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Biomedical subjects

C O Lee

Publications and source records attributed to C O Lee.

108 records · Page 6Linked to original sources

Relation between intracellular Na ion activity and tension of sheep cardiac Purkinje fibers exposed to dihydro-ouabain.

The intracellular Na ion activity (aiNa) and the contractile tension (T) of sheep cardiac Purkinje fibers were simultaneously measured employing recessed-tip Na+-selective glass microelectrodes and a mechano-electric transducer. The aiNa of 6.4 +/- 1.6 mM (mean +/- SD, n = 56) was obtained in fibers perfused with normal Tyrode's solution. The changes in aiNa and T were measured during and after the exposure of fibers to a cardiac glycoside, dihydro-ouabain (DHO) in concentrations between 5 X 10(-8) M and 10(-5) M. The exposure time to DHO was 15 min. Both aiNa and T did not change in fibers exposed to 5 X 10(-8) M DHO, and the threshold concentration for the effect of DHO appeared to be around 10(-7) M. In DHO concentrations greater than the threshold, the increases in aiNa and T strongly correlated during the onset of DHO effects. The recoveries of aiNa and T were variable and slow, being dependent on the DHO concentration. In those fibers which recovered from the effects of DHO, the time-course of aiNa recovery was similar to that of T recovery. In fibers exposed to DHO of 5 X 10(-6) M or greater, the apparent toxic effects were observed in both action potential and contraction after an initial increase in T. The fibers manifesting the apparent toxic effects has a aiNa of approximately 30 mM or greater. The results of this study indicate that the increase in aiNa is associated with the positive inotropic action of the cardiac glycoside.

Animals↗

Electrochemical properties of Na+- and K+-selective glass microelectrodes.

Electrochemical properties of Na+-selective glass microelectrodes were studied and compared with those of K+-selective glass microelectrodes. The selectivity of Na+-selective glass microelectrodes depended on the ion concentration of test solutions. With aging, resistance of Na+-selective microelectrodes increased and their selectivity for Na over K decreased. Na+-selective microelectrodes potential measured in NaCl solution remained constant with aging, while the potential measured in KCl solution decreased and became more positive. The changes in resistance and potential of Na+-selective microelectrodes may be due to the effects of the less mobile cation, i.e., H+ or K+ on the Na ion exchange in the Na-sensing region. The results indicate that Na+-selective microelectrodes must be used as soon after filling as possible. The selectivity of Na+-selective microelectrodes increased with increase of the sensitive exposed-tip length, whereas their response time became slow due to a large recessed volume, indicating requirement of an optimum exposed-tip length for intracellular applications. The changes in the properties of Na+-selective glass microelectrodes with aging contrasted with those of K+-selective glass microelectrodes in which resistance decreased and K+-selectivity increased. The K+-selective microelectrodes required aging before use for a high selectivity and low resistance. The K+-selective microelectrodes with low resistance after sufficient aging can be used without insulation to measure K+ and Na+ activities in aqueous solutions. The different properties between Na+- and K+-selective microelectrodes are understandable, because hydration of N+-selective glass is much less extensive than that of K+-selective glass.

Electric Conductivity↗

Membrane permeability during low potassium depolarization in sheep cardiac Purkinje fibers.

Exposure of sheep Purkinje fibers to low [K]o leads to marked depolarization to a stable potential of about -40 mV. This level is equivalent to the plateau of the Purkinje fiber action potential. The low [K]o depolarization could be prevented by removal of [Na]o and was modified by tetrodotoxin. The membrane potential in the depolarized state was unresponsive to changes in [Cl]o or [Ca]o and it was poorly responsive to changes in [K]o between 0 and 2 mM. Repolarization was induced by decrease in [Na]o with a slope response of 30 mV/10-fold change in [Na]o. Average internal K activity (aK) in the resting state with a [K]o of 5 mM was 121.4 mM for a membrane potential of -80 mV. During low K depolarization aK was 119.7 mM with a membrane potential of -34 mV. The depolarization was therefore due to a change in membrane permeability, with little change in aK. Upon restoration of [K]o the fiber repolarized to values transiently more negative than the prior resting potential. These transient potentials were more negative than the K equilibrium potential (VK), if it is calculated assuming a uniform [K]o. The hyperpolarization was reduced by ouabain [10(-6)] or by low [Ca]o.

