Search PubMed⌕ Search

Biomedical subjects

D Kim

Publications and source records attributed to D Kim.

At least 343 records · Page 19Linked to original sources
PubMed1995

Different properties of the atrial G protein-gated K+ channels activated by extracellular ATP and adenosine.

Extracellular ATP (ATPo) and adenosine activate G protein-gated inwardly rectifying K+ currents in atrial cells. Earlier studies have suggested that the two agonists may use separate pathways to activate the K+ current. Therefore, we examined whether the K+ channels activated by the two agonists have different properties under identical ionic conditions. In cell-attached patches, K+ channels activated by 100 microM ATP in the pipette had a single-channel conductance and mean open time of 32.0 +/- 0.2 pS and 0.5 +/- 0.1 ms, respectively, compared with 31.3 +/- 0.3 pS and 0.9 +/- 0.1 ms for the K+ channels activated by adenosine (140 mM KCl). With ATPo as the agonist, the K+ channel activity in cell-attached patches was approximately threefold lower than that in inside-out patches with 100 microM GTP in the bath. Applying ATP to the cytoplasmic side of the membrane (ATPi) produced a biphasic concentration-dependent effect on channel activity: an increase at low [mean affinity constant (K0.5) = 190 microM] and a decrease at high (K0.5 = 1.3 mM) concentrations. In contrast, with adenosine as the agonist, K+ channel activity in cell-attached patches was approximately fourfold greater than that in inside-out patches with 100 microM GTP in the bath. In inside-out patches, ATPi only augmented the K+ channel activity (K0.5 = 32 microM). These results show that although both ATPo and adenosine activate kinetically similar K+ channels in atrial cells, the channels are regulated differently by intracellular nucleotides.

Adenosine↗
PubMed1995

Preoperative assessment of the carotid bifurcation. Can magnetic resonance angiography and duplex ultrasonography replace contrast arteriography?

BACKGROUND AND PURPOSE: Noninvasive studies are used with increasing frequency to assess the carotid bifurcation before endarterectomy. Therefore, assessment of their diagnostic accuracies is essential for appropriate patient management. We prospectively evaluate two noninvasive tests, magnetic resonance angiography (MRA) and duplex ultrasonography (DU), as potential replacements for contrast arteriography (CA). METHODS: A blinded comparison of three-dimensional time-of-flight (TOF) MRA, two-dimensional TOF MRA, and DU in 176 arteries was performed. CA was used as the standard of comparison. RESULTS: Three-dimensional TOF MRA had a sensitivity of 94%, a specificity of 85%, and an accuracy of 88% for the identification of 70% to 99% stenosis; two-dimensional TOF MRA had a sensitivity and specificity that were approximately 10% lower than those of three-dimensional TOF MRA. DU resulted in a sensitivity of 94%, a specificity of 83%, and an accuracy of 86%. Combining data from three-dimensional TOF MRA and DU, allowing for CA only for disparate results, yielded a sensitivity of 100%, a specificity of 91%, and an accuracy of 94% among concordant noninvasive tests, with CA required in 16% of arteries. MRA accurately differentiated 17 carotid occlusions from 16 high-grade (90% to 99%) stenoses, whereas with DU two patent arteries were identified as occluded and one occluded artery was identified as patent. CONCLUSIONS: Three-dimensional TOF MRA is the most accurate noninvasive test. Combined use of MRA and DU results in a marked increase in accuracy to a level that obviates the need for CA in a majority of patients.

Aged↗
PubMed1995

Life-sustaining treatment preferences of hemodialysis patients: implications for advance directives.

