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D Kim

Publications and source records attributed to D Kim.

At least 469 records · Page 26Linked to original sources
PubMed1988

Cellular mechanisms underlying calcium-proton interactions in cultured chick ventricular cells.

1. Cytosolic free Ca2+ concentration ([Ca2+]i) in cardiac muscle cells is influenced by many factors including intracellular pH. Intracellular alkalinization has been shown to reduce, whereas acidification has been shown to augment [Ca2+]i. We examined the cellular mechanisms underlying Ca2+-H+ interactions using cultured chick embryo ventricular cells. 2. Cells were loaded with fura-2 or BCECF (2,7-biscarboxyethyl-5(6)-carboxy-fluorescein) and changes in time-averaged [Ca2+]i or pHi were monitored continuously using a dual-wavelength spectrofluorometer. 3. Exposure of cells to 20 mM-NH4Cl (intracellular alkalinization) produced a rapid decrease in [Ca2+]i; subsequent wash-out of NH4Cl (intracellular acidification) resulted in an increase in [Ca2+]i to levels above control. Intracellular acidification produced by elevated CO2 content also resulted in an increase in [Ca2+]i. The Na+-H+ exchange inhibitor ethylisopropylamiloride (10 microM) inhibited completely the rise but not the fall in [Ca2+]i in response to manipulation of pHi with NH4Cl. 4. In the presence of caffeine (20 mM), NH4Cl produced a decrease in [Ca2+]i similar to that observed in the absence of caffeine, but subsequent removal of NH4Cl resulted in an increase in [Ca2+]i that was distinctly smaller than that observed in the absence of caffeine. Ryanodine (10 microM) had no significant influence on NH4Cl-induced changes in [Ca2+]i. 5. Following treatment with the mitochondrial inhibitors sodium cyanide (5 mM), CCCP (carbonyl cyanide m-chlorophenyl hydrazone, 10 microM) or rotenone (10 microM), the NH4Cl-induced decrease in [Ca2+]i was markedly diminished, but wash-out of NH4Cl resulted in increases in [Ca2+]i similar to those observed in control cells. 6. Inhibition of glycolysis with 20 mM-2-deoxyglucose did not significantly alter the changes in [Ca2+]i induced by NH4Cl addition or its wash-out, but 2-deoxyglucose plus cyanide abolished the decrease in [Ca2+]i produced by intracellular alkalinization and nearly completely blocked the increase in [Ca2+]i produced by acidification. 7. In all experiments, the increase in [Ca2+]i during wash-out of NH4Cl was inhibited by ethylisopropylamiloride.(ABSTRACT TRUNCATED AT 400 WORDS)

Ammonium Chloride↗
PubMed1988

Pulmonary perfusion after rt-PA therapy for acute embolism: early improvement assessed with segmental perfusion scanning.

To determine if pulmonary perfusion was improved in acute pulmonary embolism after therapy with recombinant human tissue-type plasminogen activator (rt-PA), lung scans were obtained before and a mean of 22 hours after therapy in 19 patients. The posttherapy lung scans were compared with baseline, pretherapy scans with use of two semiquantitative methods--an anteroposterior view method, similar to that used in the Urokinase Pulmonary Embolism Trial, and a segmental method that emphasized pulmonary anatomy. There was an improvement in the defect score from 0.35 to 0.14 (P less than .01) when the anteroposterior view method was used and from 0.37 to 0.16 (P less than .01) when the segmental method was used. These encouraging results in the early posttherapy period suggest that rt-PA is especially effective in improving regional perfusion after pulmonary embolism and that a larger controlled trial of therapy with rt-PA for acute pulmonary embolism should be performed. Scoring lung scans with a segmental method is feasible and appropriate for present-day lung scan technique and should be considered in future studies.

Adult↗
PubMed1988

Mechanism of diminished contractile response to catecholamines during acidosis.

