An evaluation of beta-blockers, calcium antagonists, nitrates, and alternative therapies for stable angina.
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Adrenergic beta-Antagonists↗
Biomedical subjects
B K Lee
Publications and source records attributed to B K Lee.
Mutations affecting ligand specificity of the G-protein-coupled receptor for the Saccharomyces cerevisiae tridecapeptide pheromone.
Random mutations were generated in the G-protein-coupled receptor (Ste2p) for the tridecapeptide pheromone (alpha-factor) of Saccharomyces cerevisiae. These mutants were screened for variants that responded to antagonists. Because multiple mutations were detected in each mutant receptor recovered from the screen, site-directed mutagenesis was used to create single-site mutant receptors. Three receptors containing mutations F55V, S219P, and S259P were analyzed for their biological responses to various alpha-factor analogs and for their ligand binding profiles. Cells expressing each of the mutant receptors responded to alpha-factor as well as or better than wild-type cells in a growth arrest assay. In contrast, the binding of alpha-factor to the F55V and S219P mutant receptors was at least 10-fold reduced in comparison to wild-type receptor indicating a complex non-linear correlation between binding affinity and biological activity. Cells expressing mutant receptors responded to some normally inactive analogs in biological assays, despite the fact that these analogs had a low affinity for Ste2p. The analysis of these mutant receptors confirms previous findings that the first and sixth transmembrane regions of Ste2p are important for ligand interaction, ligand specificity, and/or receptor activation to initiate the signal transduction pathway. Changes in binding affinity of pheromone analogs to wild-type and mutant receptors indicate that residue 55 of Ste2p is involved with both ligand binding and signal transduction.
Binding Sites↗
Epidemiology of eating disordered symptoms in the Korean general population using a Korean version of the Eating Attitudes Test.
OBJECTIVE: The purposes of the present study were to estimate the proportion of subjects with a high score on the Korean version of Eating Attitudes Test--26 (KEAT-26), which may provide preliminary data regarding the prevalence rate of eating disorders in the Korean general population, and to further examine the sociocultural hypothesis of eating disorders. METHOD: Using a multi-stage questionnaire sampling method, we surveyed 3062 subjects (1249 males, 1813 females) from 3896 Korean adults in a nationwide area. RESULTS: 8.5% (260/3062) of subjects scored above the cut-off on the KEAT-26. Their demographic correlates, eating traits, and other characteristics relating to general psychopathology were similar to those of patients with eating disorders and female Caucasian controls in Western countries. DISCUSSION: These results suggest that changes in various sociocultural aspects have increased the risk of developing eating disorders in Korea, and support the sociocultural hypothesis of eating disorders.
Adult↗
Evaluation of urinary cadmium and lead as markers of background exposure of middle-aged women in Korea.
OBJECTIVE: The present study was initiated to investigate the validity of cadmium (Cd) and lead (Pb) in urine in comparison with the metals in blood as a biological marker of nonoccupational exposure of general populations to these metals as environmental pollutants. DESIGN: Peripheral blood samples, morning spot-urine samples, and 24-h total food duplicate samples were collected from 107 nonsmoking women (aged 30-59 years) in four urban and rural survey sites in Korea. METHODS: Portions of the samples were digested by heating in the presence of mineral acids, and the digests were analyzed for Cd and Pb by graphite furnace atomic absorption spectrophotometry. The metal concentrations in urine were adjusted for creatinine concentration and a specific gravity of 1.016. The analyte levels were evaluated on an individual basis (n = 107) and also on a group basis, i.e., in terms of geometric means for the survey sites (n = 4). RESULTS: Cd in urine correlated with Cd in blood on an individual as well as survey-site basis and tended to correlate with Cd in food duplicates on a group basis. The correlation of Pb in urine with Pb in blood was weaker than that of Cd in urine with Cd in blood when evaluated on an individual and survey-site basis. Pb in urine correlated with Pb in food duplicates either weakly or even negatively when examined on a survey-site basis. CONCLUSIONS: Cd in urine proved to be valid as a biological marker of environmental exposure of general populations, whereas less support was obtained for Pb in urine as an exposure marker.
Adult↗
Urinary 5-aminolevulinic acid (ALA) adjusted by creatinine: a surrogate for plasma ALA?
