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Aminolysis of Y-Substituted Phenyl 2-Thiophenecarboxylates and 2-Furoates: Effect of Modification of Nonleaving Group from 2-Furoyl to 2-Thiophenecarbonyl on Reactivity and Mechanism

  • Um, Ik-Hwan;Min, Se-Won
    • Bulletin of the Korean Chemical Society
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    • v.29 no.3
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    • pp.585-589
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    • 2008
  • Second-order rate constants (kN) have been measured for reactions of Y-substituted phenyl 2-thiophenecarboxylates (6a-h) with morpholine and piperidine in 80 mol % H2O/20 mol % DMSO at 25.0 0.1 oC. The Brnsted-type plot for the reactions of 6a-h with morpholine is linear with b lg = 1.29, indicating that the reactions proceed through a tetrahedral zwitterionic intermediate (T?). On the other hand, the Brnsted-type plot for the reactions of 6a-h with piperidine exhibits a downward curvature, implying that a change in the rate-determining step occurs on changing the substituent Y in the leaving group. Dissection of kN into microscopic rate constants (i.e., k1 and k2/k1 ratio) has revealed that k1 is smaller for the reactions of 6a-h than for those of Y-substituted phenyl 2-furoates (5a-h), while the k2/k1 ratio is almost the same for the reactions of 5a-h and 6a-h. It is also reported that modification of the nonleaving group from the furoyl (5a-h) to the thiophenecarbonyl (6a-h) does not influence pKao (defined as the pKa at the center of the Brnsted curvature) as well as the k2/k1 ratio.

Regulation of Intracellular pH by SHC1 in Saccharomyces cerevisiae (효모에서 SHC1 유전자의 이온 농도 조절에 의한 세포내 pH 항상성 유지)

  • 하승길;전준철;최의열
    • Korean Journal of Microbiology
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    • v.38 no.3
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    • pp.168-172
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    • 2002
  • Budding yeasts maintain an effective system to regulate intracellular pH in response to environmental pH fluctuation. In a previous study we reported that SHC1 plays a role in cell growth at alkaline condition, not at acid pH. We constructed a null mutant deleted an entire open reading frame for SHC1. To test whether the retardation in cell growth was caused by the absence of intracellular pH buffering capacity, we measured intracellular pH with a pH-sensitive fluorescent dye, C.SNARE. The intracellular pH of the mutant cell was much higher than that of wild-type cells, indicating that the mutant cells lack some types of buffering capacity. We also investigated the level of $Na^+ and K^+$ content with atomic mass spectroscopy after alkali shock. Wild-type cell showed a higher level of intracellular K^+$ content, whereas there was no difference in $Na^+$ level. The result suggested that K^+$ is more important in the regulation of intracellular pH in yeasts.

Interaction Characteristics of Nucleoside Analogues with Human Organic Anion Transporter 1 and 3

  • Choi, Jun-Shik;Cheon, Eun-Pa;Han, Hyo-Kyung
    • Journal of Pharmaceutical Investigation
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    • v.36 no.4
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    • pp.283-286
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    • 2006
  • The present study aimed to investigate the interaction of nucleoside analogs with human organic anion transporter 1 and 3(hOAT1 and hOAT3) that play a primary role in the tubular uptake of endogenous and exogenous organic anions in the kidney. The interactions of ddC, ara-C, ara-A and ara-U with hOAT1 and hOAT3 were examined using MDCK cells stably overexpressing hOAT1 or hOAT3. Among the tested drugs, ddC showed the highest affinity to hOAT1 with $IC_{50}$ values of 5.2 mM, while ara-A, ara-C and ara-U weakly inhibited the cellular uptake of $[^3H]-PAH$ in MDCK-hOAT1 cells at 1 mM. In contrast, all the tested drugs did not have any inhibition effect on the cellular uptake of $[^3H]-estrone$ sulfate in MDCK-hOAT3 cells over the drug concentration of 0.01-2 mM, implying that they might not interact with hOAT3. Taken all together, the present study suggests that hOAT1 could weakly interact with nucleoside analogues such as ddC, ara-C, ara-A and ara-U but the interaction with hOAT3 during the urinary excretion of these nucleoside analogues may be negligible in the kidney.

