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Biomedical subjects

K T Lee

Publications and source records attributed to K T Lee.

At least 55 records · Page 3Linked to original sources

Inducible nitric oxide synthase (iNOS) immunoreactivity and its relationship to cell proliferation, apoptosis, angiogenesis, clinicopathologic characteristics, and patient survival in pancreatic cancer.

BACKGROUND: The clinicopathological and biological significance of the expression of iNOS in pancreatic cancer remains unclear. The goal of this study was to determine the possible roles and clinical significance of iNOS expression in pancreatic cancer. METHODS: Seventy-two pancreatic adenocarcinoma tissue specimens were obtained by surgical resection. We investigated the immunohistochemical expression of iNOS in 72 patients with pancreatic cancer with respect to variable clinicopathological characteristics, proliferation activity (assessed by Ki-67 expression), apoptosis (assessed by TUNEL stain), and microvessel density (assessed by CD34 expression; angiogenesis). RESULTS: Immunohistochemical investigations demonstrated immunolabeling of tumor cells with anti-iNOS antibody. Positivity for iNOS was observed in 48/72 (66.7%). The expression of iNOS protein did not correlate with age, bilirubin, tumor marker, location, size, AJCC stage, differentiation, distant metastasis, or patient survival. No significant association was found between iNOS expression and proliferation or microvessel density in pancreatic cancer. Apoptotic index (AI) of positive iNOS expressions were significantly higher than negative expression (p < 0.001). CONCLUSION: Inducible nitric oxide synthase (iNOS) is expressed by human pancreatic cancer, and its presence is positively correlated with apoptosis of cancer cells that could provide the basis for the development of therapeutic strategies in human pancreatic cancer.

Adenocarcinoma↗

Combined computed tomographic pulmonary angiography and venography for evaluation of pulmonary embolism and lower extremity deep venous thrombosis: report of two cases.

Pulmonary embolism (PE) and deep venous thrombosis (DVT) are major causes of morbidity and mortality, which can be reduced with accurate diagnosis and proper treatment. More than 90% of PEs originate in lower-extremity DVT. Currently, evaluation of PEs and lower-extremity DVT requires 2 separate tests (ventilation-perfusion scan, computed tomographic pulmonary angiography (CTPA), or pulmonary angiography for PE and sonography, computed tomographic venography (CTV), conventional venography, or magnetic resonance venography for DVT). Combined computed tomographic pulmonary angiography and venography (CTPAV) is a new diagnostic technique that combines CTPA and CTV into a single study for the screening of PE and subdiaphragmatic DVT. CTPAV is a modified CTPA study that evaluates the subdiaphragmatic deep vein system at the time of CTPA, without additional venipuncture or contrast medium. It is easy to perform, fairly easy to interpret, readily available, and requires no invasive procedure. We present 2 cases of multiple PE and lower-extremity DVT in which CTPAV was used.

Aged↗

Serial changes of cardiac troponin-I in acute myoischemia induced by exercise treadmill test.

Cardiac troponin-I (cTn-I) is a sensitive and specific marker for the diagnosis of acute myocardial infarction (AMI). However, elevation of serum cTn-I has been observed in some unstable angina patients who have a worse prognosis than those with normal serum cTn-I levels. It is unknown whether serum cTn-I can elevate in stable angina patients with acute ischemic burden. Therefore, the purpose of this study was to determine a serial change of cTn-I in patients with acute ischemia induced by a treadmill exercise test. Thirty-five patients suspected of having coronary artery disease and five healthy medical students were enrolled into this study. Every patient received a treadmill exercise test. Cardiac troponin-I was measured by fluorescent immunoassay before the treadmill test and at 5 minutes, 1 hour, 3 hours, and 6 hours after the treadmill test. Patients with cTn-I levels of less than 0.5 ng/ml were considered normal, and those with cTn-I levels of greater than 2.0 ng/ml was considered to have AMI. The exercise test was positive in 19 of the 35 patients and negative in 16 of the 35 patients and 5 medical students. Among the 19 patients with positive treadmill exercise test, the cTn-I concentrations were abnormally increased in 7/19 (37%) patients (mean: 1.1 +/- 0.4 ng/ml; range: 0.5 to 2.0 ng/ml). One of the 16 patients with negative treadmill test showed an increase of serum cTn-I. Normal cTn-I levels were found in the other 15 patients and the 5 medical students. In conclusion, serum cTn-I levels were found to increase to some extent in one third of stable angina patients who have an acute ischemic episode induced by treadmill exercise test.

