Biomedical subjects

H K Lim

Publications and source records attributed to H K Lim.

At least 37 records · Page 2Linked to original sources

PubMed2001

Conspicuity of hepatocellular nodular lesions in cirrhotic livers at ferumoxides-enhanced MR imaging: importance of Kupffer cell number.

PURPOSE: To correlate the conspicuity of hepatocellular carcinomas and dysplastic nodules on ferumoxides-enhanced magnetic resonance (MR) images with the number of Kupffer cells in the hepatic lesions, as compared with that in background liver in histopathologic findings. MATERIALS AND METHODS: Sixty-nine histopathologically proved moderately or poorly differentiated hepatocellular carcinomas, 10 well-differentiated hepatocellular carcinomas, and 19 dysplastic nodules were retrospectively studied in 68 patients with cirrhosis who underwent ferumoxides-enhanced MR imaging. The contrast-to-noise ratio between the nodules and surrounding parenchyma was calculated at T2-weighted fast spin-echo imaging, and the difference in the number of Kupffer cells between the nodules and surrounding hepatic tissue was calculated histopathologically. The results of MR imaging and histopathologic examination were correlated. RESULTS: All 69 moderately or poorly differentiated hepatocellular carcinomas had high contrast-to-noise ratios at MR imaging and large differences in the number of Kupffer cells. Six of the 10 well-differentiated hepatocellular carcinomas had contrast-to-noise ratios of zero or nearly zero, and five of these had little difference in the number of Kupffer cells. All 19 dysplastic nodules had contrast-to-noise ratios of zero or nearly zero, and there were virtually no differences in the number of Kupffer cells. CONCLUSION: Hepatocellular nodule conspicuity at ferumoxides-enhanced MR imaging depends on differences in the number of Kupffer cells within a nodule and the surrounding cirrhotic liver; moderately or poorly differentiated hepatocellular carcinomas can be distinguished from well-differentiated hepatocellular carcinomas and dysplastic nodules.

Adult↗

PubMed2001

Hepatocellular carcinoma treated with percutaneous radio-frequency ablation: evaluation with follow-up multiphase helical CT.

PURPOSE: To determine serial changes in hepatocellular carcinomas (HCCs) treated with percutaneous radio-frequency (RF) ablation at long-term follow-up multiphase helical computed tomography (CT). MATERIALS AND METHODS: There were 43 nodular HCCs in 40 patients at follow-up CT performed not less than 12 months after RF ablation. All patients underwent follow-up multiphase helical CT immediately, 1 month, and then every 3 months after percutaneous RF ablation. The serial changes in attenuation, enhancement pattern, shape, other findings, and volume of the ablated lesions were analyzed at follow-up CT. RESULTS: Thirty-eight (88%) of 43 ablated lesions were of low attenuation, with absence of contrast material enhancement at immediate and 1-month follow-up CT, which is suggestive of successful treatment. The remaining five lesions (12%) showed peripheral nodular enhancement, suggesting residual viable tumor. Compared with volume changes at immediate follow-up CT, the mean percentages of volume change at 1, 4, 10, 16, and 19 months were 79%, 50%, 27%, 11%, and 6%, respectively. Of 43 ablated lesions, 24 (56%) were mostly round at immediate CT and remained unchanged at subsequent follow-up CT. Peripheral rim enhancement was seen in 34 (79%) of 43 lesions at immediate CT but resolved in all 34 lesions at 1-month follow-up CT. Other associated findings included iatrogenic arteriovenous shunt in 10 patients, perihepatic hemorrhage in three, and pneumothorax in one. CONCLUSION: Follow-up multiphase helical CT of HCCs treated with percutaneous RF ablation showed variable findings in the treated lesions and surrounding liver parenchyma.

Adult↗

PubMed2001

Effects of bergenin, the major constituent of Mallotus japonicus against D-galactosamine-induced hepatotoxicity in rats.

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against D-galactosamine (GalN)-induced liver damage in rats. Bergenin (50, 100 and 200 mg/kg) was given orally once daily for 7 successive days and then GalN 400 mg/kg was injected intraperitoneally to rats at 24 and 96 h after the final administration of bergenin. Pretreatment with bergenin reduced the increased enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase, gamma-glutamyltransferase and the elevated level of malondialdehyde induced by GalN. Bergenin restored the decreased hepatic contents of glutathione as well as the decreased activities of glutathione S-transferase and glutathione reductase by GalN towards normalization, suggesting that the hepatoprotective effects of bergenin may consist in maintaining adequate levels of hepatic glutathione for the removal of xenobiotics. The present results indicate that bergenin has hepatoprotective effects against GalN-induced hepatotoxicity in rats.