The purpose of this study was to describe the life-sustaining treatment preferences of dialysis patients and to compare the acceptability of two generic and a disease-specific advance directive (AD). Of 532 potentially eligible hemodialysis patients, 95 (17.9%) participated in the study. These patients completed two generic (the Centre for Bioethics Living Will and the Medical Directive) and one disease-specific (the Dialysis Living Will) AD in a randomized cross-over trial. Treatment preferences were measured by using the Centre for Bioethics Living Will. Acceptability of the AD was measured by using a 13-item advance directive acceptability questionnaire (ADAQ) for each AD, and the advance directive choice questionnaire (ADCQ) to elicit participants' preferred AD. Twenty-five percent of the participants wanted to continue dialysis in case of severe stroke, 19% in severe dementia, and 14% in permanent coma. Averaged across treatments, proportions of participants wanting treatment in various health states were: current health (86%), mild stroke (84%), moderate stroke (60%), severe stroke (21%), mild dementia (78%), moderate dementia (51%), severe dementia (14%), terminal illness (41%), and permanent coma (10%). Averaged across health states, proportions of participants wanting various types of treatment were: dialysis (58%), antibiotics (53%), transfusion (53%), surgery (48%), cardiopulmonary resuscitation (48%), respirator (47%), and tube feeding (41%). Mean ADAQ scores were: Dialysis Living Will, 71%; Centre for Bioethics Living Will, 70%; and Medical Directive, 60% (F = 8.27, P < 0.001 (repeat measures analysis of variance); the Dialysis Living Will and Centre for Bioethics Living Will scored significantly higher than the Medical Directive). The proportion of participants who said they would choose to complete each AD was: Dialysis Living Will, 28%; Centre for Bioethics Living Will, 38%; Medical Directive, 31%; and unsure, 3% (chi 2 = 1.465, df = 2, P = 0.48). In conclusion, twenty-five percent or less of hemodialysis patients want to continue dialysis in three specific health states: severe stroke, severe dementia, and permanent coma. Health states and illness severity, far more than treatment descriptions, influence preferences. Dialysis patients should be offered a generic AD, and some generic AD are more acceptable than others. Only a minority of dialysis patients will complete any AD, but the completion of written AD forms is only one element in the process of advance care planning.

Adolescent↗
PubMed1995

The incidence of drug resistant tuberculosis in 1279 Korean patients.

OBJECTIVES: In the past decade, the incidence of tuberculosis has been decreased in Korea and the nationwide survey of tuberculosis from 1965 through 1990 suggested a declining tendency of resistant organisms. But the prevalence rate of multidrug resistance of Mycobacterium tuberculosis is still a serious problem in Korea, and the aim of this study is to check the drug resistance pattern in the patients visiting University Hospital, the 3rd referral center. METHODS: We reviewed 1279 cases (522 female, 757 male, mean age 39.4 +/- 16.7) of bacteriologically proven tuberculosis seen during the period from 1986 to 1992 retrospectively. Of 1093 patients, who were indentified in previous medical history, 454 (41.5%) had a history of prior antituberculous chemotherapy. RESULTS: Resistance rate (resistant to 1 or more drugs) was 33.9%. Eleven percent of patients had resistance to a single drug (INH: 80.6%). Twenty two percent of patients had resistance to 2 or more drugs. Resistance rate is higher (47.4%) in the patients with a history of prior treatment than without a history (25.5%). CONCLUSIONS: These data suggest that the high rate of multidrug resistance in Korea did not show any decreasing tendency. So, mycobacterial culture and sensitivity tests should be recommended at initial treatment of tuberculosis and potent antituberculosis drugs are strongly recommended.

Adult↗
PubMed1995

KR-30450, a newly synthesized benzopyran derivative, activates the cardiac ATP-sensitive K+ channel.

KR-30450 (2-(2"(1",3"-dioxolone)-2-methyl-4-(2'-oxo-1'-pyrrollidinyl) -6- nitro-2H-1-benzopyren) is a newly synthesized benzopyran derivative. We examined the effect of KR-30450 on the action potential duration of isolated rat papillary muscle and on the ATP-sensitive K+ channel (KATP) activity in single rat ventricular myocytes with 3 M KCl-filled conventional microelectrode and patch clamp techniques. KR-30450 (10(-7) approximately 10(-5) M) reduced the action potential duration in a concentration-dependent manner and this was inhibited by 3 microM glibenclamide, suggesting that KATP was involved. In cell-attached patches, KR-30450 (10(-5) M) in the pipette activated the KATP which was closed by 3 microM glibenclamide. In inside-out patches, the effects of KR-30450 on KATP activity were examined before and after run-down of the channel. Before run-down, KR-30450 increased the KATP activity only in the presence of ATP and shifted the [ATP]i-KATP activity relationship to the right. After run-down, KR-30450 did not affect the KATP activity either in the presence or absence of 3 mM UDP, but increased the UDP-induced KATP activity in the presence of 1 mM ATP-gamma-S. From these results, we conclude that KR-30450 antagonizes the inhibitory effect of ATP on the KATP in a competitive manner. These effects of KR-30450 are similar to those of ER-001533 and HOE-234, but different from those of pinacidil and lemakalim.