Aged↗

Atrioventricular block in Kearns-Sayre syndrome: a case report.

The Kearns-Sayre (K-S) syndrome which includes the triad of progressive external ophthalmoplegia, pigment retinopathy, and disorder of cardiac conduction was first described in 1958. The mitochondria disorder is believed to be the cause of this syndrome. Involvement of the cardiac conduction system is the most importent prognostic factor in K-S syndrome. A 34-year-old male K-S syndrome patient, manifesting as ptosis and weakness of limbs since the age of 15 years, suffered from dizziness and weakness. Twelve-lead eletrocardiography (ECG) showed a 2:1 atrioventricular (AV) block with slow ventricular rate. Intermittent complete AV block, complete left bundle branch block and torsades de pointes were noted in Holter ECG. The electrophysiology study demonstrated prolonged HV interval (85 ms) on conduction beat and infra-His block on non-conduction beat. A VVIR mode of permanent pacemaker was implanted and the patient's condition was stable during this period of follow-up.

Adult↗

Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB.

Excessive production of hydroxyl radicals in blood and liver has previously been demonstrated by us in rats with obstructive jaundice induced by common bile duct ligation (CBDL). In this study, we demonstrate overproduction of superoxide radicals in circulating blood of CBDL rats by the lucigenin-amplified chemiluminescence technique. To pinpoint the molecular agents that mediate these processes, we measured circulating proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta ( IL-1beta), and interleukin-6 (IL-6) in controls and CBDL rats. Concentrations of these cytokines in blood of CBDL rats were markedly elevated when compared to the controls (TNF-alpha: 36.7 +/- 5.0 vs 13.8 +/- 0.5 pg/mL; IL-6: 2,814 +/- 1,740 vs 0 pg/mL; IL-1beta: 11.9 +/- 2.6 vs 0 pg/mL). The overproduction of free radicals triggered by elevated cytokines in CBDL rats was correlated with the activation of NF-kappaB in hepatic tissue. Using the TdT-mediated dUTP nick-end label staining technique, we showed that hepatic tissue sections from CBDL rats had an increase in the apoptotic index (AI). Based on these findings, we propose that the severe hepatic injury in CBDL rats is mediated by a cycle that involves the activation of NF-kappaB by combined action of proinflammatory cytokines and reactive oxygen species (ROS). NF-KB, in turn, initiates the transcription of cytokine genes (eg, IL-6, IL-8, TNF-alpha), which triggers hepatic injury, at least in part, by a free radical-mediated apoptotic mechanism. Elevated ROS may be as a positive-feedback signal that triggers NF-KB reactivation; the severe hepatic injury of CBDL rats may result from perpetuation of this vicious cycle.

Animals↗

Mucin gene expression in gallbladder epithelium with black pigment stone ascertained by in situ hybridization.

Black pigment stones are usually found in patients with liver cirrhosis or hemolytic disease. Mucoglycoproteins are present in a significant amount in black pigment stones and contribute to the matrix of gallstones. Epithelium of stone-containing gallbladders contains much more mucin than those without stones. In this study, we try to determine by in situ hybridization the mucin gene expression in black stone-containing gallbladders and try to find the diversity of mucin gene expression in gallbladders containing black pigment stones and those without stones. In situ hybridization with DIG-tailed oligonucleotides was performed on sections of paraffin-embedded tissues of gallbladders with black pigment stones (n = 10) and those without stones (n = 6) to identify the expression of MUC1, MUC2, MUC3, MUC4, MUC5B and MUC6 in gallbladder epithelium. The findings showed that (1) mRNA expression of MUC1, MUC3, MUC5B and MUC6 were found in all gallbladders with black pigment stones, while they were expressed in 33.3%, 83.3%, 83.3% and 66.7% respectively in those without stones. They were expressed more strongly and extensively in gallbladders with stones when compared to those without stones. (2) MUC2 and MUC4 labeling were absent in gallbladders without stones, while they were present in 20% and 60% of gallbladders with black pigment stones, respectively. We conclude that MUC3, MUC5B and MUC6 were the main mucin gene expression in either gallbladder with or without stones. Altered mucin gene expression occurred in gallbladders with black pigment stones, such as the presence of MUC2 and MUC4 and increased expression of MUC1, MUC3, MUC5B and MUC6 in black stone-containing gallbladders. The higher incidence and stronger labeling intensity of mucin gene expression of MUC2, MUC3, MUC5B and MUC6 in black stone-containing gallbladder may reflect abundant mucin content in these gallbladders. Increased expression of MUC2 and MUC4 in black stone-containing gallbladder epithelium indicated that intestinal metaplasia and altered mucin genes could occur in diseased gallbladders.

