Search PubMed⌕ Search

Biomedical subjects

J H Shim

Publications and source records attributed to J H Shim.

At least 19 recordsLinked to original sources
PubMed2006

Acute-phase response alters the disposition kinetics of cefepime following intravenous administration to rabbits.

The effect of experimentally induced fever on the pharmacokinetics of cefepime administered intravenously at a dose of 75 mg/kg bw was studied in six healthy rabbits. The study was conducted in two consecutive phases, separated by a washout period of 2 weeks. Infection was induced by the intravenous inoculation of 5 x 10(8) cfu of Escherichia coli 24 h before the pharmacokinetic investigation was carried out. Serial blood samples for cefepime concentration determination were obtained for 48 h following drug administration. The concentrations of cefepime in the plasma were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus subtilis ATCC 6633 as the test organism, with a level of detectability of approximately 0.10 microg/ml. Cefepime plasma concentrations versus time were evaluated by non-compartmental methods using WinNonLin. Cefepime was well tolerated and no serious adverse events were observed. Rectal temperature increased 1 degree C 24 h post injection in infected animals. Highly significant differences in the blood plasma concentrations of cefepime were observed between febrile and healthy animals at all the sampling times. This could explain the greater area under the plasma level-time curve of the drug in febrile compared with healthy animals. The results from pharmacokinetic calculations showed that both the distribution volume at steady state (V (dss)) and body clearance (CL(tot)) were affected in febrile as compared to healthy animals. The mean values of V (dss) and CL(tot) of cefepime in healthy rabbits were 1.168 L/kg and 0.303 L/kg/h, respectively. As compared with healthy animals, the mean estimates of V (dss) (0.917 L/kg) and CL(tot) (0.205 L/kg per h) of cefepime were significantly lower, whereas t (1/2lambda), MRT and AUMC were significantly higher in febrile rabbits. It is concluded that, although experimental infection had an effect on the disposition kinetics of cefepime in healthy and febrile rabbits, this was not sufficiently pronounced to require alteration of the dosage during disease.

Acute-Phase Reaction↗
PubMed2006

Determination of volatile flavor components in danggui cultivars by solvent free injection and hydrodistillation followed by gas chromatographic-mass spectrometric analysis.

The rhizome of Angelica gigas Nakai, Angelica sinensis Diels and Angelica acutiloba Kitagawa (Umbelliferae) were chopped and extracted by hydrodistillation (HD) and solvent free solid injector (SFSI) methods to obtain the volatile compounds that were then characterized and identified by gas chromatography-mass spectrometry (GC/MS). SFSI extraction yielded a generally higher amount of volatile compounds than that produced by HD. A total of 48 components [including terpenes (8), aldehydes (4), alcohol (2), coumarins (9), Phthalide (3), acids (2) and sterols (2)] were identified by SFSI and gas chromatography-mass spectrometry from the three species of danggui cultivars, whereas, 24-essential oil was obtained by HD for Korean danggui only. According to these analyses, several coumarin derivatives such as decursinol angelate (16.83%) and decursin (29.34%) were found to be the dominant ones, followed by lomatin (10.25%) and marmesin (9.33%) in Korean danggui. Furfural and butylidene phthalide were the main components in Japanese in addition to butylidene dihydro-phthalide in Chinese danggui. Some parameters affecting the extraction efficiency such as injector temperature, injection time and pre-heating time were optimized. The results showed that the SFSI-method gave a higher yield of components with higher molecular mass than hydrodistillation. SFSI required little time to prepare the sample, little sample mass and a small quantity of organic solvent was needed. It can be concluded that analysis of volatile flavor compounds by SFSI in combination with gas chromatography/mass spectrometry is a suitable monitoring technique to differentiate danggui cultivars.

Angelica↗
PubMed2006

Characterization of the relationship between serum and milk residue disposition of ceftriaxone in lactating ewes.

