Multiple system atrophy (MSA) is a neurodegenerative disease characterized by presence of α-synuclein-positive inclusions in the cytoplasm of oligodendrocytes. These glial cytoplasmic inclusions (GCIs) are considered an integral part of the pathogenesis of MSA, leading to demyelination and neuronal demise. What is most puzzling in the research fields of GCIs is the origin of α-synuclein aggregates in GCIs, since adult oligodendrocytes do not express high levels of α-synuclein. The most recent leading hypothesis is that GCIs form via transfer and accumulation of α-synuclein from neurons to oligodendrocytes. However, studies regarding this subject are limited due to the absence of proper human cell models, to demonstrate the entry and accumulation of neuronal α-synuclein in human oligodendrocytes. Here, we generated mature human oligodendrocytes that can take up neuronderived α-synuclein and form GCI-like inclusions. Mature human oligodendrocytes are derived from neural stem cells via “oligosphere” formation and then into oligodendrocytes, treating the cells with the proper differentiation factors at each step. In the final cell preparations, oligodendrocytes consist of the majority population, while some astrocytes and unidentified stem cell-like cells were present as well. When these cells were exposed to α-synuclein proteins secreted from neuron-like human neuroblastoma cells, oligodendrocytes developed perinuclear inclusion bodies with α-synuclein immunoreactivity, resembling GCIs, while the stem cell-like cells showed α-synuclein-positive, scattered puncta in the cytoplasm. In conclusion, we have established a human oligodendrocyte model for the study of GCI formation, and the characterization and use of this model might pave the way for understanding the pathogenesis of MSA.

Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). In patients, the number of glutamine residues in polyQ tracts are over 35, and it is correlated with age of onset, severity, and disease progression. Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. These pathological aggregates can be transmitted from neuron to another neuron, and this process may explain the pathological spreading of polyQ aggregates. Here, we developed an in vivo model for studying transmission of polyQ aggregates in a highly quantitative manner in real time. HTT exon 1 with expanded polyQ was fused with either N-terminal or C-terminal fragments of Venus fluorescence protein and expressed in pharyngeal muscles and associated neurons, respectively, of C. elegans. Transmission of polyQ proteins was detected using bimolecular fluorescence complementation (BiFC). Mutant polyQ (Q97) was transmitted much more efficiently than wild type polyQ (Q25) and forms numerous inclusion bodies as well. The transmission of Q97 was gradually increased with aging of animal. The animals with polyQ transmission exhibited degenerative phenotypes, such as nerve degeneration, impaired pharyngeal pumping behavior, and reduced life span. The C. elegans model presented here would be a useful in vivo model system for the study of polyQ aggregate propagation and might be applied to the screening of genetic and chemical modifiers of the propagation.
Age of Onset ; Aging ; Animals ; Complement System Proteins ; Disease Progression ; Exons ; Fluorescence ; Glutamine ; Humans ; Huntington Disease ; Inclusion Bodies ; Mass Screening ; Nerve Degeneration ; Neurodegenerative Diseases ; Neurons ; Pharyngeal Muscles ; Phenotype ; Venus

PURPOSE: The purpose of this study was to assess the value of adding digital breast tomosynthesis (DBT) to full-field digital mammography (FFDM) in the diagnostic workup of breast cancer and to determine which lesion variables affect cancer detectability in the combined modality. METHODS: Between March and May 2012, paired FFDM and DBT images were obtained from 203 women as part of a diagnostic workup for breast cancer. Images from FFDM alone, DBT alone, and DBT combined with FFDM were reviewed in separate sessions by six blinded readers. Jackknife alternative free-response receiver operating characteristic (JAFROC) figure of merit (FOM), sensitivity, and specificity were compared between the modalities. Lesion characteristics affecting the cancer detection rate when using the combined modality were also analyzed. RESULTS: Among the 203 women, 126 women had a total of 129 malignancies and 77 women had total of 77 benign lesions. The overall JAFROC FOM of the combined modality was higher than that of FFDM alone (0.827 vs. 0.775, p<0.001) and that of DBT alone was higher than that of FFDM alone (0.807 vs. 0.775, p=0.027). The overall sensitivity of the combined modality was higher than that of FFDM alone (80.0% vs. 73.2%, p<0.001) and that of DBT alone was higher than that of FFDM alone (78.3% vs. 73.2%, p=0.007). Compared to FFDM alone, the combined modality detected an additional 48 cancers. Using the combined modality, the presence of masses or microcalcifications was significantly associated with the cancer detection rate (p<0.001). CONCLUSION: The combination of DBT with FFDM results in a higher diagnostic yield than FFDM alone. Additionally, DBT alone performs better than FFDM alone. However, even when DBT is combined with FFDM, breast cancers with no discernible masses and those lacking calcifications are difficult to detect.
Breast Neoplasms ; Breast* ; Early Detection of Cancer ; Female ; Humans ; Imaging, Three-Dimensional ; Mammography* ; ROC Curve ; Sensitivity and Specificity