Adult↗

Effects of S-adenosyl-L-methionine on liver damage in experimental obstructive jaundice.

S-adenosyl-l-methionine (SAMe) is a naturally occurring molecule distributed throughout the body tissues, including the liver. It acts as a methyl group donor and as an enzyme activator in a number of biochemical reactions. Methionine is metabolized in the liver, where it is converted to SAMe by SAMe-synthetase. In patients with liver diseases, these pathways are impaired because of the decreased contents of glutathione, the major abnormality being a reduction in SAMe-synthetase activity. Exogenous SAMe may overcome the results of impaired SAMe-synthetase activities. We conducted this study to evaluate the effect of SAMe administration on liver damage induced by biliary obstruction. Rats with common bile duct ligation exhibited abnormal liver functions, increased lipid peroxide levels, and decreased reduced glutathione contents when compared with the shammed-controls, which indicated that there was oxidative stress in rats with obstructive jaundice; however, SAMe application improved these injuries. There were significant alterations of the levels of amino acid profiles in animals with obstructive jaundice. The ratio between branch chain and aromatic amino acid was depressed, which indicated that the condition of liver was worsening, but SAMe administration improved these alterations significantly. In conclusion, SAMe administration alleviated the liver damage, indicating an important hepatoprotective effect of this methyl donor.

Amino Acids↗

Cystic left atrium myxoma--a rare case report.

Myxoma is the most common primary tumor of heart. The typical picture of myxoma under echocardiography is a solid, dense echo mass and left atrium is the most common site to find it. The cystic form of myxoma is vary rare. We report a patient who received echocardiographic examination under impression of mitral valve stenosis. A multilobulated cystic mass which was like a hydatid cyst was found in the left atrium and atrioventricular flow was affected by this mass. After tumor resection, myxoma with internal hemorrhage was proved by pathology. No further recurrent myxoma was found during follow-up echocardiographic examination.

Aged↗

Hypoglycemic and hypolipidemic effects of tectorigenin and kaikasaponin III in the streptozotocin-lnduced diabetic rat and their antioxidant activity in vitro.

Tectorigenin and kaikasaponin III from the flowers of Pueraria thunbergiana showed potent hypoglycemic and hypolipidemic effects in the streptozotocin-induced diabetic rats. Intraperitoneal administration of these two compounds with 5 and 10 mg/kg, respectively, for seven days to streptozotocin-induced rats significantly reduced the blood glucose, total cholesterol, LDL- and VLDL-cholesterol and triglyceride levels when compared with those of control group. Glycitein in which 5-OH is unlinked and tectoridin (7-O-glycoside of tectorigenin) isolated from the flowers of P. thunbergiana did not improve hyperglycemia and hyperlipidemia. In addition, tectorigenin showed in vitro antioxidant effects on 1,1diphenyl-2-pirylhydrazyl (DPPH) radical, xanthine-xanthine oxidase superoxide anion radical, and lipid peroxidation in rat microsomes induced by enzymatic and non-enzymatic methods. We further found that tectorigenin and kaikasaponin III protected the Vero cell line (normal monkey kidney) from injury by hydrogen peroxide. From these findings, it seems likely that the antioxidant action of tectorigenin and kaikasaponin III may alleviate the streptozotocin-induced toxicity and contribute to hypoglycemic and hypolipidemic effects.

Animals↗

Optimization study on the formulation of roxithromycin dispersible tablet using experimental design.

This study set out to improve the physical and pharmaceutical characteristics of the present formulation using an appropriate experimental design. The work described here concerns the formulation of the dispersible tablet applying direct compression method containing roxithromycin in the form of coated granules. In this study 2(3) factorial design was used as screening test model and Central Composite Design (CCC) associated with response surface methodology was used as optimization study model to develop and to optimize the proper formulation of roxithromycin dispersible tablet. The three independent variables investigated were functional excipients like binder (X1), disintegrant (X2) and lubricant (X3). The effects of these variables were investigated on the following responses: hardness (Y1), friability (Y2) and disintegration time (Y3) of tablet. Three replicates at the center levels of the each design were used to independently calculate the experimental error and to detect any curvature in the response surface. This enabled the best formulations to be selected objectively. The effect order of each term to all response variable was X3> X2> X1> X1*X2> X2*X2> X2*X3> X3*X3> X1*X3> X1*X1 and model equations on each response variables were generated. Optimized compositions of formula were accordingly computed using those model equations and confirmed by following demonstration study. As a result, this study has demonstrated the efficiency and effectiveness of using a systematic formulation optimization process to develop the tablet formulation of roxithromycin dispersible tablet with limited experiment.

