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Biomedical subjects

H K Lim

Publications and source records attributed to H K Lim.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

Acute diverticulitis of the cecum and ascending colon: the value of thin-section helical CT findings in excluding colonic carcinoma.

OBJECTIVE: The purpose of this study was to assess the value of characteristic thin-section helical CT findings of acute diverticulitis involving the cecum and ascending colon in excluding colonic carcinoma. MATERIALS AND METHODS: Thin-section helical CT scans (5-mm collimation) of 19 consecutive patients with proven diverticulitis and 21 consecutive patients with surgically proven carcinoma involving the cecum and ascending colon were reviewed retrospectively. Two radiologists independently analyzed these parameters: degree of pericolic infiltration, mesenteric fluid, vascular engorgement, arrowhead-shaped wall thickening, air-filled diverticula, inflamed diverticula, and preserved enhancement pattern of involved colonic wall. Inter-observer agreement was assessed with a kappa statistical analysis, and the features that most distinguished diverticulitis from colonic carcinoma were selected with a stepwise logistic-regression analysis. RESULTS: The two CT findings of right-sided colonic diverticulitis that most distinguished it from colonic carcinoma were inflamed diverticula and the preservation of an enhancement pattern of the involved colonic wall. Excellent interobserver agreement (kappa > 0.60) was obtained for both findings. Inflamed diverticula (kappa = 0.80) had a mean sensitivity, specificity, and accuracy for diverticulitis of 86.8%, 92.9%, and 90.0%, respectively, in differentiating right-sided colonic diverticulitis from colonic carcinoma. Preserved wall enhancement pattern (kappa = 0.70) had a mean sensitivity, specificity, and accuracy of 89.5%, 95.3%, and 92.5%, respectively. CONCLUSION: On thin-section helical CT, an inflamed diverticula and a preserved enhancement pattern of the thickened colonic wall were the two most statistically significant CT findings of acute diverticulitis involving the cecum and ascending colon that distinguished diverticulitis from colonic carcinoma.

Acute Disease↗

Ultrasonographic evaluation of focal hepatic lesions: comparison of pulse inversion harmonic, tissue harmonic, and conventional imaging techniques.

A prospective study was performed to evaluate whether pulse inversion harmonic imaging and tissue harmonic imaging improve the lesion conspicuity and change ultrasonographic characteristics of focal hepatic lesions. Three radiologists evaluated 97 focal hepatic lesions by consensus: cirrhosis-related nodules (n = 23), metastases (n = 23), hemangiomas (n = 27), and cysts (n = 24). In our study, pulse inversion harmonic imaging was judged superior to both tissue harmonic imaging and conventional imaging in conspicuity and overall quality for cirrhosis-related nodules, metastases, and cysts (P < 0.05). Compared with conventional imaging, both pulse inversion harmonic imaging and tissue harmonic imaging provided better conspicuity, clearer internal echogenicity, and stronger through-transmission of cysts (P < 0.05). Pulse inversion harmonic imaging was judged to be better in depicting internal morphology for cirrhosis-related nodules and metastases than conventional imaging (P < 0.05). For hemangiomas, no statistically significant difference was found in all parameters except better posterior enhancement by tissue harmonic imaging than other techniques. In conclusion, pulse inversion harmonic imaging showed the best conspicuity and also enhanced characteristics of both cystic and solid hepatic lesions. Tissue harmonic imaging was judged superior to conventional imaging in evaluating cysts but was not beneficial for solid lesions. The results of this trial may be specific to the machine used for this study.

Adult↗

Control of circadian rhythms and photoperiodic flowering by the Arabidopsis GIGANTEA gene.

Photoperiodic responses in plants include flowering that is day-length-dependent. Mutations in the Arabidopsis thaliana GIGANTEA (GI) gene cause photoperiod-insensitive flowering and alteration of circadian rhythms. The GI gene encodes a protein containing six putative transmembrane domains. Circadian expression patterns of the GI gene and the clock-associated genes, LHY and CCA1, are altered in gi mutants, showing that GI is required for maintaining circadian amplitude and appropriate period length of these genes. The gi-1 mutation also affects light signaling to the clock, which suggests that GI participates in a feedback loop of the plant circadian system.

