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Biomedical subjects

D Ahn

Publications and source records attributed to D Ahn.

At least 19 recordsLinked to original sources
PubMed2001

Inhibition by clonidine of the carbachol-induced tension development and nonselective cationic current in guinea pig ileal myocytes.

Effects of clonidine, an imidazoline derivative as well as alpha2-adrenoceptor agonist, on carbachol (CCh)-evoked contraction in guinea pig ileal smooth muscle were studied using isometric tension recording. To investigate the cellular mechanisms of the inhibitory effect of clonidine, its effects on CCh-evoked nonselective cationic current (I(CCh)), voltage-dependent Ca2+ current (I(Ca)) and voltage-dependent K+ current (I(K)) was also studied using patch-clamp recording techniques in single ileal cells. Clonidine inhibited the contraction evoked by CCh (1 microM) in a concentration-dependent manner with an IC50 valve of 61.7 +/- 2.5 microM. High K+ (40 mM)-evoked contraction was only slightly inhibited even when clonidine was used at 300 microM. Externally applied clonidine inhibited I(CCh) dose-dependently with an IC50 of 42.0 +/- 2.6 microM. When applied internally via patch pipettes, clonidine was without effect. An I(CCh)-like current induced by GTPgammaS was also inhibited by bath application of clonidine. None of KU14R and BU224, both imidazoline receptor blockers, and yohimbine, an alpha2-adrenergic blocker, significantly affects the inhibitory effect of clonidine on I(CCh). Clonidine (300 microM) only slightly decreased membrane currents flowing through voltage-gated Ca2+ channels or K+ channels. These data indicate that clonidine relaxes smooth muscle contraction produced by muscarinic receptor activation and suggest that the effect of clonidine seems due mainly to inhibition of I(CCh) via acting directly on the involved cationic channel.

Adrenergic alpha-Agonists↗
PubMed2001

Mechanism of carbon monoxide-induced relaxation in the guinea pig ileal smooth muscle.

The mechanism of carbon monoxide (CO)-induced relaxation were investigated in the guinea-pig ileum. CO (10%) inhibited the 40 mM KCl-induced contraction. This effect was antagonized by ODQ (1 microM), a soluble guanylate cyclase inhibitor. In contrast, CO did not inhibit the 40 mM KCl-induced increase in cytosolic Ca2+ level ([Ca2+]i). Cumulative addition of KCl induced a graded increase in both [Ca2+]i and muscle tension. In the presence of CO, the increase in muscle tension was attenuated whereas the increase in [Ca2+]i was only slightly decreased. Thus, the [Ca2+]i-tension relationship constructed by cumulative addition of KCl shifted downwards in the presence of CO. Using the patch clamp, CO was found to have little effect on the peak Ba currents (I(Ba)) when voltage was stepped from -60 mV to 0 mV. From these results, we conclude that CO inhibits contraction of guinea-pig ileum mainly by the decrease in the sensitivity of contractile elements to Ca2+ via a cyclic GMP-dependent pathway but not by the inhibition of L-type Ca2+ channel.

Animals↗
PubMed2001

Lysophosphatidylcholine decreases delayed rectifier K+ current in rabbit coronary smooth muscle cells.

Lysophosphatidylcholine (LPC), which exists abundantly in lipid fraction of oxidized low density lipoprotein, has been implicated in enhanced agonist-induced contraction and increase of intracellular Ca2+. The effect of LPC on the activity of delayed rectifier K+ current (I(dK)), which is a major determinant of membrane potential and vascular tone under resting condition, was examined in rabbit coronary smooth muscle cells using whole cell patch clamping technique. Application of LPC to the bath solution caused a concentration-dependent inhibition of I(dK), and the concentration to produce half-maximal inhibition was 1.51 microM. This effect of LPC on I(dK) was readily reversed after washout of LPC in the bath. The steady-state voltage dependence of I(dK) was shifted to positive direction by both extra- and intracellular application of LPC. Staurosporine (100 nM) pretreatment significantly suppressed the LPC-induced inhibition of I(dK). These results suggest that LPC inhibits I(dK) in rabbit coronary smooth muscle cells by a pathway that involves protein kinase C, and the LPC-induced inhibition of I(dK) may be, at least in part, responsible for the abnormal vascular reactivity in atherosclerotic coronary artery.

