Inherited peripheral neuropathy (IPN) is caused by heterogeneous genetic mutations in more than 100 genes. So far, several treatment options for IPN have been developed and clinically evaluated using small molecules. However, gene therapy-based therapeutic strategies have not been aggressively investigated, likely due to the complexities of inheritance in IPN. Indeed, because the majority of the causative mutations of IPN lead to gainof- function rather than loss-of-function, developing a therapeutic strategy is more difficult, especially considering gene therapy for genetic diseases began with the simple idea of replacing a defective gene with a functional copy. Recent advances in gene manipulation technology have brought novel approaches to gene therapy and its clinical application for IPN treatment. For example, in addition to the classically used gene replacement for mutant genes in recessively inherited IPN, other techniques including gene addition to modify the disease phenotype, modulations of target gene expression, and techniques to edit mutant genes have been developed and evaluated as potent therapeutic strategies for dominantly inherited IPN. In this review, the current status of gene therapy for IPN and future perspectives will be discussed.

Since sclerosing hemangioma of the lung was first described by Liebow and Hubbell in 1956, there have been several reports on cases occurring as a solitary nodule; however, sclerosing hemangiomas occurring as multiple nodules are extremely rare. The histogenesis of this tumor remains controversial and there are several hypotheses of the etiology. Three separate nodules were found in a 57-year-old housewife, one found in the right middle lobe, one in the apicoposterior segment of the left upper lobe, and one in the superior segment of the left lower lobe. The only symptom or sign presented was a dry cough. Apicoposterior segmentectomy of the left upper lobe and wedge resection of the superior segment of the left lower lobe were performed. The postoperative course was uneventful and the patient was discharged on the postoperative 15th day.
Cough ; Hemangioma ; Histiocytoma, Benign Fibrous* ; Humans ; Lung Neoplasms ; Lung* ; Mastectomy, Segmental ; Middle Aged ; Pulmonary Sclerosing Hemangioma

PURPOSE: This correlational study was to examine the relationships between dementia knowledge, attitude, self-efficacy and preventive behavior of low income middled-aged women. METHODS: The subjects for this study were 125 low income middle aged women living in I city. The data were collected using the questionnaires for dementia knowledge, attitude, self-efficacy and preventive behavior. The data analysis was done by descriptive statistics, t-test, ANOVA, Pearson product moment correlation and stepwise multiple regression analysis. RESULTS: The mean of dementia knowledge was 13.96 out of 20, attitude was 43.98 out of 60, self-efficacy was 54.07 out of 75 and preventive behavior was 25.98 out of 36. The positive correlations were revealed between dementia knowledge (r=.458, p=.000), attitude (r=.498, p=.000), self-efficacy (r=.573, p=.000) and preventive behavior. The influencing factors for dementia preventive behavior were self-efficacy, belief in Buddhism and attitude which accounted for 42.5% of the total variance. CONCLUSION: Dementia knowledge, attitude and self-efficacy were identified as variables that correlate dementia preventive behavior. Also, self-efficacy is the most influential factor affecting dementia preventive behavior. On the basis of these results, it is necessary for nurses to consider using dementia knowledge and mode of efficacy expectation in order to improve dementia preventive behavior.
Buddhism ; Dementia ; Female ; Humans ; Middle Aged ; Statistics as Topic ; Surveys and Questionnaires

Extracellular beta amyloid (Aβ) plaques are the neuropathological hallmarks of Alzheimer’s disease (AD). Accordingly, reducing Aβ levels is considered a promising strategy for AD prevention. 3’-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside significantly decreased the Aβ production and this effect was accompanied with reduced sAPPβ production known as a soluble ectodomain APP fragment through β-secretases in HeLa cells overexpressing amyloid precursor proteins (APPs). This compound also increased the level of sAPPα, which is a proteolytic fragment of APP by α-secretases. In addition, 3’-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside decreased the protein level of β-secretases, but the protein levels ofA disintegrin and metalloproteinase (ADAM) family, especially ADAM10 and ADAM17, are increased. Thus, 3’-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside could be useful in the development of AD treatment in the aspect of amyloid pathology.

