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M K Lee

Publications and source records attributed to M K Lee.

At least 109 records · Page 6Linked to original sources
PubMed2000

Effects of different concentrations and volumes of formalin on pain response in rats.

BACKGROUND: Formalin test is commonly used in animal model to assess injury-produced pain response. If the total amount of formaldehyde is fixed, its concentration and volume can be easily adjusted. We evaluated the effect of two sets of three solutions of formalin (one set of same dose of formaldehyde at different concentration and volume, i.e. 2.5%--100 microL, 5%--50 microL, 10%--25 microL, and another set of same volume but at different concentrations, i.e. 2.5%--100 microL, 5%--100 microL, and 10%--100 microL) on the injury-produced pain response in rat. METHODS: Male Sprague-Dawley rats weighing 250-300 g were used. Following injection of formalin (n = 8 in each group) or saline (n = 6, control), the flinching frequencies and time spent in licking or biting the injected hind-paw in the early phase 1 (0-5 min after injection) and the late phase 2 (20-60 min after injection) were recorded. Sham-injection rats (n = 5) underwent subcutaneous insertion of the needle, but no substance was injected. RESULTS: Flinching in phase 1 and 2 was more frequent in the 2.5%--100 microL and 5%--50 microL groups than in the control group (P < 0.05). Licking (or biting) time in phase 2 in all these three groups was longer than the control group (P < 0.05). In the groups of another set of three different solutions (2.5%--100 microL, 5%--100 microL, and 10%--100 microL), flinching in phase 1 and phase 2 was also more frequent than the control group (P < 0.05). Regarding lick behavior of another set, it occurred more frequently in 2.5%--100 microL group in phase 1 and in 2.5%--100 microL group as well as 5%--100 microL group in phase 2 than the control group (P < 0.05). CONCLUSIONS: The 10%--25 microL formalin produces fewer flinching responses than other concentrations. Flinching was a biphasic behavior which was more spontaneous and active than was licking. The volume of formalin was a more important factor than the concentration of formalin in the generation of the active biphasic flinching response in the rat model.

Animals↗
PubMed2000

Comparative effects of diltiazem with enflurane or desflurane on myocardial contractility and heart rate in the isolated rat hearts.

BACKGROUND: The volatile anesthetics may reduce cardiac contractility by limiting both membrane Ca2+ entry and altering intracellular Ca2+ release. Additional pharmacological effects of calcium channel blockers could potentially enhance anesthetic-induced depression. The aim of this study was to compare the direct cardiac effects of enflurane and a new volatile anesthetic, desflurane, in combination with diltiazem on the isolated Sprague-Dawley rat heart. METHODS: After stabilization period isolated rat hearts (n = 40) were perfused with an oxygenated modified Krebs' solution at 55 mmHg equilibrated with 1, 2 and 3 MAC of enflurane (1.7, 3.4 and 5.1 vol% respectively) or desflurane (6, 12 and 18 vol% respectively) in combination with 100 ng/mL diltiazem at 36 degrees C. Isovolumetric left ventricular pressure (LVP), rate of change of ventricular pressure (dp/dt), spontaneous heart rate and coronary flow were measured. To examine the indirect metabolic effect due to autoregulation of coronary flow, O2 delivery (DO2), myocardial O2 consumption (MVO2) and percent O2 extraction (POE) were also monitored. RESULTS: Diltiazem plus enflurane or desflurane depressed LVP and dp/dt dose-dependently. Enflurane plus diltiazem significantly decreased heart rate more than desflurane plus diltiazem in a dose-dependent manner. Desflurane plus diltiazem significantly increased coronary flow more than enflurane plus diltiazem and oxygen delivery increased proportionally with coronary flow. But there were statistically insignificant dose-dependent increases in both groups. Myocardial oxygen consumption and percentage of oxygen extraction were also decreased dose-dependently in both groups. Bradydysrhythmia that accompanied atrioventricular dissociation occurred with diltiazem plus high enflurane or desflurane concentration at an incidence of 46% and 40% respectively. CONCLUSIONS: These in vitro results demonstrate that diltiazem plus enflurane or desflurane depresses left ventricular contractile function and diltiazem plus enflurane causes higher incidence of bradydysrhythmia more than equivalent levels of diltiazem plus desflurane.