The CD4+CD25+ T regulatory cells (Tregs) play an important role in immune tolerance in experimental transplantation but the clinical significance of circulating Tregs in the peripheral blood is undetermined. In 50 kidney transplant (KT) recipients, 29 healthy controls and 32 liver transplant (LT) recipients, the frequency of Tregs was measured with flow cytometry before and after transplantation. In the KT recipients, IL-10 secretion was measured with an enzyme-linked immunospot (ELISPOT) assay. The median frequency of circulating Tregs before KT was similar to that in healthy controls but significantly lower than that in LT patients before transplantation. The frequency of Tregs was significantly decreased in patients with subclinical acute rejection compared with those without subclinical acute rejection. Calcineurin inhibitors (CNIs) and anti-CD25 antibody decreased the frequency of Tregs but mTOR inhibitor did not. The frequency of donor-specific IL-10 secreting cells did not correlate with the number of Tregs. The frequency of circulating Tregs in KT recipients is strongly affected by CNIs and anti-CD25 antibody, and a low frequency of Tregs is associated with subclinical acute rejection during the early posttransplant period.
Adult ; CD4-Positive T-Lymphocytes/*immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Graft Rejection ; Humans ; Interleukin-10/metabolism ; Interleukin-2 Receptor alpha Subunit/*biosynthesis ; Kidney Failure, Chronic/blood/immunology/*therapy ; Kidney Transplantation/*methods ; Male ; Middle Aged ; Nephrology/*methods ; T-Lymphocytes, Regulatory/*immunology

PURPOSE: The effect of intra-portal infusion of glucose-insulin-potassium (GIK) solution on the energy metabolism during cold preservation was investigated using a small-animal liver transplantation model. METHODS: Fifteen white rats were divided into 3 groups: the group A (feeding group) were fed normally before experiment. The group B (fasting group) and group C (GIK group) were fasted from 3 days before experiment, by which acute nutritional deficiency state was induced. In group A and B, the whole liver was procured after intra-portal perfusion of HTK solution and serial liver biopsies were performed during the cold preservation period with 4degrees C HTK solution. In group C, intra-portal GIK solution infusion for 1 hour preceded liver graft harvest. From the liver tissues, the relative intracellular glycogen contents and the ATP concentration were measured. RESULTS: Relative glycogen contents in group A were 100% at 0 h, 64.6% at 2 h, 54.9% at 4 h, and 16.2% at 8 h; 10.3%, 8.3%, 4.9% and 0%, respectively in group B; 109.2%, 96.9%, 54.2% and 9.7%, respectively in group C. There was a temporary supercharge of ATP level in group C only at 0 h. Apoptosis was less expressed in group C comparing with group A and B. CONCLUSION: Rapid intra- portal infusion of GIK solution could make intrahepatic glycogen content fully restored to the normal level. Considering that intracellular glycogen is the main energy source during immediate post-transplant period, its restoration may contribute to improvement of post-transplant graft function.
Adenosine Triphosphate ; Animals ; Apoptosis ; Biopsy ; Cold Temperature ; Energy Metabolism ; Glucose ; Glycogen ; Humans ; Insulin ; Liver ; Liver Transplantation ; Malnutrition ; Mannitol ; Perfusion ; Potassium ; Potassium Chloride ; Procaine ; Rats ; Transplants