2009 Pandemic Influenza A(H1N1) Infections in the Pediatric Cancer Patients and Comparative Analysis with Seasonal Influenza (소아암 환자에서 2009 대유행 인플루엔자 A(H1N1) 감염의 임상적 고찰 및 계절 인플루엔자와의 비교 분석)

  • Choi, Soo Han;Yoo, Keon Hee;Ahn, Kangmo;Sung, Ki Woong;Koo, Hong Hoe;Kim, Yae Jean
    • Pediatric Infection and Vaccine
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    • v.19 no.2
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    • pp.61-70
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    • 2012
  • Purpose: This study was performed to compare the clinical characteristics of 2009 pandemic influenza A(H1N1) [A(H1N1) pdm09] and seasonal influenza A infection in the pediatric cancer patients. Methods: A retrospective review was performed in the pediatric cancer patients who had confirmed A(H1N1)pdm09 infection at Samsung Medical Center from August 2009 to February 2010. For the comparison, the medical records of pediatric cancer patients with seasonal influenza A from January 2000 to May 2009 were reviewed retrospectively. Results: Eighty-two A(H1N1)pdm09 infections were confirmed in the pediatric cancer patients. Ten patients (12.2%) developed complicated clinical course by lower respiratory infections or extrapulmonary infections; 4 pneumonia, 1 bronchitis, 1 pericarditis with pneumonia, 1 encephalitis with pneumonia, 2 meningitis and 1 pericarditis. Three patients received mechanical ventilator and ICU care. Three pediatric cancer patients (3.7%) died. The risk factors related to complicated A(H1N1)pdm09 infections were date of infection (44-45th week 2009) and nosocomial infection. When comparing with previous seasonal influenza A infections, more prompt and aggressive antiviral therapy was given in A(H1N1)pdm09 infections. Conclusion: The A(H1N1)pdm09 infections caused a various clinical manifestations including fatal cases in pediatric cancer patient during pandemic season. There was no significant difference in clinical course between influenza A(H1N1)pdm09 and seasonal influenza A infections except the antiviral treatment strategy.

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Distribution of Quinolones (Ciprofloxacin, Norfloxacin and Oxolinic acid) after Oral Administration in Carp (Cyprinus carpio) (잉어에 있어서 Quinolones (Ciprofloxacin, Norfloxacin 및 Oxolinic acid)의 경구투여에 따른 장기내 분포상)

  • Choi, Min-Soon;Park, Kwan-Ha
    • Journal of fish pathology
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    • v.18 no.3
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    • pp.269-276
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    • 2005
  • The concentrations of quinolones (oxolinic acid; OXA, norlloxacin: NRF & ciprofloxacin: CPF) after oral administration of single doses (20 mg/kg B.W.) were investigated in carp (Cyprinus carpio) kept in freshwater at 20-23$^{\circ}C$. The distribution of the drug was studied after treatment. At points timed, from 1 h to 96 hrs after administration, blood (B), liver (L), kidney (K) and muscle (M) from 5 individuals in each group were collected for analyse with microbiological bioassay method. The peak concentrations were measured at 8 h (L), 12 h (B and K) and 24 h (M) after administration regardless of treated drugs. Considerably high concentrations of CPF (13.8-19.6${\mu}g/m{\ell}$) NRF (11.8-16.9${\mu}g/m{\ell}$) and OXA (10.8-13.9 ${\mu}g/m{\ell}$) were revealed during the 24 h. At the last time point of the experiment (96 h), concentrations of all three quinolones were: OXA, 2.3-6.3 ${\mu}g/m{\ell}$ ; NRF, 3.1-4.5 ${\mu}g/m{\ell}$ ; CPF, 3.0-5.5${\mu}g/m{\ell}$ in samples. The concentrations decreased subsequently, indicating a first rapid redistribution, followed by a slow phase of elimination. The steady state was observed in blood (12-36 h), liver (12-96 h) and muscle (36-96 h) after the initiation of treatment with OXA. Concerning the compartmental concentrations, (L, K. and M/B concentration ratio), the fluctuation of the ratio was founded at different time points, among drugs. For CPF, highest tissue ratios were prolonged in the order of L>K>M (0.65-1.2/0.82-0.93/1.0-1.7) during the experiments. On the other hand, NRF presented L>K>M (0.65-1.3/0.86-1.0) till 24 h, but L>M>K (0.89-1.26) at 36-96 h. OXA showed L>K>M (0.95-2.1) at 1-8 h, M>K>L (0.51-1.0) at 12-36 hand M>L>K (1.0-2.3) at 48-96 h, respectively.