Animals↗

PubMed2001

Correlation of VEGF with contrast enhancement on dual-phase dynamic helical CT in liver tumors: preliminary study.

The purpose of this preliminary study is to elucidate that vascular endothelial growth factor (VEGF) influences contrast enhancement of hepatic tumors on computed tomography (CT). Fourteen patients with hepatic tumors (11 hepatocellular carcinomas; 3 metastatic cancers) underwent a dual-phase dynamic helical CT or computed tomographic hepatic arteriography. The attenuation of each mass was determined as hyperattenuation, isoattenuation or hypoattenuation with respect to the adjacent nontumorous parenchyma. Gun-needle biopsy was done for each tumor, and paraffin sections were immunostained with anti- VEGF antibody by the avidin-biotin-peroxidase complex method. The pathologic grade was made by intensity (1 +, 2+, 3+) and area (+/-, 1 +, 2+). The tumor ranged 2.0-14.0 cm in size (mean, 5.8 cm). In arterial phase, the intensity was not correlated with the degree of enhancement (p=0.086). However, the correlation between the attenuation value of hepatic arterial phase and the area of positive tumor cells was statistically significant (p=0.002). VEGF may be the factor that enhances the hepatic mass with water-soluble iodinated contrast agent in CT.

Adult↗

PubMed2001

Detection of parenchymal abnormalities in acute pyelonephritis by pulse inversion harmonic imaging with or without microbubble ultrasonographic contrast agent: correlation with computed tomography.

The purpose of this study was to evaluate the ability of pulse inversion harmonic imaging with or without microbubble ultrasonographic contrast agent in depicting renal parenchymal changes in acute pyelonephritis. The study population included 30 patients with acute pyelonephritis and 10 healthy volunteers. Pulse inversion harmonic imaging with or without contrast agent was compared with conventional ultrasonography and tissue harmonic imaging in terms of detection and conspicuity of renal abnormalities. The detection and conspicuity of renal parenchymal abnormalities in acute pyelonephritis on tissue harmonic imaging, pulse inversion harmonic imaging, and contrast-enhanced pulse inversion harmonic imaging were significantly better than those on conventional ultrasonography. In 2 of 10 healthy volunteers all 4 techniques yielded false-positive diagnoses of parenchymal abnormalities. In conclusion, tissue harmonic imaging and pulse inversion harmonic imaging are sensitive techniques for depicting renal parenchymal lesions in acute pyelonephritis. Despite relatively lower specificities and negative predictive values, these techniques are thought to be useful for the depiction of subtle parenchymal changes in acute pyelonephritis.

Acute Disease↗

PubMed2001

A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry.

A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s (CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2C19, CYP2A6, and CYP2C8) was developed. This method uses an in vitro cocktail of specific substrates (midazolam, bufuralol, diclofenac, ethoxyresorufin, S-mephenytoin, coumarin, and paclitaxel) and fast gradient liquid chromatography tandem mass spectrometry. The assay incubation time is 20 min, which is in the linear range for all of the substrates, and the analysis time is 4 min/sample. Substrate specificity was confirmed by incubating Escherichia coli-expressed enzymes with the cocktail. Potent specific inhibitors of the seven enzymes (ketoconazole, quinidine, sulfaphenazole, tranylcypromine, quercetin, furafylline, and 8-methoxypsoralen) were evaluated in cocktail and individual substrate incubations. Five of these inhibitors were further studied to determine more precise IC(50) values for inhibition of the seven enzymes. The IC(50) values obtained in both cocktail and individual incubations were in good agreement with published values. This cocktail method offers an efficient, robust way to determine the cytochrome P450 inhibition profile of large numbers of compounds. The enhanced throughput of this method greatly facilitates its use to assess CYP inhibition as a drug candidate selection criterion.

Chromatography, Liquid↗

PubMed2000

Effect of short-term ethanol on the proliferative response of Swiss 3T3 cells to mitogenic growth factors.