Arabidopsis↗

Rapid drug metabolite profiling using fast liquid chromatography, automated multiple-stage mass spectrometry and receptor-binding.

Rapid drug metabolite profiling can be achieved using fast chromatographic separation and fast mass spectrometric scanning without compromising the separation efficiency. Fast chromatographic separations of drug and its metabolites can be achieved by eluting from a short narrow-bore guard cartridge column (20 x 2 mm I.D., 3 microns BDS Hypersil C8) at flow-rate of 1.0 ml/min and with a gradient volume greater than 90 column volumes. The need for chromatographic separation is important for automated data dependent multiple-stage mass spectrometry (MSn) experimentation. The total analysis time of 8 min permits profiling of metabolites in a 96-well plate in 13 h. The narrow chromatographic peaks resulting from the high flow-rate require the use of a mass spectrometer capable of fast scan speed due to the need to perform multiple MS experiments within the same chromatographic analysis. A method has been developed for screening potentially biologically active in vitro microsomal metabolites by affinity binding with a receptor. After separation by centrifugal ultrafiltration, the bound ligands are released and characterized by LC-MS. In vitro microsomal metabolites of tamoxifen, raloxifene and adatanserin were screened for potential biological activity using this method. The in vitro metabolites of tamoxifen captured by the receptor include N-demethyltamoxifen and three species of hydroxytamoxifen; these data are consistent with those from a conventional binding study and bioassay. In addition, both hydroxyraloxifene and dihydroxyraloxifene are also recognized by the receptor. The specificity of the molecular recognition process is illustrated by the absence of binding with control microsomal incubate and with adatanserin and its metabolites. Therefore, active metabolites can be rapidly profiled by fast LC, automated MSn, and receptor binding. This information can be obtained quickly and can add value to the drug discovery process.

Animals↗

NMDA receptor antagonists enhance 5-HT2 receptor-mediated behavior, head-twitch response, in PCPA-treated mice.

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic 5-HT2 receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompetitive (MK-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsynaptic 5-HT2 receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin 5-HT2 receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the postsynaptic 5-HT2 receptors.

Animals↗

Antinarcotic effects of the velvet antler water extract on morphine in mice.

The present study was undertaken to investigate the antinarcotic effects of velvet antler water extract (VAWE) from Cervus elaphus on morphine. Morphine-induced analgesic action was measured by tail-flick method. Morphine-induced hyperactivity and reverse tolerance were evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. Dopamine (DA) receptor supersensitivity in mice displaying morphine-induced reverse tolerance was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine. The repeated administration of VAWE significantly inhibits the development of morphine-induced analgesic tolerance, physical dependence, reverse tolerance and postsynaptic DA receptor supersensitivity. But a single administration of VAWE did neither antagonize morphine-induced analgesia nor inhibit morphine-induced hyperactivity. From the above results, it is presumed that VAWE may be useful for prevention and therapy of the adverse actions of morphine caused by the repeated administration of morphine.

Animals↗

Inhibitory effects of velvet antler water extract on morphine-induced conditioned place preference and DA receptor supersensitivity in mice.

The repeated administration of morphine in mice produced conditioned place preference (CPP) and postsynaptic dopamine (DA) receptor supersensitivity. CPP effects were evaluated assessing the increased time spent by the mice to morphine and the inhibition of CPP by the decreased time spent by the mice in the nonpreferred compartment. Postsynaptic DA receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist. The oral administration of velvet antler water extract (VAWE) from Cerrus elaphus, prior to the morphine treatment in mice inhibited the development of morphine-induced CPP and postsynaptic DA receptor supersensitivity. These results suggest that the inhibitory effects of VAWE on morphine-induced CPP may be closely related to the recovery of dysfunction in the dopaminergic system produced by morphine because both phenomena were inhibited by VAWE. But a single administration of VAWE did not inhibit apomorphine-induced climbing behavior, indicating that antidopaminergic activity was not produced by a single administration of VAWE at the postsynaptic DA receptors. From the above results, it is presumed that VAWE may be useful for prevention and therapy of the adverse actions of morphine.