[ $^1H$ ] Nuclear Magnetic Resonance Study of Ferroelectric $(NH_4)_3H(SO_4)_2$

  • Choi, S.H.;Han, K.S.;Kwon, S.K.;Nam, S.K.;Choi, H.H.;Lee, Moo-Hee;Lim, Ae-Ran
    • Journal of the Korean Magnetic Resonance Society
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    • v.11 no.2
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    • pp.64-72
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    • 2007
  • [ $^1H$ ] nuclear magnetic resonance (NMR) experiments have been performed at 30 - 300 K and 7 T to investigate dynamics of hydrogen bond network in the single crystal $(NH_4)_3H(SO_4)_2$. The two proton sites, ammonium proton and hydrogen-bond proton, are identified from the $^1H$ NMR MAS spectrum at 340 K. As temperature decreases, the $^1H$ NMR spectrum shifts to the higher frequency side with a larger linewidth. The spectrum at 65 K shows a distinctive change in line shape toward the ferroelectric transition at 63 K. The measured values of $T_1$ for ammonium and hydrogen-bond protons are similar in the whole range of temperature. $T_1$ of $^1H$ NMR shows a gradual decrease down to 120 K and starts to steeply increase below 100 K. Then $T_1$ shows abrupt decrease below 70 K with a sharp minimum at 63 K, where the ferroelectric transition occurs. This temperature dependence of spectrum and $T_1$ clearly prove that the large change in the dynamics of hydrogen bond network is associated with the ferroelectric phase transition at 63 K.

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The Effects of Ionic Strength on Polytungstate Ions Equilibrium in KCl Solution (다중텅그스텐산 이온평형에 대한 이온세기의 영향. 염화칼륨용액에서)

  • Ahn Sangwoon
    • Journal of the Korean Chemical Society
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    • v.18 no.3
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    • pp.157-170
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    • 1974
  • The effects of ionic strength on the polynucleation reaction of tungstate ions and the protonized reaction of polytungstate ions have been investigated in the range of ionic strength from 1 M to 4 M KCl.The hexatungstate ions and the protonized forms of hexatungstate ions are formed in the tungstate solutions whose ionic strengths are 1 M to 4 M KCl. The equilibrium constants for the formation of hexatungstate ions and the protonized forms of hexatungstate ions are calculated in the range of ionic strength from 1 M to 4M KCl. The enthalpy changes for the formation of hexatungstate ions and the protonized forms of hexatungstate ions are as follows; $7H^++{6WO_4}^{2-}={HW_6O_{21}}^{5-}+3H_2O\;\;{\Delta}H^{\circ}=-62.4{\pm}0.6$$H^++{HW_6O_{21}}^{5-}={H_2W_6O_{21}}^{4-}\;\;{\Delta}H+_1^{\circ}=-4.12{\pm}0.10$$H^++{H_2W_6O_{21}}^{4-}={ H_3W_6O_{21}}^{3-}\;\;{\Delta}H_2^{\circ}=-4.36{\pm}0.30$ The free energy and entropy changes for the above reactions have been also calculated. A linear relation is formed between $log k_{6,7}$ and ionic strength, and $log k_1\;or\;log k_2\;vs{\cdot}{\mu}.$ $log k_{6,7}\;=\;D{\mu}+I,\;\;where\;D\;=\;1.66{\pm}0.02$$log k_1\;=\;D_1{\mu}+I_1,\;\;where\;D_1\;=\;-8.065{\pm}0.001$$log k_2\;=\;D_2{\mu}+I_2,\;\;where\;D_2\;=\;-0.376{\pm}0.006$

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The PGC-II Polymorphism of the Peroxisome Proliferator-activated Receptor ${\gamma}$ Coactivator $1{\alpha}$ (PGC-$1{\alpha}$) Gene in Korean Subjects with the Metabolic Syndrome

  • Im, Sun-Ok;Kim, In-Sik;Kang, Sang-Sun;Hyun, Sung-Hee
    • Biomedical Science Letters
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    • v.18 no.2
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    • pp.139-145
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    • 2012
  • RFLP of PGC-$1{\alpha}$ gene of 285 Korean women was analyzed by PCR and HpaII restriction. We evaluated the correlation between PGC 1 genotypes and biochemical results, using the results of RFLP. Study subjects were divided into 3 groups: normal group (who has been average value of serum biochemical analysis), upper group (who has been higher value than average value), and low group (who have been lower value than average value). The frequencies of $H_1H_1$, $H_1H_2$, and $H_2H_2$ genotypes were 92 (32%), 85 (32%), and 108 (38%) respectively, and the ratio between $H_1$ and $H_2$ alleles was 1:1.1. There were no meaningful differences between biochemical results and PGC-$1{\alpha}$ genotypes in the normal group. But, in upper group, there was significant difference in total cholesterol (P=0.04) level. In the result of Turkey multiple comparison test, the P value of $H_1H_1$ and $H_2H_2$ was 0.059. In upper group, there were noticeable differences also in triglyceride (P=0.034) level and glucose (P=0.043) level, respectively. There were important differences between $H_1H_1$ type and $H_1H_2$ type in triglyceride (P=0.029) level and between $H_1H_2$ type and $H_2H_2$ type in glucose (P=0.040) level. This study may provide the PGC-$1{\alpha}$ genotype patterns for the amounts of lipid and glucose in the serum. $H_2$ allele (Ser482) of PGC-$1{\alpha}$ gene may be related with upper group in Korean women.

