• Applied Chemistry for Engineering
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• v.10 no.6
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• pp.895-901
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• 1999

The acid characteristics of ${\beta}$-zeolites was modified by the different calcination conditions in order to remove template and the post-treatments such as ammonium ion exchange and HCl treatment. Alkylation of benzene with propene and isopropanol was carried out over the catalysts to investigate the effect of acid characteristics on the selectivity to cumene in this reaction. The $Br{\ddot{o}}nsted$ acidity(IR $3610cm^{-1}$ band) of ${\beta}$-zeolite was significantly reduced by a deep bed calcination compared to that of ${\beta}$-zeolite calcined in a shallow bed. Moreover, extraframework aluminum species which did not show acidity were produced by the framework dealumination on the deep bed calcined ${\beta}$-zeolite. $Br{\ddot{o}}nsted$ acidity of deep bed calcined ${\beta}$-zeolite was significantly recovered by ammonium ion exchange, however, it was partially recovered by a weak HCl treatment. It was found that the framework aluminum as well as the extraframework aluminum were extracted by a strong HCl treatment. The selectivity to cumene was shown to be about 95% on the shallow bed calcined ${\beta}$-zeolite, however, it decreased to 90% on the deep bed calcined one. The post-treatment such as ammonium exchange and weak HCl treatment enhanced the selectivity to cumene up to 93% by the partial recovery of $Br{\ddot{o}}nsted$ acidity. Propene was proved to be a good alkylating agent for the selectivity to cumene compared to isopropanol.

• Journal of Life Science
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• v.19 no.1
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• pp.1-8
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• 2009

In this paper, to elucidate the further mechanisms of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced growth arrest, we investigated the effect of MNNG on cell cycle and proliferation in U937 cells, a p53-null human myeloid leukemia cell line. It was found that MNNG causes an arrest at the G2/M phase of the cell cycle and induces apoptosis, which is closely correlated to inhibition of cyclin B1 and cyelin-dependent kinase (Cdk) 2-associated kinase activities. MNNG treatment in. creased protein and mRNA levels of the Cdk inhibitor p21(WAF1/CIP1), and activated the reporter construct of a p21 promoter. By using p21 promoter deletion constructs, the MNNG-responsive element was mapped to a region between 113 and 61 relative to the transcription start site. These data indicate that in U937 cells MNNG can circumvent the loss of wild-type p53 function and induce critical downstream regulatory events leading to transcriptional activation of p21. Present results indicate that the p53-independent up-regulation of p21 by MNNG is likely responsible for the inhibition of cyclin/Cdk complex kinase activity rather than the down-regulation of cyclins and Cdks expression. These novel phenomena have not been previously described and provide important new insights into the possible biological effects of MNNG.

• Applied Chemistry for Engineering
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• v.17 no.3
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• pp.235-242
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• 2006

Liquid phase alkylation of biphenyl (BP) was studied over large pore zeolites. Selective formation of the least bulky products, 4,4'-diisopropylbiphenyl (4,4'-DIPB) occurred only in the isopropylation of BP over some large pore molecular sieves. H-mordenites (MOR) gave the highest selectivity among them. The dealumination of MOR enhanced catalytic activity and the selectivity of 4,4'-DIPB because of the decrease of coke-deposition. Non-selective catalysis occurs on external acid sites over MOR with the low $SiO_2/Al_2O_3$ ratio because severe coke-deposition deactivates the acid sites inside the pores by blocking pore openings. The selectivity of DIPB isomers was changed with reaction temperature. Selective formation of 4,4'-DIPB was observed at moderate temperatures such as $250^{\circ}C$, whereas the decrease of the selectivity of 4,4'-DIPB occurred at higher temperatures as $300^{\circ}C$. However, 4,4'-DIPB was almost exclusive isomer in the encapsulated DIPB isomers inside the pores even at high temperatures. These decreases of the selectivity of 4,4'-DIPB are due to the isomerization of 4,4'-DIPB on the external acid sites. Some 12-membered molecular sieves, such as SSZ-24, MAPO-5 (M:Mg, Zn, Si), SSZ-31, and ZSM-12, which have straight channels, gave 4,4'-DIPB with moderate to high selectivity; however; SSZ-55, SSZ-42, and MAPO-36 (M: Mg, Zn) gave lower selectivity because of cages in 12-membered one dimensional channels. Three dimensional H-Y and Beta zeolites also yield 4,4'-DIPB in low yield because of their wide circumstances for the isopropylation of BP. The increasing the size of alkylating agent enhanced the shape-selective alkylaiton even for the zeolites, such as UTD-1. The ethylation of BP to ethylbiphenyls (EBPs) and diethylbiphenyls (DEBPs) over MOR was non-selective. The ethylation of BP to EBPs was controlled kinetically. However, there was difference in reactivity of EBPs and DEBPs for their further ethylation. 4-EBP was ethylated preferentially among the isomers, although the formation of 4,4'-DEBP was less selective. The least bulky 4-EBP and 4,4'-DEBP have the highest reactivity among EBPs and DEBPs for the ethylation to polyethylbiphenyls (PEBPs). These results show that the environments of MOR pores are too loose for shape selective formation of the least bulky isomers, 4-EBP and 4,4'-DEBP in the ethylation of BP, and that MOR pores have enough space for the further ethylation of 4,4'-DEBP.

