS1 was significantly reduced, indicating that HIF-1α played important roles in the hypoxiainduced expression of these targets. After transfection of cells with UPK1A siRNA, UPK1A and UPK1A-AS1 levels were reduced. Moreover, transfection of cells with UPK1A-AS1 siRNA downregulated both UPK1A-AS1 and UPK1A. RNase protection assays demonstrated that UPK1A and UPK1A-AS1 formed a duplex; thus, transfection with UPK1A-AS1 siRNA decreased the RNA stability of UPK1A. Overall, these results indicated that UPK1A and UPK1A-AS1 expression increased under hypoxic conditions in a HIF-1α-dependent manner and that formation of a UPK1A/UPK1A-AS1 duplex affected RNA stability, enabling each molecule to regulate the expression of the other.

Risk of osteoporosis in patients with chronic inflammatory neuropathy- a population-based cohort study.

The risk of osteoporosis in patients with chronic inflammatory neuropathy (CIN) has not been evaluated in detail. We conducted a population-based case-control study nested in a retrospective cohort to analyze osteoporosis risk among patients with CIN using a nationwide database. Patients with CIN based on the Korean Classification of Disease diagnostic code were included and were matched to controls. A Cox proportional hazards regression model was used to evaluate the effect of CIN on osteoporosis. After propensity score matching, 585 CIN patients and 585 controls were selected. Patients with CIN had an increased osteoporosis risk (hazard ratio [HR] = 2.293, 95% confidence interval [CI] 1.460-3.601) compared with controls. The osteoporosis risk was higher among male patients with CIN than among male controls (HR = 5.404, 95% CI 2.252-12.969), while there were no significant differences among women. Among the CIN patients, the average daily dose of corticosteroids was higher in those who developed osteoporosis (19.6 mg [10.8-49.3]) than those who did not (16.2 mg [7.2-29.1], p = 0.001). The osteoporosis risk among CIN patients is higher than among controls. High risk of osteoporosis in male patients may indicate that osteoporosis in CIN patients results from the disease itself or related treatments.

MiR-200c downregulates HIF-1α and inhibits migration of lung cancer cells.

BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor with a pivotal role in physiological and pathological responses to hypoxia. While HIF-1α is known to be involved in hypoxia-induced upregulation of microRNA (miRNA) expression, HIF-1α is also targeted by miRNAs. In this study, miRNAs targeting HIF-1α were identified and their effects on its expression and downstream target genes under hypoxic conditions were investigated. Cell migration under the same conditions was also assessed. METHODS: microRNAs that target HIF-1α were screened using 3'-untranslated region luciferase (3'-UTR-luciferase) reporter assays. The expression levels of HIF-1α and its downstream target genes after transfection with miRNA were assessed using quantitative RT-PCR and western blot analyses. The effect of the miRNAs on the transcriptional activity of HIF-1α was determined using hypoxia-responsive element luciferase (HRE-luciferase) assays. Cell migration under hypoxia was examined using the wound-healing assay. RESULTS: Several of the 19 screened miRNAs considerably decreased the luciferase activity. Transfection with miR-200c had substantial impact on the expression level and transcription activity of HIF-1α. The mRNA level of HIF-1α downstream genes decreased in response to miR-200c overexpression. MiR-200c inhibited cell migration in normoxia and, to a greater extent, in hypoxia. These effects were partly reversed by HIF-1α expression under hypoxic conditions. CONCLUSION: miR-200c negatively affects hypoxia-induced responses by downregulating HIF-1α, a key regulator of hypoxia. Therefore, overexpression of miR-200c might have therapeutic potential as an anticancer agent that inhibits tumor hypoxia.

Effect of thymectomy in elderly patients with non-thymomatous generalized myasthenia gravis.