Extracellular beta amyloid (Aβ) plaques are the neuropathological hallmarks of Alzheimer’s disease (AD). Accordingly, reducing Aβ levels is considered a promising strategy for AD prevention. 3’-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside significantly decreased the Aβ production and this effect was accompanied with reduced sAPPβ production known as a soluble ectodomain APP fragment through β-secretases in HeLa cells overexpressing amyloid precursor proteins (APPs). This compound also increased the level of sAPPα, which is a proteolytic fragment of APP by α-secretases. In addition, 3’-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside decreased the protein level of β-secretases, but the protein levels ofA disintegrin and metalloproteinase (ADAM) family, especially ADAM10 and ADAM17, are increased. Thus, 3’-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside could be useful in the development of AD treatment in the aspect of amyloid pathology.

PURPOSE: To analyze the causes of delayed detection of lung cancer on chest radiographs. MATERIALS AND METHODS: We retrospectively reviewed 105 cases in which an initial diagnosis of lung cancer, based on anexamination of plain radiographs, had been missed or misinterpreted. All occurred between October 1993 and April1997. We reviewed the initial chest radiographs and compared the features noted with those seen on later chestradiographs and computed tomographic (CT) images. RESULTS: Undetected lung cancer was identified in 56 patients(56/105, 53.3%) It had been hidden by superim-posed structures (41, 73.2%), overlapped by combined benign diseases(12, 21.4%), or the nodules were subtle(3, 5.4%). Of the 41 lung cancers hidden by a superimposed structure, thecentral type accounted for 29 (70.7%) and the peripheral type for 12 (29.3%). The 29 central type had been hiddenby the left hilum (n=15), the right hilum (n=10), the heart (n=3), or a rib (n=1). The twelve peripheral type werehidden by a rib (n=7), the heart (n=2), the diaphragm (n=2), or the left hilum (n=1). Of the 12 lung cancersoverlapped by combined benign diseases, pulmonary tuberculosis (n=6), pleural effusion (n=4), congestive heartfailure (n=1), and dif-fuse interstitial lung disease (n=1) were present at the time of interpretation. Themisinterpreted lung cancers were identified in 49 patients (49/105, 46.7%) and were seen to be combined withbenign disease (16, 32.6%), or as obstructive pneumonia without a central mass (15, 30.6%), air-spaceconsolidation (7, 14.3%), cavity (7, 14.3%), double lesion (2, 4.1%), or young age below 26 years (2, 4.1%). Ofthe 16 lung cancers misinterpreted as combined disease, pulmonary tuberculosis (n=14) and pleural disease (n=2)had been initially diagnosed. CONCLUSION: Most commonly, lung cancer was missed or misinterpreted because it washidden by a normal structure or combined with a benign disease. Perceptual errors can be reduced by appropriatetechniques and the scrutiny of trouble spots such as the parahilar, retrocardiac, retrodiaphragmatic and costalregions. Errors in the analysis of lung cancer can be reduced by increased awareness of growth patterns anduncommon man-ifestations of the disease.
Diagnosis ; Diaphragm ; Estrogens, Conjugated (USP) ; Heart ; Humans ; Lung Diseases ; Lung Diseases, Interstitial ; Lung Neoplasms* ; Lung* ; Pleural Diseases ; Pleural Effusion ; Pneumonia ; Radiography, Thoracic* ; Retrospective Studies ; Ribs ; Thorax* ; Tuberculosis

PURPOSE: Methamphetamine is an ongoing illegal drug problem worldwide, and its use in South Korea has spread over the last few years. In this study, a clinical review of patients who visited emergency medical centers with positive methamphetamine tests was conducted. METHODS: Patients underwent methamphetamine screening based on physician suspicion over a period of 13 years. Their patient characteristics, clinical features, and drug administration properties were described. RESULTS: A total of 297 patients were included, with 19 positive methamphetamine results. Patient age ranged from 21 to 84, with a mean of 37.52. Additionally, 13 were male and 6 were female. The mean BP, PR, RR were 131/82 mmHg, 94/min, 20/min. Saturation levels were all over 95%. Five patients had a psychiatric history. Patient showed varied symptoms ranging from mental changes to chest discomfort. In addition, seven showed abnormal electrocardiography findings and one showed elevated cardiac enzyme levels. Other laboratory results revealed no significantly abnormal results. Six patients also suffered from related trauma. The majority of patients consumed the methamphetamine orally, with unknown motivation at unknown locations. Most were transported by 119 and six CONCLUSION: Patients who showed positive results to a methamphetamine screening test in Korea visited the emergency medical center mostly by 119 and were unaware of or reluctant to reveal the fact that they had ingested methamphetamine. Emergency physicians should be more aware of the possibility that a patient may have consumed methamphetamine.
Electrocardiography ; Emergencies* ; Female ; Humans ; Korea ; Male ; Mass Screening ; Methamphetamine* ; Motivation ; Poisoning ; Republic of Korea ; Thorax

