BACKGROUND/AIMS: To report the long-term survival and tumor recurrence outcomes in patients with superficial esophageal cancer (SEC) after complete non-curative endoscopic resection (ER). METHODS: We retrieved ER data for 24 patients with non-curatively resected SEC. Non-curative resection was defined as the presence of submucosal and/or lymphovascular invasion on ER pathology. Relevant clinical and tumor-specific parameters were reviewed. RESULTS: The mean age of the 24 study patients was 66.3±8.3 years. Ten patients were closely followed up without treatment, while 14 received additional treatment. During a mean follow-up of 59.0±33.2 months, the 3- and 5-year survival rates of all cases were 90.7% and 77.6%, respectively. The 5-year overall survival rates were 72.9% in the close observation group and 82.1% in the additional treatment group (p=0.958). The 5-year cumulative incidences of all cases of recurrence (25.0% vs. 43.3%, p=0.388), primary EC recurrence (10.0% vs. 16.4%, p=0.558), and metachronous EC recurrence (16.7% vs. 26.7%, p=0.667) were similar between the two groups. CONCLUSIONS: Patients with non-curatively resected SEC showed good long-term survival outcomes. Given the similar oncologic outcomes, close observation may be an option with appropriate caution taken for patients who are medically unfit to receive additional therapy.
Esophageal Neoplasms* ; Follow-Up Studies ; Humans ; Incidence ; Pathology ; Recurrence* ; Survival Rate

Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-delta (PKC-delta) in ALI has been a controversial topic. Here we investigated PKC-delta function in ALI using PKC-delta knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-delta KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-delta inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-delta-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-delta inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-delta inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.
Acute Lung Injury* ; Animals ; Capillary Permeability* ; Endothelial Cells ; Lung ; Mice ; Mortality ; Neutrophils ; Protein Kinase C-delta* ; Protein Kinases* ; Pulmonary Edema

Catechol-O-methyltransferase (COMT) inhibitors are used to increase the bioavailability of therapeutic L-dopa. We examined the effi cacy of entacapone in Parkinson’s disease patients who had daily “off” duration of ≤2 hours, and carried different COMT polymorphisms. A total of 168 PD patients were recruited from 19 centers. Subjects were administered with 100–200 mg of entacapone in combination with each dose of L-dopa for 2 months. The clinical effi cacy was evaluated based on the activities of daily living (ADL), score on the Unifi ed Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) stage, and Clinical Global Impression (CGI). COMT polymorphisms were genotyped. 3-O-methyldopa (3-OMD) levels were measured before and after the administration of entacapone. Entacapone administration produced signifi cant improvements in the total daily “on” duration, ADL, UPDRS score, and H&Y stage. Nineteen patients (11.3%) had the low-activity COMT genotype, 68 patients (40.5%) had the intermediate-activity COMT genotype, and 81patients (48.2%) had the high-activity COMT genotype. The effi cacy, and adverse effects of entacapone therapy did not differ between the three groups. There was a signifi cant reduction in 3-OMD, but this did not differ among the three genotypes. Entacapone provided an increased “on” duration and improved motor function in all COMT genotypes.

Single nucleotide polymorphisms (SNPs) are the most abundant forms of human genetic variations and resources for mapping complex genetic traits and disease association studies. We have constructed a linkage disequilibrium(LD) map of chromosome 22 in Korean samples and compared it with those of other populations, including Yorubans in Ibadan, Nigeria (YRI), Centred'Etude du Polymorphisme Humain (CEPH) reference families (CEU), Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) in the HapMap database. We genotyped 4681 of 111,448 publicly available SNPs in 90 unrelated Koreans. Among genotyped SNPs, 4167 were polymorphic. Three hundred and five LD blocks were constructed to make up 18.6% (6.4 of 34.5 Mb) of chromosome 22 with 757 tagSNPs and 815 haplotypes(frequency > or = 5.0%). Of 3430 common SNPs genotyped in all five populations, 514 were monomorphic in Koreans. The CHB + JPT samples have more than a 72% overlap with the monomorphic SNPs in Koreans, while the CEU + YRI samples have less than a 38% overlap. The patterns of hot spots and LD blocks were dispersed throughout chromosome 22, with some common blocks among populations, highly concordant between the three Asian samples. Analysis of the distribution of chimpanzee-derived allele frequency (DAF), a measure of genetic differentiation, Fst levels, and allele frequency difference (AFD) among Koreans and the HapMap samples showed a strong correlation between the Asians, while the CEU and YRI samples showed a very weak correlation with Korean samples. Relative distance as a quantitative measurement based upon DAF, Fst, and AFD indicated that all three Asian samples are very proximate, while CEU and YRI are significantly remote from the Asian samples. Comparative genome-wide LD studies provide useful information on the association studies of complex diseases.
Asian Continental Ancestry Group ; Chromosomes, Human, Pair 22 ; Gene Frequency ; Genetic Variation ; Haplotypes ; HapMap Project ; Humans ; Nigeria ; Polymorphism, Single Nucleotide ; Tokyo