Animals↗

Regenerative nodules in liver cirrhosis: findings at CT during arterial portography and CT hepatic arteriography with histopathologic correlation.

PURPOSE: To determine the appearance of regenerative nodules in patients with liver cirrhosis at computed tomography (CT) during arterial portography (CTAP) and CT hepatic arteriography (CTHA). MATERIALS AND METHODS: CTAP and CTHA of the liver were performed in 28 consecutive patients with hepatocellular carcinoma (HCC) who were scheduled to undergo partial resection of the liver. Helical CTAP was performed after contrast material injection into the superior mesenteric artery followed by helical CTHA after contrast material injection into the hepatic artery. CT scans were analyzed for the presence of identifiable nodules and their size; results were correlated with gross and microscopic findings. RESULTS: Resected livers showed cirrhosis in 20 patients, chronic hepatitis in four, and normal liver in four. Among the 20 patients with cirrhosis, regenerative nodules were demonstrated as enhancing 3-10 mm nodules surrounded by lower attenuation fibrous septa 0.8-1.5 mm thick at CTAP in seven patients and nonenhancing nodules of the same size surrounded by enhancing fibrous septa at CTHA in 15 patients. The degree of fibrosis determined the conspicuity of nodules. CONCLUSION: Regenerative nodules in cirrhotic liver are visualized as enhancing nodules surrounded by lower attenuation thin septa at CTAP and nonenhancing nodules surrounded by enhancing fibrous septa at CTHA. CTHA is more sensitive than CTAP in depicting regenerative nodules (P < .005).

Carcinoma, Hepatocellular↗

Upper gastrointestinal tract malignant obstruction: initial results of palliation with a flexible covered stent.

The authors treated 21 patients with inoperable upper gastrointestinal tract malignant obstruction from the esophagus to the duodenum by means of intubation with a flexible covered stent with fluoroscopic guidance. Stent placement was successful and relief of dysphagia was immediate in 18 (86%) patients, without serious complication. The average dysphagia score decreased from 2.6 (dysphagia to liquids) to 1.0 (dysphagia to normal solid food). Placement of a flexible covered stent provides easy, safe, and effective palliation of upper gastrointestinal malignant obstruction.

Adult↗

Splanchnic arterial stenosis or occlusion: diagnosis at Doppler US.

PURPOSE: To determine the diagnostic accuracy of Doppler ultrasonography (US) in the detection of high-grade stenosis or occlusion of the celiac artery (CA) and superior mesenteric artery (SMA) and validate the previously reported Doppler US criteria. MATERIALS AND METHODS: During a recent 36-month period, 82 patients were prospectively examined with Doppler US of the splanchnic arteries and with lateral abdominal aortography, regardless of their abdominal symptoms. The previously reported diagnostic criteria with the fasting peak systolic velocity measurement were prospectively used in all patients. The results of Doppler US were compared with those of lateral aortography. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Doppler US for the detection of 70% or greater CA stenosis or occlusion were 100%, 87%, 57%, 100%, and 89%, respectively; for 70% or greater SMA stenosis or occlusion, these values were 100%, 98%, 93%, 100%, and 99%, respectively. CONCLUSION: Owing to its high accuracy in the diagnosis of high-grade splanchnic arterial stenosis or occlusion, Doppler US can be used as a screening method to help detect CA or SMA stenosis or occlusion and can reduce the use of unnecessary, invasive angiography.

Aged↗

Low-grade gastric mucosa-associated lymphoid tissue lymphoma: correlation of radiographic and pathologic findings.