Anesthetics, Inhalation↗
PubMed1999

Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: a report from the children's cancer group.

We have determined the prognostic significance of hypodiploidy (<46 chromosomes) in a large cohort of children with acute lymphoblastic leukemia (ALL) treated by the Children's Cancer Group. Among 1,880 patients, 110 (5.8%) had hypodiploid karyotypes: 87 had 45 chromosomes, 15 had 33 to 44 chromosomes, none had 29 to 32 chromosomes, and 8 had 24 to 28 chromosomes (near-haploidy). Six-year event-free survival (EFS) estimates for patients with 45 chromosomes, 33 to 44 chromosomes, or 24 to 28 chromosomes were 65% (standard deviation [SD], 8%), 40% (SD, 18%), and 25% (SD, 22%), respectively (log rank, P =.002; test for trend, P =.0009). The combined hypodiploid group had worse outcome than nonhypodiploid patients, with 6-year EFS of 58% (SD, 7%) and 76% (SD, 2%), respectively (P <.0001). EFS for the subgroup with 45 chromosomes was similar to that of patients with pseudodiploidy (P =.43) or 47 to 50 chromosomes (P =.76). None of the patients with 24 to 28 chromosomes had a t(4;11), a t(9;22), or a t(1;19), and most received highly intensive therapy. The adverse risk associated with 33 to 44 and 24 to 28 chromosomes remained significant in multivariate analyses adjusted for important risk factors including age, white blood cell count, and Philadelphia chromosome status. Thus, hypodiploidy with less than 45 chromosomes, particularly 24 to 28 chromosomes, is a significant adverse risk factor despite treatment with contemporary intensive therapies.

Child↗
PubMed1999

Binding of Bacillus thuringiensis Cry1Ac toxin to Manduca sexta aminopeptidase-N receptor is not directly related to toxicity.

Bacillus thuringiensis Cry1Ac delta-endotoxin specifically binds a 115-kDa aminopeptidase-N purified from Manduca sexta midgut. Cry1Ac domain III mutations were constructed around a putative sugar-binding pocket and binding to purified aminopeptidase-N and brush border membrane vesicles (BBMV) was compared to toxicity. Q509A, R511A, Y513A, and 509-511 (QNR-AAA) eliminated aminopeptidase-N binding and reduced binding to BBMV. However, toxicity decreased no more than two-fold, indicating activity is not directly correlated with aminopeptidase-N binding. Analysis of toxin binding to aminopeptidase-N in M. sexta is therefore insufficient for predicting toxicity. Mutants retained binding, however, to another BBMV site, suggesting alternative receptors may compensate in vivo.

Acetylgalactosamine↗
PubMed1999

Pharmacokinetics and organ distribution of cyclosporin A incorporated in liposomes and mixed micelles.

The commercially available intravenous dosage form of cyclosporin A (C-CsA) contains a solubilizing agent, polyoxyethylated castor oil, which has been reported to be toxic. To replace the toxic solubilizing agent present in C-CsA, liposomal and mixed micellar preparations were made to solubilize CsA by the proliposome method and characterized. Furthermore, pharmacokinetics and organ distributions of these preparations were evaluated in comparison to C-CsA, which is micellar. The mean size of liposomal preparation (L-CsA) composed of DPPC/PA (molar ratio 3/1) and CsA was 43.6 nm and that of mixed micellar preparation (M-CsA) composed of DMPC/DSPE-PEG (molar ratio 95/5) and CsA was 6.5 nm. The solubilization of CsA was 2-fold greater in mixed micellar solution than in liposomes (0.06 vs 0.03 mg of CsA/mg of lipid). L-CsA, M-CsA and C-CsA were intravenously administered into rats via the femoral vein to analyze pharmacokinetics and organ distribution of CsA. M-CsA was not significantly different from C-CsA in every pharmacokinetic parameter studied. However, L-CsA resulted in 30% decrease in AUC and 55% increase in Cl(t) compared with C-CsA (P<0. 05), without any significant differences in MRT, V(dss) and t(1/2). In addition, the distributions of M-CsA and L-CsA in different organs were not significantly different from those of C-CsA (0.05), except for a 51% decrease of M-CsA in the spleen at 4 h and a 33% increase of L-CsA in the liver at 4 h (P<0.05). These findings demonstrate that the liposomal preparation composed of DPPC/PA and CsA shows slightly different pharmacokinetics and organ distribution patterns from C-CsA, whereas the mixed micellar preparation composed of DMPC/DSPE-PEG and CsA exhibits similar patterns to C-CsA, as expected. Furthermore, these results suggest that those mixed micellar and liposomal preparations can replace C-CsA containing the toxic solubilizing agent, thus providing useful alternative dosage forms for intravenous administration of CsA.