To examine mechanisms of diminished contractile response to catecholamines during acidosis, we studied contractile properties, beta-adrenergic receptor properties, and intracellular pH of intact, cultured myocardial cells from chick embryo ventricle at pH 7.4 and 6.8. Contractile response was measured with an optical-video system. On changing the superfusing buffer from pH 7.4 to 6.8 there was a decline in contractile amplitude to 80% of control by 20 min. Fluorimetrically determined intracellular pH declined over a similar time course from 7.11 +/- 0.05 to 6.96 +/- 0.07 (P less than 0.05). After 45 min at pH 6.8 the contractile response to 1 microM isoproterenol was less than half of the response at pH 7.4. Antagonist and agonist ligand-binding properties of the beta-adrenergic receptor were determined in the intact cells under conditions identical to those for the contractility studies. With the use of the hydrophilic antagonist [3H]CGP-12177 that selectively labels cell-surface receptors, agonist competition studies demonstrated that acidosis had no significant effect on antagonist or agonist affinity but decreased beta-receptor number from 21 +/- 3 to 11 +/- 3 fmol/mg protein (P less than 0.02). It is probable that a decline in the number of beta-receptors on the cell surface contributes to contractile hyporesponsiveness to catecholamines during acidosis.

Acidosis↗
PubMed1988

Foundation funding and psychiatric research.

Support for psychiatric research is limited to a relatively small number of funding sources. Foundations--nonprofit entities that support a variety of social, medical, educational, and other activities--are a potentially important source. The authors describe the role and structure of foundations, discuss historical trends in foundation support for research in mental illness, and present the results of a study of the extent to which foundations support mental health research. The results of this study confirm the paucity of foundation support for mental health research but show important differences and similarities among the foundations that support research in this field.

Foundations↗
PubMed1988

Modulation of myoglobin-H2O2-mediated peroxidation reactions by sulfhydryl compounds.

The ability of specific low molecular weight sulfhydryl compounds to inhibit the myoglobin-H2O2 peroxidation of uric acid and arachidonic acid was investigated. alpha-Mercaptopropionyl glycine, N-acetylcysteine, and reduced glutathione inhibited both the oxymyoglobin and metmyoglobin H2O2-mediated peroxidation of uric acid in a dose-dependent manner. The IC50 for each drug ranged between 20 to 100 microM and was dependent on the presence of a reduced sulfhydryl group since neither oxidized glutathione nor methionine effectively blocked uric acid peroxidation. Similar inhibition of oxymyoglobin and metmyoglobin H2O2-mediated peroxidation of arachidonic acid was also observed with alpha-mercaptopropionyl glycine, reduced glutathione, and cysteine. Under conditions of this assay, the ferrous form of myoglobin and H2O2 produced approximately three times the amount of formaldehyde from dimethylsulfoxide than ferric myoglobin (metmyoglobin) and H2O2. However, metmyoglobin and H2O2 were more effective than either oxymyoglobin and deoxymyoglobin in mediating arachidonic acid peroxidation. Further, neither mannitol nor benzoic acid (known scavengers of .OH) effectively blocked myoglobin H2O2-induced peroxidation of either uric acid or arachidonic acid. Visible absorption spectra of oxymyoglobin and metmyoglobin after incubation with H2O2 indicates the formation of a relatively stable ferriperoxide derivative of myoglobin. The formation of the ferriperoxide myoglobin derivative was partially inhibited by the addition of reduced sulfhydryl compounds. These data are consistent with the hypothesis that during reperfusion injury of the ischemic myocardium, the phagocytic cell or intracellular-derived H2O2 may react with myoglobin and initiate peroxidation reactions independent of .OH formation leading to cell injury. The cardioprotective effects of alpha-mercaptopropionyl glycine and other sulfhydryl-containing compounds during reperfusion injury may be attributed, at least in part, to their ability to inhibit myoglobin-H2O2-mediated peroxidation reactions.