5-Aminolevulinic acid (ALA) is the first intermediate substrate in the heme synthetic pathway and is the substrate of aminolevulinic acid dehydratase (ALAD, porphobilinogen synthase). Because lead effectively inhibits ALAD activity, resulting in accumulation of ALA in urine and blood, urinary ALA (ALAU) has been used as a biomarker for lead exposure or early biologic effect of lead. Intraindividual variation in urinary excretion of ALA requires the use of 24-hour urine samples or adjustment of single urine samples by other normalizing variables, such as urinary creatinine concentration. Previous studies of ALAU concentration have used various adjustment methods; however, few have compared creatinine-adjusted ALAU concentration with ALA concentration in plasma (ALAP) from subjects with low (< 30 micrograms/dL) to moderate (< 60 micrograms/dL) levels of blood lead. To determine if creatinine-adjusted ALAU is associated with ALAP, we measured ALAU, ALAP, and urinary creatinine in 65 Korean lead workers with blood lead concentrations in the range of 14-60 micrograms/dL. ALAU, ALAU/creatinine, or ALAU/log creatinine all correlated with ALAP. However, ALAU/creatinine correlated more closely with ALAP based on Spearman's r (rs = 0.40, P, = 0.0009), supporting the use of ALA/creatinine in single urine samples as a surrogate for ALAP.
Adult↗
Hemodynamic effects of the geometric dimensions of graft vessels in coronary artery bypass graft models.
The objectives of this investigation are to evaluate the rheologic properties in atherosclerotic disease treated with the various coronary artery bypass graft (CABG) models by numerical analysis, we used four different CABG models for the assessment of spatial fluctuation in wall shear stress, pressure variation and mass flow rate with Carreau model and Navier-Stokes equation. Wall shear stress was higher in a naturally tapered model (model 1) and a constant (non-tapered) diameter of the graft vessel the same as the distal LAD (model 4) than in others. Pressure variation along the native coronary artery and graft vessels was higher in a model 4, model 1 than in a reverse tapering model (model 2) and a constant diameter of the graft vessel the same as the proximal LAD (model 3). The mass flow rate of the distal part (kg/sec,.m(o)) was the highest in model 3. This study suggests that in vitro spatial simulation following CABG revealed that small caliber or tapered graft vessels have adverse hemodynamic effects on the native and graft vessels. By this technique it is possible to simulate the optimal distribution of local hemodynamic variables in patients treated with CABG, also to minimize the degeneration of graft vessel.
Computer Simulation↗
Computed numerical analysis of the biomechanical effects on coronary atherogenesis using human hemodynamic and dimensional variables.
The objectives of this investigation were to evaluate biomechanical factors in the atherosclerotic process using human in vivo hemodynamic parameters and computed numerical simulation qualitatively and quantitatively. The three-dimensional spatial patterns of steady and pulsatile flows in the left coronary artery were simulated, using a finite volume method. Coronary angiogram and Doppler ultrasound measurement of the proximal left coronary flow velocity were performed in humans. Inlet wave velocity distribution obtained from in vivo data of the intravascular Doppler study allowed for input of in vitro numerical simulation. Hemodynamic variables, such as flow velocity, pressure and shear stress of the left anterior descending coronary bifurcation site were calculated. We found that there were spatial fluctuation of flow-velocity and recirculation areas at the curved outer wall of the left anterior descending coronary artery, which were due to the differences of flow-velocity and shear stress, especially during the declaration phase of pulsatile flow. This study suggests that rheologic properties may be a part of the atherogenic process in the coronary bifurcated and curved areas.
Biomechanical Phenomena↗
Experimental hypercholesterolemia induces ultrastructural changes in the elastic laminae of rabbit aortic valve.
Atherosclerosis is the most severe problem in the high-pressure systemic circulation and similar changes also occur in the high-pressure loading valve. This study was designed to test the hypothesis that early atherosclerosis, induced by a high cholesterol diet in rabbits, is characterized by significant ultrastructural change in the elastic laminae of the aortic valve. However, it is not known whether this process is also taking place in the cardiac valve at the early stage of atherosclerosis. Animals were fed either a high cholesterol diet (n = 5) or a control diet (n = 5) for 10-12 weeks. Histologic analysis demonstrated that subendothelial thickening and foam-cell infiltration were evident in the arterialis of aortic valves. Confocal microscopy revealed an altered pattern characterized by fragmentation and disorganization of the arterialis elastic laminae of hypercholesterolemic valves. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal valves, the arterialis elastic laminae of hypercholesterolemic valves decreased in percentage of their elastin content (29.03 +/- 1.10% vs. 42.94 +/- 1.35%, p = 0.023). Immunohistochemical staining for matrix metalloproteinase-3 (MMP-3) revealed MMP-3 immunoreactivity was increased in hypercholesterolemic valves, predominantly in the arterialis. This study demonstrated that early atherosclerosis, induced by a high cholesterol diet in rabbits, is characterized by significant ultrastructural change in the elastic laminae of the aortic valve. The arterialis endothelium of the aortic valve may be a more atherosclerosis-prone area compared with the ventricularis. The presence of ultrastructural defect in the elastic laminae may play a role in chronic degenerative change and a resultant valvular dysfunction.