Action Potentials↗
PubMed1994

Engineered tyrosine residues serve as the local probes to detect a kinetic intermediate in the folding of ribose-binding protein.

Ribose-binding protein (RBP) consists of two alpha/beta globular units; the N domain being composed of four helices (I, II, III and IX) and six sheets (A, B, C, D, E and K), and the C domain with five helices (IV, V, VI, VII and VIII) and six sheets (F, G, H, I, J and L). The two domains are connected by three strands. In the previous study, tyrosine residues in the RBP were substituted by phenylalanine to examine the fluorescence property of each chromophore. Since the three tyrosine residues are scattered in the two domains of RBP, residues 32 and 261 in the N domain and 115 in the C domain, we were able to monitor the state of protein folding using unaltered tyrosine as a local probe. The final structures of the mutant proteins show little differences from those of wild-type as judged by circular dichroism spectra. The equilibrium and kinetic folding behaviors of the mutant RBPs were examined by fluorescence spectroscopy. The equilibrium data obtained from the mutant RBPs conform to the two-state transition involving the native and unfolded species. However, kinetic studies indicate that there exists an intermediate formed transiently during the folding or unfolding process, which was not detected in equilibrium experiments. In unfolding kinetics of the mutant protein retaining only the N domain tyrosine residues, a striking change in fluorescence was observed as an initial jump, suggesting the presence of a partial unfolding step of RBP around the Tyr32 chromophore, since the fluorescence of Tyr261 does not change upon folding. This occurred immediately after mixing with 0.6 to 1 M range of guanidine hydrochloride and was completed in less than three seconds of the mixing dead time. The partial increase of fluorescence appears to be due to the dissociation of a quenching group, the carboxyl side-chain of Asp249 located on helix IX, from the Tyr32 fluorophore. The successive unfolding process reflects a process of release from the second quenching group at Asp2 on the sheet A. The substitution at Tyr261 on sheet K by phenylalanine reveals an additional kinetic phase in refolding, in which the folding from unfolded into an intermediate form seems similar to wild-type in time scale, whereas the next step leading to the formation of native protein becomes slower.(ABSTRACT TRUNCATED AT 400 WORDS)

Carrier Proteins↗
PubMed1994

Endoluminal stenting of a subclavian artery stenosis to treat ischemia in the distribution of a patent left internal mammary graft.

Subclavian artery stenosis is a rare cause of recurrent myocardial ischemia in patients who have undergone left internal mammary-coronary artery bypass grafting. A patient with this syndrome was successfully treated by placement of Palmaz biliary stents in the left subclavian artery. Angiographic and hemodynamic evidence of restricted subclavian flow resolved following stenting, as did the patient's unstable angina syndrome. Endoluminal stenting of the proximal subclavian artery for the treatment of coronary-subclavian steal can be performed safely and provides an alternative to other forms of surgical or percutaneous (PTCA, directional atherectomy) revascularization for treatment of this disorder.

Aged↗
PubMed1994

Microcirculatory dynamics of neuropeptide Y.

