Reactive oxygen species (ROS) are harmful to cellular components such as proteins, DNA and lipids. The continuous production of ROS during the respiratory electron transfer process has been regarded as the major cause of aging. However, the discoveries of proteins whose structure and function switch with cellular ROS suggest that ROS are active players in cellular regulation. OxyR is the first protein whose ROS-regulated mechanism was revealed by the atomic structure studies. The distantly-located two cysteines in OxyR form a disulfide bond by reaction with ROS, resulting in conformational and functional switches in the protein. The heat shock protein 33 is another protein that is activated by increased level of cellular ROS. Many other cellular proteins including protein tyrosine phosphatases are also regulated by ROS. This review focuses on the structure and function of the ROS-regulated proteins and their implications on the ROS's cellular roles. Detailed studies on the ROS-generating protein machinery and the ROS-regulated proteins should contribute to the therapeutic control of ROS-related diseases and aging processes.
Aging ; DNA ; Electrons ; Heat-Shock Proteins ; Protein Tyrosine Phosphatases ; Proteins ; Reactive Oxygen Species

No abstract available.
Reactive Oxygen Species

BACKGROUND: The regurgitative valvular heart diseases are important underlying diseases that result in congestive heart failure, and the prevalence increase with the increasing age. Early detection and management of the regurgitative valvular heart disease could decrease the morbidity and mortality rate of the elderly. METHODS: We reviewed medical records of 425 patients who visited KonKuk University Medical Center ChungJu Hospital for the echocardiography between April 1994 to September 2000. 281 out of 425 patients were diagnosed with regurgitative valvular heart disease, and they were analyzed according to their age, sex, underlying disease, and accompaniment of congestive heart failure. Also the relationships between the regurgitative valvular heart disease and fractional shortening(FS), and also with ejection fraction(EP) were analyzed. RESULTS: There were 281 patients diagnosed with regurgitative valvular heart disease. Greatest number of patients was diagnosed with MR, followed by AR, TR and PR, accordingly. The prevalence of regurgitative valvular heart disease increased as the age increased. The prevalence of regurgitative valvular heart disease in male patients were 74% and for female patients, 62%. For patients with hypertension, it was 59%, and for DM patients it was 60%. For patients with past history of ischemic heart disease, or congestive heart failure, the prevalences of regurgitative valvular heart disease were high. FS for the patients with regurgitative valvular heart disease was 28.91% compared 32.69% for the patients without regurgitative valvular heart disease. EF for the patients with regurgitative valvular heart disease was 54% compared to the 60% for without regurgitative valvular heart disease. The FS for patients with symptomatic regurgitative valvular heart disease was 23.86% compared to 27.7% for asymptomatic group. The EF for symptomatic regurgitative valvular heart disease was 46.2% compared to 52.3% for asymptomatic group. CONCLUSION: When 2D-echocardiography was performed on elderly patients who were older than 65 years of age, most of them featured degenerative structural changes in valves and deterioration of valvular functions resulting in regurgitative valvular heart disease. When patients had any symptoms or underlying diseases, the decrease in cardiac function and high prevalence of regurgitative valvular heart disease were apparent. Therefore in elderly patients, even if they are asymptomatic or without any underlying diseases, aggressive diagnostic approaches and early intervention may delay the progress of valvular heart disease.
Academic Medical Centers ; Aged* ; Chungcheongbuk-do ; Early Intervention (Education) ; Echocardiography ; Female ; Heart Failure ; Heart Valve Diseases* ; Humans ; Hypertension ; Male ; Medical Records ; Mortality ; Myocardial Ischemia ; Prevalence

Homophilic interaction of the L1 family of cell adhesion molecules plays a pivotal role in regulating neurite outgrowth and neural cell networking in vivo. Functional defects in L1 family members are associated with neurological disorders such as X-linked mental retardation, multiple sclerosis, low-IQ syndrome, developmental delay, and schizophrenia. Various human tumors with poor prognosis also implicate the role of L1, a representative member of the L1 family of cell adhesion molecules, and ectopic expression of L1 in fibroblastic cells induces metastasis-associated gene expression. Previous studies on L1 homologs indicated that four N-terminal immunoglobulin-like domains form a horseshoe-like structure that mediates homophilic interactions. Various models including the zipper, domain-swap, and symmetry-related models are proposed to be involved in structural mechanism of homophilic interaction of the L1 family members. Recently, cryo-electron tomography of L1 and crystal structure studies of neurofascin, an L1 family protein, have been performed. This review focuses on recent discoveries of different models and describes the possible structural mechanisms of homophilic interactions of L1 family members. Understanding structural mechanisms of homophilic interactions in various cell adhesion proteins should aid the development of therapeutic strategies for L1 family cell adhesion molecule-associated diseases.
Cell Adhesion ; Crystallography, X-Ray ; Escherichia coli ; Humans ; Immunoglobulins/chemistry ; Neural Cell Adhesion Molecule L1/*chemistry/*metabolism ; *Neurites/chemistry/metabolism ; Protein Conformation ; *Protein Interaction Domains and Motifs

