The overt effects of the anticancer drugs such as cisplatin and taxol appear to be DNA modification and microtubule stabilization respectively. But the mechanism by which these drugs affect tumor cell cycle perturbation and their correlation to apoptosis and cytotoxicity are not well understood, especially in combined sequential treatment of cisplatin and paclitaxel (taxol). In this study, to elucidate the action mechanisms as a function of cell cycle changes and cytotoxicities and to determine the adequate treatment sequence of cisplatin and taxol to acquire more enhanced cytotoxic effects when they are combined, we evaluated the cell cycle perturbations and its correlation to cytotoxic effects, which is measured by the extents of apoptosis and the fractions of cellular debris and live cells after combination treatment of cisplatin and taxol changing their treatment sequences in NIHOVCAR-3 ovarian cancer cell line. Our results were as follows; (1) The accumulation in S phase inhibited the entrance of tumor cells to G2M phase when the cisplatin treatment was preceded to taxol in their combination. (2) The tumor cells were not accumulated in S phase but most of them entered to and accumulated in G2M phase and they were leading to cell death when the taxol treatment was preceded to cisplatin in their combination. (3) Apoptotic peaks in taxol pretreatment group were detected earlier and persisted longer than that of cisplatin pretreatment group. (4) The cytotoxicities represented by the decreased fractions of live cells and the increased fractions of cellular debris were higher in taxol pretreatment group than those of cisplatin pretreatment group. These results suggested that the taxol pretreatment is more effective in combination of cisplatin and taxol and the relative decrease in the cytotoxicity in cisplatin pretreatment group was considered to be derived from the inhibition of entrance of tumor cells to G2M and protected them from the action by taxol. From these results, we concluded that the taxol pretreatment will enhance the cytotoxic effects to tumor cells when cisplatin and taxol will be administered and it indicates that correlations between cell cycle perturbation, apoptosis and cell death have to be considered in the future combination treatment of other drugs and in the development of new treatment regimens.
Apoptosis ; Cell Cycle* ; Cell Death* ; Cell Line* ; Cisplatin* ; DNA ; Microtubules ; Ovarian Neoplasms ; Paclitaxel* ; S Phase

The plasmepsins are the aspartic proteases of malaria parasites. Treatment of aspartic protease inhibitor inhibits hemoglobin hydrolysis and blocks the parasite development in vitro suggesting that these proteases might be exploited their potentials as antimalarial drug targets. In this study, we determined the genetic variations of the aspartic proteases of Plasmodium vivax (PvPMs) of wild isolates. Two plasmepsins (PvPM4 and PvPM5) were cloned and sequenced from 20 P. vivax Korean isolates and two imported isolates. The sequences of the enzymes were highly conserved except a small number of amino acid substitutions did not modify key residues for the function or the structure of the enzymes. The high sequence conservations between the plasmepsins from the isolates support the notion that the enzymes could be reliable targets for new antimalarial chemotherapeutics.
Amino Acid Sequence ; Animals ; Aspartic Endopeptidases/*genetics ; Base Sequence ; Cloning, Molecular ; Conserved Sequence ; DNA, Protozoan/chemistry/genetics ; Human ; Molecular Sequence Data ; Plasmodium vivax/*enzymology/genetics/isolation & purification ; Polymerase Chain Reaction ; Sequence Alignment ; Sequence Analysis, DNA ; Support, Non-U.S. Gov't

BACKGROUND: Woods are capable of causing allergic or irritant contact dermatitis which typically occurs on exposed areas. Because Bolivian rosewood exclusively contains the strong sensitizer R-3,4-dimethoxydalbergione, an increasing number of cases of irritant and allergic contact dermatitis has been reported. CASE REPORT: A 49-year-old, male, wood worker, who handled a variety of woods, developed allergic contact dermatitis. A patch test confirmed a positive reaction to one of the exotic woods, Bolivian rosewood. Allergens found in Bolivian rosewood caused this patient's dermatitis, which cleared when he avoided this wood. CONCLUSION: Exotic woods such as Bolivian rosewood can induce occupational contact dermatitis. Measures to lower the incidence of work-related dermatitis are needed in the workplace. Especially, when cutting or sanding woods, workers should wear proper personal protection.
Allergens ; Dermatitis ; Dermatitis, Allergic Contact* ; Dermatitis, Contact ; Erythema Multiforme* ; Erythema* ; Humans ; Incidence ; Male ; Middle Aged ; Patch Tests ; Silicon Dioxide ; Wood

