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Biomedical subjects

C Kim

Publications and source records attributed to C Kim.

At least 73 records · Page 4Linked to original sources

Medical therapy or coronary artery bypass graft surgery for chronic stable angina: an update using decision analysis.

PURPOSE: Randomized trials comparing medical and surgical therapies for the treatment of chronic stable angina were completed in the early 1980s. Therapies developed since then have decreased mortality and myocardial infarction rates from coronary artery disease. Using decision analysis and incorporating current recommendations for treatment, we simulated a trial comparing coronary artery bypass graft surgery and medical therapy. METHODS: A Markov decision analysis model was constructed to compare the 5-year and 10-year outcomes of a simulated trial of medical therapy versus bypass surgery for stable chronic angina. Baseline data were obtained from a meta-analysis of trials comparing the two treatments. Data on risk reduction from contemporary therapies were obtained from randomized trials and meta-analyses. RESULTS: All subgroups experienced modest gains in survival with current therapies. At 5 years, the survival rate was 90% in the medical group (an absolute gain of 6%) and 94% in the surgical group (an absolute gain of 4%). Similar results were obtained for patients with triple-vessel disease. Among patients with a low ejection fraction, the 5-year survival rate was 85% for medical patients and 92% for surgical patients. Sensitivity analyses did not substantially affect the conclusions. CONCLUSION: Advances in the treatment of chronic stable angina have improved the outcome both for patients treated initially with surgery and for those treated initially with medical therapy. The improvements were of similar magnitude in both groups, so the fundamental conclusions of the bypass trials are unchanged.

Adult↗

Effect of cataract extraction on blue-on-yellow visual field.

PURPOSE: It is assumed that cataract can influence the results of blue-on-yellow perimetry. However, actual sensitivity change in blue-on-yellow perimetry before and after cataract surgery has not been fully demonstrated. METHODS: Prospective. SETTING: Institutional. STUDY POPULATION: Twenty-two eyes of 22 consecutive patients without ocular pathology, other than cataract, known to influence visual field undergoing cataract surgery. OBSERVATION PROCEDURES: Both white-on-white (W-W) and blue-on-yellow (B-Y) perimetries. MAIN OUTCOME MEASURES: Global indexes including mean deviation and other pertinent data of white-on-white and blue-on-yellow perimetries were compared before and after cataract surgery. RESULTS: Mean deviation was improved after cataract surgery in both white-on-white perimetry (from -6.88 dB to -3.36 dB, P <.0001) and blue-on-yellow perimetry (from -12.22 dB to -3.64 dB, P <.0001, paired t test). However, the mean difference between preoperative and postoperative mean deviation in blue-on-yellow perimetry (8.58 +/- 3.96 dB) was significantly higher than that of white-on-white perimetry (3.52 +/- 2.69 dB; P <.0001, unpaired t test). That is, the change in mean deviation was greater in blue-on-yellow perimetry than in white-on-white perimetry by a factor of 2.4 times. CONCLUSION: Cataract causes predominantly a general reduction of sensitivity in both blue-on-yellow and white-on-white perimetries, and the general reduction of blue-on-yellow sensitivity is far greater than that of white-on-white sensitivity.

Adult↗

Transscleral suture fixation of posterior chamber lenses combined with trabeculectomy.