Both adaptive and deleterious responses of cells to ethanol are likely triggered by short-term interactions of the cells with ethanol. Many studies have demonstrated the direct effect of ethanol on growth factor-stimulated cell proliferation. Using Swiss 3T3 cells whose growth was inhibited by ethanol in a concentration-dependent manner, we further investigated the molecular mechanisms of acute ethanol treatment by examining its effect on EGF- and PDGF-mediated cellular signaling systems for the mitogenic function. Tyrosine autophosphorylation of the growth factor receptors was partially prevented by ethanol in intact cells. When ethanol was included before or after EGF stimulation, no effect on the receptor signaling was observed. Here we also report that ethanol inhibits activation of ERK induced by both EGF and PDGF. EGF-induced JNK activation was reduced but PDGF-induced rapid JNK activation was delayed by the addition of ethanol. The balance between its inhibitory and stimulatory effect on the signaling molecules might determine the rate of cell growth.

3T3 Cells↗

PubMed2000

Effects of acetylbergenin against D -galactosamine-induced hepatotoxicity in rats.

The hepatoprotective effects of acetylbergenin were examined against D -galactosamine (GalN)-induced liver damage in rats, compared with that of bergenin reported previously. Acetylbergenin was synthesized from acetylation of bergenin, isolated from Mallotus japonicus, to increase lipophilic and physiological activities. Acetylbergenin was administered orally once daily for 7 days and then GalN (400 mg kg(-1), i.p.) was injected at 24 h and 96 h after the final administration of acetylbergenin. Acetylbergenin reduced the elevated serum enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma -glutamyltransferase and the formation of hepatic malondialdehyde induced by GalN. Acetylbergenin also significantly restored towards normalization the decreased levels of glutathione and the decreased activities of glutathione S-transferase and glutathione reductase induced by GalN. Therefore, these results suggest that acetylbergenin has hepatoprotective effects against GalN-induced hepatotoxicity by inhibiting lipid peroxidation and maintaining an adequate level of GSH for the detoxification of xenobiotics as underlying hepatoprotective mechanisms. In addition, lipophilic acetylbergenin showed more activity in the hepatoprotection than that of the much less lipophilic bergenin reported previously.

Analysis of Variance↗

PubMed2000

Production and characterization of recombinant guamerin, an elastase-specific inhibitor, in the methylotrophic yeast Pichia pastoris.

The elastase-specific inhibitor, guamerin, was expressed and secreted into a culture medium using the methylotrophic yeast Pichia pastoris, and the resulting recombinant guamerin was purified from the culture media using a two-step procedure composed of a hydrophobic interaction and reverse-phase chromatography. Up to 90 g/L of dry cell weight, the guamerin-producing recombinant P. pastoris was cultivated and guamerin was secreted into the culture medium at a level of 0.69 g/L. The recombinant guamerin was highly purified (>98%) with a recovery yield of 68%. Analyses of the purified guamerin revealed the same N-terminal amino acid sequence, amino acid composition, and molecular mass as found in the native leech protein. The recombinant guamerin exhibited the tight binding to porcine pancreatic elastase. Furthermore, the recombinant guamerin did not produce a humoral immune response in mice.

Amino Acid Sequence↗

PubMed2000

Enantioselective preparation of metoprolol and its major metabolites.

To obtain the standard compounds of metoprolol for a pharmacokinetic study, a convenient synthetic procedure to prepare enantiomers of metoprolol (3a) and its major metabolites, 2-4-(2-hydroxy-3-isopropylamino)propoxyphenylethanol (3b) and 4-(2-hydroxy-3-isopropylamino)propoxyphenylacetic acid (4), was developed from their respective starting materials, 4-(2-methoxyethyl)phenol (1a), 4-(2-hydroxyethyl)phenol (1b) and methyl 4-hydroxyphenylacetate (1c). These phenolic compounds (1a, b, c) were converted in situ to their corresponding phenoxides with sodium hydroxide treatment followed by (R)- or (S)-epichlorohydrin treatment. The resulting epoxides 2 were transformed to 3 through reaction with isopropylamine. Ester 3c was hydrolyzed to the metabolite 4. Measured using the HPLC method on chiral column without any derivatization, the optical purity of enantiomers of metoprolol and o-demethylated metabolite 3b ranged between 96-99% ee and that of enantiomers of carboxylic acid metabolite 4 ranged 91% ee.

Adrenergic beta-Antagonists↗

PubMed2000

Production characteristics of interferon-alpha using an L-arabinose promoter system in a high-cell-density culture.

