Atopic dermatitis, one of the most important skin diseases, is characterized by both skin barrier impairment and immunological abnormalities. Although several studies have demonstrated the significant relationship between atopic dermatitis and immunological abnormalities, the role of hydroxyeicosatetraenoic acids (HETE) in atopic dermatitis remains unknown. To develop chiral methods for characterization of 12-HETE enantiomers in a 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model and evaluate the effects of 12-HETE on atopic dermatitis, BALB/c mice were treated with either DNCB or acetone/olive oil (AOO) to induce atopic dermatitis, after which 12(R)- and 12(S)-HETEs in the plasma, skin, spleen, and lymph nodes were quantified by chiral liquid chromatography-tandem mass spectrometry. 12(R)- and 12(S)-HETEs in biological samples of DNCB-induced atopic dermatitis mice increased significantly compared with the AOO group, reflecting the involvement of 12(R)- and 12(S)-HETEs in atopic dermatitis. These findings indicate that 12(R)- and 12(S)-HETEs could be a useful guide for understanding the pathogenesis of atopic dermatitis.
Animals ; Biomarkers/blood/metabolism ; *Chromatography, Liquid ; Dermatitis, Atopic/*chemically induced ; Dinitrochlorobenzene/adverse effects ; Female ; Humans ; Hydroxyeicosatetraenoic Acids/blood/*metabolism ; Irritants/adverse effects ; Mice ; Mice, Inbred BALB C ; Models, Animal ; *Tandem Mass Spectrometry

Inorganic phosphate (Pi) plays a critical role in diverse cellular functions, and regulating the Pi balance is accomplished by sodium-dependent Pi co-transporter (NPT). Pulmonary NPT has recently been identified in mammalian lungs. However, to date, many of the studies that have involved Pi have mainly focused on its effect on bone and kidney. Therefore, current study was performed to discover the potential effects of low Pi on the lung of developing transgenic mice expressing the renilla/firefly luciferase dual reporter gene. Two-weeks old male mice divided into 2 groups and these groups were fed either a low PI diet or a normal control diet (normal: 0.5% Pi, low: 0.1% Pi) for 4 weeks. After 4 weeks of the diet, all the mice were sacrificed. Their lungs were harvested and analyzed by performing luciferase assay, Western blotting, kinase assay and immunohistochemistry. Our results demonstrate that low Pi affects the lungs of developing mice by disturbing protein translation, the cell cycle and the expression of fibroblast growth factor-2. These results suggest that optimally regulating Pi consumption may be important to maintain health.
Animals ; Blotting, Western ; Carrier Proteins/metabolism ; Immunohistochemistry ; Lung/drug effects/enzymology/*growth & development/metabolism ; Male ; Mice ; Mice, Transgenic ; Phosphoproteins/metabolism ; Phosphorus, Dietary/*administration & dosage ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Sodium-Phosphate Cotransporter Proteins, Type IIa/*metabolism

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.
Antineoplastic Agents, Phytogenic/*pharmacology ; Apoptosis/drug effects ; Benzylisoquinolines/*pharmacology ; Carcinoma/*drug therapy ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Extracellular Signal-Regulated MAP Kinases/*antagonists & inhibitors ; Humans ; Lung Neoplasms/*drug therapy

Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 x : 30 microgram/kg and 50 x : 150 microgram/kg). A slight anti-tumoral effect was observed in all 10 x groups compared to the control. In the 50 x groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-beta. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition.
Adenocarcinoma/*drug therapy ; Alanine Transaminase/blood ; Animals ; Antineoplastic Agents/chemistry/pharmacology ; Blood Urea Nitrogen ; Dose-Response Relationship, Drug ; Immunoglobulins/*chemistry/*pharmacology ; Interferon Alfa-2a/chemistry/pharmacology ; Interferon-alpha/*chemistry/*pharmacology ; Mice ; Mice, Nude ; Neoplasms, Experimental/*drug therapy ; Polyethylene Glycols/chemistry/pharmacology ; Recombinant Fusion Proteins/chemistry/pharmacology