OBJECTIVES: We report a case of n-hexane-induced occupational peripheral polyneuropathy. The patient had been cleaning mobile phone cases using n-hexane for 3 years without proper protection in the workplace. Method : Physical examinations, detailed history taking, laboratory studies and electrophysiological study were done. The n-hexane concentration in the ambient air of the workplace was analysed. RESULTS: The findings of the electrophysiological study revealed that the worker's neurologic symptoms were due to peripheral polyneuropathy. The average n-hexane concentration in the ambient air sampled at the workplace for 59 minutes was 1411.24ppm, from which the 8 hour time-weighted-average(TWA) was estimated as 882ppm. Because other alternative causes for peripheral polyneuropathy were ruled out by laboratory findings and detailed history taking, this TWA level strongly suggested that the disease was caused by n-hexane exposure. Conclusion : Although the neuro-toxicity of n-hexane is relatively well known, many problems have been identified in the management of this toxic material in terms of preventing toxic diseases in the workplace. We expect that this case will help in the planning of health management strategies for using n-hexane in the workplace.
Cellular Phone* ; Humans ; Neurologic Manifestations ; Physical Examination ; Polyneuropathies*

OBJECTIVES: This cross-sectional study investigated the relationship between job stress and needlestick injury the nurses at a University hospital in Incheon, Korea. METHODS: A questionnaire survey was conducted targeting 476 nurses, of which 320 (67.2%) questionnaires were returned and 256 (53.8%) were regarded as being reliable data for analyses. We estimated the relation of job stress to needlestick injury using univariate and multiple logistic regression analyses. RESULTS: One hundred sixty-five nurses (64.5%) had suffered at least one needlestick injury (included sharp injuries) during the previous year. After adjusting for potential confounders, we found that the high job control group was less likely than the other group to experience needlestick injury (OR=0.51, 95% CI=0.27-0.97). Job demand and social support, however, were unrelated to needlestick injury. The high job strain group was more likely to experience needlestick injury (OR=2.57, CI=1.13-5.83) than the low job strain group. CONCLUSIONS: Our results tend to suggest that nurses who were in the low job control or high job strain status were more likely to suffer a high rate of needlestick injury.
Cross-Sectional Studies ; Incheon ; Korea ; Logistic Models ; Needlestick Injuries* ; Questionnaires

OBJECTIVES: To evaluate the association of urinary 2-naphthol level and air pollution caused by exposure to smoking, traffic and residential factors. METHODS: The study subjects consisted of 300 university students in Incheon. The questionnaires concerning subject characteristics, smoking amount, traffic, distance between housing and main road, heating and cooking fuel including urinary cotinine levels were checked. RESULTS: There was not any significant association between urinary 2-naphthol level and age, sex, body mass index, distance from mainroad, traffic, heating and cooking fuel. The urinary 2-naphthol level was higher in smokers or high urinary cotinine level group(p=0.0001)than in nonsmokers or low urinary cotinine group. After adjusting for age, sex, and body mass index in the basic model, the 2-naphthol level was also higher in the smokers or high urinary cotinine level group, too(p<0.0005). The model included both traffic and residential variables and it had a good fitness as compared to other models. CONCLUSIONS: It has been known that as one of PAH metabolites, urinary 2-naphthol is a respiration-selective biological marker. We showed that tabacco smoking has a much stronger effects on urinary 2-naphthol levels than when subjects were exposed to air pollution, such as traffic, and other residential factors at the same time.
Air Pollution ; Biological Markers ; Body Mass Index ; Cooking ; Cotinine ; Heating ; Hot Temperature ; Housing ; Humans ; Incheon ; Questionnaires ; Smoke* ; Smoking*

Angiotensin II type 1 receptor blocker (ARB), which is frequently prescribed in patients with glomerulonephritis (GN), is suggested to increase the risk of cancer. We registered 3,288 patients with renal biopsy and analyzed the relationship between the use of renin-angiotensin-aldosterone system (RAAS) blockade and the incidence of cancer or cancer mortality. After renal biopsy, cancer developed in 33 patients with an incidence rate of 1.0% (95% of CI for incidence: 0.7%-1.3%). There was no difference in the cancer incidence among the groups according to the use of angiotensin-converting enzyme inhibitors (ACEI) or ARB: 1.2% in the None (23/1960), 0.7% in the ARB-only (5/748), 0.4% in the ACEI-only (1/247), and 1.2% in the ACEI-ARB (4/333) (P = 0.487) groups. The cancer mortality was 2.1%, 0.4%, 0.0%, and 0.3% in None, ACEI-only, ARB-only, and ACEI-ARB group, respectively (P < 0.001). The risk of cancer mortality in patients with ARB was only 0.124 (0.034-0.445) compared to that of non-users of ARB by Cox's hazard proportional analysis. In conclusion, prescription of ACEI or ARB in patients with GN does not increase cancer incidence and recipients of ARB show rather lower rates of all-cause mortality and cancer mortality.
Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ; Female ; Follow-Up Studies ; Glomerulonephritis/complications/diagnosis/*drug therapy ; Humans ; Incidence ; Kidney/pathology ; Male ; Middle Aged ; Neoplasms/complications/*epidemiology/mortality ; Renin-Angiotensin System/*drug effects ; Retrospective Studies ; Risk Factors