Arachidonic Acids↗
PubMed1988

An aid to axillary dissection.

Abduction facilitates axillary dissection. Full abduction with the hand behind the head permits maximal operative exposure. This is due to the posterior axillary wall passing anteriorly and displacing the axillary contents into a superficial position. This movement is demonstrated roentgenographically.

Arm↗
PubMed1987

Mechanism of the positive inotropic effect of milrinone in cultured embryonic chick ventricular cells.

Milrinone, a potent positive inotropic and vasodilating agent, has shown promise in the clinical treatment of congestive heart failure, but significant controversy about its mechanism of action exists. To approach these mechanistic problems in a non-innervated, non-diffusion-limited system, the effects of milrinone on cultured embryonic chick ventricular cells were examined. At 37 degrees C in physiologic buffer, milrinone produced a rapid, concentration-dependent increase in amplitude of contraction that was 45% of the maximum increment in contraction produced by elevated extracellular calcium; the EC50 was 8 microM. This peak response was quantitatively similar to the contractile response produced by isobutyl methylxanthine, a potent phosphodiesterase inhibitor. Milrinone inhibited 70% of total phosphodiesterase activity of cultured ventricular cells with an EC50 of 11 microM. Exposure to 1 X 10(-4) M milrinone resulted in rapid increase in cyclic AMP content to levels greater than 100% above control within 4 min. The same concentration also produced a 43% increase in the rate of transsarcolemmal 45Ca uptake. The stimulation of 45Ca uptake rate was similar to the response produced by 1 microM isoproterenol and could be completely abolished by 10 microM verapamil. Thus, in cultured embryonic chick myocardial cells, the positive inotropic effect of milrinone is largely, if not entirely, attributable to phosphodiesterase inhibition, leading to intracellular cyclic AMP accumulation and stimulation of transsarcolemmal calcium influx via the slow calcium channel.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Early reversal of right ventricular dysfunction in patients with acute pulmonary embolism after treatment with intravenous tissue plasminogen activator.

To assess abnormalities of right heart function and their reversal with thrombolysis in pulmonary embolism, serial imaging and Doppler echocardiographic studies were performed before and after a 6 hour intravenous infusion of 80 to 90 mg of recombinant tissue-type plasminogen activator (rt-PA) in seven patients with segmental or lobar acute pulmonary embolism. None of the five men and two women had known prior pulmonary hypertension. Substantial clot lysis and improvement in pulmonary blood flow, as determined by serial pulmonary angiography and perfusion lung scanning, were achieved in all. Coincident with clot lysis, pulmonary artery systolic pressure decreased (from 42 +/- 11 to 26 +/- 7 mm Hg, p less than 0.005), right ventricular diameter decreased (from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm, p less than 0.005) and left ventricular diameter increased (from 3.7 +/- 0.9 to 4.4 +/- 0.6 cm, p less than 0.01). Right ventricular wall movement, initially mildly, moderately or severely hypokinetic in one, two and four patients, respectively, normalized in five and improved to mild hypokinesia in two. Tricuspid regurgitation was present before lytic therapy in six patients. In five, flow velocity in the tricuspid regurgitant jets indicated a peak systolic right ventricular minus right atrial pressure gradient of 25 to 52 mm Hg. Tricuspid regurgitation was detected early after lytic therapy in only two patients. Systolic septal flattening was noted before but not after lysis. These findings confirm that pulmonary emboli may result in appreciable right ventricular dysfunction and dilation, resultant tricuspid regurgitation, abnormal septal position and decreased left ventricular size.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Thrombolytic therapy of acute pulmonary embolism: current status and future potential.