Animals↗
PubMed2001

Capsaicin-induced relaxation in rabbit coronary artery.

In the present study mechanism of inhibitory effects of capsaicin on the contractility of rabbit coronary artery were studied by measurement of isometric tension and intracellular Ca2+ concentration. Capsaicin (1 microM to 30 microM) relaxed the coronary artery pre-contracted with prostaglandin (PG) F2alpha (1 microM) in a concentration-dependent manner. The PGF2alpha-induced increase in intracellular Ca2+ concentration was also inhibited. The effects of capsaicin were readily reversed by washing capsaicin from the bath. Capsaicin-induced relaxation was not attenuated by pretreatment with capsazepine (1 microM), a blocker of vanilloid receptor or ruthenium red (1 microM), a blocker of non-selective cation channel. Previous exposure to a high concentration of capsaicin (100 microM) or repeated application of capsaicin did not eliminate the relaxation response to subsequent application of capsaicin. Increasing the external K+ concentration to 80 mM significantly attenuated the capsaicin-induced relaxation with simultaneous change in intracellular Ca2+ concentration. Pretreatment with iberiotoxin (100 nM), a blocker of Ca2+-activated K+ channel, only partially inhibited the capsaicin-induced relaxation. However, application of 4-aminopyridine (4-AP, 1 mM), a blocker of delayed rectifier K+ current significantly inhibited the capsaicin-induced relaxation with concomitant attenuation of the effect on intracellular Ca2+ concentration. These results indicate that capsaicin may have a direct relaxing effect on the smooth muscle contractility, and relaxation may be due to activation of the 4-AP-sensitive, delayed rectifier K+ channels in the rabbit coronary artery.

4-Aminopyridine↗
PubMed2000

Population frequency distributions of HDL, HDL(2), and HDL(3) cholesterol and apolipoproteins A-I and B in healthy men and women and associations with age, gender, hormonal status, and sex hormone use: the Stanford Five City Project.

BACKGROUND: The purpose of this study is to present population-based frequency distribution data for several lipoprotein-related variables and to examine their associations with gender, age, menopausal status, and sex hormone use. METHODS: High-density lipoprotein cholesterol (HDL-C), HDL(2)-C, HDL(3)-C, apolipoprotein (Apo) A-I, and Apo B were measured in a population-based sample of 1, 027 healthy adults from four California cities who participated in the 1989-1990 survey of the Stanford Five City Project. These data were examined cross-sectionally with sociodemographic and other related variables. RESULTS: Relative to men, all of the HDL-related parameters-HDL-C, HDL(2)-C, HDL(3)-C, Apo A-I-were significantly higher and Apo B levels were significantly lower among women (P < 0. 001). Menopausal status was not associated with HDL-related parameters, but Apo B levels were higher in post- versus premenopausal women (P < 0.001). Among women, HDL-C and Apo A-I levels were higher in oral contraceptive and estrogen replacement therapy users (P = 0.003). Most of the significant findings remained statistically significant after adjusting for age, body mass index, smoking, energy expenditure, and alcohol intake. CONCLUSIONS: These population-based data indicate that gender, menopausal status, and the use of sex hormones among women are associated with differential levels of one or more of HDL-C, HDL(2)-C, HDL(3)-C, Apo A-I, and Apo B, independent of age and a broad set of lifestyle factors.

Adult↗
PubMed2000

Associations of HDL, HDL(2), and HDL(3) cholesterol and apolipoproteins A-I and B with lifestyle factors in healthy women and men: the Stanford Five City Project.

