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Biomedical subjects

C Y Cho

Publications and source records attributed to C Y Cho.

At least 19 recordsLinked to original sources
PubMed2000

Ligand-dependent interactions of coactivators steroid receptor coactivator-1 and peroxisome proliferator-activated receptor binding protein with nuclear hormone receptors can be imaged in live cells and are required for transcription.

Members of the nuclear receptor superfamily are thought to activate transcription by recruitment of one or more recently identified coactivator complexes. Here we demonstrate that both peroxisome proliferator-activated receptor binding protein (PBP) and steroid receptor coactivator-1 (SRC-1) are required for ligand-dependent transcription of transiently transfected and chromosomally integrated reporter genes by the estrogen receptor (ER) and retinoic acid receptor (RAR). To examine ligand-dependent interactions between nuclear receptors and specific coactivators in living cells, these proteins were tagged with cyan (CFP) and yellow (YFP) mutants of the green fluorescent protein. Fluorescence resonance energy transfer (FRET) from the CFP to the YFP indicated interaction between the receptor and coactivator. CFP fusions to RAR or its ligand-binding domain exhibited rapid ligand-dependent FRET to YFP-tagged nuclear receptor interaction domains of the coactivators SRC-1 and PBP. The ER-ligand-binding domain, unlike RAR, also exhibited some basal interaction with coactivators in unstimulated cells that was abolished by the receptor antagonists tamoxifen or ICI182,780. Inhibition of FRET by tamoxifen but not ICI182,780 could be reversed by estradiol, whereas estradiol-enhanced FRET could not be inhibited by either antagonist, indicating that ligand effects can show varying degrees of hysteresis. These findings suggest that ligand-dependent transcriptional activities of the RAR and ER require concurrent or sequential recruitment of SRC-1 and PBP-containing coactivator complexes.

Carrier Proteins↗
PubMed2000

A genetically encoded, fluorescent indicator for cyclic AMP in living cells.

Cyclic AMP controls several signalling cascades within cells, and changes in the amounts of this second messenger have an essential role in many cellular events. Here we describe a new methodology for monitoring the fluctuations of cAMP in living cells. By tagging the cAMP effector protein kinase A with two suitable green fluorescent protein mutants, we have generated a probe in which the fluorescence resonance energy transfer between the two fluorescent moieties is dependent on the levels of cAMP. This new methodology opens the way to the elucidation of the biochemistry of cAMP in vivo.

Adrenergic alpha-Agonists↗
PubMed2000

A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's disease.

OBJECTIVE: To assess the efficacy and safety of Cerebrolysin over 4 weeks in patients with probable Alzheimer's disease (AD). DESIGN: A 4-week randomized, double-blind, placebo-controlled, multicenter clinical trial. An unequal (Cerebrolysin:placebo = 2:1) randomization was used to assign more patients to the treatment group. SETTINGS: University medical centers and community geriatric hospitals in Korea. PARTICIPANTS: Fifty-three men and women at least 50 years of age admitted to hospitals with mild to moderate AD and otherwise in good health. INTERVENTION: The treatment group (n = 34) received Cerebrolysin (30 mL Cerebrolysin in 100 mL physiologic saline IV) once a day from Monday to Friday for 4 weeks. The control group (n = 19) received placebo. MEASUREMENTS: Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinical Global Impression of Severity/ Change (CGIS/C). Secondary outcome measures included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Katz Index of Activities of Daily Living (ADL), and Lawton Instrumental Activities of Daily Living (IADL) Scale. RESULTS: After 4 weeks of treatment, Cerebrolysin-treated patients demonstrated significant improvements in the ADAS-Cog (P = .02), CGIS/C (P = .01), and MMSE (P = .04) compared with placebo-treated patients. Among Cerebrolysin-treated patients, 82%, 62%, and 44% were rated improved on ADAS-Cog, CGIS/C, and MMSE, respectively, compared with 31.6%, 22%, and 17% of placebo-treated patients, respectively. However, there were no significant improvements in the Cerebrolysin group compared with the placebo group on the GDS, ADL, and IADL. There were no dropouts in either groups, with 100% compliance to Cerebrolysin and placebo. Only one patient reported a febrile sensation, which was transient and mild in severity. CONCLUSIONS: This study indicates that Cerebrolysin is a safe drug that improves the cognitive deficits and global function in patients with mild to moderate AD. Long-term efficacy and safety of Cerebrolysin in Alzheimer's patients should be evaluated in the future.