Single nucleotide polymorphisms (SNPs) are the most abundant forms of human genetic variations and resources for mapping complex genetic traits and disease association studies. We have constructed a linkage disequilibrium(LD) map of chromosome 22 in Korean samples and compared it with those of other populations, including Yorubans in Ibadan, Nigeria (YRI), Centred'Etude du Polymorphisme Humain (CEPH) reference families (CEU), Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) in the HapMap database. We genotyped 4681 of 111,448 publicly available SNPs in 90 unrelated Koreans. Among genotyped SNPs, 4167 were polymorphic. Three hundred and five LD blocks were constructed to make up 18.6% (6.4 of 34.5 Mb) of chromosome 22 with 757 tagSNPs and 815 haplotypes(frequency > or = 5.0%). Of 3430 common SNPs genotyped in all five populations, 514 were monomorphic in Koreans. The CHB + JPT samples have more than a 72% overlap with the monomorphic SNPs in Koreans, while the CEU + YRI samples have less than a 38% overlap. The patterns of hot spots and LD blocks were dispersed throughout chromosome 22, with some common blocks among populations, highly concordant between the three Asian samples. Analysis of the distribution of chimpanzee-derived allele frequency (DAF), a measure of genetic differentiation, Fst levels, and allele frequency difference (AFD) among Koreans and the HapMap samples showed a strong correlation between the Asians, while the CEU and YRI samples showed a very weak correlation with Korean samples. Relative distance as a quantitative measurement based upon DAF, Fst, and AFD indicated that all three Asian samples are very proximate, while CEU and YRI are significantly remote from the Asian samples. Comparative genome-wide LD studies provide useful information on the association studies of complex diseases.
Asian Continental Ancestry Group ; Chromosomes, Human, Pair 22 ; Gene Frequency ; Genetic Variation ; Haplotypes ; HapMap Project ; Humans ; Nigeria ; Polymorphism, Single Nucleotide ; Tokyo

Myristoylated alanine-rich C kinase substrate (MARCKS) is a widely distributed protein kinase C (PKC) substrate and has been implicated in actin cytoskeletal rearrangement in response to extracellular stimuli. Although MARCKS was extensively examined in various cell culture systems, the physiological function of MARCKS in the central nervous system has not been clearly understood. We investigated alterations of cellular distribution and phosphorylation of MARCKS in the hippocampus following kainic acid (KA)-induced seizures. KA (25 mg/kg, i.p.) was administered to eight to nine week-old C57BL/6 mice. Behavioral seizure activity was observed for 2 h after the onset of seizures and was terminated with diazepam (8 mg/kg, i.p.). The animals were sacrificed and analyzed at various points in time after the initiation of seizure activity. Using double-labeling immunofluorescence analysis, we demonstrated that the expression and phosphorylation of MARCKS was dramatically upregulated specifically in microglial cells after KA-induced seizures, but not in other types of glial cells. PKC alpha, beta I, beta II and delta, from various PKC isoforms examined, also were markedly upregulated, specifically in microglial cells. Moreover, immunoreactivities of phosphorylated MARCKS were co-localized in the activated microglia with those of the above isoforms of PKC. Taken together, our in vivo data suggest that MARCKS is closely linked to microglial activation processes, which are important in pathological conditions, such as neuroinflammation and neurodegeneration.
Up-Regulation/drug effects ; Time Factors ; Seizures/chemically induced/*metabolism ; Protein Kinase C-delta/analysis ; Protein Kinase C-alpha/analysis ; Protein Kinase C/*analysis ; Protein Biosynthesis/drug effects ; Phosphorylation/drug effects ; Microscopy, Confocal ; Microglia/cytology/drug effects/*metabolism ; Mice, Inbred C57BL ; Mice ; Membrane Proteins/*analysis/metabolism ; Kainic Acid/*toxicity ; Isoenzymes/analysis ; Intracellular Signaling Peptides and Proteins/*analysis/metabolism ; Immunohistochemistry ; Animals

PURPOSE: To improve the management of a medical linear accelerator, the records of operational failures of a Varian CL2100C over a ten year period were retrospectively analyzed. MATERIALS AND METHODS: The failures were classified according to the involved functional subunits, with each class rated into one of three levels depending on the operational conditions. The relationships between the failure rate and working ratio and between the failure rate and outside temperature were investigated. In addition, the average life time of the main part and the operating efficiency over the last 4 years were analyzed. RESULTS: Among the recorded failures (total 587 failures), the most frequent failure was observed in the parts related with the collimation system, including the monitor chamber, which accounted for 20% of all failures. With regard to the operational conditions, 2nd level of failures, which temporally interrupted treatments, were the most frequent. Third level of failures, which interrupted treatment for more than several hours, were mostly caused by the accelerating subunit. The number of failures was increased with number of treatments and operating time. The average life-times of the Klystron and Thyratron became shorter as the working ratio increased, and were 42 and 83% of the expected values, respectively. The operating efficiency was maintained at 95% or higher, but this value slightly decreased. There was no significant correlation between the number of failures and the outside temperature. CONCLUSION: The maintenance of detailed equipment problems and failures records over a long period of time can provide good knowledge of equipment function as well as the capability of predicting future failure. More rigorous equipment maintenance is required for old medical linear accelerators for the advanced avoidance of serious failure and to improve the quality of patient treatment.
Humans ; Particle Accelerators* ; Retrospective Studies