Animals↗
PubMed1999

Mortality in North Korean migrant households: a retrospective study.

BACKGROUND: A deteriorating economy, coupled with a series of natural disasters in 1995-97, led to a severe food crisis in North Korea. Although the country has received substantial international aid since 1996, demographic assessments of crisis impact have been limited. We assessed mortality trends in North Korea since 1995. METHODS: At 15 randomly selected sites in China, 440 North Korean adult migrants were interviewed during July-September, 1998. Respondents were asked about births, deaths, and migration patterns in their households between mid-1994 and mid-1998, and about household food sources. The respondents also provided basic demographic information about the households of their relatives. We compared mortality rates from migrant households with data from the 1993 census and with data about households of non-migrant relatives. FINDINGS: Households that included a recent migrant to China showed increasing mortality: crude death rates rose from 28.9 per 1000 in 1995, to 45.6 per 1000 in 1996, and to 56.0 per 1000 in 1997 (p=0.0001), with a 3-year average rate of 42.8 per 1000. The crude 3-year birth rate was 11.0 per 1000. Average household size declined from 4.0 at the beginning of 1995 to 3.4 at the end of 1997 (p=0.0002). Among 259 households of non-migrant relatives, the crude death rate was 43.2 per 1000 and the crude birth rate was 8.8 per 1000. In these households, the 3-year trend of increasing mortality was significant (p=0.001), as was the decline in average household size from 4.3 at the beginning of 1995 to 3.7 at the end of 1997 (p=0.0001). INTERPRETATION: Among North Korean households that include a recent migrant to China, mortality has increased and household size has declined since 1995. This trend raises concern about the state of the general population, at least in the province of North Hamkyong, from where most of the migrants originated.

Adolescent↗
PubMed1999

Phospholipid-based microemulsions of flurbiprofen by the spontaneous emulsification process.

The purpose of this study was to investigate the possibility for parenteral delivery of flurbiprofen without chemical modification using a phospholipid-based microemulsion system. Microemulsions composed of ethyl oleate, lecithin and distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG) were prepared using ethanol as a cosolvent. The effect of formulation variables on the particle size of the microemulsion was investigated. Flurbiprofen concentrations in plasma and various organs after the intravenous administration of flurbiprofen-loaded microemulsion were measured and compared with those after the intravenous administration of flurbiprofen axetil-entrapped emulsion (Lipfen(R), 50 mg/5 ml as flurbiprofen axetil) and flurbiprofen solution. Phospholipid-based microemulsions could solubilize more than 10 mg ml-1 of flurbiprofen at the ratio of vehicle to drug at least 10:1, if the oil contents (10 or 20%) of common parenteral emulsions were used. The half-life, AUC and MRT of flurbiprofen loaded in microemulsion (ethyl oleate:lecithin:DSPE-PEG:flurbiprofen=8:3:1:1.2) increased significantly. The biodistribution of flurbiprofen loaded in this microemulsion was quite different from others. Reticuloendothelial uptake of flurbiprofen loaded in microemulsion decreased compared with that in solution or Lipfen(R). It is concluded that the current microemulsion system might be applicable to formulate the parenteral dosage form of poorly water-soluble flurbiprofen without chemical modification.

Animals↗
PubMed1999

Development of dried liposomes containing beta-galactosidase for the digestion of lactose in milk.