The present study was planned to investigate the serum disposition kinetics and the pattern of ceftriaxone elimination in milk and urine of lactating ewes (n = 6) following i.v. and i.m. administration. A crossover study was carried out in two phases separated by 15 days. Ceftriaxone was administered at a dosage of 10 mg/kg b.w. in all animals. Serum, milk and urine samples were collected between 0 and 72 h and a modified agar diffusion bioassay method was used to determine the percentage of protein binding and to measure serum, urine and milk concentrations of ceftriaxone. The drug was detected between 5 min and 48 h postdosing. Concentrations of 0.56 (10 h) and 0.52 (12 h), 0.22 (10 h) and 0.19 (12 h), and 2.18 (24 h) and 2.11 (48 h) mug/mL were measured in serum, milk and urine following i.v. and i.m. administration, respectively. Individual pharmacokinetic parameters were determined by fitting a two-compartment model to the serum and one-compartment open model to the milk concentration-time profiles. After i.v. dosing, the elimination rate constant and elimination half-life were 0.4 +/- 0.05/h and 1.75 +/- 0.02 h, respectively. The volume of distribution at steady state (V(dss)) of 0.28 +/- 0.15 L/kg reflected limited extracellular distribution of the drug with total body clearance (Cl(tot)) of 0.14 +/- 0.10 L/h/kg. Following i.m. administration, the mean T(max obs), C(max obs), t(1/2el) and AUC values for serum data were: 0.75 h, 23.16 +/- 2.94 microg/mL, 1.77 +/- 0.24 h and 67.55 +/- 6.51 microgxh/mL, respectively. For milk the data were: 1.0 h, 8.15 +/- 0.71 mug/mL, 2.2 +/- 0.34 h and 26.6 +/- 5.14 microgxh/mL, respectively. The i.m. bioavailability was 83.6% and the binding percentage of ceftriaxone to serum protein was 33%. Concentrations of ceftriaxone in milk produced by clinically normal mammary glands of ewes were consistently lower than in serum; the kinetic value AUC(milk)/AUC(serum) and C(max milk)/C(max serum) ratios was<0.4. These low values indicated poor distribution and penetration of ceftriaxone from the bloodstream to the mammary gland of lactating ewes following both routes.

Animals↗
PubMed2004

Electronic structures of RTe2 (R = La,Ce): a clue to the pressure-induced superconductivity in CeTe1.82.

Electronic structures of RTe2 (R=La,Ce) have been investigated by using the local spin density approximation (LSDA) and the LSDA + U (U: on-site Coulomb interaction) band methods. Both LaTe2 and CeTe2 show the very similar Fermi surface nesting features along the [100] direction, which drive the charge-density wave (CDW) instability in the Te(1) sheets. The contribution near E(F) from Ce 4f states is negligible in agreement with the measured ARPES spectra. In the semimetallic CDW-distorted RTe2, both Te vacancy and pressure induce the charge transfer from Te(1) 5p to R 5d states, producing the enhanced density of states at E(F). We suggest that these increased self-doped Te(1) 5p hole carriers are responsible for the pressure-induced superconductivity in nonstoichiometric CeTe1.82.

Journal Article↗
PubMed2003

Use of the Keele injector for sample introduction for gas chromatographic analysis of vinclozolin in lettuces.

We examined a Keele injector for sample introduction for gas chromatographic analysis of vinclozolin treated in lettuces. Samples in milligram quantity were introduced into a glass tube in a Keele injector at a gas chromatograph injection port. The glass tube was then crushed to allow the sample to carry onto a capillary column in a normal manner. The standard calibration curve for quantitative detection of vinclozolin was obtained by determining vinclozolin spiked in samples at variable concentrations. The calibration curve showed a linear response to vinclozolin ranging from 0.05 to 1.0 microg/g, giving a slope value of 174.8, the y-intercept value of -2.8146 and the mean r2-value of 0.9994. Limit of quantification for vinclozolin was 0.05 microg/g by this method, comparable to 0.01 microg/g by a normal injector. When samples treated previously with vinclozolin were determined by the Keele injector, vinclozolin was found to be about 30% lower as compared to a normal method, suggesting about 70% recovery of the spiked vinclozolin by the Keele injector. From these results, the Keele injector was suggested to be potential for sample introduction in gas chromatographic analysis of vinclozolin in lettuce samples.

Chromatography, Gas↗
PubMed2003

Matrix formalism of electromagnetic wave propagation through multiple layers in the near-field region: application to the flat panel display.