Using high-cell-density culture of Escherichia coli under the control of an L-arabinose promoter (ParaB), several factors affecting the production of recombinant protein and the formation of inclusion bodies were studied. The inducer, L-arabinose, showed a maximal induction level above 10.7 mM in the final concentration. The concentration of inducer also affected the partition of interferon-alpha (IFN-alpha) into the soluble form and inclusion bodies. Induction kinetics of the rate of accumulation of IFN-alpha on the ParaB promoter showed a slower rate than those of other promoter systems, for example T7, lac or tac. These innate characteristics of ParaB enabled cells to grow continuously in spite of the metabolic burden induced by the expression of foreign protein. The duration time of induction could control the expression of both soluble and insoluble protein. The ratio of yeast extract to glycerol (N/C ratio) in feeding media significantly affected both the production level of recombinant protein and inclusion body formation. The reason for decreasing specific bioactivity during induction can be explained by the increased proportion of inclusion bodies in the total expressed IFN-alpha.

Animals↗

PubMed2000

Hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated rats.

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against carbon tetrachloride (CCl(4))-induced liver damage in rats. Bergenin at a dose of 50, 100 or 200 mg/kg was administered orally once daily for successive 7 days and then a mixture of 0.5 ml/kg (ip) of CCl(4) in olive oil (1:1) was injected two times each at 12 and 36 h after the final administration of bergenin. The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase due to CCl(4) treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. In addition, bergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl(4)-intoxicated rats in a dose dependent fashion. The results of this study clearly indicate that bergenin has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.

Animals↗

PubMed2000

Antihepatotoxic activity of bergenin, the major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated hepatocytes.

To determine the antihepatotoxic activity of bergenin from Mallotus japonicus, carbon tetrachloride (CCl4)-induced cytotoxicity in primary cultured rat hepatocytes has been adopted as an assay system. Bergenin significantly reduced the activities of glutamic pyruvic transaminase and sorbitol dehydrogenase released from the CCl4-intoxicated hepatocytes. The antihepatotoxicity of bergenin was also evidenced by elevating the activities of glutathione S-transferase and glutathione reductase, and content of glutathione in the CCl4-intoxicated hepatocytes. From these results, it is assumed that bergenin exerted antihepatotoxicity against CCl4-induced cytotoxicity through glutathione-mediated detoxification as well as free radical suppressing activity.

Alanine Transaminase↗

PubMed2000

Protective effects of bergenin, the major constituent of Mallotus japonicus, on D-galactosamine-intoxicated rat hepatocytes.

This study was designed to investigate the effects of bergenin against D-galactosamine-induced injury in primary cultured rat hepatocytes. Bergenin (100 microM) decreased the release of glutamic pyruvic transaminase and sorbitol dehydrogenase by 62 and 50%, respectively, into hepatocyte medium incubated for 14 h with 1.5 mM galactosamine. Decreased RNA synthesis by 1.5 mM galactosamine was recovered 2.5 times compared with that of control hepatocytes at 100 microM bergenin. Therefore, the present results suggest that bergenin show hepatoprotective effects against galactosamine-intoxicated rat hepatocytes by inhibiting the release of glutamic pyruvic transaminase and sorbitol dehydrogenase as well as by increasing RNA synthesis.

Alanine Transaminase↗

PubMed2000

Anti-inflammatory effects of fangchinoline and tetrandrine.

Fangchinoline and tetrandrine are the major alkaloids from Stephania tetrandrae S. Moore which has been used traditionally for the treatment of inflammatory diseases in oriental countries including Korea. Both fangchinoline and tetrandrine showed anti-inflammatory effects on mouse ear edema induced by croton oil. In addition, the effects of fangchinoline and tetrandrine on cyclooxygenase, murine interleukin-5 (mIL-5) and human interleukin-6 (hIL-6) were examined in vitro to investigate the anti-inflammatory action mechanisms. One hundred micromolar of fangchinoline showed 35% of inhibition on cyclooxygenase, but the same concentration of tetrandrine did not show any inhibition. On the other hand, 12.5 microM of tetrandrine exhibited 95% of inhibition on mIL-5 activity, while fangchinoline did not show any effects. However, 4 microM of fangchinoline and 6 microM of tetrandrine showed 63 and 86% of inhibitions on hIL-6 activity, respectively. These results suggest that biochemical mechanisms of fangchinoline and tetrandrine on anti-inflammation are significantly different even though they are similar in chemical structure.