• The Journal of the Korean Society for Microbiology
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• v.22 no.2
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• pp.175-184
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• 1987

The use of alkylating agent cyclophosphamide(CY), a widely used antitumor drug is well known as a potent immunosuppressant and has been used as a probe for investigating the functional capabilities of lymphocyte subsets of both T and B cells that play an important role in the regulation of the immune response. The present study was undertaken in an effort to assess the effects of CY on immunological memory in murine model. CY, given as a single dose of CY(250mg/kg) before sensitization with sheep red blood cells(SRBC) enhanced the primary response of Arthus and delayed-type hypersensitivity(DTH), as measured by footpad swelling reaction, but suppressed their tertiary DTH response. The similar CY pretreatment enhanced both the primary and tertiary hemagglutinin(HA) responses to SRBC, and the tertiary antibody response against polyvinylpyrroridone(PVP), a thymus-independent antigen but not the primary response against PVP. CY, given as a single dose of 250mg/kg 2 days before the primary immunization and two doses of 100mg/kg 2 days before the secondary and tertiary immunization, markedly suppressed the tertiary DTH and HA responses to SRBC. However, CY, given as small multiple daily doses(10mg/kg) over 4 days before sensitization but not after sensitization, enhanced the secondary HA response to SRBC. Contact sensitivity to dinitrofluorobenzene(DNFB) was suppressed by the drug, given either as a single large dose(300mg/kg) or as multiple dose(10mg/kg) administered 2 days before, together with or after DNFB sensitization. This suppression was more pronounced and more significant when CY was given as multiple dose. However, the enhancement of the secondary contact sensitivity to DNFB by CY was not clear-cut. The splenectomy appears to increase the enhancing effect of CY on contact sensitivity. These results suggest that CY selectively influences the immune response depending on the time of the drug administration relative to immunization and that the secondary or tertiary immune response involve memory cells with different susceptibilities to CY. Moreover, these results suggest that multiple low doses may sesectivley inhibit suppressor T cell proliferation involving DTH, HA or contact sensitivity without effecting helper T cells, but high doses presumably inhibit helper T cells and suppressor T cells with effecting B cells.

• Journal of Life Science
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• v.31 no.2
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• pp.223-228
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• 2021

Cyclophosphamide (CP) is widely used in cancer and lymphoma treatments and as an immunosuppressant drug. CP is a DNA alkylating agent that metabolizes into 4-hydrocyclophosphamide (4H-CYP) and aldophosphamide in hepatocytes. However, its metabolites cause DNA synthesis disorder, leading to apoptosis and toxic side effects. The development of technology to minimize this side effect is essential to improve CP's clinical application. Various bioactive compounds have been reported to have anti-cancer and antioxidant functions and preventive or therapeutic roles in metabolic diseases. Many researchers have attempted to minimize the side effects and improve the efficacy of these drugs together with the use of bioactive compounds. Ulmus macrocarpa Hance has been used for the treatment of edema, mastitis, stomach pain, tumors, cystitis, and other inflammatory diseases. The aim of this study was to investigate at the histological level the protective function of U. macrocarpa Hance against CP's side effects and any potential toxic effect of U. macrocarpa Hance in the liver and kidney. Water extracts of U. macrocarpa Hance reduced CP-induced toxicity and did not induce any histological damage in the liver and kidney. Therefore, U. macrocarpa Hance would be applicable in the pharmaceutical industry.