BACKGROUND: Measures of the two major high-density lipoprotein (HDL) subfractions, HDL(2) and HDL(3), and the major apolipoproteins of HDL and low-density lipoprotein (LDL), Apo A-I and Apo B, may be etiologically important factors in the development of coronary artery disease. The association of lifestyle factors with these lipoprotein-related variables remains unclear. METHODS: HDL-C, HDL(2)-C, HDL(3)-C, Apo A-I, and Apo B levels were determined in a population-based sample of 1,027 healthy women and men aged 25-64 years, from four California cities who participated in the 1989/1990 survey of the Stanford Five City Project. In this cross-sectional study we examined the independent associations of these lipoprotein-related variables with body mass index (BMI), cigarette smoking, daily energy expenditure, alcohol intake, dietary intake, and hormone use (oral contraceptives and estrogen replacement therapy). RESULTS: In general, BMI and alcohol intake were the strongest independent predictors of the lipoprotein-related variables. The negative association of BMI with HDL-C was attributable primarily to the association with the HDL(2)-C subfraction, while for alcohol intake the positive association with HDL-C was attributable primarily to the association with HDL(3)-C, particularly in men. Among men, but not women, energy expenditure was a significant independent predictor of each of the lipoprotein-related variables, with positive associations observed for HDL-C, HDL(2)-C, HDL(2)-C, and Apo A-I and a negative association observed for Apo B (P < 0.005). CONCLUSIONS: Data from this population-based sample suggest that specific lifestyle factors are more strongly associated with some lipoprotein-related variables than with others, with notable gender differences.

Adult↗
PubMed2000

Functional comparison of Egr3 transcription factor isoforms: identification of an activation domain in the N-terminal segment absent from Egr3beta, a major isoform expressed in brain.

Recent studies indicate that the Egr family of transcription regulatory factors plays a key role in nervous system development and plasticity. In prior studies, we demonstrated that multiple isoforms of the Egr3 transcription regulatory factor are expressed in brain and appear to be generated by use of alternative translation start sites. To compare the functional activity of these isoforms, we have examined their ability to stimulate transcription of a luciferase reporter construct driven by the Egr response element. Analysis of a series of N-terminal truncation constructs indicates that Egr3 contains two distinct activation domains: one located in the segment upstream of Met(106), the start site of the major truncated isoform Egr3beta, and the other located C-terminal to all of the alternative translation start sites used to generate Egr3 isoforms detected in brain. We confirmed this inference by demonstrating that each of these segments is able to drive transcription when fused to the GAL4 DNA binding domain. Taken together, these studies indicate that the internal translation start sites present in Egr3 are used to generate Egr3 isoforms lacking the activation domain located N-terminal to Met(106).

Alternative Splicing↗
PubMed1999

Visiting elective students at the University of Toronto from the Korea University Medical College.

OBJECTIVES: The main goal of the international elective programme was to provide the Korean students with a cross-cultural educational environment. DESIGN: This programme was carried out on a voluntary basis during the summer vacation, rotating students through various clinical divisions in the teaching hospital. SETTING: The University of Toronto. SUBJECTS: Medical students from the Korea University Medical College. RESULTS: The students found the student-teacher relationship to be much more open and liberal. Due to a different curricular structure, the Canadians have better clinical skills and problem-solving abilities in real clinical settings. The cultural differences perceived by the students during the elective programme led them to believe that educational reform in Korea imperatively requires curricular change, but more importantly, a change in our traditional psychological and behavioural traits which derive from Confucianism. CONCLUSIONS: Extreme politeness, passiveness and blind respect for teachers, which are encouraged by Confucianism, are not effective in higher education. All the elective students, as well as the Canadian preceptors, believe that this programme is an invaluable asset.

Cross-Cultural Comparison↗
PubMed1999

Changes in plasma leptin during the treatment of diabetic ketoacidosis.

To test the hypothesis that insulin regulates leptin, we measured the plasma leptin concentration before and during treatment of diabetic ketoacidosis (DKA), a condition characterized by extreme insulin deficiency. The study included 17 patients with type 1 diabetes (7 males and 10 females), aged 10+/-1 yr (mean +/- SE), with a body mass index of 17.6+/-1.9 kg/m2. Patients were treated with continuous insulin infusion and fluid and electrolyte replacement. Plasma leptin was measured every 6 h in the first 24 h, during which patients received a total insulin dose of 0.6-2.0 U/kg. Plasma leptin concentrations were also measured in a control group of 29 stable type 1 diabetic children (12 males and 17 females) and 25 healthy children (11 males and 14 females), aged 11+/-1 yr, with a body mass index of 18.5+/-1.1 kg/m2. Before treatment, plasma leptin concentrations were significantly lower in patients with DKA than those in diabetic and healthy controls (4.9+/-1.2 vs. 9.0+/-1.8 and 11.2+/-2.1 ng/mL, respectively; P < 0.05). In the DKA patients, plasma leptin increased to 6.4+/-1.5, 7.5+/-1.9, 9.1+/-2.7, and 8.9+/-2.5 at 6, 12, 18, and 24 h, respectively, after starting treatment (P = 0.001). Thus, leptin levels increased by 38+/-10% and 92+/-38% within 6 and 24 h of starting treatment. There was no difference in the change in plasma leptin by 24 h between subjects who could eat (n = 7) and those who could not (n = 10). The plasma leptin increase was paralleled by a rise in insulin level and a decline in glucose and cortisol levels at 6 and 24 h. In conclusion, DKA was associated with decreased plasma leptin concentrations. Treatment resulted in a significant increase in plasma leptin, which may be due to the effect of insulin on leptin production. Our data lend support to the hypothesis that insulin is the link between caloric intake and plasma leptin.

