Numerous studies have established a link between autophagy and aging; however, the relationship has not been clearly defined. Aging is a very complex process caused by the accumulation of various factors due to the gradual failure of cellular maintenance. Recent studies have shown that autophagy reduces the stress responses induced by starvation, reactive oxygen species, and the accumulation of intracellular proteins and organelles through cytoprotection, clearance of damaged mitochondria, and lysosomal degradation. Here, we summarize our current understanding of the relationship between autophagy and the aging process.
Aging* ; Autophagy* ; Caloric Restriction ; Cytoprotection ; Mitochondria ; Organelles ; Proteins ; Reactive Oxygen Species ; Starvation

Numerous studies have established a link between autophagy and aging; however, the relationship has not been clearly defined. Aging is a very complex process caused by the accumulation of various factors due to the gradual failure of cellular maintenance. Recent studies have shown that autophagy reduces the stress responses induced by starvation, reactive oxygen species, and the accumulation of intracellular proteins and organelles through cytoprotection, clearance of damaged mitochondria, and lysosomal degradation. Here, we summarize our current understanding of the relationship between autophagy and the aging process.
Aging* ; Autophagy* ; Caloric Restriction ; Cytoprotection ; Mitochondria ; Organelles ; Proteins ; Reactive Oxygen Species ; Starvation

Autophagy is a self-degradation system of cellular components through an autophagosomal-lysosomal pathway. Over the last 15 yr, yeast genetic screens led to the identification of a number of genes involved in the autophagic pathway. Most of these autophagy genes are present in higher eukaryotes and regulate autophagy process for cell survival and homeostasis. Significant progress has recently been made to better understand the molecular mechanisms of the autophagy machinery. Especially, autophagy process, including the regulation of autophagy induction through mTOR and the nucleation and elongation in autophagosome formation through class III phosphatidylinositol 3-kinase complex and ubiquitin-like conjugation systems, became evident. While many unanswered questions remain to be answered, here, we summarize the recent process of autophagy with emphasis on molecules and their protein complexes along with advanced molecular mechanisms that regulate the autophagy machinery.
Autophagy/genetics/*physiology ; Carrier Proteins/genetics/metabolism ; Class III Phosphatidylinositol 3-Kinases/genetics/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; Microtubule-Associated Proteins/genetics/metabolism ; Models, Biological ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Small Ubiquitin-Related Modifier Proteins/genetics/metabolism

A 60-year-old woman with end stage liver cirrhosis caused by genotype 2 hepatitis C virus (HCV) infection received an orthotopic liver transplantation (OLT). The patient was negative for the hepatitis B surface antigen (HBsAg) and positive for the anti-hepatitis B surface antibody (anti-HBs) prior to and one and a half months following the OLT. Due to reactivation of hepatitis C, treatment with interferon-alpha and Ribavirin started two months following the OLT and resulted in a sustained virological response. We performed a liver biopsy because a biochemical response was not achieved. Surprisingly, liver pathology showed HBsAg-positive hepatocytes with a lobular hepatitis feature, which had been negative in the liver biopsy specimen obtained one and a half months post-OLT. High titers of both HBsAg and HBeAg were detected, while anti-HBs antibodies were not found. Tests for IgM anti-hepatitis B core antibody and anti-delta virus antibodies were negative. The serum HBV DNA titer was over 1x10(7) copies/mL. A sequencing analysis showed no mutation in the "a" determinant region, but revealed a mixture of wild and mutant strains at an overlapping region of the S and P genes (S codon 213 (Leu/Ile); P codons 221 (Phe/Tyr) and 222 (Ala/Thr)). These findings suggest that de novo hepatitis B can develop in patients with HCV infection during the post-OLT period despite the presence of protective anti-HBs.
Antibodies ; Biopsy ; Codon ; DNA ; Female ; Genotype ; Hepacivirus ; Hepatitis ; Hepatitis B ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis C ; Hepatocytes ; Humans ; Immunoglobulin M ; Interferon-alpha ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Middle Aged ; Ribavirin ; Superinfection ; Viruses