Whether thymectomy is beneficial in elderly patients with myasthenia gravis (MG) is unclear. Thus, we assessed whether conducting thymectomy in MG patients aged ≥ 50 years is beneficial. This retrospective cohort study included patients with MG between 1990 and 2018. Thymectomy and control cohorts were selected from among the population of MG patients with an age at onset of ≥ 45 years and elevated concentrations of acetylcholine-receptor antibodies. Patients with evidence of thymic malignancy were excluded. Of these patients, those who underwent thymectomy at the age of ≥ 50 years were designated as the thymectomy group and those who received only medical treatment were designated as the medical treatment group. We compared the Myasthenia Gravis Foundation of America post-intervention status between the thymectomy and medical treatment groups. Landmark analysis was conducted with the landmark set at 24 months. A total of 34 and 105 patients were classified into the thymectomy and medical treatment groups, respectively. Before landmark analysis, the thymectomy group had a higher cumulative incidence of pharmacologic remission (p = 0.009) and complete stable remission (p = 0.022) than the medical treatment group. After landmark analysis, the thymectomy group had a 2.22-fold (95% confidence interval 1.01-4.80) increased chance of achieving pharmacologic remission compared to the medical treatment group after adjustment for age, sex, and disease severity. No significant difference was observed in the rate of relapse after pharmacological remission between the thymectomy (16.7%) and medical treatment groups (21.4%). In conclusion, thymectomy may have a beneficial effect in elderly patients with non-thymomatous generalized MG.

Partial Conduction Block as an Early Nerve Conduction Finding in Neurolymphomatosis.

BACKGROUND AND PURPOSE: Neurolymphomatosis is a rare manifestation of hematological malignancy and is characterized by direct infiltration of the peripheral nervous system. The objective of this study was to identify the clinical and electrophysiological features of neurolymphomatosis. METHODS: We retrospectively analyzed the medical records of 13 patients with neurolymphomatosis. Seven (54%) of the patients were men, and the median age at symptom onset was 60.0 years. RESULTS: The most common type of underlying malignancy was diffuse large B-cell lymphoma (69%). Twelve patients had painful asymmetric neuropathies. The median survival time after diagnosis was 7 months, and 12 patients died during the study period. Thirty-eight motor nerve conduction studies (NCSs) were performed in the affected nerves. Ten and 28 motor nerves were classified into the conduction-block and simple-axon-degeneration groups, respectively. The median time interval between symptom onset and the NCS was significantly shorter in the conduction-block group than in the simple-axon-degeneration group (p=0.032). However, no significant differences in the motor nerve conduction velocities, terminal latencies, and distal compound muscle action potential amplitudes were identified between the conduction-block and simple-axon-degeneration groups. The conduction-block group showed excessive temporal dispersion in only five of the ten NCSs (50%). Follow-up NCSs revealed that partial conduction blocks had changed into axonal degeneration patterns. CONCLUSIONS: This is the first study to analyze the electrophysiological features of patients with neurolymphomatosis. Our findings showed that a partial conduction block is not rare and is an early nerve conduction abnormality in neurolymphomatosis.

FAT1 Gene Alteration in Facioscapulohumeral Muscular Dystrophy Type 1.

Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array. Recent studies revealed that the FAT1 expression is associated with disease activity of FSHD, and the FAT1 alterations result in myopathy with a FSHD-like phenotype. We describe a 59-year-old woman with both contracted D4Z4 repeat units and a FAT1 mutation. Shoulder girdle muscle weakness developed at the age of 56 years, and was followed by proximal leg weakness. When we examined her at 59 years of age, she displayed asymmetric and predominant weakness of facial and proximal muscles. Muscle biopsy showed increased variation in fiber size and multifocal degenerating fibers with lymphocytic infiltration. Southern blot analysis revealed 8 D4Z4 repeat units, and targeted sequencing of modifier genes demonstrated the c.10331 A>G variant in the FAT1 gene. This FAT1 variant has previously been reported as pathogenic variant in a patient with FSHD-like phenotype. Our study is the first report of a FAT1 mutation in a FSHD1 patient, and suggests that FAT1 alterations might work as a genetic modifier.

Clinical Characteristics of Spinal Muscular Atrophy in Korea Confirmed by Genetic Analysis.