OBJECTIVE: To evaluate the outcome of transscleral suture-fixated posterior chamber intraocular lens (PCIOL) implantation in glaucoma patients when combined with a trabeculectomy. DESIGN: A retrospective study of 56 consecutive glaucoma patients with a minimum follow-up of 6 months after transscleral suture-fixated PCIOL implantation combined with trabeculectomy. SETTING: Patients were drawn from the clinical glaucoma practice of the Kresge Eye Institute, Detroit, MICHIGAN: PATIENTS: Fifty-six eyes of 56 consecutive chronic glaucoma patients who had undergone transscleral suture-fixated PCIOL implantation in combination with a trabeculectomy were included in the analysis. RESULTS: The mean follow-up time was 38.5 +/- 19.1 months. Mean intraocular pressure (IOP) was significantly reduced, from 22.9 +/- 10.9 mmHg before surgery to 16.7 +/- 6.7 mmHg at the last follow-up visit (P = 0.0005), with the mean number of medications used also significantly decreased, from 2.3 +/- 0.9 to 1.9 +/- 0.9 (P = 0.0002). Postoperative IOP control to 21 mmHg or less was achieved or maintained in 84% of patients. Visual acuity improved or remained stable within two Snellen lines of the preoperative level in 39 eyes (70%) and within three Snellen lines in 45 eyes (80%) at the last follow-up visit. Overall, 46% to 68% of the patients had both stable visual acuity and satisfactory pressure control at the last postoperative visit, depending on criteria of varying stringency. However, 19 eyes (34%) required one or more additional surgical interventions for pressure control. Patients with anterior chamber intraocular lens (ACIOL) complications, diabetes mellitus, or a preoperative IOP level of more than 21 mmHg on maximum tolerated medications were especially prone to requiring additional surgical interventions. CONCLUSIONS: We conclude that transscleral suture-fixated PCIOL implantation can be combined successfully with a trabeculectomy and can be useful in glaucoma patients in need of both visual rehabilitation and IOP control. However, patients with ACIOL complications, diabetes, or preoperative IOP of more than 21 mmHg on maximum tolerated medications were prone to requiring additional surgical interventions.

Aged↗

Effect of ginsenosides on voltage-dependent Ca(2+) channel subtypes in bovine chromaffin cells.

In previous reports we have shown that ginsenosides inhibit high threshold voltage-dependent Ca(2+) channels in neuronal cells. However, these studies did not show whether ginsenosides-induced inhibition of Ca(2+) currents discriminates among the various Ca(2+) channel subtypes, although it is known that there are at least five different Ca(2+) channel subtypes in neuronal cells. In this study we investigated the effect of ginsenosides on high threshold voltage-dependent Ca(2+) channel subtypes using their selective Ca(2+) channel blockers nimodipine (L-type), omega-conotoxin GVIA (N-type), or omega-agatoxin IVA (P-type) in bovine chromaffin cells. We could observe that ginsenosides inhibited high threshold voltage-dependent Ca(2+) currents in a dose-dependent manner. The IC(50) was about 120 microgram/ml. Nimodipine had no effect on ginsenosides response. However, the effect of ginsenosides on Ca(2+) currents was reduced by omega-conotoxin GVIA, omega-agatoxin IVA, and mixture of nimodipine, omega-conotoxin GVIA, and omega-agatoxin IVA. These data suggest that ginsenosides are negatively coupled to three types of calcium channels in bovine chromaffin cell, including an omega-conotoxin GVIA-sensitive (N-type) channel, an omega-agatoxin IVA-sensitive (P-type) channel and nimodipine/omega-conotoxin GVIA/omega-agatoxin VIA-resistant (presumptive Q-type) channel. Thus, the selective regulation of voltage-dependent Ca(2+) subtypes by ginsenosides in bovine chromaffin cell could be the cellular basis of antistress effects induced by ginseng.

Animals↗

The transcriptional regulator Yin Yang 1 activates the myelin PLP gene.

Inauguration of the myelin program in developing oligodendrocytes requires the activation of those genes that encode the myelin proteins and the enzymes responsible for the synthesis and degradation of myelin lipids. An activator of the most abundantly expressed myelin protein, proteolipid protein (PLP), has been identified in a yeast one-hybrid system. The ubiquitously expressed zinc finger protein Yin Yang 1 (YY1) recognizes the myelin PLP promoter in vitro and in vivo. When overexpressed in an oligodendrocyte cell line, YY1 enhances transcription of the PLP promoter. A truncated version of YY1 that includes only the four zinc finger domains has little effect. The binding site for YY1 in the PLP promoter (site 3) fits the YY1 consensus site and DNA-protein complexes containing site 3 can be supershifted with an antibody directed against YY1 protein. Moreover, oligonucleotides with a mutated version of the PLP promoter site 3 are unable to bind to nuclear proteins or to compete for binding in a gel shift system. Finally, mutation of this site greatly reduces the activity of a 1-kb PLP promoter region in transfected glial cells. Our results suggest that PLP is a target gene for the transcriptional regulator YY1. This versatile transcription factor and nuclear matrix protein may boost transcription of the PLP gene to meet the demands of actively myelinating oligodendrocytes.