Animals↗
A woman who had a stroke, then a myocardial infarction.
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Adult↗
Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers.
The first intermediate substrate in the heme synthetic pathway, 5-aminolevulinic acid (ALA), is neurotoxic in animal models and may be responsible for some of the adverse neurologic outcomes in lead poisoning and porphyria in adult humans. ALA is a substrate for the enzyme aminolevulinic acid dehydratase (ALAD; EC 4.2.1.24), which is encoded by the ALAD gene containing 2 co-dominant alleles, 1 and 2. We measured plasma ALA (ALAP) and urinary ALA (ALAU) in 65 Korean lead workers, of whom 44 were homozygous for ALADI (ALAD1-1 genotype) and 21 were heterozygous for ALAD (ALAD1-2 genotype). ALAP in subjects with the ALAD1-1 genotype was significantly higher than in those with the ALAD1-2 genotype (Wilcoxon rank sum test, P = 0.01). No difference between ALAD genotypes was found for age, zinc protoporphyrin (ZPP), blood lead levels (PbB), ALAU, or ALAU adjusted for creatinine. ALAP was significantly correlated with ZPP (Spearman's r = 0.38, P = 0.002) and with PbB (r = 0.34, P = 0.006), and marginally with employment duration (r = 0.22, P = 0.08). ALAP remained significantly elevated (P = 0.032) in ALAD1-1 subjects after adjustment for PbB and age by multiple linear regression. These results suggest that ALAD1-1 subjects respond differently and may be more susceptible than ALAD1-2 subjects to the ALA-mediated neurotoxic effects of lead.
Adult↗
Ethnic variation in the prevalence of a common NAD(P)H quinone oxidoreductase polymorphism and its implications for anti-cancer chemotherapy.
The NAD(P)H quinone oxidoreductase (NQO1:EC 1.6.99.2) is an important biotransformation enzyme system that is also known to metabolize important novel chemotherapeutic compounds. The gene that codes for this enzyme has recently been found to be polymorphic in humans. Here, we describe the ethnic distribution of the polymorphism and note that this may have implications for anti-tumour drug development and use.
Antineoplastic Agents↗
Lemierre's syndrome.
Lemierre's syndrome is an acute medical condition characterized by anaerobic oropharyngeal infection leading to septic thrombophlebitis of the internal jugular vein. The illness is often complicated by septic pulmonary emboli and distant metastatic infections. Treatment consists of surgical drainage of purulent collections and long-term intravenous antibiotic therapy. Although Lemierre's syndrome is rare, it is potentially fatal and remains an important entity for clinicians to recognize and treat appropriately.
Abscess↗
delta-Aminolevulinic acid dehydratase genotype modifies four hour urinary lead excretion after oral administration of dimercaptosuccinic acid.
OBJECTIVES: Previous research suggests that binding of lead by delta-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA). METHODS: 57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD1-1, ALAD1-2) from among all current workers in the two plants (n = 290). Subjects with ALAD1-1 (n = 38) were frequency matched with subjects with ALAD1-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead. RESULTS: Blood lead concentrations ranged from 11 to 53 micrograms/dl, with a mean (SD) of 25.4 (10.2) micrograms/dl. After 5 mg/kg DMSA orally, the workers excreted a mean (SD) 85.4 (45.0) micrograms lead during a four hour urine collection (range 16.5-184.1 micrograms). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALAD1-2 excreted, on average, 24 micrograms less lead during the four hour urine collection than did subjects with ALAD1-1 (P = 0.05). ALAD genotype seemed to modify the relation between plasma delta-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALAD1-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALAD1-1 (P value for interaction = 0.01). CONCLUSIONS: DMSA chelatable lead may partly reflect the stores of bioavailable lead, and the current data indicate that subjects with ALAD1-2 have lower stores than those with ALAD1-1. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead-for example, by differential binding of current lead stores or by differences in long-term retention and deposition of lead.
Administration, Oral↗
Nutritional evaluation of women in urban and rural areas in Korea as studied by total food duplicate method.