The hydrolyzed-lactose milk for lactase-deficient subjects has a sweeter taste than whole milk, and some subjects dislike its taste. In order to cope with this shortcoming, we examined whether beta-galactosidase, which hydrolyzes lactose, added to the whole milk in the form of dried liposomes, would be able to digest lactose in milk following the lysis of liposomes in the presence of bile salts. Dried liposomes containing beta-galactosidase were prepared in the presence of trehalose by the dehydration-rehydration vesicle method to overcome the instability of the conventional liposome suspension. The stability of liposomal membranes was evaluated by measuring the activity of entrapped beta-galactosidase under various storage conditions. By treating liposomes with trehalose, which was found to prevent the fusion of liposomes and the leakage of entrapped drug, the entrapping efficiency increased up to fourfold. Over 95% of dried liposomes which had been stored at 17 degrees C for 60 days were reconstituted to liposomes upon rehydration process. From the stability study, dried liposomes were found to retain 87% of beta-galactosidase activity at 17 degrees C after 60 days and to be more stable than the multilamellar vesicle suspension prepared without trehalose. The lysis study showed that dried liposomes were hardly lyzed in the simulated gastric fluid with pepsin, but lyzed immediately more than 90% in 0.01 M deoxycholic acid. Lactose hydrolysis in the presence of deoxycholic acid after the addition of dried liposome-entrapped beta-galactosidase to whole milk was proportional to the quantity of entrapped beta-galactosidase and the amount of dried liposomes added. These results demonstrate that beta-galactosidase entrapped in liposome is stable and reconstituted mostly upon rehydration, and can digest lactose in milk after the efficient lysis of liposomes in the presence of bile salts. This study implies that beta-galactosidase entrapped in liposome may be applied to whole milk for lactase-deficient subjects.

Animals↗
PubMed1999

Identification of determinants of interaction between CXCR4 and gp120 of a dual-tropic HIV-1DH12 isolate.

Using a panel of chimeric viruses and their chimeric envelope glycoproteins, we have previously reported that the V1/V2 or the V3 regions of a dual-tropic primary human immunodeficiency virus type 1 (HIV-1) isolate (HIV-1DH12) could individually confer CXCR4 usage when introduced into the backbone of a macrophage-tropic (M-tropic) virus isolate (HIV-1AD8). In this study, chimeric CXCR4-CXCR2 chemokine receptors were employed to identify the determinants involved in the interaction between CXCR4 and the dual-tropic HIV-1DH12 gp120. Our results indicate that (i) HIV-1DH12 gp120 interacts primarily with the extracellular domains 1 (E1) and 2 (E2) of CXCR4, (ii) the V1/V2 and the V3 regions interact with different domains of CXCR4, and (iii) the V1/V2 region plays a more critical role in the interaction between CXCR4 and HIV-1DH12 gp120. Combining our data and those of others suggests that the pattern of CXCR4 usage is highly dependent on HIV-1 isolates. In addition, an M-tropic virus may evolve to become dual-tropic by first acquiring the ability to interact with CXCR4 through the V1/V2 region of gp120.

HIV Envelope Protein gp120↗
PubMed1999

Application of dynamic computed tomography for measurements of local aortic elastic modulus.

A novel computed tomographic (CT) technique used for the instantaneous measurement of the dynamic elastic modulus of intact excised porcine aortic vessels subjected to physiological pressure waveforms is described. This system was comprised of a high resolution X-ray image intensifier based computed tomographic system with limiting spatial resolution of 3.2 mm-1 (for a 40 mm field of view) and a computer-controlled flow simulator. Utilising cardiac gating and computer control, a time-resolved sequence of 1 mm thick axial tomographic slices was obtained for porcine aortic specimens during one simulated cardiac cycle. With an image acquisition sampling interval of 16.5 ms, the time sequences of CT slices were able to quantify the expansion and contraction of the aortic wall during each phase of the cardiac cycle. Through superficial tagging of the adventitial surface of the specimens with wire markers, measurement of wall strain in specific circumferential sectors and subsequent calculations of localised dynamic elastic modulus were possible. The precision of circumferential measurements made from the CT images utilising a cluster-growing segmentation technique was approximately +/- 0.25 mm and allowed determination of the dynamic elastic modulus E(dyn) with a precision of +/- 8 kPa. Dynamic elastic modulus was resolved as a function of the harmonics of the physiological pressure waveform and as a function of the angular position around the vessel circumference. Application of this dynamic CT (DCT) technique to seven porcine thoracic aortic specimens produced a circumferential average (over all frequency components) E(dyn) of 373 +/- 29 kPa. This value was not statistically different (p < 0.05) from the values of 430 +/- 77 and 390 +/- 47 kPa obtained by uniaxial tensile testing and volumetric measurements respectively.