Failure of mitotic checkpoint machinery leads to the chromosomal missegregation and nuclear endoreduplication, thereby driving the emergence of aneuploidy and tetraploidy population. Although abnormal nuclear ploidy and the resulting impairment of mitotic checkpoint function are typical physiological event leading to human hepatocellular carcinoma, any mutational change of mitotic checkpoint regulators has not yet been discovered. Therefore, we investigated the mutation of p31(comet), a recently identified mitotic checkpoint regulator, in human hepatocellular carcinoma. Of 51 human hepatocellular carcinoma tissue and 6 cell lines tested, five samples exhibited nucleotide sequence variations dispersed on four sites within the entire coding sequence. Among these sites with sequence substitutions, three were found to be missense mutation accompanied with amino acid change but one was a silent mutation. Of these sequence substitutions, two were present in both tumor and non-tumor liver tissues, suggesting the possibility of polymorphism. The present findings indicate that p31(comet) does not have an impact on the formation of aneuploidy and tetraploidy found in human hepatocellular carcinoma.
Adaptor Proteins, Signal Transducing ; Calcium-Binding Proteins/*metabolism ; Carcinoma, Hepatocellular/genetics/*metabolism ; Carrier Proteins/*genetics/metabolism ; Cell Cycle Proteins/*genetics/*metabolism ; Cell Line, Tumor ; Humans ; Liver Neoplasms/genetics/*metabolism ; *Mutation ; Nuclear Proteins ; Polyploidy ; Repressor Proteins/*metabolism

OBJECTIVES: The reliability and validity of the Korean version of Hamilton Depression Rating Scale (K-HDRS) were examined in Korean patients depressive symptoms. METHODS: 33 inpatients and 70 outpatients diagnosed as major depressive disorder or depressive episode of bipolar I disorder according to the DSM-IV criteria were assessed with K-HDRS, Clinical Global Impression score(CGI), Beck Depression Inventory (BDI) and Montgomery-Aberg Depression Rating Scale (MADRS). RESULTS: Internal consistency (Cronhach's alpha coefficeint=0.76) and interrater reliability (r=0.94, p<0.001) were statistically significant. Principal axis factoring analysis revealed 4 factors that accounted for 50.4% of the total variance. The correlations of K-HDRS with CGI, BDI and MADRS were 0.84, 0.54, 0.58 respectively. CONCLUSION: These results showed that the K-HDRS could be a reliable and valid tool for the assessment of depressive Korean patients. The K-HDRS will be a useful tool for assessing depressive symptoms in Korea.
Axis, Cervical Vertebra ; Depression* ; Depressive Disorder, Major ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Inpatients ; Korea ; Outpatients ; Reproducibility of Results*

Potential toxicological interactions of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibuthyl phthalate (DBP) on ozone were investigated after 32- and 52-wk exposures using hprt mutation assay. Male and female B6C3F1 mice exposed to ozone (0.5 ppm), NNK (1.0 mg/kg), DBP (5,000 ppm), and two or three combinations of these toxicants 6 h per day for 32- and 52-wk showed increases in the frequencies of TG rlymphocytes compared to the control groups. Additive interactions were noted from two combination groups compared to the ozone alone in both sexes of 32- and 52-wk studies. The most common specific mutation type in the hprt genes of test materials-treated male and female mice was transversion with very few transition. The results indicate that such dominant transversion may be responsible for toxicity and combined exposure to ozone, NNK, and DBP induces additive genotoxicities compared to ozone alone.
Animals ; Carcinogens/*toxicity ; DNA Mutational Analysis ; Dibutyl Phthalate/*toxicity ; Drug Combinations ; Female ; Hypoxanthine Phosphoribosyltransferase/*genetics ; Male ; Mice ; Mutagenicity Tests ; *Mutation/drug effects ; Nitrosamines/*toxicity ; Ozone/*toxicity ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/drug effects/enzymology

Evidences show that eukaryotic mRNAs can perform protein translation through internal ribosome entry sites (IRES). 5'-Untranslated region of the mRNA encoding apoptotic protease-activating factor 1 (Apaf-1) contains IRES, and, thus, can be translated in a cap-independent manner. Effects of changes in protein translation pattern through rapamycin pretreatment on 4-(methylnitrosamino)-1-(3-pyridyl)-butanone(NNK, tobacco-specific lung carcinogen)-induced apoptosis in human bronchial epithelial cells were examined by caspase assay, FACS analysis, Western blotting, and transient transfection. Results showed that NNK induced apoptosis in concentration- and time-dependent manners. NNK-induced apoptosis occurred initially through cap-independent protein translation, which during later stage was replaced by cap-dependent protein translation. Our data may be pplicable as the mechanical basis of lung cancer treatment.
Antibiotics, Antineoplastic/pharmacology ; Apoptosis/*drug effects ; Apoptotic Protease-Activating Factor 1 ; BH3 Interacting Domain Death Agonist Protein ; Blotting, Western ; Bronchi/metabolism/*pathology ; Carcinogens/*pharmacology ; Carrier Proteins/metabolism ; Caspases/metabolism ; Cytochromes c/metabolism ; Dose-Response Relationship, Drug ; Epithelial Cells/metabolism/*pathology ; Eukaryotic Initiation Factor-4E/metabolism ; Flow Cytometry ; Humans ; Nitrosamines/*pharmacology ; Protein Biosynthesis ; Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; RNA Cap-Binding Proteins/*physiology ; Sirolimus/pharmacology ; Time Factors ; bcl-2-Associated X Protein