• Molecules and Cells
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• v.45 no.12
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• pp.886-895
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• 2022

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.

• Development and Reproduction
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• v.13 no.2
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• pp.105-114
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• 2009

Ethane 1,2-dimethane sulfonate (EDS) is a well-known alkylating agent used as selective Leydig cell (LC) toxicant to create a testicular dysfunction model. Previous studies including our own clearly demonstrated the dramatic weight loss of the androgen dependent accessory sex organs such as epididymis, seminal vesicle and prostate gland in this 'LC knock-out' rats. The present study was performed to evaluate the effect of EDS administration on histological changes of the epididymis, seminal vesicle and prostate in adult rats. Adult male Sprague-Dawley rats (350$\sim$400 g B.W.) were injected with a single dose of EDS (75 mg/kg, i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. Tissue weights (testis, epididymis, seminal vesicle and prostate gland) were measured. The histological changes of tissue were observed by a light microscopy using hematoxylin & eosin staining. Weights of the reproductive and accessory organs progressively declined after the EDS treatments (weeks 1, 2 and 3). After this, the decrease was stopped, then gradually returned to the normal levels. There was a partial (about 60%) recovery of the epididymis weight during weeks $6{\sim}7$. The cross section of epididymis revealed an increase in thickness of the epithelium during weeks $1{\sim}3$. In contrast, considerable reduction of epithelial thickness in seminal vesicle was observed during same period. Similarly, a reduction in thickness of prostate epithelial layer was found during weeks $1{\sim}3$, then it was back to normal thickness after week 4. Taken together, the present study demonstrated that the temporally induced androgen-deficiency by EDS treatment could result the prominent alterations in histology of the accessory sex organs. Further studies on the physiological and molecular regulation of these androgen-sensitive organs using EDS model will be helpful to understand the normal and pathological development and differentiation mechanism of these organs.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.129-136
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• 1992

As it has been reported that the depolarization-induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus and various lines of evidence indicate the involvement of adenylate cyclase system in $A_1-adenosine$ post-receptor mechanism in hippocampus, it was attempted to delineate the role of adenylate cyclase system in the $A_1-receptor-mediated$ control of ACh release in this study. Slices from rat hippocampus were incubated with $[^3H]-choline$ and the release of the labelled products was evoked by electrical stimulation $(3\;Hz,\;5\;Vcm^{-1},\;2\;ms,\;rectangular\;pulses)$, and the influence of various agents on the evoked tritium-outflow was investigated. $N^6-cyclopentyladenosine$ (CPA), a specific $A_1-adenosine$ receptor agonist, in concentrations ranging from 0.1 to $10\;{\mu}M$, decreased the $[^3H]-ACh$ release in a dose-dependent manner without the changes of basal rate of release. 8-cyclopentyl-1,3-dipropylxanthine $(DPCPX,\;1{\sim}10\;{\mu}M)$, a selective $A_1-receptor$ antagonist, increased the $[^3H]-ACh$ release in a dose-related fashion with slight increase of basal tritium-release. And the CPA effects were significantly inhibited by DPCPX $(2\;{\mu}M)$ pretreatment and the dose-response curve produced by CPA was shifted to the right. The responses to N-ethylmaleimide $(NEM,\;10\;&\;30\;{\mu}M)$, a SH-alkylating agent of G-protein, were characterized by increments of the evoked ACh-release and the basal release, and the CPA effect were completely abolished by NEM pretreatment. Forskolin, a specific adenylate cyclase activator, in concentrations ranging from 0.3 to $10\;{\mu}M$, increased the evoked ACh-release in a dose-dependent manner and the CPA effects were inhibited by forskolin. These results indicate that the $A_1-adenosine$ heteroreceptor plays an important role in ACh-release via nucleotide-binding protein Gi in the rat hippocampus and that the adenylate cyclase system might be participated in this process.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.263-272
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• 1994