Recombinant human tissue-type plasminogen activator (rt-PA), a relatively clot-specific fibrinolytic agent, represents a novel and promising approach to thrombolytic therapy of pulmonary embolism. Therefore, the efficacy and safety of peripheral intravenous rt-PA therapy were assessed in 47 patients with angiographically documented pulmonary embolism. The drug regimen was 50 mg over 2 hours followed by repeat angiography and, if necessary, an additional 40 mg over 4 hours. By 6 hours, 44 of the 47 patients had angiographic evidence of clot lysis that was slight (n = 5), moderate (n = 12) or marked (n = 27). Among the 34 patients with pulmonary hypertension before treatment (mean pulmonary artery pressure exceeding 17 mm Hg), the pressure decreased from 43/17 (mean 27) to 31/13 (mean 19) mm Hg (p less than 0.0001). Fibrinogen decreased 33% from baseline at 2 hours and 42% from baseline at 6 hours. There were two major complications that required surgical control of bleeding: hemorrhage from a pelvic tumor and mediastinal tamponade in a patient 8 days after coronary artery bypass surgery. The initial results demonstrate that, among selected patients, peripheral intravenous rt-PA can rapidly and, for the most part, safely lyse pulmonary embolism within 6 hours.

Acute Disease↗
PubMed1987

Altered Ca fluxes and contractile state during pH changes in cultured heart cells.

We studied mechanisms underlying changes in myocardial contractile state produced by intracellular (pHi) or extracellular (pHo) changes in pH using cultured chick embryo ventricular cells. A change in pHo of HEPES-buffered medium from 7.4 to 6.0 or to 8.8 changed the amplitude of cell motion by -85 or +60%, and 45Ca uptake at 10 s by -29 or +22%, respectively. The pHo-induced change in Ca uptake was not sensitive to nifedipine (10 microM), but was Na gradient dependent. Changes in pHi produced by NH4Cl or preincubation in media at pH values ranging from 6.0 to 8.8 failed to alter significantly 45Ca uptake or efflux. However, larger changes in pHi were associated with altered Ca uptake. Changes in pHo from 7.4 to 6.0 or to 8.8 were associated with initial changes in 45Ca efflux by +17 or -18%, respectively, and these effects were not Na dependent. Exposure of cells to 20 mM NH4Cl produced intracellular alkalinization and a positive inotropic effect, whereas subsequent removal of NH4Cl caused intracellular acidification and a negative inotropic effect. There was, however, a lack of close temporal relationship between pHi and contractile state. These results indicate that pHo-induced changes in contractile state in cultured heart cells are closely correlated with altered transsarcolemmal Ca movements and presumably are due (at least in part) to these Ca flux changes. In contrast, pHi-induced changes in contractile state appear principally to involve altered Ca handling within the cell and/or altered Ca sensitivity of myofibrils.

Animals↗
PubMed1987

[Na]i modulates isoproterenol's effect on Ca permeability in cultured heart cells.

Isoproterenol (ISO) augments the slow inward Ca current in cardiac muscle cells. We examined the role of intracellular Na (Nai) on ISO-mediated alterations in Ca uptake in cultured chick heart cells. In 140 mM Na medium, 1 microM ISO did not measurably alter 45Ca uptake. When cells were first preincubated in Na-free medium for 5 min and then incubated in control medium with 45Ca, ISO increased 45Ca uptake by 30%. Nifedipine (10 microM), verapamil (1 microM), or dl-propranolol (1 microM) abolished the effect of ISO on 45Ca uptake. CGP 28392 (1 microM), a Ca channel agonist, increased Ca influx in a manner that was augmented by decreased Nai, similar to the ISO response. Neither ISO nor CGP 28392 altered 45Ca uptake when cells preincubated in Na-free medium were further incubated in Na-free medium containing 45Ca. Exposure of cells to Na-free medium or 25 mM K+ medium caused depolarization of the resting membrane potential to approximately -40 mV. In the absence of ISO, the 45Ca uptake in cells preincubated in Na-free or 25 mM extracellular K (Ko) medium was significantly greater than in cells preincubated in control medium. This appeared to be due partly to increased 45Ca uptake via nifedipine-sensitive pathways. These findings support the hypothesis that reduction in Nai concentration ([Na]i) enhances the ISO-induced augmentation of Ca uptake via nifedipine-sensitive pathways (presumably via slow Ca channels), probably by a direct effect on the channels.