PURPOSE: To suggest the optimal radiation fields after a surgical resection based on a nationwide survey on the principles of radiotherapy for rectal cancer in the Korean Patterns of Care Study. MATERIALS AND METHODS: A consensus committee, composed of radiation oncologists from 18 hospitals in Seoul Metropolitan area, developed a survey format to analyze radiation oncologist's treatment principles for rectal cancer after a surgical resection. The survey format included 19 questions on the principles of defining field margins, and was sent to the radiation oncologists in charge of gastrointestinal malignancies in all Korean hospitals (48 hospitals). Thirty three (69%) oncologists replied. On the basis of the replies and literature review, the committee developed guidelines for the optimal radiation fields for rectal cancer. RESULTS: The following guidelines were developed: superior border between the lower tip of the L5 vertebral body and upper sacroiliac joint; inferior border 2~3 cm distal to the anastomosis in patient whose sphincter was saved, and 2~3 cm distal to the perineal scar in patients whose anal sphincter was sacrificed; anterior margin at the posterior tip of the symphysis pubis or 2~3 cm anterior to the vertebral body, to include the internal iliac lymph node and posterior margin 1.5~2 cm posterior to the anterior surface of the sacrum, to include the presacral space with enough margin. Comparison with the guidelines, the replies on the superior margin coincided in 23 cases (70%), the inferior margin after sphincter saving surgery in 13 (39%), the inferior margin after abdominoperineal resection in 32 (97%), the lateral margin in 32 (97%), the posterior margins in 32 (97%) and the anterior margin in 16 (45%). CONCLUSION: These recommendations should be tailored to each patient according to the clinical characteristics such as tumor location, pathological and operative findings, for the optimal treatment. The adequacy of these guidelines should be proved by following the Korean Patterns of Care Study.
Anal Canal ; Cicatrix ; Consensus ; Humans ; Lymph Nodes ; Radiotherapy ; Rectal Neoplasms* ; Sacroiliac Joint ; Sacrum ; Seoul

PURPOSE: To conduct a nationwide survery on the principles in radiotherapy for rectal cancer, and develop the framework of a database of Korean Patterns of Care Study. MATERIALS AND METHODS: A consensus committee was established to develop a tool for measuring the patterns in radiotherapy protocols for rectal cancer. The panel was composed of radiation oncologists from 18 hospitals in Seoul Metropolitan area. The committee developed a survey format to analyze radiation oncologist's treatment principles for rectal cancer. The survey items developed for measuring the treatment principles were composed of 1) 8 eligibility criteria, 2) 20 items for staging work-ups and prognostic factors, 3) 7 items for principles of combined surgery and chemotherapy, 4) 9 patient set-ups, 5) 19 determining radiation fields, 6) 5 radiotherapy treatment plans, 7) 4 physical/laboratory examination to monitor a patient's condition during treatment, and 8) 10 follow-up evaluations. These items were sent to radiation oncologists in charge of gastrointestinal malignancies in all hospitals (48 hospitals) in Korea to which 30 replies were received (63%). RESULTS: Most of the survey items were replied to without no major differences between the repliers, but with the following items only 50% of repliers were in agreement:1) indications of preoperative radiation, 2) use of endorectal ultrasound, CT scan, and bone scan for staging work-ups, 3) principles of combining chemotherapy with radiotherapy, 4) use of contrast material for small bowel delineation during simulation, 5) determination of field margins, and 6) use of CEA and colonoscopy for follow-up evaluations. CONCLUSION: The items where considerable disagreement was shown among the radiation oncologists seemed to make no serious difference in the treatment outcome, but a practical and reasonable consensus should be reached by the committee, with logical processes of agreement. These items can be used for a basic database for the Patterns of Care Study, which will survey the practical radiotherapy patterns for rectal cancer in Korea.
Colonoscopy ; Consensus ; Drug Therapy ; Follow-Up Studies ; Humans ; Korea ; Logic ; Radiotherapy ; Rectal Neoplasms* ; Seoul ; Tomography, X-Ray Computed ; Treatment Outcome ; Ultrasonography