Angiotensin II type 1 receptor blocker (ARB), which is frequently prescribed in patients with glomerulonephritis (GN), is suggested to increase the risk of cancer. We registered 3,288 patients with renal biopsy and analyzed the relationship between the use of renin-angiotensin-aldosterone system (RAAS) blockade and the incidence of cancer or cancer mortality. After renal biopsy, cancer developed in 33 patients with an incidence rate of 1.0% (95% of CI for incidence: 0.7%-1.3%). There was no difference in the cancer incidence among the groups according to the use of angiotensin-converting enzyme inhibitors (ACEI) or ARB: 1.2% in the None (23/1960), 0.7% in the ARB-only (5/748), 0.4% in the ACEI-only (1/247), and 1.2% in the ACEI-ARB (4/333) (P = 0.487) groups. The cancer mortality was 2.1%, 0.4%, 0.0%, and 0.3% in None, ACEI-only, ARB-only, and ACEI-ARB group, respectively (P < 0.001). The risk of cancer mortality in patients with ARB was only 0.124 (0.034-0.445) compared to that of non-users of ARB by Cox's hazard proportional analysis. In conclusion, prescription of ACEI or ARB in patients with GN does not increase cancer incidence and recipients of ARB show rather lower rates of all-cause mortality and cancer mortality.
Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ; Female ; Follow-Up Studies ; Glomerulonephritis/complications/diagnosis/*drug therapy ; Humans ; Incidence ; Kidney/pathology ; Male ; Middle Aged ; Neoplasms/complications/*epidemiology/mortality ; Renin-Angiotensin System/*drug effects ; Retrospective Studies ; Risk Factors

A 64-year-old man was admitted for gross hematuria. Preoperative study revealed right renal cell carcinoma with inferior vena cava(IVC) tumor thrombus. Right radical nephrectomy was performed, and deep hypothermic circulatory arrest(DHCA) with retrograde cerebral perfusion(RCP) was used for extraction of tumor thrombus in the IVC. The thrombus originated from the right kidney, which extended the orifice of the gonadal vein in the left renal vein laterally, the hepatic vein superiorly, and 3 cm below the right renal vein inferiorly. The thrombus was removed completely without caval wall injury under DHCA with RCP, and the postoperative course was uneventful. He received immunotherapy with interferon, and followed up without any surgical problem.
Carcinoma, Renal Cell* ; Circulatory Arrest, Deep Hypothermia Induced* ; Gonads ; Hematuria ; Hepatic Veins ; Humans ; Immunotherapy ; Interferons ; Kidney ; Middle Aged ; Nephrectomy ; Renal Veins ; Thrombosis ; Veins ; Vena Cava, Inferior

OBJECTIVES: Incresed gamma-glutamyltransferase (GGT) concentration has mainly been used as a biologic marker of alcohol drinking and liver diseases. However, some recent reports have suggested that serum GGT concentration may be an early biomarker of oxidative stress and associated with chronic diseases like hypertension, DM, hyperlipidemia, CHD, stroke etc. In this study, we analysed the factors associated with increased serum GGT level and evaluated the clinical application of serum GGT in predicting the risk of chronic diseases. METHODS: The data were collected from 15,546 periodic health examinations, 9,660 males and 5,886 females, done at one university hospital from 2001 to 2003. We analysed self-questionnaire, physical examination and laboratory data. Statistical analyses(t-test, ANOVA, Pearson's correlation analysis, multiple regression analysis and logistic regression analysis) were done by SPSS for windows 10.0. RESULTS: Mean serum GGT levels were quite different according to age, sex, BMI, smoking and alcohol drinking (all P-value < 0.001), but were not different by regular vitamin intake or not (P-value=0.117). There was significant correlation between serum GGT level and the variables (of age, BMI, blood pressure, Hb, fasting blood sugar, total cholesterol, AST and ALT) (all P-value < 0.001). In sex-specific multiple regression analysis, increased serum GGT level was significantly associated with age, alcohol drinking, smoking, blood pressure, fasting blood sugar and ALT in males (all P-value < 0.001), and with age, alcohol drinking, smoking, Hb, blood pressure, total cholesterol and ALT in females (all P-value < 0.05). In sex-specific logistic regression analysis, increased serum GGT level was significantly associated with risk of 'clinical abnormalities'. This risk increased about 13-fold in males and 4.6-fold in females for serum GGT level over the third quatile, compared with under the first quartile. CONCLUSIONS: Serum GGT level is increased not only by alcohol drinking or liver diseases, but also by many other factors associated with chronic diseases and behavioral factors. Thus many factors should be considered in evaluating an increase in GGT level, even when within the upper normal range. Serum GGT level may be a predictor for the early development of chronic diseases.
Alcohol Drinking ; Biological Markers ; Blood Glucose ; Blood Pressure ; Cholesterol ; Chronic Disease ; Fasting ; Female ; gamma-Glutamyltransferase* ; Humans ; Hyperlipidemias ; Hypertension ; Liver Diseases ; Logistic Models ; Male ; Oxidative Stress ; Physical Examination ; Reference Values ; Smoke ; Smoking ; Stroke ; Vitamins