Anti-Bacterial Agents↗

Nutritional effects of enzymatically modified soybean oil with caprylic acid versus physical mixture analogue in obese Zucker rats.

Enzymatically modified soybean oil with caprylic acid (SL), a physical mixture of tricaprylin and soybean oil (PHY), and soybean oil as control were fed (20% of diet weight) to female obese Zucker rats. Both lipids (SL and PHY) have similar total fatty acid composition containing 23.4 mol % caprylic acid (C8:0) but have different lipid structures. After 21 days of feeding, the body weight gain was 36.4% in the SL-fed group and 35.2% in the PHY-fed group, respectively; whereas the body weight of the control group increased 41.6%. Significant differences in the respiratory exchange ratio were observed between the SL and PHY groups. However, the contents of glucose, total and high density lipoprotein (HDL) cholesterol, and very low density and low density lipoprotein (VLDL + LDL) cholesterol in serum were not significantly different between the SL- and PHY-fed groups or among the three dietary groups (control, SL, and PHY) (p < 0.05). On the other hand, plasma total cholesterol and plasma triacylglycerol (TAG) were significantly higher in SL- and PHY-fed groups than in the control group. In the liver and inguinal adipocyte TAG, C8:0 was found in the SL-fed group, whereas it was not observed in the liver and inguinal adipocyte TAG of the PHY-fed group, which suggests that positional distribution of C8:0 of the TAG molecule is an important consideration in the metabolism of lipids. This study showed that different positional distribution in TAG molecules lead to different metabolic fates, resulting in the change of fatty acid composition in liver and inguinal adipose TAG in female Zucker rats.

Adipocytes↗

Essential moiety for antimutagenic and cytotoxic activity of hederagenin monodesmosides and bisdesmosides isolated from the stem bark of Kalopanax pictus.

For the elucidation of the antimutagenic and cytotoxic principles from the stem bark of Kalopanax pictus, seven isolated components of this crude drug were tested in the Ames test and the MTT test. Hederagenin and its monodesmosides, kalopanaxsaponin A and I in addition to its bisdesmosides, kalopanaxsaponin B and H, showed potent antimutagenic activities against aflatoxin B1 (AFB1). However, they had no inhibitory effects on mutagenicity induced by the direct mutagen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). This suggested that hederagenin glycosides might effectively prevent the metabolic activation of AFB1 or scavenge the electrophilic intermediate capable of inducing mutation. Hederagenin was found to be an essential moiety for the exhibition of antimutagenicity. Moreover, hederagenin and its 3-O-glycosides were found to be cytotoxic on various tumor cell lines, P-388, L-1210, U-937, HL-60, SNU-5 and HepG2, while 3,28-di-O-glycosides of hederagenin were not cytotoxic. Hence, hederagenin and its 3-O-glycosides could be suitable for cancer treatment chemopreventive drugs.

Antimutagenic Agents↗

Sesquiterpenes from the leaves of Ligularia fischeri var. spiciformis.

From the leaves of Ligularia fischeri var. spiciformis, a new eremophilanolide, 8 alpha-methoxy-6-oxoeremophil-7(11)-en-12,8-olide (6-oxoeremophilenolide) and a eudesmane-type sesquiterpene, (+)-intermedeol were isolated. The structures were determined on the basis of 2D-NMR spectral data. Data on cytotoxicity showed that the latter was clearly more potent than the former compound.

Asteraceae↗

Differentiation-inducing effect of magnolialide, a 1 beta-hydroxyeudesmanolide isolated from Cichorium intybus, on human leukemia cells.

Cichorium intybus contains two 1beta-hydroxyeudesmanolides, magnolialide and artesin, together with several constituents. Magnolialide inhibits the growth of several tumor cell lines and appears to induce differentiation of human leukemia HL-60 and U-937 cells to monocyte/macrophage-like cells. Another 1beta-hydroxyeudesmanolide, artesin, and other constituents were inactive. The content of magnolialide was shown to be highest in the leaves of Inje cultivar among the cultivars investigated in this study.