This study investigated elementary, middle, and high school teachers' satisfaction, nutrition education, workload changes, and demands in school foodservice programs (SFPs). The subjects were 630 teachers at 12 elementary, 9 middle, and 9 high school within the nation. Ninety five percent of the teachers felt that there was a necessity for SFPs. Middle school teachers (MTs) and high school teachers (HTs) thought that it was necessary in order to reduce the students'burden of carrying lunch boxes. The teachers were relatively satisfied with their school's foodservice management types, food distribution types, meal quality, and sanitation. Elementary teachers (ETs) and HTs had a higher satisfaction than MTs. Teachers thought that SFPs had positive effects on their students' nutrition and health, enhancing desirable eating habits, and socialization. ETs had more positive opinions than MTs or HTs. ETs and MTs thought that their workload had been increased by SFPs more than HTs, but they had relatively positive opinions on the workload change. ETs taught nutrition and health through SFPs more frequently than MTs or HTs. Many teachers thought that there was a lack of appropriate teaching materials. Some teachers thought that the problems in the present SFPs were: a lack of cafeteria facilities, poor quality of meals, and management of leftovers. Their demands for SFPs were a improvement of meal quality and the establishment of cafeterias. In conclusion, MTs had more negative opinions than ETs or HTs. ETs perceived that SFPs had a function as an important educational activity as well as the supply of nutritional meals. MTs or HTs tended to consider only a meal. It is suggested that teachers, especially MTs and HTs, should modify their attitudes and recognize the educational functions of SFPs. Training programs should be developed under government auspices.
Eating ; Education ; Humans ; Lunch ; Meals ; Sanitation ; Socialization ; Teaching Materials

PURPOSES: To investigate the viral etiology of community-acquired pneumonia in Korean adults, we have detected respiratory viruses (Respiatory syncytial virus, adenovirus, influenza virus and parainfluenza virus) in the way of prospective, multi-center study. METHODS: From July 1997 to April 2000, nasal aspirates or sputum were obtained from adults patients with community pneumonia admitted to the participating hospitals and transferred immediately to the central laboratory in the Seoul National University Children's Hospital. The specimens were divided into three parts. One part was used for indirect immunofluorescent test for respiratory viruses, the other part for the culture of RSV and adenovirus in HEp-2 cell monolayer. Another part was used for the culture of influenza virus and parainfluenza virus in MDCK or LLC- MK2 cell monolayers. RESULTS: Of 317 samples, 32 (10.1%) specimens were positive for viral isolation by indirect IF staining or culture, including one dual-infected specimen (adenovirus and parainfluenza virus). Influenza virus was most commonly detected (16 specimens). Parainfluenza virus, adenovirus and RSV were detected in 10, 4 and 3 patients, respectively. All isolated influenza viruses were type A (H3N2 in 9 patients, H1N1 in 2 and unspecified in 5), and 8 out of 10 parainfluenza virus isolates were type 3. CONCLUSION: Similar to previous foreign reports, a significant portion of community-acquired pneumonia in Korean adult is caused by respiratory viruses. Our data empathized the need of referral system for viral diagnosis and of nationwide investigation on respiratory virus infections.
Adenoviridae ; Adult* ; Diagnosis ; Humans ; Orthomyxoviridae ; Paramyxoviridae Infections ; Pneumonia* ; Prospective Studies ; Referral and Consultation ; Seoul ; Sputum