BACKGROUND: Recurrent, often unpredictable, migraine attacks significantly interfere with daily functioning and productivity of patients with migraine. Quality of life measurement represents an important tool for evaluating migraine therapy and judging the impact of headache either on individuals or on society. The objective of this study was to test the reliability and validity of the translated version of MSQoL (Migraine-Specific Quality of Life) in Korean migraine patients. METHODS: Participants, migraineurs from the Samsung Medical Center Migraine Clinic, were screened using the International Headache Society migraine criteria prior to enrollment through direct interview. This survey included the MSQoL, MIDAS (Migraine Disability assessment) and STAI (State-Trait Anxiety Inventory). RESULTS: Sixty-five migraineurs were recruited. For the MSQoL, Cronbach's alpha was 0.93. Frequency and number of accompanying symptoms were predictive of the MSQoL. The negative correlation between the MSQoL scores and the MIDAS score was seen (r=-0.585, p<0.01). Similarly a negative correlation between the MSQoL scores and duration of headache was also observed (r=-0.38, p<0.01). Although a significant negative correlation between the MSQoL and STAI scores was present (r=-0.47, p<0.01), correlation between the MIDAS and the STAI scores was not significant. CONCLUSIONS: The MSQoL is a reliable and valuable migraine-specific quantitative tool to assess the degree of quality of life in Korean migraineurs. It has a potential to provide valuable information on migraineur's disability and anxiety level. The MSQoL has acceptable psychometric properties and can be used to estimate long-term outcome of migraine therapy in Korean population.
Anxiety ; Efficiency ; Headache ; Humans ; Migraine Disorders* ; Psychometrics ; Quality of Life* ; Surveys and Questionnaires* ; Reproducibility of Results*

OBJECTIVES: This randomized, multicenter, open-label, parallel clinical trial was carried to compare the therapeutic efficacy and the proportion of successful switch between 'direct switching method' and 'start-tapering switching method' when switching an antipsychotic to olanzapine. METHODS: This study included both inpatients and outpatients who fulfilled the criteria for schizophrenia as defined in the ICD-10 from 13 hospitals, and were in need to be appropriate for switching antipsychotics. Subjects were randomly assigned to one of the two switching methods. For 'direct switching method' group, previous antipsychotics were abruptly discontinued and 10mg of olanzapine was administered, whereas for 'start-tapering switching method' group, initially 10mg of olanzapine was administered and previous antipsychotics was gradually tapered for 2 weeks. Olanzapine was used for 6 weeks and the dose was adjusted within the range of 5-20mg. The therapeutic efficacy was measured with PANSS, BPRS, and CGI-Severity. A successful switching was defined as the completion of the 6 week trial without either worsening of the symptom(i.e. CGI-S score becomes worse twice consecutively) or the exacerbation of extrapyramidal symptoms(i.e. Simpson-Angus Scale scores becomes worse). RESULTS: 103 schizophrenic patients were participated in this study. There were no differences in baseline characteristics such as the demographic variables, the severity of symptoms, the history of previous antipsychotics treatments, the dosage of olanzapine used and the compliance between two groups. The proportion of successful switch was 71.1% for "direct switching method" and 82.2% for "start-tapering switching method", and there was no significant difference between the two switching methods. Also response rates to olanzapine based on total PANSS total scores were not different between the two groups(26.9% vs. 31.1%). At the time of completion of the trial, the scores of PANSS total, PANSS subscales, CGI-S and BPRS have significantly decreased after switching to olanzapine. But the changes of all scales measuring therapeutic efficacy in both endpoint and weekly analyses were not significantly different between the two switching methods. CONCLUSION: Although this study trial has many limitations and problems as an open clinical trial, the results may suggest that there were no significant differences between the two switching methods in the therapeutic efficacy. It was also found that the additional therapeutic benefits could be obtained by switching their antipsychotics to olanzapine.
Antipsychotic Agents ; Compliance ; Humans ; Inpatients ; International Classification of Diseases ; Outpatients ; Schizophrenia ; Weights and Measures