Animals↗

Influence of changes in external potassium and chloride ions on membrane potential and intracellular potassium ion activity in rabbit ventricular muscle.

1. The membrane responses of rabbit papillary muscles to rapid changes in [K](o) and [Cl](o) were measured with open-tipped micropipettes and with closed micropipettes made from K-selective glass.2. The muscle cells behaved primarily as a K electrode, and responses to changes in [K](o) with constant [Cl](o) or with constant [K](o) x [Cl](o) were substantially the same.3. When [Cl](o) was changed at a constant [K](o) the membrane potentials changed rapidly and symmetrically by a small value and remained constant for 30 min.4. Measurement of potential with K(+)-selective micro-electrodes in these experiments showed no change in intracellular K activity. In addition to permitting calculation of K permeability, these measurements reassured us that the K(+)-selective electrodes were well insulated and not influenced by electrical shunts at the impalement site.5. Although the membrane response to changes in [Cl](o) was small, it was possible to calculate that the permeability ratio (P(Cl)/P(K)), was 0.11. The Cl and K conductances were about 0.015 mmho/cm(2) and 0.09 mmho/cm(2) respectively, resulting in a conductance ratio (g(Cl)/g(K)) of about 0.17.6. The time course of depolarization by increase in [K](o) was rapid (half-time 5 sec), but repolarization on return to lower [K](o) was much slower (half-time 50 sec). The depolarization time course was easily fitted by the potential change calculated by assuming the need for K diffusion into the extracellular spaces and taking account of the logarithmic relation between membrane potential and [K](o). These calculations did not fit the time course of repolarization, which was slowed in the fashion expected from an inward-rectifying membrane.7. The influence of [K](i) on membrane potential was investigated by changes in tonicity of the external solution. Hypotonic solution produced a change in intracellular K activity close to that produced by ideal water movement. However, in hypertonic solution, intracellular K activity did not rise as much as predicted, suggesting a change in intracellular activity coefficient.

Animals↗

Activities of potassium and sodium ions in rabbit heart muscle.

Activities (a) of intracellular K and Na in rabbit ventricular papillary muslces were determined with cation-selectivve glass microelectrodes and concentrations (C) were estimated with flame photometry. The CK and aK of the muscles were 134.9 +/- 3.1 mM (mean value +/- SE) and 82.6 mM, respectively, at 25 degrees C. The corresponding CNa and aNa were 32.7 +/- 2.7 and 5.7, respectively. The apparent intracellular activity coefficients for K (gammaK) and Na (gammaNa) were 0.612 and 0.175, respectively. Similar results were obtained at 35 +/- 1 degree C. gammaK was substantially lower than the activity coefficient (0.745) of extracellular fluid (Tyrode's solution), which might be expected on the basis of a different intracellular ionic strength. gammaNa was much lower than that of extracellular fluid, and suggest that much of the Na was compartmentalized or sequestered. For external K concentrations greater than 5 mM, the resting membrane potentials agreed well with the potential differences calculated from the K activity gradients across the cell membrane as a potassium electrode. These results emphasize that potassium equilibrium potentials in heart muscle should be calculated by activities rather than concentrations.

Animals↗

Electrochemical properties of hydrated cation-selective glass membrane. A model of K+ and Na+ transport.

Electrochemical properties of cation-selective glass microelectrodes made from NAS(27-04) were studied. There was a marked fall in electrical resistance of the microelectrodes stored in 3 M KCl solution (aging). The resistance was in the range of 2 x 10(7) to 10(9) Omega, which were much lower than those estimated from the electrical resistivity of dry glass for the equivalent dimensions of microelectrode working tips. This fall in resistance was accompanied by an increase in microelectrode selectivity for K(+). The low resistance and increased K(+) selectivity are desirable features that make the microelectrode more suitable for application to biologic studies. The changes in microelectrode resistance and selectivity were interpreted to be due to hydration of the entire thickness of the glass membrane, resulting in a change in the field strength of anionic sites and formation of ionic channels in the glass membrane. Thus, the fall in resistance is explained by decrease in energy barrier, which is equivalent to the activation energy of interaction between the cations and anionic sites in the glass membrane. Some of the microelectrodes showed a transient depolarization that resembled the action potential of a biological membrane. This transient depolarization was associated with the changes in microelectrode resistance and selectivity. The transient depolarizations suggest the temporary development of wide channels in the membrane permitting free movement of hydrated cations according to the bulk electrochemical gradient.