Determination of the Langmuir and Temkin Adsorption Isotherms of H for the Cathodic H2 Evolution Reaction at a Pt/KOH Solution Interface Using the Phase-Shift Method

  • Chun Jang-H.;Jeon Sang-K.;Chun Jin-Y.
    • Journal of the Korean Electrochemical Society
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    • v.9 no.1
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    • pp.19-28
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    • 2006
  • The phase-shift method for determining the Langmuir, Frumkin, and Temkin adsorption isotherms ($\theta_H\;vs.\;E$) of H for the cathodic $H_2$ evolution reaction (HER) at a Pt/0.1 M KOH solution interface has been proposed and verified using cyclic voltammetric, differential pulse voltammetric, and electrochemical impedance techniques. At the Pt/0.1 M KOH solution interface, the Langmuir and Temkin adsorption isotherms ($\theta_H\;vs.\;E$), the equilibrium constants ($K_H=2.9X10^{-4}mol^{-1}$ for the Langmuir and $K_H=2.9X10^{-3}\exp(-4.6\theta_H)mol^{-1}$ for the Temkin adsorption isotherm), the interaction parameters (g=0 far the Langmuir and g=4.6 for the Temkin adsorption isotherm), the rate of change of the standard free energy of $\theta_H\;with\;\theta_H$ (r=11.4 kJ $mol^{-1}$ for g=4.6), and the standard free energies (${\Delta}G_{ads}^{\circ}=20.2kJ\;mol^{-1}$ for $k_H=2.9\times10^{-4}mol^{-1}$, i.e., the Langmuir adsorption isotherm, and $16.7<{\Delta}G_\theta^{\circ}<23.6kJ\;mol^{-1}$ for $K_H=2.9\times10^{-3}\exp(-4.6\theta_H)mol^{-1}$ and $0.2<\theta_H<0.8$, i.e., the Temkin adsorption isotherm) of H for the cathodic HER are determined using the phase-shift method. At intermediate values of $\theta_H$, i.e., $0.2<\theta_H<0.8$, the Temkin adsorption isotherm ($\theta_H\;vs.\;E$) corresponding to the Langmuir adsorption isotherm ($\theta_H\;vs.\;E$), and vice versa, is readily determined using the constant conversion factors. The phase-shift method and constant conversion factors are useful and effective for determining the Langmuir, Frumkin, and Temkin adsorption isotherms of intermediates for sequential reactions and related electrode kinetic and thermodynamic data at electrode catalyst interfaces.

Bfl-1/A1 Molecules are Induced in Mycobacterium Infected THP-1 Cells in the Early Time Points

  • Park, Sang-Jung;Cho, Jang-Eun;Kim, Yoon-Suk;Cho, Sang-Nae;Lee, Hye-Young
    • Biomedical Science Letters
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    • v.18 no.3
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    • pp.201-209
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    • 2012
  • Apoptosis is a physiological programmed cell death process. Tubercle bacilli inhibit apoptosis of alveolar macrophages and phagolysosome fusion. We investigated whether the Bcl-2 family anti-apoptotic member, Bfl-1/A1, plays an important role in the anti-apoptotic process during mycobacterial infection. PMA-treated human monocytoid THP-1 cells were infected with mycobacteria (H37Rv, BCG, and K-strain) at a multiplicity of infection (MOI) of 10 for 0, 1.5, 3, 6, 9, 12, 18, 24, 48, or 72 h. In addition, PMA-treated THP-1 cells were pretreated with specific inhibitors for 45 min before stimulation with mycobacteria at an MOI of 10 for 4 h. After the indicated time, the cells were subject to reverse transcription-polymerase chain reaction (RT-PCR) analysis, and a Bfl-1/A1-specific Western blot was performed. In PMA-differentiated THP-1 cells, the expression level of Bfl-1/A1 mRNA was increased by Mycobacterium tuberculosis (MTB) H37Rv infection. The mRNA level of Bfl-1/A1 peaked 3 h after MTB infection, then declined gradually until 9 h. However, Bfl-1/A1 mRNA induction gradually re-increased from 24 h to 72 h after MTB infection. No difference in Bfl-1/A1 expression was detected following infection with MTB H37Rv, K-strain, or M. bovis BCG. These results were not dependent on mycobacterial virulence. Moreover, mRNA levels of other anti-apoptotic molecules (Mcl-1, Bcl-2, and Bcl-xL) were not increased after MTB H37Rv or K-strain infection. These results suggest that mycobacteria induce the innate immune host defense mechanisms that utilize Bfl-1/A1 molecules at early time points, regardless of virulence.