The objective of this study was to review the clinical characteristics of patients with spinal muscular atrophy and to emphasize the importance of performing genetic mutational analysis at initial patient assessment. This is a single center oriented, retrospective, and descriptive study conducted in Seoul, South Korea. Genetic mutational analysis to detect the deletion of exon 7 of the SMN1 gene on chromosome 5q13 was performed by multiplex ligation-dependent probe amplification. Clinical features, electrodiagnostic study results, muscle biopsy results, and laboratory test results were reviewed from patient medical records. Of all 28 patients (15 males and 13 females), all showed bilateral symmetric proximal dominant weakness. Among them, 3 patients were classified as type I, 14 patients as type II, and 11 patients as type III. Twenty-five patients had scoliosis and eight of these patients received surgical treatment for scoliosis with improvement in clinical outcomes. Ventilator support was used in 15 patients. In terms of the diagnostic process, 15 patients had completed an electrodiagnostic study and muscle biopsy before genetic testing, and six of these patients were initially misdiagnosed with myopathy. Owing to the similar clinical features of SMA and congenital myopathy, an electrodiagnostic study and muscle biopsy could create confusion in the correct diagnosis in some cases. Therefore, it is recommended that genetic mutation analysis should be conducted along with an electrodiagnostic study or muscle biopsy in the diagnostic process for spinal muscular atrophy.

The Epidemiology of Myasthenia Gravis in Korea.

PURPOSE: An epidemiological study of myasthenia gravis (MG) has not been performed in Korea. The purpose of this study was to estimate the prevalence and incidence of MG in Korea. MATERIALS AND METHODS: Health Insurance Review and Assessment (HIRA) data from 2010 to 2014 were searched for MG codes as defined by the International Classification of Diseases, 10th revision. After identifying MG cases, we estimated the prevalence and annual incidence of MG based on the HIRA database and Korean population data. RESULTS: During the study period, 10138 MG cases were identified. The prevalence of MG was 10.42 cases per 100000 people in 2010 and this increased every year to 12.99 cases per 100000 people in 2014. The average incidence of MG between 2011 and 2014 was 0.69 cases per 100000 person-years. The prevalence and incidence were higher in the older (≥ 50 years) age group than in the younger (<50 years) age group [prevalence: 9.26 vs. 19.24 per 100000, relative risk 2.077, 95% confidence interval (CI) 1.976-2.183, p<0.001; incidence: 0.47 vs. 1.18 per 100000, relative risk 2.490, 95% CI 2.006-3.091, p<0.001]. CONCLUSION: This study was the first nationwide population-based epidemiological study of MG in Korea. The prevalence and incidence of MG were consistent with those of previous studies. We found an increase in the prevalence of MG and a predominance of elderly MG patients.

Spinal cord involvement in Behçet's disease.

BACKGROUND: Spinal cord involvement in Behçet's disease is not well studied. OBJECTIVE: To evaluate the clinical, laboratory and magnetic resonance imaging characteristics of spinal cord involvement in Behçet's disease. METHODS: We retrospectively reviewed 10 spinal cord involvements in seven patients with Behçet's disease. RESULTS: The median age of onset for spinal cord involvement was 32 (23-45 years). Two patients showed a secondary progressive course. Cerebrospinal fluid findings revealed mild to moderate pleocytosis and/or elevated protein levels. In eight spinal cord involvements, the lesion was longer than three vertebrae. Serum anti-aquaporin-4 antibody was negative in all four patients tested. CONCLUSIONS: Longitudinally extensive transverse myelitis is a characteristic manifestation of spinal cord involvement in Behçet's disease.

Serum interleukin-27 expression in patients with myasthenia gravis.

Myasthenia gravis (MG)(1) is an autoimmune disease directed at the neuromuscular junction, and cytokines are thought to contribute to its immunopathogenesis. Interleukin-27 (IL-27)(2) plays a complex and pleiotropic role in immune responses associated with T helper cells. To assess the role of IL-27 in MG, we determined serum IL-27 levels in MG patients (n=32) compared to healthy controls (n=50). The median serum IL-27 level was significantly higher in MG patients (35.947pg/mL) than in controls (19.885pg/mL). Furthermore, serum IL-27 was significantly higher in early onset MG. This study suggests the possibility that IL-27 might contribute to MG pathogenesis or immunoregulation.