Alkaloids↗

PubMed2000

Segmental wall thickening in the colonic loop distal to colonic carcinoma at CT: importance and histopathologic correlation.

PURPOSE: To determine the importance of the finding of segmental wall thickening in the colonic loop distal to colonic carcinoma at computed tomography (CT) by means of histopathologic correlation. MATERIALS AND METHODS: Thirteen consecutive patients whose helical CT scans showed segmental wall thickening (>1 cm in maximal width, >5 cm in length) in the colonic loop distal to colonic carcinoma were included. The thickness and length of an involved segment, location, morphologic tumor type, CT patterns of wall thickening, and pericolic changes were evaluated. Surgical pathologic findings in all 13 patients were correlated with CT findings. RESULTS: The involved segment distal to the colonic carcinoma showed circumferential wall thickening with a preserved wall layer pattern at CT. Pericolic changes of varying degrees were seen in 10 patients. Histopathologic examination revealed submucosal and subserosal edema (n = 6), chronic inflammation and fibrosis (n = 5), or both (n = 1), and no histopathologic alteration (n = 1). The tumors were mostly fungating (n = 11), larger than 5 cm in the greatest dimension (n = 12), located in the ascending colon (n = 10), and extended to pericolic adipose tissue (n = 11). CONCLUSION: Colonic carcinoma, especially a large fungating type involving the ascending colon with pericolic infiltration, can produce segmental wall thickening in the distal segment at CT, which represents edema or colitis at histopathologic examination.

Adult↗

PubMed2000

Hepatocellular carcinoma treated with percutaneous radio-frequency ablation: usefulness of power Doppler US with a microbubble contrast agent in evaluating therapeutic response-preliminary results.

PURPOSE: To evaluate the usefulness of power Doppler ultrasonography (US) with a microbubble contrast agent in assessing the therapeutic response of hepatocellular carcinomas (HCCs) treated with percutaneous radio-frequency (RF) ablation. MATERIALS AND METHODS: Forty patients with 45 nodular HCC lesions 1.0-3.8 cm in diameter underwent power Doppler US before and after intravenous injection of a microbubble contrast agent. The same procedures were repeated after US-guided percutaneous RF ablation. The results of these studies were compared with those of three-phase helical computed tomography (CT) performed immediately after RF ablation. RESULTS: Before RF ablation, nonenhanced power Doppler US demonstrated flow signals within tumor in 33 of 45 HCCs. After contrast agent administration, flow signals increased or newly appeared in all cases. After RF ablation, none of the ablated tumors showed intratumoral flow signals at nonenhanced power Doppler US, whereas six showed marginal intratumoral flow signals at contrast agent-enhanced power Doppler US. These six tumors were found to have small enhancing foci, suggestive of viable tumor, in corresponding areas at immediate follow-up CT. Additional RF ablation or transcatheter arterial chemoembolization was performed in these tumors. CONCLUSION: The results of power Doppler US with a microbubble contrast agent in HCCs treated with RF ablation correlated well with those of contrast-enhanced CT. Preliminary data suggest that contrast-enhanced power Doppler US can be a promising noninvasive technique for assessing therapeutic response.

Adult↗

PubMed2000

N-Methyl-D-aspartate receptor antagonists enhance the head-twitch response, a 5-hydroxytryptamine2 receptor-mediated behaviour, in reserpine-treated mice.

In this study, N-methyl-D-aspartate (NMDA)-receptor antagonists enhanced the head-twitch response induced by 5-hydroxytryptamine (5-HT) in reserpine-treated mice. To minimize the risk of any indirect involvement of NMDA-receptor antagonists (D(-)-2-amino-5-phosphonopentanoic acid (AP-5), D(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP), (+)-5-methyl-10,11-dihydroxy-5H-dibenzo-[a,d]-cyclohepten-5,10-imi ne (MK-801), ketamine, dextrorphan and dextromethorphan) with 5-HT neurones, vesicle stores of monoamines, especially 5-HT, were depleted with reserpine. In addition, the enhancement of 5-HT-induced head-twitch response was inhibited by apomorphine and NMDA as well as ritanserin in reserpine-treated mice. These results support our previous conclusion that NMDA receptors play important roles in the glutamatergic modulation of 5-HTergic function at the postsynaptic 5-HT2 receptors in mice.

Adrenergic Uptake Inhibitors↗