Action Potentials↗

Activities of sodium and potassium ions in epithelial cells of small intestine.

Intracellular molar Na(+) activity (a(Na)), measured with cation-selective glass microelectrodes, in epithelial cells of isolated bullfrog small intestine immersed at 26 degrees C in a sodium sulfate Ringer solution containing mannitol was 0.0144 +/- 0.0031 (average value plus or minus standard deviation). The corresponding K(+) activity (a(K)) was 0.0854 +/- 0.0060. Combination of these values with previous estimates of intracellular Na(+) and K(+) concentrations under identical conditions indicated that a substantial fraction of the cellular Na(+) is in an osmotically inactive state. When the cells were exposed to a Ringer solution in which 26 millimoles of mannitol per liter were replaced by 3-O-methyl glucose, highly significant decreases in a(K) and a(Na) were observed. The decrease in a(K) was proportionately larger than the corresponding decrease in a(Na).

Animals↗

Sodium and potassium activities in normal and "sodium-rich" frog skeletal muscle.

In frog sartorius muscles immersed for 2 hours at 26 degrees C in normal Ringer solution, the intrafiber potassium concentration, C(K)(in millimoles per liter), was 123 +/- 2 (mean value plus or minus standard error), and the potassium activity, a(K) (in millimoles per liter), was 90 +/- 1.0. The corresponding sodium concentration and activity were 20 +/- 1 and 6.5 +/- 0.4, respectively. After overnight immersion in K+-free Ringer solution the values were: CK, 97 +/- 2; aK, 81.5 +/- 1.6; CNa, 47 +/- 2; and aNa, 11.2 +/- 0.6. The changes in aK and aNa during storage were not consistent with an exchange between predominantly "free" fiber K+ and external Na+. These results suggest that the Na+ taken up during overnight immersion largely replaced adsorbed or sequestered K+ in the fibers.

Animals↗

Lacrimal canalicular obstructions: safety and effectiveness of balloon dilation.

PURPOSE: Balloon dilation of the lacrimal canaliculi has been considered contraindicated because of possible damage to the canaliculi. The purpose of this study was to assess the safety and effectiveness of balloon dilation in treatment of obstruction of the lacrimal canaliculus. MATERIALS AND METHODS: Fluoroscopically guided balloon dilation was performed in 26 eyes of 21 consecutive patients with epiphora due to lacrimal canalicular obstruction confirmed at dacryocystography. Nine of 26 eyes had complete obstruction and 17 eyes had incomplete obstruction. RESULTS: Technical failure occurred in one eye. Only one acute complication (punctal slitting) and no late complications occurred. At 7 days after balloon dilation, 14 of 17 eyes (82%) with incomplete obstruction and five of nine eyes (56%) with complete obstruction showed complete or partial resolution of epiphora with patency of the lacrimal drainage system. At 6-month follow-up, that improvement was maintained in seven of 17 eyes (41%) with incomplete obstruction and three of nine eyes (33%) with complete obstruction. CONCLUSIONS: Although the 6-month recurrence rate is rather high, balloon dilation seems to be safe and valuable as an initial therapy for patients with obstruction of the lacrimal canaliculus.

Catheterization↗

P-glycoprotein (Pgp) does not affect the cytotoxicity of flavonoids from Sophora flavescens, which also have no effects on Pgp action.