PURPOSE: The purpose of this study was to investigate the usefulness of the ultrasonography as a screening test for thyroid diseases. MATERIALS AND METHODS: For 7 months, thyroid ultrasonography (7.5 MHz linear array) was performed prospectively by radiologists on 1,316 subjects who do not have a history of the thyroid disease. We analyzed the morphological abnormalities of thyroid gland and these were classified as the nodulal, cystic and diffuse types in accordance with the gender and ages of the patients. We performed ultrasound-guided fine needle aspiration in 21 patients who had sonographic features that were suggestive of malignant thyroid nodules. Physical examination was performed for all subjects by clinicians before the thyroid ultrasonography, and we compared the detectability of thyroid lesions between ultrasonography and physical examination. RESULTS: Thyroidal abnormalities were detected in 94 (7.1%) of 1,316 subjects. Among the 94 patients, 72 (5.5%) showed as nodules, 18 (1.4%) showed as cysts and 4 (0.3%) showed as diffuse abnormalities. The result of the ultrasound-guided aspiration on 21 patient showed 4 malignant nodules, 16 benign nodules and 1 undetermined nodule. Physical examination detected abnormalities in only 12 patients (12.8%) of the 94 patients, which were showed as nodules, cysts and the diffuse type by ultrasonography. CONCLUSION: Thyroid disease of the general population was relatively common and the detection rate with performing physical examination for the thyroid nodule, cyst and the diffuse type was lower than that for ultrasonography. Thyroid ultrasonography is a useful screening modality for detecting thyroid diseases.
Biopsy, Fine-Needle ; Early Detection of Cancer ; Humans ; Mass Screening* ; Physical Examination ; Prospective Studies ; Thyroid Diseases ; Thyroid Gland* ; Thyroid Nodule ; Ultrasonography*

We investigated the role of autophagy in SNUC5/5-FUR, 5-fluorouracil (5-FU) resistant SNUC5 colon cancer cells. SNUC5/5-FUR cells exhibited low level of autophagy, as determined by light microscopy, confocal microscopy, and flow cytometry following acridine orange staining, and the decreased level of GFP-LC3 puncta. In addition, expression of critical autophagic proteins such as Atg5, Beclin-1 and LC3-II and autophagic flux was diminished in SNUC5/5-FUR cells. Whereas production of reactive oxygen species (ROS) was significantly elevated in SNUC5/5-FUR cells, treatment with the ROS inhibitor N-acetyl cysteine further reduced the level of autophagy. Taken together, these results indicate that decreased autophagy is linked to 5-FU resistance in SNUC5 colon cancer cells.
Acridine Orange ; Autophagy* ; Colon* ; Colonic Neoplasms* ; Cysteine ; Flow Cytometry ; Fluorouracil* ; Microscopy ; Microscopy, Confocal ; Reactive Oxygen Species

The relation of Nogo-B to atherosclerotic plaque progression is not well understood. Thus, the purpose of this study was to assess the expression of Nogo-B in fibroatheromas (FA) of different stages, classified using virtual histology intravascular ultrasound (VH-IVUS) analysis in 19 autopsied cases of non-sudden cardiac death. VH-IVUS imaging analysis was performed 30 mm from the ostium of each coronary artery. VH-IVUS revealed 11 early FAs (34.5+/-8.3 yr), 12 late FAs (42.6+/-16.6 yr), 8 thick-cap FAs (TkCFAs) (46.4+/-11.1 yr), and 6 thin-cap FAs (TCFAs) (51.8+/-6.8 yr). TkCFAs and TCFAs were defined as advanced FA. FA progression advanced with age (P=0.04). VH-IVUS analysis of small, early FAs showed smaller necrotic cores and relatively less calcium compared to more advanced FAs with large necrotic cores (P<0.001). Histopathology and immunohistochemical stains demonstrated that early or late FAs had smaller necrotic cores, less empty space of decalcification, and greater Nogo-B expression compared to advanced FAs (vs. early FA, P=0.013; vs. late FA, P=0.008, respectively). These findings suggest that FA progression is inversely associated with Nogo-B expression. Local reduction of Nogo-B may contribute to plaque formation and/or instability.
Adult ; Age Factors ; Coronary Artery Disease/*diagnosis/pathology/ultrasonography ; Coronary Vessels/*pathology/*ultrasonography ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Myelin Proteins/*metabolism ; Ultrasonography, Interventional

Previously, we demonstrated that galangin (3,5,7-trihydroxyflavone) protects human keratinocytes against ultraviolet B (UVB)-induced oxidative damage. In this study, we investigated the effect of galangin on induction of antioxidant enzymes involved in synthesis of reduced glutathione (GSH), and investigated the associated upstream signaling cascades. By activating nuclear factor-erythroid 2-related factor (Nrf2), galangin treatment significantly increased expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS). This activation of Nrf2 depended on extracellular signal-regulated kinases (ERKs) and protein kinase B (AKT) signaling. Inhibition of GSH in galangin-treated cells attenuated the protective effect of galangin against the deleterious effects of UVB. Our results reveal that galangin protects human keratinocytes by activating ERK/AKT-Nrf2, leading to elevated expression of GSH-synthesizing enzymes.
Catalytic Domain ; Extracellular Signal-Regulated MAP Kinases ; Glutamate-Cysteine Ligase ; Glutathione Synthase ; Glutathione* ; Humans* ; Keratinocytes* ; Proto-Oncogene Proteins c-akt