Animals↗

Inhibition effect of new farnesol derivatives on all-trans-retinoic acid metabolism.

All-trans-retinoic acid (atRA) is a promising anticancer and antiwrinkle drug. However, its clinical application is limited because it is rapidly metabolized by the induced cytochrome P450 (P450). In this study, farnesol derivatives are proposed as new inhibitors to prevent P450-mediated metabolism. The farnesol derivatives were suc-farnesol and mal-farnesol, which were synthesized by the chemical conjugation of farnesol with succinic anhydride and maleic anhydride, respectively. The inhibition effects of farnesol, farnesoic acid, and farnesol derivatives on the atRA metabolism were evaluated in microsome and in AMC-HN-6 cells. In the microsome experiment, suc-farnesol and mal-farnesol strongly inhibited atRA metabolism at 10(minus;4) mol/L concentration by as much as 61% and 77%, respectively. In the cell experiment, the inhibition effects of farnesol derivatives on the atRA metabolism showed similar tendency as the results in the microsome experiment, even if the effect was somewhat decreased. Effects of farnesoic acid and farnesol, however, were not significant. This research suggests that carboxylic end groups, such as atRA and hydrophobicity, might be important factors causing the higher inhibition effect, and that derivatization of farnesol can be 1 method to develop new inhibitors of atRA metabolism.

Antimetabolites↗

Unstable angina in the myocardial infarction triage and intervention registry (MITI): short- and long-term outcomes in men and women.

BACKGROUND: Studies of unstable angina have focused on hospital mortality; long-term mortality studies have been limited by small numbers of patients or health care providers. The objectives of this study were to determine whether men and women with unstable angina had different presentations, mortality rates, and procedure utilization. METHODS: We analyzed a prospective observational registry of 4305 men (60%) and 2847 women (40%) with unstable angina who were admitted to coronary care units in King County, Washington, between 1988 and 1994. We compared the rates of symptoms, survival, and procedure utilization between sexes after adjustment for age, race, insurance status, and medical history. RESULTS: Women were older and had higher rates of hypertension and congestive heart failure than men but had lower rates of cigarette smoking, previous myocardial infarction, and previous procedure use (P <.0001). Women had significantly higher rates of dyspnea, nausea, and epigastric pain and less diaphoresis than men did (P <.0001). Women underwent fewer procedures, but after adjustment for age and medical history this difference was no longer significant except for coronary bypass grafting (odds ratio 0.50, 95% confidence interval [CI] 0.37-0.69); after index hospitalization, men and women underwent procedures at similar rates. Although women had higher rehospitalization rates than men, early mortality (odds ratio 0.89, 95% CI 0.55-1.4) and late mortality (hazard ratio 0.98, 95% CI 0.95-1.0) were similar between men and women after adjustment for age. CONCLUSIONS: Women and men with unstable angina have different risk factors and symptoms upon presentation but have similar procedure use and mortality rates.

Aged↗

Pharmacologic stress testing for coronary disease diagnosis: A meta-analysis.

BACKGROUND: Although noninvasive pharmacologic stress tests are widely used, their relative performance is not clear. We compared the performance of pharmacologic stress tests combined with echocardiography or nuclear imaging for the diagnosis of coronary disease. METHODS: We performed a regression meta-analysis of published data. We included studies published between January 1975 and June 1999 in which subjects underwent echocardiographic or single-photon emission computed tomography (SPECT) stress testing with adenosine, dipyridamole, or dobutamine for diagnosis of coronary artery disease. All subjects also underwent coronary angiography. Two independent reviewers abstracted population characteristics, technical factors, methodologic factors, and results and calculated test sensitivity and specificity. RESULTS: Eighty-two studies met the inclusion criteria. The sensitivity of dipyridamole SPECT imaging, 89% (95% CI, 84%-93%), was higher than that of dipyridamole echocardiography, but the specificity of dipyridamole SPECT imaging, 65% (95% CI, 54%-74%), was lower than that of dipyridamole echocardiography. Dipyridamole and adenosine tests had similar sensitivities and specificities. The sensitivity of dobutamine echocardiography, 80% (95% CI, 77%-83%) was similar to that of dobutamine SPECT imaging, but dobutamine echocardiography had a higher specificity, 84% (95% CI, 80%-86%) than dobutamine SPECT imaging did. CONCLUSIONS: The findings of our study can be used to guide the selection of the optimal pharmacologic stress test for each patient. Maximum sensitivity can be attained by use of a vasodilator combined with SPECT imaging. Maximum specificity can be attained by use of a vasodilator with echocardiography. The highest combination of sensitivity and specificity can be attained with dobutamine echocardiography.