Animals↗
PubMed1999

Inhibitory activity of monoamine oxidase by coumarins from Peucedanum japonicum.

Four coumarins were isolated from chloroform extract of the root of Peucedanum japonicum and identified as praeruptorin A(1), xanthotoxin (2), psoralen (3) and bergapten (4) on the basis of spectroscopic methods. The inhibitory activities of these coumarins on monoamine oxidase prepared by mouse brain were tested. The IC50 values of them were shown to be 27.4 microM (1), 40.7 microM (2), 35.8 microM (3), and 13.8 microM (4), in vitro.

Animals↗
PubMed1999

Two eosinophil granule proteins, eosinophil peroxidase and major basic protein, inhibit mucin release from hamster tracheal surface epithelial cells in primary culture.

OBJECTIVES AND DESIGN: Effects of eosinophil proteins on airway goblet cell mucin release were investigated using primary hamster tracheal surface epithelial (HTSE) cell cultures. MATERIALS AND METHODS: HTSE cells were metabolically labeled using 3H-glucosamine and chased in the presence of varying concentrations of eosinophil proteins. The amount of 3H-mucin in the spent media was measured by Sepharose CL-4B gel-filtration column chromatography. Possible cytotoxicity by the eosinophil proteins was assessed by measurements of both lactic dehydrogenase and mucin release during as well as after the treatment period. RESULTS: (1) Neither eosinophil cationic protein nor eosinophil-derived neurotoxin affected mucin release at concentrations up to 10(-6) M; (2) both major basic protein (MBP) and eosinophil peroxidase (EPO) inhibited mucin release in a dose-dependent fashion, and the inhibitory effect by these proteins appeared to be reversible; (3) neither MBP nor EPO caused any apparent cytotoxicity at concentrations up to 10(-6) M. CONCLUSION: Eosinophil proteins such as MBP and EPO inhibit mucin release from primary HTSE cells without causing any apparent cytotoxicity.

Animals↗
PubMed1999

Metabolic effect of decreasing nonesterified fatty acid levels with acipimox in hyperthyroid patients.

Glucose intolerance is often found in patients with hyperthyroidism, but the pathogenetic mechanisms are not fully understood. Since lipolysis is increased in hyperthyroidism, elevated plasma nonesterified fatty acids (NEFAs) may contribute to abnormal glucose metabolism in hyperthyroidism. The aim of this study was to investigate whether decreasing the plasma NEFA level with acipimox can affect glucose metabolism in hyperthyroidism. We performed an intravenous glucose tolerance test (IVGTT) with acipimox 250 mg or placebo in six untreated hyperthyroid men and six age- and body mass index (BMI)-matched controls. Fasting plasma NEFA levels were significantly higher in the hyperthyroid patients versus the controls (997.0 +/- 303.4 v290.5 +/- 169.1 micromol/L, P < .001). Plasma NEFAs decreased rapidly with acipimox treatment in both controls and hyperthyroid patients. In the controls, the glucose disappearance constant (K(G)) was not different for acipimox treatment versus placebo (2.18 +/- 0.62 v 2.42 +/- 1.00% x min(-1)). In hyperthyroid patients, acipimox treatment increased the K(G) significantly compared with placebo treatment (2.44 +/- 0.84 v 1.58 +/- 0.37% x min(-1), P < .05). Changes in K(G) values with acipimox treatment were inversely correlated with changes in plasma NEFA levels (r = -.65, P < .05). Acipimox treatment increased the acute insulin response (AIR) in hyperthyroid patients (943 +/- 381 v 698 +/- 279 microU/mL x min, P < .05), whereas it did not change the AIR in controls. Changes in the AIR with acipimox treatment correlated significantly with changes in the K(G) (r = .70, P < .05). There was a weak correlation between changes in the AIR with acipimox treatment and changes in plasma NEFA levels (r = -.55, P = .06). In summary, decreasing the plasma NEFA level with acipimox in hyperthyroid patients increases both the K(G) and AIR during an IVGTT. These findings suggest that the abnormal glucose metabolism in hyperthyroidism could be attributed, at least in part, to the increase of plasma NEFA.

