Association Study between 5-HT2A Receptor and DRD3 Receptor Gene Polymorphism and Clinical Response to Atypical Antipsychotics in Patients with Schizophrenia / 신경정신의학

OBJECTIVES: This study was performed based on the hypothesis that the interindividual differences in clinical response to atypical antipsychotics might be associated with serotonin 2A receptor(5-HT2A) gene and(or) dopamine D3 receptor(DRD3) gene polymorphisms. METHODS: Seventy-five patients(39 men, 36 women) who met DSM-IV criteria for Schizophrenia at the Asan Medical Center were selected for the analysis of the medical records and subsequent interview. A written informed consent was obtained prior to the study and the privacy protection was kept throughout the course. Clinical Global Impression(CGI) Scale was applied after 4 weeks of treatment to assess the response to atypical antipsychotics. All patients in this study were administered olanzapine(n=39), risperidone(n=52) or clozapine(n=4). According to CGI scale, the patients were classified in 7 groups ; very much improvement ; much improvement ; minimal improvement ; no change ; minimal worsening ; much worsening ; very much worsening. The first and second groups were regarded as responders while the other groups were non-responders. Patients were genotyped for 5-HT2A by PCR(Msp I) for detection of T102 and C102 alleles. And they were also genotyped for DRD3 Ser9Gly polymorphism by PCR(Bal I). We conducted the statistical analyses to detect association between responders and non responders with chi-square tests. RESULTS: The patients who were shown no or minimally improved patients were sorted to non-responders(n=42, men 24, women 18) and the other patients shown much or very much improved were grouped as responders(n=33, men 15, women 18). The differences in demographic variables(age, sex), age of onset, and duration of illness were not statistically significant between the two groups. T102 allele is more frequent in non-responders(56.0%) than responders(45.5%), however, this difference is not statistically significant(p=0.20). Gly9 allele is near equal between non-responders and responders (65.5%, 65.2%). Genotype frequencies of the two groups also is not a statistically significant for 5-HT2A T102C(p=0.28) and DRD3 Ser9Gly(p=0.90). CONCLUSION:These results do not show significant associations among 5-HT2A gene, DRD3 gene and clinical response to atypical antipsychotics. On the assumption that responses to atypical antipsychotics are mediated by these two receptors, we can draw two possibilities. First, 5-HT2A and DRD3 genes may not be the functional variants related with responses to atypical antipsychotics. Second possibility is that the unknown variations which might be in linkage disequilibrium with the 5-HT2A T102C polymorphism and DRD3 Ser9Gly polymorphism may be associated with the response to atypical antipsychotics in schizophrenia. However, it is possible that the small number of subjects and ethnic difference of allele frequency of marker polymorphism could induce false negative results.

Fibroblast growth factor-induced Thymidylate Synthase activity and expression in the serum-starved UMR 106-01 osteoblast cells / 대한정형외과연구학회지

PURPOSE: In the present study, the effects of bFGF on the early responses of proliferation of UMR 106-01 osteoblast cells during cell cycle reentry from the latent(G0/G1) to the proliferative periods(S/M) were investigated. MATERIALS AND METHODS: The synchronized cell culture method using the serum starvation was utilized. After the addition of bFGF, the time courses of protein synthesis, DNA synthesis, thymidylate synthase(TS) activity, TS mRNA level and expression of c-fos were determined. RESULTS: 87% UMR 106-01 cells were synchronized to G0/G1 by serum starvation for seven days in the medium containing 0.1% serum. The protein level began to increase 3 hours after bFGF treatment and reached the maximum at 18 hours. TS activity began to increase 3 hours after the bFGF treatment and reached its peak at 6 hours while its mRNA level, determined by quantitative PCR, reached the maximum at 12 hours. The expression of c-fos protein, determined by western blot analysis and immunocytochemistry, increased 3 hours after bFGF treatment. On the contrary, these prominent changes and responses to bFGF were not observed in the case of using non-synchronized cells cultured in the medium containing 10% serum. CONCLUSION: Based on these data it can be concluded that bFGF-induced DNA synthesis in the early proliferative phase is due to increases in both TS activity and mRNA amount and that the increase in c-fos expression and TS activity occur before the increase in TS mRNA level.

Fibroblast growth factor-induced Thymidylate Synthase activity and expression in the serum-starved UMR 106-01 osteoblast cells / 대한정형외과연구학회지

PURPOSE: In the present study, the effects of bFGF on the early responses of proliferation of UMR 106-01 osteoblast cells during cell cycle reentry from the latent(G0/G1) to the proliferative periods(S/M) were investigated. MATERIALS AND METHODS: The synchronized cell culture method using the serum starvation was utilized. After the addition of bFGF, the time courses of protein synthesis, DNA synthesis, thymidylate synthase(TS) activity, TS mRNA level and expression of c-fos were determined. RESULTS: 87% UMR 106-01 cells were synchronized to G0/G1 by serum starvation for seven days in the medium containing 0.1% serum. The protein level began to increase 3 hours after bFGF treatment and reached the maximum at 18 hours. TS activity began to increase 3 hours after the bFGF treatment and reached its peak at 6 hours while its mRNA level, determined by quantitative PCR, reached the maximum at 12 hours. The expression of c-fos protein, determined by western blot analysis and immunocytochemistry, increased 3 hours after bFGF treatment. On the contrary, these prominent changes and responses to bFGF were not observed in the case of using non-synchronized cells cultured in the medium containing 10% serum. CONCLUSION: Based on these data it can be concluded that bFGF-induced DNA synthesis in the early proliferative phase is due to increases in both TS activity and mRNA amount and that the increase in c-fos expression and TS activity occur before the increase in TS mRNA level.

The Effect of Heat Shock Response on the Tumor Necrosis Factor-alpha-induced Acute Lung Injury in Rats / 결핵

BACKGROUND: Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-alpha. METHODS: We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250-350 g. The heated rats were raised their rectal temperature to 41degrees C and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of I125 in the right lung divided by counts per minutes of I125 in 1.0 ml of blood. All data are expressed as means+/-SE. RESULTS: There is no difference in acute lung leak index (0.099+/-0.024 vs 0.123+/-0.005) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats (4.58+/-0.79 U/g) compared with heat-unpretreated rats (7.32+/-0.97 U/g) (P= 0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index (0.137+/-0.012) and lung MPO activity (5.51+/-1.04 U/g) compared with those of heat-unpretreated and TNF-administered rats (0.186+/-0.016, 14.34+/-1.22 U/g) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment CONCLUISON: The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.

Analysis of MDR1(multidrug resistance) gene expression in bladder tumor and renal cell carcinoma by polymerase chain reaction / 대한비뇨기과학회지

The expression of the multidrug resistance gene (MDR1, gene) is the main mechanism of tumor resistance to anticancer drugs. MDR1 gene encodes P-glycoprotein which functions as an efflux pump for some anticancer drugs such as vinblastine and doxorubicin. Polymerase chain reaction is the recent technology with allows direct analysis of a unique segment present in the genome of e single cell. We used the new method to analyze the levels of MDR1 mRNA in the tissue samples of kidney, bladder and their tumors, using the polymerase chain reaction. High levels of MDR1 gene expression were revealed in 3 of 4 (75%) normal kidney and in 2of 4 (50%) of renal cell carcinoma tissues. MDR1 gene expression was not observed in 3 normal bladder tissues but low levels of MDR1 gene expression was not observed in 6 of8 (75%) bladder tumor tissues. The polymerase chain reaction may be e highly sensitive, specific, rapid and convenient method in measuring the level of MDR1 gene expression, compared with conventional blot methods.