We used the hamster cheek pouch microcirculation to investigate by intravital microscopy the effects of neuropeptide Y (NPY) on arteriolar diameter, leukocyte adhesion to microvascular endothelium, and postcapillary venular permeability. We applied NPY topically for 3 min at concentrations of 10(-7), 10(-9), and 10(-11) M. We quantified arteriolar diameter and permeability changes by digital image analysis. We used the mass of fluorescein isothiocyanate-Dextran 150 accumulated around postcapillary venules (10-30 microns) to calculate extravasation rates of macromolecules. We also measured the number of adhering white cells per 100-microns length of postcapillary venules using acridine orange to label white blood cells. At the applied doses, NPY did not alter either microvascular permeability to macromolecules or leukocyte adhesion to microvascular walls. NPY, in a dose-dependent manner, constricted arterioles ranging in control diameter from 10 to 60 microns. Vasoconstriction was strongest in arterioles ranging in diameter from 30 to 39 microns at a concentration of NPY of 10(-7) M. The Y1-type NPY receptor agonist, Leu31, Pro34-NPY, was as potent as NPY, whereas the carboxy-terminal fragment NPY 13-36 had no activity, indicating that the hamster cheek pouch microvasculature expresses the Y1 type of NPY receptor. We also blocked alpha-adrenergic receptors to test whether norepinephrine is required for NPY-induced vasoconstriction. This blockade did not inhibit the vasoconstriction caused by exogenous NPY. Our results demonstrate that (1) NPY modulates microvascular hemodynamics by changes in arteriolar diameter, (2) the NPY receptor on the hamster cheek pouch microvasculature is of the Y1 type, and (3) exogenous NPY-induced vasoconstriction is independent of the activity of endogenous norepinephrine.

Animals↗
PubMed1994

Relationships of Na+ and K+ concentrations to GRP, CGRP, and calcitonin immunoreactivities and Na+,K(+)-ATPase (NKA) inhibitory activity in human breast cyst fluid.

BACKGROUND: Although the etiology of gross cystic disease of the breast is unknown, elevated cyst concentrations of potassium (K+) (> 60 mM/L) may be related to symptoms. The purpose of this study was to clarify the mechanism(s) of K+ accumulation in breast cysts. METHODS: We assayed cyst fluids for factors known to exert effects on K+ transport, namely, endogenous digitalis-like inhibitors of Na+,K(+)-ATPase (NKA) and the neuropeptides gastrin-releasing peptide (GRP), calcitonin (CT), and calcitonin gene-related peptide (CGRP). RESULTS: Cyst fluid K+ was directly correlated with cyst volume, cyst NKA inhibitory activity (in ouabain equivalents), and cyst concentrations of calcitonin, GRP, and CGRP. Cyst fluid Na+ was inversely correlated with cyst fluid K+, cyst NKA inhibitory activity, cyst volume, and cyst fluid concentrations of calcitonin, GRP, and CGRP. NKA inhibitory activity correlated directly with GRP and CGRP. Immunocytochemistry localized GRP to breast cyst lining cells and areas of ductal and lobular epithelial hyperplasia in biopsies of 15 of 15 cysts and in 5 of 5 breast carcinomas, but not in (0 of 5) normal breast biopsies. Specificity of GRP staining was demonstrated by total abolition of reactivity after adsorption with synthetic GRP, but not after adsorption with synthetic substance P, neurokinin A, or neurokinin B. CONCLUSIONS: We conclude that both the concentrations of endogenous digitalis-like factors and the neuropeptides calcitonin, GRP, and CGRP in human breast cyst fluids are related to the concentrations of K+ and Na+ in breast cysts and to cyst volume.

Adult↗
PubMed1994

A new process for the production of clinical dextran by mixed-culture fermentation of Lipomyces starkeyi and Leuconostoc mesenteroides.

A mixed-culture fermentation system was designed for the production of size-limited dextrans. This process was simpler and more economical than traditional methods. It required the establishment of microbial consortia of Lipomyces starkeyi ATCC 74054 and Leuconostoc mesenteroides ATCC 10830. Controlling initial conditions, growth, and enzyme production by both organisms controlled the product size. In this process, both strains were grown separately and then mixed. Dextran fermentation was then allowed to proceed. At the desired time (and molecular size), the fermentation was harvested. The optimum pH and temperature for production of clinical dextran (75,000 MW) were 5.2 (+/- 0.1) and 28 (+/- 0.5) degrees C, respectively. Varying the ratio of L. mesenteroides to L. starkeyi in the inoculum did not significantly affect either the final cell ratios or dextran production.