Activities of Daily Living↗
PubMed1999

Cyclic and linear oligocarbamate ligands for human thrombin.

Several classes of compounds have been tested as potential inhibitors of the serine protease thrombin, an important regulator of blood coagulation cascades. We describe here the discovery of a new class of thrombin inhibitors based on an unnatural carbamate biopolymer. Oligocarbamate thrombin inhibitors were identified through the screening of diverse cyclic trimer, cyclic tetramer, and linear tetramer libraries using the one bead, one peptide method. Whereas the cyclic trimer oligocarbamate ligands bound thrombin with modest affinity, a cyclic tetramer oligocarbamate inhibited thrombin with an apparent Ki of 31 nM. Linear oligocarbamate tetramers bound thrombin with inhibition constants in the 100-nM range. These nonpeptidic, oligomeric molecules may provide the basis for further drug development and studies of thrombin ligand interactions.

Animals↗
PubMed1999

Changes of neonatal mortality rate between 'pre' and 'post' surfactant period.

The objective of this study was to determine how the neonatal mortality rate has changed since surfactant (S) therapy was introduced in our Neonatal Intensive Care Unit (NICU), and to evaluate the efficacy of surfactant therapy in respiratory distress syndrome (RDS) patients. Incidences of risk babies such as outborns, prematurity, low birth weight infants and RDS, and neonatal mortality rates were compared between 'pre' (control, 1988 to 1991, n=4,861) and 'post' S period (study, 1993 to 1996, n=5,430). In RDS patients of 'post' S period, neonatal mortality rate was compared between S-treated and non-treated patients, and chest X-ray and ventilatory parameters were compared between pre- and post-72 hr of surfactant treatment. Surfactant therapy showed short term effects, judging by the decrease of early neonatal deaths and improvement of chest X-ray and ventilatory parameters in RDS patients. The overall neonatal mortality rate had a tendency to decrease in spite of increased incidences of risk babies in 'post' S period but it was less than expected. The reasons were thought to be that we had a high proportion of risk babies, and there was some bias in patient selection for surfactant therapy and its use. In conclusion, with the active prevention of risk baby delivery and appropriate use of surfactant, better results could be expected.

Biological Products↗
PubMed1998

Dressing the part.

Wound care after cutaneous surgery can play an integral role in wound healing. Wound care regimens have changed dramatically over the last 35 years as the physiology of wound healing has become better understood. Foremost is the improvement in wound healing achieved by keeping the wound occluded and moist. This observation has led to an explosion of a whole new category of occlusive dressings at the surgeon's disposal in healing postoperative wounds. These dressings have numerous applications as discussed previously. Generally, for acute surgical wounds, occlusive dressings are most useful for split-thickness wounds, such as graft donor sites and after dermabrasion, chemical peel, or laser treatment, and full-thickness wounds allowed to heal by secondary intention. Occlusive dressings may have greater benefit for the treatment of chronic ulcers of varying etiologies. The different categories of dressings share the common disadvantage of being relatively expensive. For routine sutured wounds, the authors prefer the readily available and inexpensive Telfa-type dressing combined with a topical antibiotic ointment. Topical antiseptics are useful for reducing bacterial counts on intact skin in preparation for surgery. Povidone-iodine (Betadine) and chlorhexidine gluconate (Hibiclens) have emerged as the two agents of choice. However, antiseptics have been shown to be toxic to healing tissue, and should not be used on open wounds. In contrast, topical antibiotic ointments are safe to use on open wounds, effective in preventing wound infections, and promote wound healing by maintaining a moist wound environment. The authors prefer the combination antibiotic ointment Polysporin for routine postoperative wound care. Antibiotic prophylaxis in dermatologic surgery to prevent wound infection is appropriate in certain cases. Surgery performed on grossly contaminated or infected skin requires a full 7 to 10 day course of antibiotics. Procedures in anatomic areas considered contaminated as well as in clean areas with significant environmental or patient risk factors may benefit from antibiotic prophylaxis. The choice of antibiotics should be based on the organism most likely to cause wound infection at the particular surgical site. Evidence supports giving a single preoperative dose 1 hour before surgery with a second dose possible 6 hours later if the procedure is prolonged or delayed. The risk of bacterial endocarditis after dermatologic surgery is not known. Antibiotics are indicated for any procedure on obviously infected skin, but are not routinely required for very minor procedures, such as small biopsies, on intact skin. Antibiotic prophylaxis may be prudent for those patients classified as high risk by the (AHA). The antibiotic chosen should again cover the organism most likely to cause infection. One dose can be given 1 hour before surgery and repeated 6 hours postoperatively. Finally, wound healing can be greatly impacted by what the patient does or does not do after leaving the office. Therefore, wound care instructions should be clear, detailed, and provided in both oral and written form. Information should also be provided about what to expect as the wound heals.