Sophoraflavanone, kurarinone (GS08), norkurarinol (GS11), kurarinol (GS12) and kushenol K are cytotoxic flavonoids isolated from Sophora flavescens. In this study, we tested the cytotoxicity of those flavonoids to human cancer cells including P-glycoprotein (Pgp)-expressing HCT15 cells and its multidrug resistant subline, HCT15/CL02 cells. HCT15/CL02 cells revealed resistance to GS08, GS11 and GS12 about 2 fold in comparison with HCT15 cells. Nonetheless, verapamil, a Pgp inhibitor, could not increase the cytotoxicity of all the flavonoids tested. We also investigated that the flavonoids could modulate the Pgp action. At nontoxic concentrations, the flavonoids could not effect on the cytotoxicity of paclitaxel, a well-known Pgp-substrate. The flavonoids also had no effects on the accumulation of rhodamine 123 in all the cells tested at 10 microM. From the results, we concluded that Pgp had no effect on the cytotoxicity of the flavonoids, and the flavonoids also had no effect on the action of Pgp. Our results also suggested that HCT15/CL02 cells had additional mechanisms for drug resistance distinct from Pgp overexpression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Psammaplin A, a natural phenolic compound, has inhibitory effect on human topoisomerase II and is cytotoxic to cancer cells.

We evaluated the topoisomerase II (Topo II) inhibitory activity of psammaplin A (PSA), a naturally occurring biphenolic compound, and its cytotoxicity to some human cancer cells including P-glycoprotein (Pgp)-overexpressing multidrug resistant (MDR) cell line. PSA completely inhibited the DNA relaxation activity of Topo II at 75.0 microM. It also completely inhibited the DNA decatenation activity of Topo II at 75.0 microM, and showed about 50% inhibitory activity at 18.8 microM. In the cytotoxicity assay, the effective concentrations that cause 50% inhibition of cell growth (EC50) were 0.48, 0.39, 1.83 and 3.76 microM to A549, SK-OV-3, HCT15 and HCT15/CL02 (MDR cell line established from HCT15 cells) cancer cells, respectively. In the presence of 8.0 microM of verapamil (VER), a well-known MDR modulator, the EC50 of PSA to HCT15/CL02 cells was reduced about 2.1 fold. Meanwhile, the EC50s of standard Topo II inhibitory drugs such as doxorubicin, etoposide and mitoxantrone to HCT15/CL02 cells were reduced about 8.5, 9.3 and 8.1 fold in the presence of 8.0 microM VER, respectively. From the results, we conclude that PSA has Topo II inhibitory activity, and its cytotoxicity to cancer cells is not so strongly affected by Pgp-associated MDR phenotype in comparison with some Topo II inhibitory anticancer drugs used in the clinic.

Adenosine Triphosphate↗

Effects of flavonoids on the growth and cell cycle of cancer cells.

In this study, we investigated the cytotoxicities of flavone (F01), 3-hydroxyflavone (F02), 6- hydroxyflavone (F03), 7-hydroxyflavone (F04), 3,6-dihydroxyflavone (F05), 5,7-dihydroxyflavone (F06) and 5,6,7-trihydroxyflavone (F07) to human cancer cells including P- glycoprotein (Pgp)-expressing HCT15 cells and its multidrug resistant subline, HCT15/CL02 cells. We also examined the effects of those flavonoids on the cell cycle of these cancer cells. HCT15/CL02 cells did not reveal resistance to all the flavonoids tested in comparison with HCT15 cells. In cell cycle analysis, all the flavonoids tested, except F01 and F04, reduced the G0/G1 population of SF295 cells at growth inhibitory concentrations, and increased G2/M (F02, F03 and F06) or S (F05 and F07) populations. In addition, F02 and F03 decreased the G2/M and G0/G1 population, and increased the S and G2/M population in HCT15 cells, respectively. Meanwhile, in HCT15/CL02 cells, F02 and F03 decreased the G0/G1 populations and increased the S population. In conclusion, we deemed that the flavonoids tested had diverse cytotoxic mechanisms, and exerted their cell growth inhibitory or killing activity by distinctive ways in different cells.

Cell Cycle↗

Gynecologic cancers: Part. I--Risk factors.

Gynecologic cancers will account for approximately 81,000 new cases of cancer this year. Although much is known about the risk factors for cervical, ovarian, and endometrial cancers, less is known about vaginal and vulvar cancer risk factors. Generally, risk factors and associations for gynecologic cancers are behavioral, reproductive, hormonal, and genetic related. Research continues to verify and refute the impact of certain factors. All nurses must be knowledgeable about the risk factors and associations for these cancers.