Animals↗
PubMed1987

Effect of phorbol esters on contractile state and calcium flux in cultured chick heart cells.

Phorbol esters are potent tumor promoters that have been widely used in studies of transmembrane signaling because of their ability to activate protein kinase C. To study the effect of phorbol esters (and indirectly, the role of protein kinase C) on cardiac muscle contractility, we examined the effects of phorbol myristate acetate (PMA) on contractile state, transmembrane 45Ca fluxes, and cytosolic free Ca concentration ([Ca]i) using spontaneously contracting cultured chick ventricular cells. PMA produced a concentration- and time-dependent decrease in the amplitude of cell motion [half maximum inhibitory concentration (IC50) = 130 nM] with maximal effect (54 +/- 5% of control) observed at 1 microM. PMA (1 microM) reduced 45Ca uptake rate by 16 +/- 4% (P less than 0.05) and the size of the rapidly exchangeable Ca pool by 11 +/- 2% (P less than 0.05) but did not alter the 45Ca efflux rate. In fura-2-loaded cells, PMA produced a decrease in [Ca]i from 96 +/- 7 to 72 +/- 5 nM (mean +/- SE; P less than 0.05) with a time course similar to that of alteration in contractile amplitude. PMA had no effect on cellular Na content. Phorbol didecanoate (1 microM), a phorbol diester that does not activate protein kinase C, produced no significant changes in contractile amplitude, 45Ca fluxes, or [Ca]i. These results indicate that PMA influences transsarcolemmal Ca uptake, and thus the excitation-contraction process, and suggest that protein kinase C may modulate myocardial Ca homeostasis and contractile state.

Animals↗
PubMed1987

Relations among sodium pump inhibition, Na-Ca and Na-H exchange activities, and Ca-H interaction in cultured chick heart cells.

Sodium pump inhibition in cardiac muscle cells is associated with changes in intracellular sodium, calcium, and hydrogen concentrations as well as in membrane ion transport activity. We examined further the functional relations among these entities using cultured chick ventricular cells. [Ca]i and pHi were determined from fluorescence signals obtained from cells loaded with fura-2 or BCECF, respectively. Ouabain (100 microM) elevated [Ca]i eightfold and decreased pHi by 0.11 unit (a 30% increase in [H+]). In the presence of 10 microM ethylisopropylamiloride, a potent inhibitor of Na-H exchange, ouabain elevated [Ca]i 3.5-fold and reduced pHi by 0.16 unit (a 48% increase in [H+]). Exposure to sodium-free (sodium replaced with potassium) medium produced a twelvefold increase in [Ca]i and a 0.12 pH unit decrease in pHi. In cells treated with 100 microM ouabain, exposure to sodium-free (lithium) medium resulted in a 22-fold sustained increase in [Ca]i and a rapid intracellular acidification (pH 7.15 to 6.60). The effect of ouabain or sodium-free medium on pHi was abolished in calcium-free medium; addition of 1 mM Ca rapidly increased [Ca]i and decreased pHi. In cells treated with subtoxic (3 microM) or toxic (100 microM) concentrations of ouabain, initial 24Na uptake rates were significantly greater than in control cells and were significantly reduced in the presence of 10 microM ethylisopropylamiloride. We conclude that ouabain (100 microM) produces intracellular acidification as a result of sodium pump inhibition; calcium accumulation via Na-Ca exchange, and subsequent Ca-H interaction within the cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1987

Control of cytosolic calcium activity during low sodium exposure in cultured chick heart cells.