PURPOSE: To improve the management of a medical linear accelerator, the records of operational failures of a Varian CL2100C over a ten year period were retrospectively analyzed. MATERIALS AND METHODS: The failures were classified according to the involved functional subunits, with each class rated into one of three levels depending on the operational conditions. The relationships between the failure rate and working ratio and between the failure rate and outside temperature were investigated. In addition, the average life time of the main part and the operating efficiency over the last 4 years were analyzed. RESULTS: Among the recorded failures (total 587 failures), the most frequent failure was observed in the parts related with the collimation system, including the monitor chamber, which accounted for 20% of all failures. With regard to the operational conditions, 2nd level of failures, which temporally interrupted treatments, were the most frequent. Third level of failures, which interrupted treatment for more than several hours, were mostly caused by the accelerating subunit. The number of failures was increased with number of treatments and operating time. The average life-times of the Klystron and Thyratron became shorter as the working ratio increased, and were 42 and 83% of the expected values, respectively. The operating efficiency was maintained at 95% or higher, but this value slightly decreased. There was no significant correlation between the number of failures and the outside temperature. CONCLUSION: The maintenance of detailed equipment problems and failures records over a long period of time can provide good knowledge of equipment function as well as the capability of predicting future failure. More rigorous equipment maintenance is required for old medical linear accelerators for the advanced avoidance of serious failure and to improve the quality of patient treatment.
Humans ; Particle Accelerators* ; Retrospective Studies

BACKGROUND/AIMS: Carcinogenesis is characterized by the abnormal regulation of cell cycle. The abnormal expression of the regulators of cell cycle may be related to the prognosis. Since the clinical significance of the expression of the three proteins in colorectal carcinomas is still controversial, we evaluated the prognostic value of the expression of cyclin E, p27 and mutant p53 in stage II colorectal cancer. METHODS: The expression levels of cyclin E, p27 and mutant p53 proteins in 41 patients with stage II colorectal carcinomas were analyzed by immunohistochemistry. RESULTS: In the univariate analysis, the level of CEA at diagnosis was associated with disease relapse. In the multivariate analysis, the clinicopathological variables such as age, gender, site of primary tumor, tumor size, state of tumor differentiation and preoperative plasma CEA level were not associated with disease relapse. When Kaplan-Meier survival curves were constructed to determine the prognosis, cyclin E, p27 and mutant p53 expressions did not predict poor prognosis. CONCLUSIONS: Our results suggested that the expression of cyclin E, p27 and mutant p53 proteins did not predict the clinical outcome in the stage II colorectal carcinomas.
Adenocarcinoma/chemistry/*diagnosis/mortality/pathology ; Adult ; Aged ; Aged, 80 and over ; Cell Cycle Proteins/*analysis ; Colorectal Neoplasms/chemistry/*diagnosis/mortality/pathology ; Cyclin E/*analysis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein p53/*analysis/genetics ; Survival Rate ; Tumor Markers, Biological/analysis ; Tumor Suppressor Proteins/*analysis

Bovine mastitis is an infectious disease with a major economic influence on the dairy industry worldwide. Many factors such as environment, pathogen, and host affect susceptibility or resistance of an individual cow to bovine mastitis. Recently, there has been considerable interest in defining genetic and immunological markers that could be used to select for improved disease resistance. In this study we have analyzed the lymphocyte subpopulations of mastitis-resistant and susceptible cows using monoclonal antibodies specific for bovine leukocyte differentiation antigens and flow cytometry. We have also used a microarray typing technique to define the bovine leukocyte antigen (BoLA) class I and class II haplotypes associated with resistance or susceptibility to bovine mastitis. A striking finding of the present study is that susceptibility to mastitis was associated with major histocompatibility complex (MHC) haplotypes that have only a single set of DQ genes. The study also revealed that susceptible cows had CD4:CD8 ratios of less than one in both their mammary gland secretions and peripheral blood. These results raise the possibility that the number of DQ genes that a cow has and/or a cow's CD4:CD8 ratio could be used as indicators of susceptibility to bovine mastitis.
Alleles ; Animals ; Antigens, Differentiation/immunology ; Cattle ; Cell Count/veterinary ; Female ; Flow Cytometry/veterinary ; Genetic Predisposition to Disease ; Histocompatibility Antigens/genetics/immunology ; Korea ; Leukocytes, Mononuclear/cytology/*immunology/microbiology ; Lymphocyte Subsets/*immunology/microbiology ; Mastitis, Bovine/genetics/*immunology/microbiology ; Oligonucleotide Array Sequence Analysis/veterinary ; Statistics, Nonparametric