Adenosine↗

Cadmium in caribou (Rangifer tarandus) kidneys: speciation, effects of preparation and toxicokinetics.

Caribou kidney is a major source of cadmium (Cd) in the traditional diets of many aboriginal communities in the Arctic. In order to characterize the risk of Cd exposure, we studied the speciation of Cd in caribou kidneys and how, it can be affected by food preparation. Cd in caribou kidneys was bound to metallothionein (MT) (40%) high molecular weight proteins (50-500 kDa) (30%) and existed as free ions (10%). There was no change in Cd concentrations after the samples were baked at 350 degrees C for 30 min but the MT level was significantly decreased. Food preparation also denatured the high molecular weight proteins, resulting in a significant increase of free Cd. The toxicokinetics of Cd in caribou kidney was studied using a rodent model. Four groups (n = 6) of adult Sprague-Dawley rats were fed with rat chow with the addition of one of the following: 10% veal kidney with 0 microg/g Cd, 10% veal kidney spiked with CdCl2 to make up to 66 microg Cd; 10% caribou kidney containing 20 microg/g Cd and 10% caribou kidney containing 66 microg/g Cd. After 14 days, Cd accumulation increased with dose but less than 1% of the dosed Cd accumulated in the liver and kidney of rats. The percentage of Cd accumulated in the liver was higher in the group fed with caribou kidney than that dosed with spiked veal kidney. Our results suggest that caribou kidney is a major source of Cd exposure among the Arctic populations but moderate consumption may be considered unavoidable.

Absorption↗

Setting a local research agenda for women's health: The National Centers of Excellence in Women's Health.

Although women's health research expanded greatly in the past 10 years, significant gaps in knowledge remain. Prioritization and promotion of research will help assure continuing progress in closing such gaps and improving the health of women. Although a comprehensive agenda for the new millennium has been developed at the national level, the process for establishing a local research agenda is not well defined. The purpose of this study was to describe criteria for and barriers to establishing a local research agenda in women's health. A secondary aim was to describe mechanisms for identifying women's health researchers and for facilitating multidisciplinary research. Directors of Research at National Centers of Excellence in Women's Health (CoEs) (n = 18) were surveyed by mail for this information. The results indicate that the local research agenda should emphasize health issues that are prevalent in women, research that is likely to establish treatment, psychosocial/cultural factors, and quality of life issues. The process of setting a research agenda should include input from the communities served as well as from scientists. Critical evaluation of scientific strengths and weaknesses is an essential preliminary step in prioritizing research opportunities in order to implement and evaluate a research agenda in women's health.

Academic Medical Centers↗

Topical verapamil in glaucoma filtration surgery.

PURPOSE: Because of the reported antifibroblastic effect of verapamil, a calcium-channel blocker, we investigated the potential benefit of adjunctive topical verapamil in patients undergoing glaucoma filtration surgery. METHODS: This prospective, double-masked, randomized study included 56 eyes of 56 consecutive patients with chronic open-angle glaucoma undergoing trabeculectomy (primary or surgical revision of failed trabeculectomy), trabeculectomy combined with cataract surgery, or Molteno drainage device implantation. Postoperatively, the treated eyes received verapamil (0.25%) or one drop of placebo four times a day for 1 month in addition to 1% prednisolone four times a day and corticosteroid-antibiotic ophthalmic ointment at bedtime. RESULTS: There were no significant differences in preoperative mean intraocular pressure, mean number of medications, and glaucoma severity between the verapamil and placebo groups. There were also no significant differences between the two groups in filtration success rate, mean intraocular pressure, and mean number of medications on postoperative days 1, 4, or 7 and at postoperative months 1, 2, 3, 4, 5, and 6 (P > 0.05). CONCLUSION: There was no significant benefit of adjunctive topical verapamil when it was used after trabeculectomy, trabeculectomy combined with cataract surgery, or Molteno drainage device implantation.