BACKGROUND/AIMS: The aim of our study was to define the potential role of virologic response at 12 months of treatment (VR12) in predicting subsequent virologic and clinical outcomes in adefovir (ADV)-treated lamivudine-resistant chronic hepatitis B. METHODS: Two hundred and four patients with lamivudine-resistant chronic hepatitis B virus (HBV) treated with ADV monotherapy were included. Serum HBV DNA was quantified by real-time polymerase chain reactions. VR12 was defined as a HBV DNA level of less than 4 log10 copies/mL after 12 months of ADV treatment. RESULTS: VR12 was observed in 110 of the 204 patients (54%). The mean HBV DNA reductions from baseline after 12 months of ADV treatment were 3.8 and 1.9 log10 copies/mL in patients with and without VR12, respectively (p<0.001). The hepatitis B "e" antigen (HBeAg) seroconversion rates in patients with and without VR12 were 32% and 14% at 12 months treatment, respectively (p=0.018), and 40% and 27% at 24 months of treatment (p=0.032). The genotypic mutation rates to ADV in patients with and without VR12 were 0% and 6% at 12 months of treatment, respectively (p=0.033), and 21% and 42% at 24 months (p=0.012). The rates of viral breakthrough in patients with and without VR12 were 0% and 7% at 12 months of treatment, respectively (p=0.072), and 9% and 25% at 24 months (p=0.006). CONCLUSIONS: Patients without VR12 may need to switch to or add on other potent antiviral drugs in their medical regimens.
Adenine ; Antiviral Agents ; DNA ; Drug Resistance ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Mutation Rate ; Organophosphonates ; Polymerase Chain Reaction ; Viruses

BACKGROUND: Monoclonal antibodies (mAbs) recognizing Class III epitope of CD34 are essential for flow cytometric diagnosis of leukemia. METHODS: 27H2 mAb was developed from a mouse alternatively immunized with human acute leukemia cell lines, KG1 and Molm-1. Using flow cytometric analysis of various leukemic cell lines and peripheral blood, immunohistochemical study of frozen tonsil, we characterized 27H2 mAb. Antigen immunoprecipitated with 27H2 mAb immunobloted with anti-CD34 mAb. A case of bone marrow sample of acute lymphoblastic leukemia (ALL) patient was obtained at CBNU Hospital. For epitope identification enzyme treatment with neuraminidase and O-sialoglycoprotein endopeptidase (OSGE) and blocking assay with known classIII mAb (HPCA-2) were done. RESULTS: Only KG1 and Molm-1 revealed positive immunoreactivity. Immunohistochemical staining disclosed strong membranous immunoreactivity on high endothelial venules. Antigen immunoprecipitated by 27H2 mAb showed approximately 100 kDa sized band immunoblotted with anti-CD34 under non-reducing conditions. Epitope recognized by 27H2 mAb disclosed resistancy to both neuraminidase and OSGE treatment and completely blocked with known class III mAb preincubation. CD34 positive leukemic cells in BM of pre B cell ALL patient detected by FITC-conjugated 27H2 and HPCA-2 were identified with similar sensitivity. CONCLUSION: A novel murine mAb recognizing class III epitope of human CD34 with high affinity, which is useful for flow cytometric diagnosis of leukemia, was developed.
Animals ; Antibodies, Monoclonal ; Bone Marrow ; Cell Line ; Humans ; Leukemia ; Metalloendopeptidases ; Mice ; Neuraminidase ; Palatine Tonsil ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Venules

PURPOSE: To evaluate mortality and morbidity of very low birth weight infants(VLBW infants) born in the Busan area from 1996 to 2005. METHODS: A total of eight neonatal intensive care units (4 university hospitals and 4 general hospitals) in Busan participated in this study. A total of 1,414 VLBW infants were divided into three groups: period I, 1996 to 2000; period II, 1999 to 2002; period III, 2003 to 2005, based on date of birth. We performed a retrospective review of medical records of VLBWinfants and compared the survival rate, morbidity and mortality over the three periods. RESULT: The number of VLBW infants admitted to 8 NICUs in 1996-2005 was a total of 1,414 (1.3% incidence, mean gestational age 29.1+/-2.7 wk, mean birth weight 1158+/-235 g), including 361 (24.7%) extremely low birth weight infants (ELVW infants) who were less than 1,000 g at birth weight. Overall survival rate of VLBW infants was 66.1%. The survival rate of VLBW infants increased significantly over the three periods (period I:57.6%, period II:67.8%, period III:75.7%, P<0.01). Overall survival rate of ELBW infants was 33.8%, and increased from 26.4% in period I to 44.2% in period III (P<0.01). The incidence of respiratory distress syndrome was 45.1%; patent ductus arteriosus, 16.4%; bronchopulmonary dysplasia, 13.1%; blood culture positive sepsis, 12.7%; necrotizing enterocolitis, 6.6%; severe intracranial hemorrhage, 6.5%; and severe retinopathy of prematurity, 5.9%. The main causes of death were respiratory distress syndrome and sepsis. CONCLUSION: Overall survival rate of very low birth weight infant in Busan area during the last 10 years was 66.1%, and increased significantly over the three periods.
Birth Weight ; Bronchopulmonary Dysplasia ; Busan* ; Cause of Death ; Ductus Arteriosus, Patent ; Enterocolitis, Necrotizing ; Gestational Age ; Hospitals, University ; Humans ; Incidence ; Infant* ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Very Low Birth Weight* ; Intensive Care Units, Neonatal ; Intracranial Hemorrhages ; Medical Records ; Mortality ; Parturition ; Retinopathy of Prematurity ; Retrospective Studies ; Sepsis ; Survival Rate