PURPOSE: To describe upper gastrointestinal (Gl) examination findings of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to correlate them with pathologic examination findings. MATERIALS AND METHODS: A retrospective review of upper Gl examinations was performed in 25 patients with proved low-grade gastric MALT lymphomas. Upper Gl examinations were reviewed for common findings and most probable diagnosis, and these findings were correlated with pathologic findings in resected specimens in 15 patients. RESULTS: The common findings at upper Gl examination included mucosal nodularity (n = 13), ulcer (n = 12), rugal thickening (n = 6), mass (n = 4), and enlarged areae gastricae (n = 2). The most probable diagnoses were early gastric carcinoma (n = 7), advanced gastric carcinoma (n = 6), gastritis (n = 9), and lymphoma (n = 3). Of 17 lesions found on resected specimens, six ulcers and two masses were not depicted at barium study. Disorganized convergent rugae projecting to multiple points and vague ulcer margins were present in four and seven lesions, respectively. Multiple ulcers were seen in two patients. CONCLUSION: Although the common radiographic and pathologic findings observed in low-grade gastric MALT lymphomas were similar to those of gastric carcinomas or gastritis, disorganized convergent rugae, vague ulcer margins, and multiplicity of lesions may be helpful in differentiating them from gastric carcinomas or gastritis.

Adult↗

Acute diverticulitis of the cecum and ascending colon: thin-section helical CT findings.

OBJECTIVE: Our objective was to describe thin-section helical CT findings of acute diverticulitis of the cecum and ascending colon in 12 patients. CONCLUSION: Thin-section helical CT is able to reveal inflamed diverticula in acute diverticulitis of the cecum and ascending colon, which are diagnostic of this disease. Preservation of the enhancing pattern of the colonic wall was the most common helpful ancillary finding.

Acute Disease↗

Assessment of pancreatic invasion in patients with advanced gastric carcinoma: usefulness of the sliding sign on sonograms.

OBJECTIVE: The purpose of our study was to determine the value of the sliding sign on sonograms in evaluating direct pancreatic invasion of advanced gastric carcinoma. SUBJECTS AND METHODS: Sonography was performed prospectively on 70 patients with pathologically proven advanced gastric carcinoma. Sonography was directed at the detection of motion between the gastric mass and the pancreas. When the gastric mass showed complete sliding motion against the pancreas or partial sliding motion with a preserved echogenic fat plane between the two organs on respiration or on extrinsic compression with a transducer (positive sliding sign), patients were considered to have no pancreatic invasion. When the gastric mass had no sliding motion against the pancreas or partial sliding motion with a disrupted echogenic fat plane between the two organs (negative sliding sign), patients were considered to have pancreatic invasion. After sonography, all patients underwent surgery and the results of sonography were compared with the findings at surgery and pathology. RESULTS: Of the 70 patients, 17 had pancreatic invasion and 53 had no evidence of pancreatic invasion at surgery and pathology. The sliding sign on sonography yielded an 80% sensitivity, 96% specificity, and 90% accuracy for the diagnosis of pancreatic invasion. CONCLUSION: Application of the sliding sign on sonography was simple and highly accurate in the diagnosis of pancreatic invasion by advanced gastric carcinoma. The sliding sign may prove useful in the preoperative detection of pancreatic invasion by gastric carcinoma when CT has been inconclusive.

Carcinoma↗

Foci of eosinophil-related necrosis in the liver: imaging findings and correlation with eosinophilia.

OBJECTIVE: The purpose of our study was to describe CT and sonographic findings of foci of eosinophil-related hepatic necrosis and to correlate those findings with eosinophil counts in the peripheral blood. MATERIALS AND METHODS: We retrospectively reviewed 17 helical CT and 16 sonographic examinations (including follow-up examinations) in 10 patients with pathologically proven foci of eosinophil-related necrosis. Underlying causes were anisakiasis (n = 2), malignant neoplasms (n = 3), hypereosinophilic syndrome (n = 3), and idiopathic (n = 2). CT and sonographic images were reviewed by consensus by three radiologists, with an emphasis on the morphology and distribution of foci. Imaging findings were correlated with eosinophil counts in the peripheral blood. RESULTS: All foci of eosinophil-related necrosis were observed as focal hypoattenuating lesions on all phases of helical CT and as focal hypoechoic lesions on sonography. Foci varied in size and were round or oval. The number of these foci seemed to be in proportion to the percentage of eosinophils in the peripheral blood. Most foci showed interval regression on follow-up CT or sonography as peripheral blood eosinophil counts decreased. CONCLUSION: Foci of eosinophil-related necrosis cause focal hepatic lesions of varying size, shape, and number on helical CT and sonography. The number and extent of these foci were closely correlated to eosinophil counts in the peripheral blood.

Eosinophilia↗