We have developed an electromagnetic (EM) wave propagation theory through a single layer and multiple layers in the near-field and far-field regions, and have constructed a matrix formalism in terms of the boundary conditions of the EM waves. From the shielding efficiency (SE) against EM radiation in the near-field region calculated by using the matrix formalism, we propose that the effect of multiple layers yields enhanced shielding capability compared to a single layer with the same total thickness in conducting layers as the multiple layers. We compare the intensities of an EM wave propagating through glass coated with conducting indium tin oxide (ITO) on one side and on both sides, applying it to the electromagnetic interference (EMI) shielding filter in a flat panel display such as a plasma display panel (PDP). From the measured intensities of EMI noise generated by a PDP loaded with ITO coated glass samples, the two-side coated glass shows a lower intensity of EMI noise compared to the one-side coated glass. The result confirms the enhancement of the SE due to the effect of multiple layers, as expected in the matrix formalism of EM wave propagation in the near-field region. In the far-field region, the two-side coated glass with ITO in multiple layers has a higher SE than the one-side coated glass with ITO, when the total thickness of ITO in both cases is the same.

Journal Article↗
PubMed2003

Lower trunk muscle activity during the tennis serve.

Prior electromyographic (EMG) analyses of the tennis serve have focused on the muscles in the hitting arm and shoulder region. This preliminary study aimed to examine the muscle activation patterns of selected lower trunk muscles during three different types of tennis serve--flat, topspin, and slice. Five male highly skilled tennis players completed 10 trials for each type of serve. Surface EMG electrodes were used to monitor the rectus abdominis (RA), external oblique (EO), internal oblique (IO), and lumbar erector spinae (ES) muscles. For each subject, the two trials with the highest self-reported ratings were analysed. Average EMG levels during each phase of a tennis serve for each muscle were analysed using a non-parametric ANOVA design. No major differences in muscle activation pattern were found across different serve types, and bilateral differences in muscle activation were more pronounced in RA and EO than in IO and ES muscles. The abdominal muscles were more active in the topspin than in the other two types of serves during the upward swing of the racket. An appreciable amount of abdominal/low back and bilateral co-activation was observed during certain phases of the serve. The co-activation of lower trunk muscles may help to stabilise the lumbar spine during the arch back and forward swing phases of the serve. The results reinforce the importance of abdominal and low back exercises in the strength and rehabilitation programs designed for tennis players.

Abdomen↗
PubMed2001

Both E6 and E7 oncoproteins of human papillomavirus 16 inhibit IL-18-induced IFN-gamma production in human peripheral blood mononuclear and NK cells.

Cervical carcinoma is the predominant cancer among malignancies in women throughout the world, and human papillomavirus (HPV) 16 is the most common agent linked to human cervical carcinoma. The present study was performed to investigate the mechanisms of immune escape in HPV-induced cervical cancer cells. The presence of HPV oncoproteins E6 and E7 in the extracellular fluids of HPV-containing cervical cancer cell lines SiHa and CaSki was demonstrated by ELISA. The effect of HPV 16 oncoproteins E6 and E7 on the production of IFN-gamma by IL-18 was assessed. E6 and E7 proteins reduced IL-18-induced IFN-gamma production in both primary PBMCs and the NK0 cell line. FACS analysis revealed that the viral oncoproteins reduced the binding of IL-18 to its cellular surface receptors on NK0 cells, whereas there was no effect of oncoproteins on IL-1 binding to its surface IL-1 receptors on D10S, a subclone of the murine Th cell D10.G4.1. In vitro pull-down assays also revealed that the viral oncoproteins and IL-18 bound to IL-18R alpha-chain competitively. These results suggest that the extracellular HPV 16 E6 and E7 proteins may inhibit IL-18-induced IFN-gamma production locally in HPV lesions through inhibition of IL-18 binding to its alpha-chain receptor. Down-modulation of IL-18-induced immune responses by HPV oncoproteins may contribute to viral pathogenesis or carcinogenesis.

Adjuvants, Immunologic↗
PubMed2001

Evaluation of the catalytic mechanism of AICAR transformylase by pH-dependent kinetics, mutagenesis, and quantum chemical calculations.