Biotechnology↗
PubMed1994

Production and selection of mutants of Leuconostoc mesenteroides constitutive for glucansucrases.

After chemical mutagenesis using ethyl methane sulfonate, we isolated mutants constitutive for glucansucrases from Leuconostoc mesenteroides NRRL B-512FM, B-1142, and B-1355. Those mutants produced glucansucrases when grown on D-glucose as well as on sucrose. They produced higher glucansucrase activities (3 to 22 times) when grown on D-glucose than the parent strains grown on sucrose. Glucansucrases from mutants B-1355C and B-1142C grown on glucose formed glucans that were highly resistant to Penicillium dextranase hydrolysis. Mutant B-512FMC dextransucrase formed the same kind of dextran as the parent strain; however, it showed higher thermal stability, even when dextran was absent.

Biotechnology↗
PubMed1994

Properties of Leuconostoc mesenteroides B-512FMC constitutive dextransucrase.

Leuconostoc mesenteroides B-512FMC, a constitutive mutant for dextransucrase, was grown on glucose, fructose, or sucrose. The amount of cell-associated dextransucrase was about the same for the three sugars at different concentrations (0.6% and 3%). Enzyme produced in glucose medium was adsorbed on Sephadex G-100 and G-200, but much less enzyme was adsorbed when it was produced in sucrose medium. Sephadex adsorption decreased when the glucose-produced enzyme was preincubated with dextrans of molecular size greater than 10 kDa. The release of dextransucrase activity from Sephadex by buffer (20 mM acetate, pH 5.2) was the highest at 28 degrees-30 degrees C. The addition of dextran to the enzyme stimulated dextran synthesis but had very little effect on the temperature or pH stability. Dextransucrase purified by ammonium sulfate precipitation, hydroxyapatite chromatography, and Sephadex G-200 adsorption did not contain any carbohydrate, and it synthesized dextran, showing that primers are not necessary to initiate dextran synthesis. The purified enzyme had a molecular size of 184 kDa on SDS-PAGE. On standing at 4 degrees C for 30 days, the native enzyme was dissociated into three inactive proteins of 65, 62, and 57 kDa. However, two protein bands of 63 and 59 kDa were obtained on SDS-PAGE after heat denaturation of the 184-kDa active enzyme at 100 degrees C. The amount of 63-kDa protein was about twice that of 59-kDa protein. The native enzyme is believed to be a trimer of two 63-kDa and one 59-kDa monomers.

Biotechnology↗
PubMed1994

Characterization of an inhibitor of nitric oxide synthase in human-hand veins.

The enzyme nitric oxide synthase mediates synthesis of nitric oxide (NO) from 1-arginine in endothelial cells. NO, also known as endothelium-dependent relaxing factor (EDRF), diffuses to smooth muscle cells where it leads to cGMP production and dilation. We characterized the potency, efficacy and time course of NG-monomethyl-l-arginine (l-NMMA) as an inhibitor of bradykinin-mediated, endothelium-dependent dilation using the human hand-vein compliance technique. We also compared the efficacy of l-NMMA with methylene blue, an inhibitor of guanylate cyclase, in blocking bradykinin-mediated vasodilation. l-NMMA potently inhibited bradykinin-induced venodilation with a log ED50 of 3.74 +/- 0.52 (geometric mean of 5.5 micrograms/min). Responses to bradykinin (0.27-555 ng/min) were tested in veins pre-constricted with the alpha-adrenergic agonist phenylephrine. l-NMMA (25 micrograms/min) decreased bradykinin's maximal venodilatory response from 90 +/- 22% to 39 +/- 15% (p < 0.05). Complete recovery of bradykinin venodilation was obtained within 155 minutes after stopping l-NMMA infusion, indicating that its effects were reversible. In another set of experiments we compared the efficacy of methylene blue to l-NMMA; methylene blue decreased bradykinin-mediated venodilatory response to 53 +/- 17%; when l-NMMA was added, the response was further decreased to 32 +/- 9% (p < 0.002). We conclude that l-NMMA is a very efficacious NO synthase inhibitor in human veins and it is likely functionally reversible.

Adult↗