We investigated the roles of sodium-calcium exchange, sarcoplasmic reticulum, and mitochondria in Cai homeostasis in cultured chick ventricular cells. Specifically, the influence of low sodium medium on contractile state, calcium fluxes, and cytosolic free [Ca] [( Ca]i) was examined. [Ca]i was measured using fura-2. Mean [Ca]i in control medium was 126 +/- 14 nM. Exposure of cells to sodium-free or sodium- and calcium-free medium (choline-substituted) resulted in contracture development, which returned toward the baseline level over 2-3 minutes. The Nao-free contracture was associated with a tenfold increase in [Ca]i (1,280 +/- 110 nM) followed by a gradual decrease to a level fourfold above control [Ca]i (460 +/- 58 nM). Nao- and Cao-free contracture was associated with a fivefold increase in [Ca]i (540 +/- 52 nM) followed by a rapid decrease to below 80 nM. Sodium-free medium failed to produce an increase in [Ca]i or contracture in cells preexposed to calcium-free medium, although caffeine, when subsequently added to sodium- and calcium-free medium, was able to elicit a transient increase in [Ca]i and contracture. Brief, 5-second preperfusion of cells with La3+ (1 mM) or EGTA (1 mM) abolished the Nao-free contracture and the increase in [Ca]i. In the presence of 20 mM caffeine, removal of Nao resulted in minimal changes in the resting position of the cell although 45Ca uptake and [Ca]i were increased in response to sodium-free medium; the subsequent decrease in [Ca]i was greatly slowed. Addition of caffeine during the relaxation phase of the sodium-free contracture produced an additional transient contracture and transient increase in [Ca]i. Ryanodine (1 microM) abolished this effect of caffeine. Caffeine or ryanodine abolished Nao- and Ca-free contracture. CCCP (2 microM), a potent oxidative phosphorylation inhibitor, did not significantly affect calcium efflux rate. In the presence of 2 microM CCCP, removal of sodium resulted in an augmented contracture signal and a rise in [Ca]i, followed by a slow decrease. We conclude that removal of extracellular sodium enhances transsarcolemmal entry of calcium via sodium-calcium exchange, but this effect alone does not lead to the development of sodium-free contracture. Calcium displaceable by lanthanum or EGTA appears to contribute to Nao-free or Nao- and Cao-free contracture. Studies using caffeine and ryanodine suggest that removal of Nao leads to release of calcium from the sarcoplasmic reticulum (presumably via calcium-induced calcium release).(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗
PubMed1987

Effect of thyroid hormone on slow calcium channel function in cultured chick ventricular cells.

The hyperthyroid state is associated with increased myocardial contractility. To clarify responsible mechanisms, we examined the effects of thyroid hormone on slow Ca channels, beta-adrenergic receptors, transsarcolemmal 45Ca flux and cytosolic free calcium in cultured chick ventricular cells. Compared with cells grown without triiodothyronine (T3), cells grown in 10 nM T3 possessed 67% (P less than 0.05) more dihydropyridine 3H-PN200-110 binding sites, 24% (P less than 0.05) more beta-adrenergic antagonist 3H-CGP12177 binding sites, a 57% (P less than 0.05) greater nifedipine-sensitive initial 45Ca uptake rate, and a 31% (P less than 0.05) greater nifedipine-sensitive 45Ca uptake rate in response to BAY k 8644. Time-averaged mean intracellular free Ca concentration ([Ca]i) measured with fura-2, total protein content, and dissociation constant values for 3H-PN200-110 or 3H-CGP12177 binding was not significantly different in the two groups of cells. BAY k 8644 (1 microM) increased mean [Ca]i 2.85- or 2.16-fold in cells grown with or without 10 nM T3, respectively. l-Isoproterenol (1 microM) increased [Ca]i 1.53- or 1.28-fold in cells grown with or without 10 nM T3, respectively. We conclude that thyroid hormone augments transsarcolemmal Ca influx, at least in part via slow Ca channels associated with increased numbers of these channels. T3-treated cells appear to be more responsive to the effects of BAY k 8644 or isoproterenol on [Ca]i.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