The catalytic mechanism of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (AICAR Tfase) is evaluated with pH dependent kinetics, site-directed mutagenesis, and quantum chemical calculations. The chemistry step, represented by the burst rates, was not pH-dependent, which is consistent with our proposed mechanism that the 4-carboxamide of AICAR assists proton shuttling. Quantum chemical calculations on a model system of 5-amino-4-carboxamide imidazole (AICA) and formamide using the B3LYP/6-31G level of theory confirmed that the 4-carboxamide participated in the proton-shuttling mechanism. The result also indicated that the amide-assisted mechanism is concerted such that the proton transfers from the 5-amino group to the formamide are simultaneous with nucleophilic attack by the 5-amino group. Because the process does not lead to a kinetically stable intermediate, the intramolecular proton transfer from the 5-amino group through the 4-carboxamide to the formamide proceeds in the same transition state. Interestingly, the calculations predicted that protonation of the N3 of the imidazole of AICA would reduce the energy barrier significantly. However, the pK(a) of the imidazole of AICAR was determined to be 3.23 +/- 0.01 by NMR titration, and AICAR is likely to bind to the enzyme with its imidazole in the free base form. An alternative pathway was suggested by modeling Lys266 to have a hydrogen-bonding interaction with the N3 of the imidazole of AICAR. Lys266 has been implicated in catalysis based on mutagenesis studies and the recent X-ray structure of AICAR Tfase. The quantum chemical calculations on a model system that contains AICA complexed with CH3NH3+ as a mimic of the Lys residue confirmed that such an interaction lowered the activation energy of the reaction and likewise implicated the 4-carboxamide. To experimentally verify this hypothesis, we prepared the K266R mutant and found that its kcat is reduced by 150-fold from that of the wild type without changes in substrate and cofactor Km values. The kcat-pH profile indicated virtually no pH-dependence in the pH range 6-10.5. The results suggest that the ammonium moiety of Lys or Arg is important in catalysis, most likely acting as a general acid catalyst with a pK(a) value greater than 10.5. The H267A mutant was also prepared since His267 has been found in the active site and implicated in catalysis. The mutant enzyme showed no detectable activity while retaining its binding affinity for substrate, indicating that it plays a critical role in catalysis. We propose that His267 interacts with Lys266 to aid in the precise positioning of the general acid catalyst to the N3 of the imidazole of AICAR.

Binding Sites↗
PubMed2000

Human AICAR transformylase: role of the 4-carboxamide of AICAR in binding and catalysis.

We have prepared 4-substituted analogues of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to investigate the specificity and mechanism of AICAR transformylase (AICAR Tfase). Of the nine analogues of AICAR studied, only one analogue, 5-aminoimidazole-4-thiocarboxamide ribonucleotide, was a substrate, and it was converted to 6-mercaptopurine ribonucleotide. The other analogues either did not bind or were competitive inhibitors, the most potent being 5-amino-4-nitroimidazole ribonucleotide with a K(i) of 0.7 +/- 0.5 microM. The results show that the 4-carboxamide of AICAR is essential for catalysis, and it is proposed to assist in mediating proton transfer, catalyzing the reaction by trapping of the addition compound. AICAR analogues where the nitrogen of the 4-carboxamide was derivatized with a methyl or an allylic group did not bind AICAR Tfase, as determined by pre-steady-state burst kinetics; however, these compounds were potent inhibitors of IMP cyclohydrolase (IMP CHase), a second activity of the bifunctional mammalian enzyme (K(i) = 0.05 +/- 0.02 microM for 4-N-allyl-AlCAR). It is proposed that the conformation of the carboxamide moiety required for binding to AICAR Tfase is different than the conformation required for binding to IMP CHase, which is supported by inhibition studies of purine ribonucleotides. It is shown that 5-formyl-AICAR (FAICAR) is a product inhibitor of AICAR Tfase with K(i) of 0.4 +/- 0.1 microM. We have determined the equilibrium constant of the transformylase reaction to be 0.024 +/- 0.001, showing that the reaction strongly favors AICAR and the 10-formyl-folate cofactor. The coupling of the AICAR Tfase and IMP CHase activities on a single polypeptide allows the overall conversion of AICAR to IMP to be favorable by coupling the unfavorable formation of FAICAR with the highly favorable cyclization reaction. The current kinetic studies have also indicated that the release of FAICAR is the rate-limiting step, under steady-state conditions, in the bifunctional enzyme and channeling is not observed between AICAR Tfase and IMP CHase.

Adenosine Monophosphate↗
PubMed2000

Design, synthesis, and biological evaluation of fluoronitrophenyl substituted folate analogues as potential inhibitors of GAR transformylase and AICAR transformylase.