Female↗

Gynecologic cancers: Part. II--risk assessment and screening.

Screening interventions for gynecologic cancers involve identifying risk factors and high-risk groups of women, counseling for risk factor reduction, and recommending early detection strategies. All nurses can conduct gynecologic risk assessments, and advanced practice nurses can perform physical exams. All women must be knowledgeable about risk factors because gynecologic cancers are curable when diagnosed in the early stages. Nursing interventions include developing culturally sensitive programs and educational materials for targeted populations and educating women in all groups to raise awareness about gynecologic cancer risks.

Age Distribution↗

Quality of life and breast cancer survivors. Psychosocial and treatment issues.

PURPOSE: This study was conducted to determine the relationship between social support, extent of breast cancer surgery, length of time since surgery, geographic location, and overall quality of life (QOL) in breast cancer survivors. Additionally, the motivational factors for survivors to volunteer in a community rehabilitation program were assessed. DESCRIPTION OF STUDY: A convenience sample of 134 survivors who had undergone mastectomies were invited to participate. Study packets including an information letter, a demographic sheet, and Ferrans and Powers Quality of Life-Cancer Version questionnaire were mailed. The return of completed forms was considered consent. RESULTS: The sample (N = 100) consisted mostly of married women (75%) who had surgery a mean of 14 years previously. Findings indicated that there is no correlation between marital status and the number or type of support persons and overall QOL. Interestingly, unmarried women were found to have a better perceived QOL than married women, although the difference was not statistically significant. There was no significant difference between extent of surgery, length of time since surgery, and geographic location with overall QOL. Thematic analysis of motivation to volunteer revealed an underlying theme of helping with sharing knowledge/providing information and giving emotional support for all age groups. Other themes were personal gain; giving back to the program, others, and God; and assisting others in avoiding a negative experience. CLINICAL IMPLICATIONS: Quality of life is a dynamic, multifaceted process through which perceptions, viewpoints, and behaviors change as a result of the various experiences throughout the survival period. These findings demonstrate that social support plays a vital role in promoting overall QOL in breast cancer survivors. The development of supportive behaviors by healthcare providers and Reach for Recovery volunteers is essential in providing this social support for breast cancer survivors. Growth in understanding and relieving the psychological stress that new cancer survivors endure is an area that warrants particular attention. Additionally, these participants indicated their need and willingness to share their experiences. Support is needed to provide survivors with the opportunity to function as volunteers. Program developers and evaluators must work together to ensure this support on a consistent basis.

Adult↗

Novel multidrug-resistance modulators, KR-30026 and KR-30031, in cancer cells.

The present study was performed to evaluate the ability of KR-30026 and KR-30031 to overcome multidrug resistance (MDR) by measuring the cytotoxicity of paclitaxel and the rate of rhodamine accumulation, which were then compared with verapamil. KR-30026 potentiated the paclitaxel-induced cytotoxicity of HCT15 to over 60 fold greater than that of verapamil, and KR-30031 was equipotent with verapamil (EC50: 0.00066, 0.04 and 0.05 nM at 4.0 micrograms/ml, respectively). KR-30026 and KR-30031 were without effect on paclitaxel-induced cytotoxicity to SK-OV-3 cells, as well as on tamoxifen-induced cytotoxicity to HCT15, HCT15/CL02 and SK-OV-3 cells. Maximal rhodamine accumulation by KR-30026, KR-30031 and verapamil were similar in HCT15 cells, while KR-30026 was more potent than verapamil in HCT15/CL02 cells (721 and 440%, respectively). To evaluate the cardiac toxicity of KR-30026 and KR-30031, the changes of tension in isolated rat aorta and left ventricular pressure (LVP) in guinea pig heart were determined; KR-30026 and KR-30031 were 15-40 and 25-70 fold less potent than verapamil, respectively. These results suggest that KR-30026 and KR-30031 are active modulators of MDR with potentially minimal cardiovascular toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