Administration, Topical↗

Chemokine regulation of hematopoiesis and the involvement of pertussis toxin-sensitive G alpha i proteins.

Chemokines have been implicated in regulation of various aspects of hematopoiesis, including negative regulation of the proliferation of immature subsets of myeloid progenitor cells (MPCs), chemotaxis of MPCs, and survival enhancement of MPCs after delayed growth factor addition. Since chemokine receptors are seven-transmembrane-spanning G-protein-linked receptors and the chemotactic effect in vitro of the CXC chemokine SDF-1 is pertussis toxin (PT)-sensitive, implying the involvement of G alpha i proteins as mediators of SDF-1-induced chemotaxis, we evaluated the effects of PT on other chemokine actions influencing MPCs. While the in vitro survival-enhancing effects of SDF-1 on GM-CSF and steel factor-dependent mouse bone marrow granulocyte macrophage progenitors (CFU-GM) were pertussis toxin-sensitive, the suppressive effects of the CC chemokine MIP-1 alpha and the CXC chemokine IL-8 on colony formation by GM-CSF and steel factor-sensitive CFU-GM were insensitive to pertussis toxin. These results suggest that not all chemokine-mediated effects on MPCs are necessarily mediated through pertussis toxin-sensitive G alpha i proteins.

Animals↗

Oxidation of phenolate siderophores by the multicopper oxidase encoded by the Escherichia coli yacK gene.

A gene (yacK) encoding a putative multicopper oxidase (MCO) was cloned from Escherichia coli, and the expressed enzyme was demonstrated to exhibit phenoloxidase and ferroxidase activities. The purified protein contained six copper atoms per polypeptide chain and displayed optical and electron paramagnetic resonance (EPR) spectra consistent with the presence of type 1, type 2, and type 3 copper centers. The strong optical A(610) (E(610) = 10,890 M(-1) cm(-1)) and copper stoichiometry were taken as evidence that, similar to ceruloplasmin, the enzyme likely contains multiple type 1 copper centers. The addition of copper led to immediate and reversible changes in the optical and EPR spectra of the protein, as well as decreased thermal stability of the enzyme. Copper addition also stimulated both the phenoloxidase and ferroxidase activities of the enzyme, but the other metals tested had no effect. In the presence of added copper, the enzyme displayed significant activity against two of the phenolate siderophores utilized by E. coli for iron uptake, 2,3-dihydroxybenzoate and enterobactin, as well as 3-hydroxyanthranilate, an iron siderophore utilized by Saccharomyces cerevisiae. Oxidation of enterobactin produced a colored precipitate suggestive of the polymerization reactions that characterize microbial melanization processes. As oxidation should render the phenolate siderophores incapable of binding iron, yacK MCO activity could influence levels of free iron in the periplasm in response to copper concentration. This mechanism may explain, in part, how yacK MCO moderates the sensitivity of E. coli to copper.

Amino Acid Sequence↗

Key role for sulfur in peptide metabolism and in regulation of three hydrogenases in the hyperthermophilic archaeon Pyrococcus furiosus.

The hyperthermophilic archaeon Pyrococcus furiosus grows optimally at 100 degrees C by the fermentation of peptides and carbohydrates. Growth of the organism was examined in media containing either maltose, peptides (hydrolyzed casein), or both as the carbon source(s), each with and without elemental sulfur (S(0)). Growth rates were highest on media containing peptides and S(0), with or without maltose. Growth did not occur on the peptide medium without S(0). S(0) had no effect on growth rates in the maltose medium in the absence of peptides. Phenylacetate production rates (from phenylalanine fermentation) from cells grown in the peptide medium containing S(0) with or without maltose were the same, suggesting that S(0) is required for peptide utilization. The activities of 14 of 21 enzymes involved in or related to the fermentation pathways of P. furiosus were shown to be regulated under the five different growth conditions studied. The presence of S(0) in the growth media resulted in decreases in specific activities of two cytoplasmic hydrogenases (I and II) and of a membrane-bound hydrogenase, each by an order of magnitude. The primary S(0)-reducing enzyme in this organism and the mechanism of the S(0) dependence of peptide metabolism are not known. This study provides the first evidence for a highly regulated fermentation-based metabolism in P. furiosus and a significant regulatory role for elemental sulfur or its metabolites.