Since it was been reported that the depolarization-induced ACh release is inhibited by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus, a large body of experimental data on the post-receptor mechanism of this process has been accumulated. But, the post-receptor mechanism of presynaptic $A_1-adenosine$ receptor on the ACh release has not been clearly elucidated yet. Therefore, it was attempted to clarify the post-receptor mechanisms of the $A_1-adenosine$ receptor-mediated control of ACh release in this study. Slices from rat hippocampus were equilibrated with $^3H-choline$ and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 $VCm^{-1}$, 2ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Adenosine, in concentrations ranging from $0.3{\sim}300\;{\mu}M$, decreased the ACh release in a dose-dependent manner, without affecting the basal rate of release. The adenosine effects were significantly inhibited by $DPCPX\;(2\;{\mu}M)$, a selective $A_1-receptor$ antagonist. The responses to N-ethylmaleimide $(10&30{\mu}M)$, a SH-alkylating agent of G-protein, were characterized by increments of the evoked ACh-release and the basal release, and the adenosine effects were completely abolished by NEM pretreatment. PDB $(1{\sim}10\;{\mu}M)$, a specific protein kinase C (PKC) activator, increased, whereas PMB $(0.03{\sim}1\;mg)$, a PKC inhibitor, decreased the evoked ACh-release, and the adenosine effects were not affected by these agents. Nifedipine $(1\;{\mu}M)$, a $Ca^{2+}\;-channel$ blocker of dihydropyridine analogue, significantly inhibited the adenosine effect, but glibenclamide, a $K^+-channel$ blocker, did not. Finally, 8-bromo cyclic AMP $(100\;&\;300{\mu}M)$, a membrane-permeable analogue of cAMP, did not alter the ACh release, but adenosine effects were inhibited by pretreatment with large dose of 8-br-cAMP $(300\;{\mu}M)$. These results indicate that the decrement of the evoked ACh-release by $A_1-adenosine$ receptor is mediated by the G-protein, and nifedipine-sensitive $Ca^{2+}-channel$ and adenylate cyclase system are coupled partly to this effect, and that protein kinase C and glibenclamide-sensitive $K{^+}-channel$ are not involved in this process.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.1-11
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• 1996

Since it has been reported that the depolarization-induced norepinephrine (NE) release is inhibited by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus, a large body of experimental data on the post-receptor mechanism of this process has been accumulated. But, the post-receptor mechanism of presynaptic $A_1-adenosine$ receptor on the NE release has not been clearly elucidated yet. Therefore, it was attempted to clarify the post-receptor mechanisms of the $A_1-adenosine$ receptor-mediated control of NE release in this study. Slices from rat hippocampus were equilibrated with $^3H-norepinephrine$ and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 $Vcm^{-1}$, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Adenosine, in concentrations ranging from $1{\sim}30{\mu}M$, decreased the NE release in a dose-dependent manner, without affecting the basal rate of release. The adenosine effects were significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, $2{\mu}M$), a selective $A_1-receptor$ antagonist. The responses to N-ethylmaleimide (NEM, 10 & $30{\mu}M$), a SH-alkylating agent of G-protein, were characterized by increments of the evoked NE-release and the basal release, and the adenosine effects were completely abolished by NEM pretreatment. $4{\beta}-Phorbol$ 12,13-dibutyrate (PDB, $1{\mu}M$), a specific protein kinase C (PKC) activator, increased the evoked NE release, whereas polymyxin B sulfate (PMB,0.1 mg), a PKC inhibitor, decreased the release, and the adenosine effects were inhibited by these agents. Nifedipine $(1{\mu}M)$, a $Ca^{2+}-channel$ blocker of dihydropyridine analogue, did not affect the adenosine effect. Tetraethylammonium (TEA, 3 mM) increased the evoked NE release, and inhibited the adenosine effects, but glibenclamide, a ATP dependent $K^+-channel$ blocker, did not. Finally, 8-bromo cyclic AMP (100 & $300{\mu}M$), a membrane-permeable analogue of cAMP, did not alter the NE release, but adenosine effects were inhibited by pretreatment with 8br-cAMP. These results suggest that the decrement of the evoked NE-release by $A_1-adenosine$ receptor is mediated by the C-protein, which is coupled to protein kinase C, adenylate cyclase system and TEA sensitive $K^+-channel$, and that nifedipine-sensitive $Ca^{2+}-channel$ and glibenclamide-sensitive $K^+-channel$ are not involved in this process.