MicroRNA library screening identifies growth-suppressive microRNAs that regulate genes involved in cell cycle progression and apoptosis.

Micro(mi)RNAs play important and varied roles in tumorigenesis; however, the full repertoire of miRNAs that affect cancer cell growth is not known. In this study, an miRNA library was screened to identify those that affect the growth of A549 tumor cells. Among 300 miRNAs, miR-28-5p, -323-5p, -510-5p, -552-3p, and -608 were the most effective in inhibiting cell growth. More specifically, overexpressing miR-28-5p, -323-5p, and -510-5p induced G1 arrest, as determined by flow cytometry, whereas that of miR-608 induced cell death in a caspase-dependent manner. Moreover, several genes involved in apoptosis and cell cycle progression were downregulated upon overexpression of each of the five miRNAs, with the functional targets of miR-552-3p and miR-608 confirmed by microarray, quantitative real-time PCR, and luciferase reporter assay. In miR-608-transfected cells, B cell lymphoma 2-like 1 (BCL2L1), D-type cyclin 1 (CCND1), CCND3, cytochrome b5 reductase 3 (CYB5R3), phosphoinositide 3-kinase regulatory subunit 2 (PIK3R2), specificity protein 1 (SP1), and phosphorylated Akt were all downregulated, while Bcl-2-interacting killer (BIK) was upregulated. Moreover, miR-608 was determined to have a suppressive function on tumor growth in an NCI-H460 xenograft model. These findings provide insights into the roles of five miRNAs in growth inhibition and their potential function as cancer therapeutics.

Predictive factors for myasthenic crisis after videoscopic thymectomy in patients with myasthenia gravis.

INTRODUCTION: Predictive factors for myasthenic crisis after transsternal thymectomy have been reported, but little is known about myasthenic crisis after videoscopic thymectomy (MCAVT). METHODS: We investigated 146 myasthenia gravis patients who underwent videoscopic thymectomy. RESULTS: Patients with MCAVT had a lower forced vital capacity (FVC) (2.1 vs. 3.0 L, P < 0.001) than those without. Low-frequency repetitive nerve stimulation showed decremental responses of the orbicularis oculi (47.1% vs. 18.1%, P = 0.001) and nasalis muscles (54.1% vs. 21.4%, P < 0.001), which were more pronounced in patients with MCAVT than those without. According to multivariate analysis, FVC (OR 0.144, 95% confidence interval [CI], 0.044-0.479, P = 0.002) and decremental response of orbicularis oculi (odds ratio, 1.029; 95% CI, 1.001-1.058, P = 0.044) were independently associated with MCAVT. CONCLUSIONS: FVC and decremental response of orbicularis oculi were associated with MCAVT.

A rare case of hepatic T-cell rich B-cell lymphoma (TCRBCL) in a juvenile dog.

A 7-month-old castrated male French Bull dog was presented with vomiting, lethargy, anorexia and weight loss of 2 weeks duration. The patient's history and clinical manifestations of suspected hepatopathy were subjected to ultrasonography, radiography, biochemical investigations and cytology of hepatic lesion. The cytologic impression was hepatic lymphoma, which was later confirmed by histopathology. The neoplastic cells were strongly diffusely immunoreactive for PAX5, but not immunoreactive for CD3, and B lymphocyte specific clonal proliferation was detected using by assay of antigen receptor rearrangement. Large numbers of immunoreactive mature non-neoplastic lymphocytes were admixed with the neoplastic cell population. Therefore, the immunohistochemical results were definitively consistent with a T-cell rich B-cell lymphoma (TCRBCL). This is the first description of a hepatic TCRBCL in a juvenile dog showing a poor response to aggressive chemotherapy.

Inhibition of cell proliferation and migration by miR-509-3p that targets CDK2, Rac1, and PIK3C2A.