Culture Media↗

Evaluation of pulsed-field gel electrophoresis in epidemiological investigations of meningococcal disease outbreaks caused by Neisseria meningitidis serogroup C.

Since 1990, the frequency of Neisseria meningitidis serogroup C (NMSC) outbreaks in the United States has increased. Based on multilocus enzyme electrophoresis (MEE), the current molecular subtyping standard, most of the NMSC outbreaks have been caused by isolates of several closely related electrophoretic types (ETs) within the ET-37 complex. We chose 66 isolates from four well-described NMSC outbreaks that occurred in the United States from 1993 to 1995 to evaluate the potential of pulsed-field gel electrophoresis (PFGE) to identify outbreak-related isolates specific for each of the four outbreaks and to differentiate between them and 50 sporadic isolates collected during the outbreak investigations or through active laboratory-based surveillance from 1989 to 1996. We tested all isolates collected during the outbreak investigations by four other molecular subtyping methods: MEE, ribotyping (ClaI), random amplified polymorphic DNA assay (two primers), and serotyping and serosubtyping. Among the 116 isolates, we observed 11 clusters of 39 NheI PFGE patterns. Excellent correlation between the PFGE and the epidemiological data was observed, with an overall sensitivity of 85% and specificity of 71% at the 95% pattern relatedness breakpoint using either 1.5 or 1.0% tolerance. For all four analyzed outbreaks, PFGE would have given public health officials additional support in declaring an outbreak and making appropriate public health decisions.

Arizona↗

Modulation of Chelidonii herba on GABA activated chloride current in rat PAG neurons.

Modulation of Chelidonii herba on gamma-aminobutyric acid (GABA) activated chloride current in the acutely dissociated periaqueductal gray (PAG) neuron was studied by nystatin-perforated patch-clamp technique. High concentrations of Chelidonii herba elicited ion current, that was blocked by bicuculline. Low concentrations reduced the GABA activated current in PAG. Two types of inhibitory action of Chelidonii herba on GABA activated current have been implicated in PAG. One is the inhibitory action of Chelidonii herba on GABA was abolished by naltrexone and the other is that of Chelidonii herba was potentiated by naltrexone. In addition, all of two types of action of Chelidonii herba are linked to pertussis toxin-sensitive GTP-binding proteins. These results suggest that the inhibitory modulation of Chelidonii herba on GABA activated current via G-proteins in PAG neuron is an important analgesic mechanism.

Animals↗

Mechanism of cooperative effects of rhinovirus and atopic sensitization on airway responsiveness.

To elucidate the mechanistic interplay between rhinovirus (RV) exposure and atopic sensitization in regulating airway smooth muscle (ASM) responsiveness, isolated rabbit ASM tissue and cultured human ASM cells were passively sensitized with sera from atopic asthmatic or nonatopic nonasthmatic (control) subjects in the absence and presence of inoculation with RV serotype 16. Relative to control subjects, atopic asthmatic serum-sensitized and RV-inoculated ASM exhibited significantly increased contractility to acetylcholine, impaired relaxation to isoproterenol, and enhanced release of the proinflammatory cytokine interleukin-1beta. These effects were potentiated in atopic asthmatic serum-sensitized ASM concomitantly inoculated with RV and inhibited by pretreating the tissues with monoclonal blocking antibodies against intercellular adhesion molecule (ICAM)-1 (CD54), the host receptor for RV serotype 16, or lymphocyte function-associated antigen (LFA)-1 (CD11a/CD18), the endogenous counterreceptor for ICAM-1. Moreover, RV inoculation was found to potentiate the induction of mRNA and surface protein expression of FcepsilonRII (CD23), the low-affinity receptor for IgE, in atopic asthmatic serum-sensitized ASM. Collectively, these observations provide new evidence demonstrating that 1) RV exposure and atopic sensitization act cooperatively to potentiate induction of proasthmatic changes in ASM responsiveness in association with upregulated proinflammatory cytokine release and FcepsilonRII expression and 2) the effects of RV exposure and atopic sensitization are mediated by cooperative ICAM-1-coupled LFA-1 signaling in the ASM itself.

Acetylcholine↗