Antibiotic Prophylaxis↗
PubMed1998

Detecting balance deficits in frequent fallers using clinical and quantitative evaluation tools.

OBJECTIVE: This investigation sought to determine whether older idiopathic frequent fallers could be distinguished from healthy older adults on the basis of balance and movement coordination tests. A secondary objective was to determine the relationships among clinical balance test scores, balance performance data obtained by accelerometry, and quantitative motor coordination tests. DESIGN: Two group comparison designs. SETTING: A motor control research laboratory in a university setting. PARTICIPANTS: The 16 subjects recruited for this study included eight healthy older subjects and eight age-matched idiopathic fallers. MEASUREMENTS: Each participant's balance performance was assessed by accelerometry, as well as by coordination and clinical tests. Accelerometry scores, obtained by 1g accelerometers placed at the hip and on the head, were made with eyes open or closed, either standing on the floor or on a wedge of compliant foam. Clinical balance scores were obtained using variants of Romberg's test and the functional reach test. Motor coordination tests obtained included the heel-to-toe transition and rapid stepping tests. MAIN RESULTS: Statistically significant differences were obtained between groups for all accelerometry variables except root mean square. All accelerometry variables were successful in discriminating between head and hip sites. Moreover, the amplitude of sway obtained from accelerometry data identified significant differences among the four test conditions. The Romberg test, using right leg alone with eyes open, showed a significant difference between fallers and healthy older subjects. Walking velocity was significantly faster for normal older subjects than for fallers (1.10 m/sec vs 0.80 m/sec). No significant between-group differences were obtained using the functional reach test. Coordination skills yielded significant between-group differences using the rapid stepping test but no significant differences between groups with the heel-toe transition test. CONCLUSION: Accelerometry is an inexpensive and clinically useful technique that can distinguish between healthy older people and idiopathic frequent fallers. In conjunction with clinical procedures and commercially available tests to assess motor coordination, these techniques can identify older individuals susceptible to frequent falls.

Accidental Falls↗
PubMed1998

The association between chronic illness and functional change among participants in a comprehensive geriatric assessment program.