BACKGROUND AND OBJECTIVE: Nasal polyposis is a chronic inflammatory disease with structural modification of the mucosal epithelium and the lamina propria. In one of recent studies related to the lamina propria, the myofibroblast, which is a potent inducer of extracellular matrix (ECM) synthesis, was found to increase the pedicle area of the nasal polyp. In this study, we intended to quantify epithelial cell proliferation of the polyp. We also tried to identify the active area of epithelial proliferation within nasal polyp and to compare it with the active area of ECM synthesis. MATERIALS AND METHODS: During the endoscopic surgery of nasal polyposis patients, anatomically intact polyp, uncinate process, inferior turbinate and middle turbinate were sampled. The normal nasal mucosa of the inferior turbinate and the septum were obtained from patients who underwent septoplasty. The proliferation cell nuclear antigen (PCNA) expression in the samples were quantified by immunohistochemistry. The PCNA index of the two groups were compared. RESULTS: Epithelial proliferation of the nasal polyp was found to be more active than the normal nasal mucosa. The active area of epithelial proliferation within the nasal polyp was the body area. CONCLUSION: The active area of epithelial proliferation was different from the pedicle area, which is the active area of ECM production.
Epithelial Cells* ; Epithelium ; Extracellular Matrix ; Humans ; Immunohistochemistry ; Mucous Membrane ; Myofibroblasts ; Nasal Mucosa* ; Nasal Polyps* ; Polyps ; Proliferating Cell Nuclear Antigen ; Turbinates

Subacute necrotizing lymphadenitis, or Kikuchi's disease, primarily affects the cervical lyrnph nodes of lung adults and has a self-limited clinical course. Differential diagnoses are malignant lymphoma and systemic lupus erythematosus. Recurrence rate is low as 3.3%, and there have been a few reports describing the recurrence of the disease. The symptoms in almost all recurrent cases were similar to those of the early stages of the disease. The etiology of the disease remains unknown, but various viral infections and autoimmune processes have been postulated to be the cause. A 6-year-old boy presented with a fever of approximately 40C degrees, painless lumps on both sides of the neck, and intermittent abdominal pain for 2 weeks. Subacute necrotizing lymphadenitis was diagnosed 3 years before admission, which was reported by us in 1996. Diagnosis of recurred subacute necrotizing lymphadenitis was confirmed by histological examination of the lymph node. We report a recurred case of subacute necrotizing lymphadenitis during childhood.
Abdominal Pain ; Adult ; Child ; Diagnosis ; Diagnosis, Differential ; Fever ; Histiocytic Necrotizing Lymphadenitis ; Humans ; Lung ; Lupus Erythematosus, Systemic ; Lymph Nodes ; Lymphadenitis ; Lymphoma ; Male ; Neck ; Recurrence

BACKGROUND: Peroxisome proliferator activated receptor-gamma (PPAR-gamma) is a nuclear receptor that regulate adipocyte differentiation and modulate intracellular insulin-signaling events. As such, PPARgamma is a candidate gene for several human disorders including obesity and type 2 diabetes mellitus. The objective of our study was to examine the relationship between genetic variation of PPARgamma2 and diabetes and obesity in Korean subjects. METHODS: We studied 99 subjects with type 2 diabetes mellitus, 128 obesity patients and 97 controls. Screening for mutation at codon 12 and 115 of PPARgamma2 were carried out by PCR-RFLP analyses. Statistical significance was evaluated by Chi-square test. RESULTS: The allele frequency of the Pro12Ala PPARgamma2 variant were 0.05 in controls, 0.06 in type 2 diabetes group, and 0.07 in obesity group (p=0.47). Pro115Gln variant were only proline homozygote in all groups. Genotype frequencies were also similar and conformed to expectations of the Hardy-Weinberg rule. The presence of PPARgamma2 gene variant was no associated with concentrations of total cholesterol, triglyceride, HDL-cholesterol, and also with fasting glucose. CONCLUSION: We concluded that the Pro12Ala and Pro115Gln PPARgamma2 missense mutation may not be associated with type 2 diabetes mellitus and obesity in Korean patients.
Adipocytes ; Cholesterol ; Codon ; Diabetes Mellitus, Type 2* ; Enzyme-Linked Immunosorbent Assay ; Fasting ; Gene Frequency ; Genetic Variation ; Genotype ; Glucose ; Homozygote ; Humans ; Liver Cirrhosis ; Mass Screening ; Mutation, Missense ; Obesity* ; Peroxisomes ; PPAR gamma* ; Proline ; Triglycerides