Carbon dioxide is widely used for a variety of purposes. As it is a normal constituent of air, the public generally regards it as safe. Although low concentrations of carbon dioxide are not harmful to human beings, high concentrations are toxic, and can cause serious harm, including cardiac arrest. Only a limited number of cases of carbon dioxide intoxication have been reported in Korea, and they have all been mild, with no cases of cardiac arrest following acute exposure to high concentrations of carbon dioxide, reported previously. We describe a case of carbon dioxide poisoning following an explosion of a carbon dioxide tank, which led to cardiac arrest in a 66-yearold patient. This cardiac arrest could have been avoided if the patient was fully aware of the hazardous effects and serious consequences of exposure to high concentrations of carbon dioxide.

PURPOSE: Charcot-Marie-Tooth disease (CMT) is a peripheral neuropathy mainly divided into CMT type 1 (CMT1) and CMT2 according to the phenotype and genotype. Although molecular pathologies for each genetic causative have not been revealed in CMT2, the correlation between cell death and accumulation of misfolded proteins in the endoplasmic reticulum (ER) of Schwann cells is well documented in CMT1. Establishment of in vitro models of ER stress-mediated Schwann cell death might be useful in developing drug-screening systems for the treatment of CMT1. MATERIALS AND METHODS: To develop high-throughput screening (HTS) systems for CMT1, we generated cell models using transient expression of mutant proteins and chemical induction. RESULTS: Overexpression of wild type and mutant peripheral myelin protein 22 (PMP22) induced ER stress. Similar results were obtained from mutant myelin protein zero (MPZ) proteins. Protein localization revealed that expressed mutant PMP22 and MPZ proteins accumulated in the ER of Schwann cells. Overexpression of wild type and L16P mutant PMP22 also reduced cell viability, implying protein accumulation-mediated ER stress causes cell death. To develop more stable screening systems, we mimicked the ER stress-mediated cell death in Schwann cells using ER stress inducing chemicals. Thapsigargin treatment caused cell death via ER stress in a dose dependent manner, which was measured by expression of ER stress markers. CONCLUSION: We have developed genetically and chemically induced ER stress models using Schwann cells. Application of these models to HTS systems might facilitate the elucidation of molecular pathology and development of therapeutic options for CMT1.
Cell Death ; Cell Survival ; Charcot-Marie-Tooth Disease* ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Genotype ; Mass Screening* ; Mutant Proteins ; Myelin P0 Protein ; Myelin Sheath ; Pathology, Molecular ; Peripheral Nervous System Diseases ; Phenotype ; Schwann Cells ; Thapsigargin

BACKGROUND: We describe herein the application of whole exome sequencing (WES) for the molecular genetic diagnosis of a large Korean family with dominantly inherited myopathy. CASE REPORT: The affected individuals presented with slowly progressive proximal weakness and ankle contracture. They were initially diagnosed with limb-girdle muscular dystrophy (LGMD) based on clinical and pathologic features. However, WES and subsequent capillary sequencing identified a pathogenic splicing-site mutation (c.1056+1G>A) in COL6A1, which was previously reported to be an underlying cause of Bethlem myopathy. After identification of the genetic cause of the disease, careful neurologic examination revealed subtle contracture of the interphalangeal joint in the affected members, which is a characteristic sign of Bethlem myopathy. Therefore, we revised the original diagnosis from LGMD to Bethlem myopathy. CONCLUSIONS: This is the first report of identification of COL6A1-mediated Bethlem myopathy in Korea, and indicates the utility of WES for the diagnosis of muscular dystrophy.
Ankle ; Capillaries ; Contracture ; Diagnosis* ; Exome* ; Humans ; Joints ; Korea ; Molecular Biology* ; Muscular Diseases* ; Muscular Dystrophies ; Muscular Dystrophies, Limb-Girdle ; Neurologic Examination