OBJECTIVE: To examine the association between chronic illness and functional status change during a 3-year period in older people enrolled in an in-home comprehensive geriatric assessment (CGA) and preventive care program. DESIGN: Secondary analysis of data from a longitudinal cohort study. SETTING: Santa Monica, California. PARTICIPANTS: Two hundred two community-dwelling older persons (mean age at baseline was 81 years, 70% were women, and 72% reported good health) randomized to the intervention group in a trial of in-home comprehensive geriatric assessment and preventive care. MEASUREMENTS: We studied 13 common chronic illnesses/conditions determined clinically from an annual comprehensive evaluation by gerontologic nurse practitioners (GNPs) in consultation with study geriatricians. These target conditions included hypertension, osteoarthritis, coronary artery disease, obesity, undernutrition, urinary incontinence, sleep disorders, falls, gait/balance disorders, hearing and vision deficits, depression, and unsafe home environment. The dependent variable was functional change as measured by instrumental activities of daily living (IADL) and basic activities of daily living (BADL) assessed at baseline and annually for 3 years by independent research personnel. Potential confounding variables, including comorbid conditions and other subject characteristics, were controlled for in the analyses. RESULTS: Although functional status was similar at baseline, the presence of certain target conditions in this sample was associated significantly with functional decline in IADL and BADL during the 3-year period. Four conditions (gait/balance disorders, depression, unsafe home environment, and coronary artery disease) were associated with significant declines in IADL, and four conditions (gait/balance disorders, depression, hypertension, and urinary incontinence) were associated with significant declines in BADL. Conversely, subjects with obesity had no significant change in IADL or BADL throughout the study period and had less decline in IADL compared with nonobese subjects. CONCLUSIONS: Certain chronic conditions, particularly gait/balance disorders and depression, are associated with significant decline in functional status in older persons who receive CGA. These findings may help identify older persons at risk for greatest functional decline despite participation in CGA and may also suggest the need for more effective intervention strategies in these individuals.

Activities of Daily Living↗
PubMed1995

Novel biopolymers for drug discovery.

The solid phase synthesis and generation of libraries of "unnatural biopolymers" is described. These polymers are characterized by novel backbones and building blocks, the properties of which may modify their pharmacological and folding properties.

Biopolymers↗
PubMed1993

An unnatural biopolymer.

A highly efficient method has been developed for the solid-phase synthesis of an "unnatural biopolymer" consisting of chiral aminocarbonate monomers linked via a carbamate backbone. Oligocarbamates were synthesized from N-protected p-nitrophenyl carbonate monomers, substituted with a variety of side chains, with greater than 99 percent overall coupling efficiencies per step. A spatially defined library of oligocarbamates was generated by using photochemical methods and screened for binding affinity to a monoclonal antibody. A number of high-affinity ligands were then synthesized and analyzed in solution with respect to their inhibition concentration values, water/octanol partitioning coefficients, and proteolytic stability. These and other unnatural polymers may provide new frameworks for drug development and for testing theories of protein and peptide folding and structure.

Amino Acid Sequence↗
PubMed1992

Dietary arginine requirement of young rainbow trout (Oncorhynchus mykiss).

1. Two growth trials were conducted with young rainbow trout (Oncorhynchus mykiss) to determine the dietary arginine requirement under conditions of rapid weight gain at 15 degrees C. 2. The growth requirement does not exceed 4.2 g arginine/16 g dietary nitrogen and, thus, is much lower than the value of 6.0 g arginine/16 g dietary nitrogen presently listed by the NRC for Chinook salmon and widely applied to all Salmonids. 3. Comparison of the present results with the arginine requirement of the chick reveals remarkable similarity despite the phylogenetic distance between the two species, and demonstrates the need to re-evaluate, as anomalously high, the presently-accepted value for Chinook salmon.

Animal Nutritional Physiological Phenomena↗
PubMed1992

Methionine intake in rainbow trout (Oncorhynchus mykiss), relationship to cataract formation and the metabolism of methionine.

Young rainbow trout were given diets containing graded levels of methionine for 16 wk. Analysis of the weight gain and food efficiency data showed the methionine requirement to be not more than 0.76% of the diet (1.9% of dietary protein). Activities of regulatory enzymes of the transulfuration pathway, methionine adenosyltransferase and cystathionine synthase in trout liver were not altered by changes in methionine intake. Concentrations of free serine in liver and plasma of the trout were high at low levels of methionine intake but fell as dietary methionine increased. This implied decreased flux through cystathionine synthase at low methionine intakes. Large increases in liver and plasma taurine occurred at high methionine intakes, implying enhanced transulfuration activity. Liver ornithine decarboxylase activity was reduced at the lowest level of dietary methionine used but the activity of S-adenosylmethionine decarboxylase was unchanged. Eye lenses of the trout given these diets were examined by a scanning lens monitor. Analysis of focal length variability with this equipment demonstrated that, if abnormality of the lens is to be avoided, a higher concentration of dietary methionine (0.96% or 0.6% methionine + 0.36% cystine) is needed than that required to maximize growth.