Nutrient intake was studied by the total food duplicate method in 141 adult working women (at the ages of 21 to 56 years) in four regions (Seoul, Pusan, Chunan and Haman) in Korea. Clinical, hematological and anthropometrical examinations were conducted in parallel. The nutrient intakes were estimated in reference to the weight of each food item and the national standard food composition tables for Korean population, and evaluated in comparison with the nationally recommended dietary allowances (RDA). The intakes were essentially sufficient when evaluated on a group basis. Plant-based foods were major sources of both protein (67%) and lipid (72%). Dinner was the most substantial sources of all nutrients. Further evaluation on an individual basis taking 80-120% RDA as acceptable showed that young people (at the ages of 20-29 years) and those in Seoul had highest prevalence of insufficient intake of nutrients, especially energy, protein and iron. Consumption of rice, the traditional staple food, was the lowest in Seoul and in the youngest groups as compared with others. The prevalence of overweight cases was also the lowest in the Seoul participants. The two observations when combined apparently suggest the difficulties in public nutrition.
Adult↗
The effect of diphenyl-dimethyl-dicarboxylate on cyclosporine-A blood level in kidney transplants with chronic hepatitis.
An adequate blood level of cyclosporine-A (CsA) is essential to keep graft function in kidney transplants. Due to a narrow therapeutic index and highly variable pharmacokinetic properties associated with CsA, drug interactions may have a significant impact on the immunosuppressive efficacy or toxicity of CsA. Numerous drug interactions of potential clinical significance involving CsA have been reported. Dephenyl-dimethyl-dicarboxylate (PMC), a hepatotonic drug, is a substance derived from the synthesis of Schizandrae fructus elements. We have experienced two cases of drug interaction between CsA and PMC in kidney transplants with chronic hepatitis. In both cases, CsA troughs decreased markedly to a subtherapeutic level following administration of PMC. We, therefore, suggest that PMC could decrease the CsA trough level and thus a close monitoring of the CsA trough level is necessary during a PMC therapy.
Chronic Disease↗
Signaling mechanism of PMA-induced differentiation of K562 cells.
We have studied the signaling pathways responsible for the monocytic and/or megakaryocytic differentiation of K562 cells. The results demonstrated that although the mitogen-activated protein kinase (MAPK) was activated during the phorbol myristate acetate (PMA)-induced monocytic and/or megakaryocytic differentiation of K562 cells, the overexpression of Ha-ras which can activate the MAPK did not induce the monocytic and/or megakaryocytic differentiation of K562 cells. Instead PMA-induced megakaryocytic differentiation of K562 cells was inhibited by the pretreatment of pyrrolidine dithiocarbamate, a specific nuclear factor kappaB (NF-kappaB) inhibitor. Taken together, these results suggest that the activation of NF-kappaB rather than that of MAPK might be involved in the PMA-induced megakaryocytic differentiation of K562 cells.
Cell Differentiation↗
A 73-year-old man with hypertension and syncope.
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Aged↗
Association of somatotropin (BST) gene polymorphism at the 5th exon with selection for milk yield in Holstein cows.
A selection project produced control cows from continuous matings with breed average bulls for predicted transmitting ability for milk (PTA-milk) in 1964 and select cows from matings to four of the highest PTA-milk bulls each year since 1964. Blood samples were collected in 1992 when milk yield difference of select and control line cows exceeded 3,800 kg of milk/305-day lactation. Genomic DNA from control (n = 49) and select (n = 101) cows was analyzed for the presence of variants associated with amino acid position 127 (leucine, AluI[+]; valine, AluI[-]) of bovine somatotropin (bST). Amplification of a 428 base-pair fragment of the bST gene from individual cows, subsequent restriction enzyme (AluI) digestion, and separation resulting fragments indicated three genotypes AluI(+/+), AluI(+/-), and AluI(-/-) in 110, 39, and 1 animal(s), respectively. Gene frequencies of leucine127 and valine 127 alleles were similar for control (0.867m 0.133) and select (0.861, 0.139) animals. United States Department of Agriculture-PTA values were compared between the two genotypes, AluI(+/+) and AluI(+/-). Estimated breeding value for milk (EBV-milk) and average yield deviation for milk (AYD-milk) were not associated with genotype for control animals. However, presence of the valine allele was correlated with decreased EBV-milk (P = 0.03) and AYD-milk (P = 0.16) in select animals and accounted for a decrease of approximately 170 kg of EBV-milk and 240 kg of AYD-milk.
Animals↗