BACKGROUND/AIMS: Two percent glutaradehyde has been the reference disinfectant for high-level disinfection, but often requires long period of exposure up to 45 minutes. The aims of this study were to evaluate the effectiveness of a new endoscope disinfectant that uses 0.2% peracetic acid, and to compare the culture-positive rate in each different endoscopes and washers used. MEHTODS: Three endoscopes and two washers that differed in purchase year were used. They were cleansed manually and disinfected with peracetic acid for 10 minutes. A total of 86 gastroduodenal endoscopic sessions were included in the study. RESULTS: Overall culture-positive rate was 37.2%, majority of which came from washings of biopsy channel. There was a significant difference in culture-positive rate according to the machine used. Culture positive rate was 11.4% in recently purchased endoscope and washer used. Of the 28 Helicobactor pylori positive cases, there was one Helicobactor pylori DNA PCR positive case, but no Helicobactor pylori was found. CONCLUSIONS: When new endoscope and washer is used, peracetic acid is effective as a disinfectant. Significant difference in culture rate according to the different machine used might come from the aging effect and difference of cleansing power of the washer.
Aging ; Biopsy ; Disinfection* ; DNA ; Endoscopes* ; Peracetic Acid* ; Polymerase Chain Reaction

PURPOSE: Numerous investigations have been conducted in order to determine the potential carcinogenic or chemopreventive activity of capsaicin. The aim of this study is to characterize the effects of capsaicin on colon cancer cells, and provide valuable information concerning the application of capsaicin in chemoprevention as well as for therapeutic purposes. METHODS: CoLo320DM and LoVo cells (human colon cancer cell line) were treated with capsaicin. In order to access cell viability and altered morphology, an MTT assay was performed and the cells were microscopically examined. Decreasing DNA staining was accessed by FACS. The cells were stained with FITC labeled annexin V and analyzed by FACS to detect cellular membrane alteration during apoptosis. The cells were stained with DiOC6(3) and Hydroethidine and analyzed by FACS in order to access ROS and dleta psi m. RESULTS: Capsaicin decreased cell viability in a dose-dependent manner. Capsaicin produced a cell morphology corresponding to the apoptotic features including cell shrinkage and chromatic condensation. Capsaicin treated cells induced a loss of nuclear DNA leading to hypoploidy in a dose-dependent manner. Cells were excluded by double staining with PI and FITC labeled annexin v and detected by FACS. We show that treatment of CoLo320DM, L0Vo cells with increasing concentrations of capsaicin parallel an increase in the percentage of red fluorescent cells (HE-->Eth) that reflect ROS hypergeneration and a decrease in the percentage of green fluorescent cells that reflect delta psi m disruption. CONCLUSION: These results clearly demonstrate that capsaicin-induced colon cancer cell death is apoptotic.
Annexin A5 ; Apoptosis* ; Capsaicin ; Cell Death ; Cell Line* ; Cell Survival ; Chemoprevention ; Colon* ; Colonic Neoplasms* ; DNA ; Fluorescein-5-isothiocyanate ; Humans* ; Membranes

We report treatment of a 24-year-old man with membranous glomerulonephritis (MGN) who developed a solitary choroidal tuberculoma in association with miliary tuberculosis during steroid therapy. In June 1995, the patient had developed nephrotic syndrome. He had refused renal biopsy at that time. So we treated him with corticosteroids having assumed a diagnosis of minimal change nephrotic syndrome. After initial corticosteroids and diuretics therapy for 5 months, his generalized edema resolved but proteinuria (3 positive) continued, suggesting the presence of other forms of glomerulonephritis. Renal biopsy performed in January 1996. The patient was diagnosed as having MGN. The patient was closely observed over a period of 34 months and remained stable without steroid therapy. However at 34 months, generalized edema was again noted and steroid therapy at high dosage was initiated. After 5 months of steroid therapy, he developed miliary tuberculosis and a solitary choroidal mass. An antituberculosis chemotherapeutic regimen was started and after a further 5 months, all clinical symptoms and signs of the pulmonary lesion were resolved and a measurable shrinking of the choroidal mass was recorded.
Adult ; Case Report ; Choroid Diseases/*etiology ; Glomerulonephritis, Membranous/*complications ; Human ; Male ; Tuberculoma/*etiology