The examination results of a novel series of potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide transformylase (AICAR Tfase) are reported. These agents incorporate an electrophilic fluoronitrophenyl group that can potentially react with an active site nucleophile or the substrate GAR/AICAR amine via nucleophilic aromatic substitution.

Animals↗
PubMed2000

Significance of serum and tissue carcinoembryonic antigen for the prognosis of gastric carcinoma patients.

BACKGROUND AND OBJECTIVES: Carcinoembryonic antigen (CEA) has been widely accepted as a tumor marker useful in the diagnosis and management of colorectal carcinoma. When CEA levels are positive in patients with gastric carcinoma, they could be useful prognostic indicators. The value of CEA as a tumor marker for gastric carcinoma, however, remains a matter of controversy. The purpose of this study was to determine whether preoperative serum CEA value and tissue CEA staining are useful prognostic indicators for gastric carcinoma. METHODS: We measured preoperative serum CEA levels by radioimmunoassay and stained tissue CEA production by tumor cells from gastric carcinomas using immunohistochemical staining in patients with gastric carcinoma. RESULTS: The patients with preoperative serum CEA levels >10.0 ng/mL had a more prominent serosal invasion, much more lymph node involvement, more advanced stage and more poorly differentiated than did the patients with preoperative serum CEA levels <5.0 ng/mL. The survival rate of patients with serum CEA levels >10.0 ng/mL was poorer than those of patients with serum CEA levels between 5.0 and 10.0 ng/mL, and those of patients with serum CEA levels <5.0 ng/mL (P < 0.05). The preoperative serum CEA levels and tumor CEA-positivity were correlated (P < 0.05). In patients with lymph node metastases, the CEA-positivity (78.0%) was higher than in patients without lymph node metastasis (63.2%) (P < 0.05). A correlation was also found between the depth of tumor invasion and tissue CEA-positivity (P < 0.001). The postoperative survival rate was significantly better in the CEA-negative staining group (78.0%) than in the CEA-positive staining group (60.0%). CONCLUSIONS: These data suggest that preoperative serum CEA levels and staining for CEA in gastric carcinoma tissue sections may have a predictive value in determining prognostic information for patients with resectable gastric carcinoma.

Carcinoembryonic Antigen↗
PubMed2000

The Unexpected Catalytic Properties of a Heterodimer of GAR Transformylase.

We have developed an efficient expression and purification protocol for a heterodimer of glycinamide ribonucleotide transformylase that was identified in incremental truncation libraries, a general combinatorial method for protein fragment complementation (M. Ostermeier, A. E. Nixon, J. H. Shim, and S. J. Benkovic, [1999], Proc. Natl. Acad. Sci. USA 96, 3562-3567). This heterodimer (B13) containing both a bisection point and a deletion in conserved residues close to the active site was expressed and purified in high yield using Intein methodology. The N-terminus fragment (1-111) and C-terminus fragment (M114-212) were also expressed separately as stable proteins. When these two fragments were mixed together, they associate at a highly specific 1:1 ratio to give only the active heterodimer, B13. The activity of B13 is comparable to that of the wild type and the pH-dependent kinetics of B13 turned out to be nearly identical to those of the wild type, indicating that B13 operates in the same mechanism as the wild type. This result demonstrated that cutting within conserved regions is a viable domain separation and confirmed the generality of using incremental truncation for protein fragment complementation.

Journal Article↗
PubMed2000

Imposex in the rock shell, Thais clavigera, as evidence of organotin contamination in the marine environment of Korea.

Imposex was measured in the rock shell, Thais clavigera, from the coast of the Korean peninsula. Frequency of imposex was 0% at two reference sites, but at 47 out of 61 sites, frequency of imposex was recorded as 100%. The degree of imposex was relatively high at the sites near a harbor and a shipyard. Tributyltin (TBT) and triphenyltin (TPT) concentrations in T. clavigera ranged from 5 to 508 ng/g and from 3 to 2460 ng/g, respectively. A significant positive relationship was found between degree of imposex and organotin concentration, whereas a significant negative relationship was obtained between female-to-male sex ratio and the degree of imposex. During a field transplantation of T. clavigera from a pristine area to a port, TBT and TPT were accumulated in T. clavigera, and imposex was induced. T. clavigera shows considerable potential as a bioindicator species of the adverse effects of TBT and TPT contamination.

Animals↗