Animals↗

Detection of genetic alterations in the human gastric cancer cell lines by two-dimensional analysis of genomic DNA.

We examined genomic DNA from each of three human-derived gastric cancer cell lines, using the technique of restriction landmark genomic scanning (RLGS) which allows monitoring of approximately 2, 000 NotI landmarks. The resulting DNA spots from cancer cell DNA were compared with those in normal mucosa or gastric primary tumor. In all, 9 intense spots were detected from two of the three cancer cell lines. Two highly intensified spots were common in the two cancer cell lines and proven to be originated from DNA region containing the human c-myc proto-oncogene on chromosome 8. The degree of amplification of c-myc DNA was similar to each other and was estimated to be 60-fold as compared to those from normal mucosa DNA. On the basis of chromosome-assigned RLGS (CA-RLGS), other spots were assigned to each chromosome, such as one on chromosome 8, two each from chromosome 20, and three on one of chromosome 9-12. The remaining spot seems to be due to demethylation of a repetitive element. Twenty-four spot that were lost due to either homozygous deletion or methylation on corresponding NotI cleavage sites were commonly observed in all cancer cells. These spots were also assigned to each chromosome: one each from chromosome 2, 6, 7, 13, 14, 16, and 20, two each from chromosome 3 and 5, and nine from chromosome 9-12 by CA-RLGS. Many of the multi-copy spots corresponding to ribosomal RNA genes were greatly decreased due mainly to methylation on CpG islands along with minor rDNA variants, indicating that only minor rRNA genes may be silenced in these cancer cells. These results show that the present alterations detected by RLGS might be useful for identification of candidate genes inactivated or expressed unexpectedly in tumor development and tumor progression in the stomach.

Base Sequence↗

Avoiding hypothermia in trauma: use of the flameless heater pack, meal ready to eat, as a field-expedient means of warming crystalloid fluid.

Forward-deployed medical units do not have the capability to warm intravenous (i.v.) fluids before their administration. We intend to demonstrate a field-expedient means of warming i.v. fluids and preventing hypothermia using the flameless heater available in the Meal, Ready to Eat (MRE). Room-temperature and refrigerated lactated Ringer's solution were organized into three data collection groups using either one or two MRE heaters. The temperature change of the fluid was recorded. Average temperature increases ranged from 15.8 to 31.2 degrees C in times ranging from 8 to 20 minutes. Therefore, we conclude that the flameless MRE heater provides a simple, field-expedient means of warming i.v. fluids before their administration.

Cooking↗

The effect of fluvastatin on fibrinolytic factors in patients with hypercholesterolemia.

Several studies have shown cardiovascular benefit in treating hypercholesterolemia with HMG-CoA reductase inhibitor. However, in addition to the lowering of cholesterol, the beneficial effects of this inhibitor reflect other pharmacological activities. Whether these beneficial effects are partly mediated by changes in fibrinolytic factors remains to be proven, since clinical studies on the effects of HMG-CoA reductase inhibitors on fibrinolytic factors have not yielded consistent results. The purpose of this study was to evaluate the effects of fluvastatin on fibrinolytic factors in hypercholesterolemic patients. After 6 weeks on a low-fat, low-cholesterol diet, 23 outpatients known to have primary hypercholesterolemia with low density lipoprotein cholesterol (LDL-C) > or = 130 mg/dl with at least 2 risk factors or fasting LDL-C > or = 160 mg/dl were selected for the study. Venous blood samples were collected at baseline and at 8 weeks after fluvastatin therapy (40 mg/day) to measure of tissue plasminogen activator (t-PA), plasminogen activators inhibitor-1 (PAI-1), fibrinogen, D-dimer and lipid profile. After 8 weeks of therapy, fluvastatin reduced serum cholesterol by 11% (261.9 mg/dl vs 233.2 mg/dl, P < 0.01) and LDL-C by 22% (191.9 mg/dl vs 149.3 mg/dl, P < 0.01). D-dimer was significantly decreased (0.38 ng/L vs 0.28 ng/L, P = 0.02) and tPA, PAI-1 and fibrinogen tended to decrease after therapy. Fluvastatin therapy improved fibrinolytic profile; the result of this study may in part explain the benefit of HMG-CoA reductase inhibitor on cardiovascular system other than lipid lowering.

Aged↗