CDK2 is a key regulator of cell cycle progression. In this study, we screened for miRNAs targeting CDK2 using a luciferase-3'-untranslated region reporter assay. Among 11 hit miRNAs, miR-509-3p reduced CDK2 protein levels and significantly inhibited cancer cell growth. Microarray, Western blotting, and luciferase reporter analyses revealed additional targets of miR-509-3p, including Rac1 and PIK3C2A. Overexpression of miR-509-3p induced G1 cell-cycle arrest and inhibited colony formation and migration. RNAi experiments indicated that the growth-inhibitory effects of miR-509-3p may occur through down-regulation of CDK2, Rac1, and PIK3C2A. Targeting of multiple growth regulatory genes by miR-509-3p may contribute to effective anti-cancer therapy.

Whole-genome analysis in Korean patients with autoimmune myasthenia gravis.

PURPOSE: The underlying cause of myasthenia gravis (MG) is unknown, although it likely involves a genetic component. However, no common genetic variants have been unequivocally linked to autoimmune MG. We sought to identify the genetic variants associated with an increased or decreased risk of developing MG in samples from a Korean Multicenter MG Cohort. MATERIALS AND METHODS: To determine new genetic targets related to autoimmune MG, a whole genome-based single nucleotide polymorphisms (SNP) analysis was conducted using an Axiom™ Genome-Wide ASI 1 Array, comprising 598375 SNPs and samples from 109 MG patients and 150 neurologically normal controls. RESULTS: In total, 641 SNPs from five case-control associations showed p-values of less than 10⁻5. From regional analysis, we selected seven candidate genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, and SACS) for further analysis. CONCLUSION: The present study suggests that a few genetic polymorphisms, such as in RYR3, CACNA1S, and SLAMF1, might be related to autoimmune MG. Our findings also encourage further studies, particularly confirmatory studies with larger samples, to validate and analyze the association between these SNPs and autoimmune MG.

Functional outcomes in Duchenne muscular dystrophy scoliosis: comparison of the differences between surgical and nonsurgical treatment.

BACKGROUND: While most studies of Duchenne muscular dystrophy scoliosis focus on technical and radiographic indices, functional status is a more important factor to consider in the management of Duchenne muscular dystrophy. The objectives of the current study were to compare the pulmonary function, radiographic outcome, and functional recovery, with use of validated questionnaires, in surgically and nonsurgically treated patients with Duchenne muscular dystrophy who have scoliosis. METHODS: Sixty-six patients (forty treated surgically and twenty-six treated nonsurgically) with a minimum follow-up of two years were included in this study. Forced vital capacity, radiographic parameters (the Cobb angle, lordosis, and pelvic obliquity), and functional status, according to the modified Rancho scale and manual muscle test, were measured preoperatively and at the time of the final follow-up. The Muscular Dystrophy Spine Questionnaire (MDSQ) was completed at the final follow-up evaluation. RESULTS: Pulmonary function, functional scores (manual muscle test and modified Rancho scale), and radiographic measurements, except for lordosis, were similar for both groups at the time of the initial consultation (p > 0.05). At the time of the final follow-up, all radiographic parameters were significantly improved in the surgical group compared with the nonsurgical group. The mean score (and standard deviation) on the manual muscle test was not significantly different between the surgical and nonsurgical groups (23.2 ± 8.3 versus 22.8 ± 6.3; p = 0.828). The mean score on the modified Rancho scale also showed similar results in the groups (3.9 ± 0.3 and 4.04 ± 0.3, respectively; p = 0.088). The surgical group had higher mean MDSQ scores than the nonsurgical group (35.1 ± 14.7 and 26.9 ± 9.9, respectively; p = 0.008). Both groups showed a decrease in forced vital capacity at the time of the final follow-up, but the deterioration of forced vital capacity was significantly slower (p = 0.035) in the surgical group (268 ± 361 mL) than in the nonsurgical group (536 ± 323 mL). CONCLUSIONS: Surgery in patients who had Duchenne muscular dystrophy with scoliosis improved function and decreased the rate of deterioration of forced vital capacity compared with patients treated conservatively. However, the muscle power and forced vital capacity decreased in both groups.