Amino Acids↗
PubMed1991

Dietary excesses of leucine influence growth and body composition of rainbow trout.

This study examined the hypothesis that a diet containing excess leucine may promote protein deposition in the body of rainbow trout. Diets were formulated with wheat germ meal and crystalline amino acids as major nitrogen sources. In Experiment 1, diets containing 1.1, 1.5, 2.2, 2.7, 3.5, 4.5, 6.0 and 6.5% leucine in wheat germ meal-crystalline amino acid diets were fed to fingerling rainbow trout. Diets containing up to 6.5% leucine did not inhibit weight gain or food intake. Body protein concentration tended to decrease as dietary leucine increased. In Experiment 2, fish were fed similar diets containing 3.3, 6.2, 9.2 and 13.4% leucine. After 10-11 wk of feeding, gross lesions including scoliosis, deformed opercula, scale deformities, scale loss, spongiosis of epidermal cells and scale regeneration were observed in 20% of the fish fed diets containing 13.4% leucine. High dietary leucine did not depress plasma valine or isoleucine concentrations. Therefore, the gross lesions could be attributed to a toxic effect of excess dietary leucine. Polyamine concentrations, which were used as a metabolic indicator for growth, were not significantly different in the tissues of fish receiving different treatments, thus supporting the hypothesis that increasing dietary leucine did not increase body protein deposition.

Amino Acids, Branched-Chain↗
PubMed1991

Escherichia coli aspartate carbamoyltransferase: the probing of crystal structure analysis via site-specific mutagenesis.

Crystal structures are known for aspartate carbamoyltransferase (ATCase) in the T and R states, with and without the allosteric activator adenosine triphosphate (ATP) or inhibitor cytidine triphosphate (CTP). Visual inspection of X-ray crystal structures does not provide all of the information necessary for the determination of structure--function relationships in protein molecules. This problem is compounded because the crystalline states of the molecule may introduce effects due to crystal packing, restricted flexibility and less than optimum enzymatic conditions. Therefore, alternative techniques are required to test mechanisms conjectured from three-dimensional crystal structures of proteins. The technique of site-specific mutagenesis allows the researcher to test structure--function models based on three-dimensional structures and to obtain further insight into characteristics of the enzyme. Site-specific mutagenesis has been used to probe residues believed to be critical in the structure and function of ATCase. Selection of residues to be mutated has depended extensively on three-dimensional crystal structures of the enzyme. To date, 48 site-specific mutations at 37 different amino acid sites have been published. Although a total of 118 mutants at 58 different sites has been communicated to our laboratory, only published mutants will be considered in this review. In this paper, we compile for the first time, review, and analyze the site-specific mutants of ATCase. Site-specific mutagenesis of proteins has become a powerful technique in modern-day molecular biology, especially in studying a molecule as large as aspartate carbamoyltransferase. In this review, the role of site-specific mutagenesis of ATCase is discussed and improvements in the analysis are suggested.

Amino Acid Sequence↗
PubMed1987

The distribution of zinc and copper in plasma, erythrocytes and erythrocyte membranes of rainbow trout (Salmo gairdneri).

1. The zinc and copper concentration of plasma was determined in rainbow trout, lake trout, walleye and whitefish. 2. These fish had mean plasma zinc concentrations ranging from 9.3 to 15.1 ppm and copper concentrations from 0.6 to 1.3 ppm. 3. In rainbow trout, the concentration of zinc and copper is greater in the erythrocyte membrane than in the total erythrocyte. 4. Ultrafilterable plasma zinc and copper concentration in rainbow trout was determined to be 0.03 and 0.019 ppm, respectively. 5. Dialysis of rainbow trout plasma against 20 mM EDTA results in removal of 99% of the zinc and 88% of the copper from plasma proteins.

Animals↗