Administration, Oral↗
PubMed1999

Effects of ginsenosides on bovine adrenal tyrosine hydroxylase.

The present study was undertaken to investigate the effects of ginsenosides on bovine adrenal tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. Ginsenoside-Rb1, Rc, Re and Rg, inhibited the TH activity by 51.5, 25.4, 31.3, 44.3 and 43.3%, respectively, at a concentration of 80 microg/ml. Ginsenoside-Rb1, Rc, Re and Rg1 exhibited noncompetitive inhibition of TH activity with a substrate L-tyrosine. From these results, it is presumed that the effects of ginsenosides on TH activity observed in vitro might be also produced in vivo, and thereby the inhibitory effects of ginsenosides on TH activity may be partially responsible for the antidopaminergic action of ginsenosides by reducing the availability of dopamine at the presynaptic dopamine receptor in vivo.

Adrenal Glands↗
PubMed1999

Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform.

Filamentous tau aggregates are hallmarks of tauopathies, e.g., frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC). Since FTDP-17 tau gene mutations alter levels/functions of tau, we overexpressed the smallest human tau isoform in the CNS of transgenic (Tg) mice to model tauopathies. These mice acquired age-dependent CNS pathology similarto FTDP-17 and ALS/PDC, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Inclusions were present in cortical and brainstem neurons but were most abundant in spinal cord neurons, where they were associated with axon degeneration, diminished microtubules (MTs), and reduced axonal transport in ventral roots, as well as spinal cord gliosis and motor weakness. These Tg mice recapitulate key features of tauopathies and provide models for elucidating mechanisms underlying diverse tauopathies, including Alzheimer's disease (AD).

Aging↗
PubMed1999

Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility.

In order to evaluate the role of inherited variation in the estrogen receptor (ESR1) gene in human breast cancer, we determined intronic sequences flanking each ESRI exon; identified multiple SNPs and length polymorphisms in the ESR1 coding sequence, splice junctions and regulatory regions; and genotyped families at high risk of breast cancer and population-based breast cancer patients and controls. Of 10 polymorphic sites in ESR1, four are synonymous SNPs, two are nonsynonymous SNPs and four are length polymorphisms; five are novel. No ESR1 polymorphisms were associated with breast cancer, either in the high-risk families or the case-control study. We therefore conclude that inherited genetic variation is not a mechanism by which the estrogen receptor is commonly involved in breast cancer development.

5' Untranslated Regions↗
PubMed1999

Inhibitory effects of higenamine on dopamine content in PC12 cells.

The inhibitory effects of (+/-)-higenamine, a benzylisoquinoline alkaloid, on dopamine biosynthesis in PC12 cells were investigated. Higenamine decreased the intracellular dopamine content dose-dependently and showed 55.2% inhibition of dopamine content in PC12 cells at a concentration of 20 microM with 24 h incubation. The IC50 value of higenamine was 18.2 microM. Dopamine content was lowered and reached minimal level at 12-24 h after exposure to higenamine. In this condition, tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, was also inhibited by the treatment of higenamine in PC12 cells (21.9% inhibition at 20 microM). Higenamine at 20 microM lowered the intracellular Ca2+ concentration by 33.1% inhibition relative to control in PC12 cells. These results suggest that the inhibition of tyrosine hydroxylase activity by higenamine might partially contribute to the decrease in dopamine content in PC12 cells.

Alkaloids↗