Blood Glucose↗
PubMed1999

Observational learning in children with Down syndrome and developmental delays: the effect of presentation speed in videotaped modelling.

Children with severe developmental delays (three with Down syndrome and three with autism as the primary diagnosis) observed a videotaped model performing two basic dressing skills without prompting, verbal or otherwise, or explanation by an instructor. In a within-subjects design, dressing skills that were presented at a relatively slow presentation speed through videotaped modelling were eventually performed better than those presented at a relatively fast speed. These data in combination with evidence from this laboratory that passive modelling of basic skills is more effective than interactive modelling (e.g., Biederman, Fairhall, Raven, & Davey, 1998; Biederman, Davey, Ryder, & Franchi, 1994; Biederman, Ryder, Davey, & Gibson, 1991) suggest that standard instructional techniques warrant reexamination both from the basis of instructional effectiveness and the efficient use of the allotment of teacher time.

Child↗
PubMed1997

Can we identify who will adhere to long-term physical activity? Signal detection methodology as a potential aid to clinical decision making.

Signal detection methodology was used to identify the best combination of predictors of long-term exercise adherence in 269 healthy, initially sedentary adults ages 50-65 years. Less educated individuals who were assigned to supervised home-based exercise of either higher or lower intensity and who were less stressed and less fit at baseline than other individuals had the greatest probability of successful adherence by the 2nd year. Overweight individuals assigned to a group-based exercise program were the least likely to be successful 2 years later. Predictors of short-term (1-year) adherence were generally similar to predictors of 2-year adherence. Signal detection analysis may be useful for identifying subgroups of people at risk for underadherence who subsequently might be targeted for intervention.

Aged↗
PubMed1996

Calculating intraocular lens power in eyes with keratoconus using videokeratography.

A patient with keratoconus had cataract extraction and intraocular lens (IOL) implantation in both eyes. The IOL power was determined using keratometric values (K-values) measured by standard keratometry in the right eye and videokeratography in the left eye. The ideal IOL power and the K-value that would have led to the ideal IOL power were determined from the postoperative refraction at 6 weeks. The ideal K-value was compared with the K-values derived from videokeratography and standard keratometry. Refraction at 6 weeks postoperatively was 5.60 and 1.00 diopter more myopic than the aim in the right and left eye, respectively. The mean power in ring 3 in videokeratography of the left eye was the same as the ideal K-value calculated using the Holladay formula. Determining IOL powers with videokeratography-derived K-values might be more accurate than standard keratometry in patients with keratoconus.

Follow-Up Studies↗
PubMed1996

The effects of dietary ellagic acid on rat hepatic and esophageal mucosal cytochromes P450 and phase II enzymes.

Ellagic acid (EA), a naturally occurring plant polyphenol possesses broad chemoprotective properties. Dietary EA has been shown to reduce the incidence of N-2-fluorenylacetamide-induced hepatocarcinogenesis in rats and N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumors. In this study changes in the expression and activities of specific rat hepatic and esophageal mucosal cytochromes P450 (P450) and phase II enzymes following dietary EA treatment were investigated. Liver and esophageal mucosal microsomes and cytosol were prepared from three groups of Fisher 344 rats which were fed an AIN-76 diet containing no EA or 0.4 or 4.0 g/kg EA for 23 days. In the liver total P450 content decreased by up to 25% and P450 2E1-catalyzed p-nitrophenol hydroxylation decreased by 15%. No changes were observed in P450 1A1, 2B1 or 3A1/2 expression or activities or cytochrome b5 activity. P450 reductase activity decreased by up to 28%. Microsomal epoxide hydrolase (mEH) expression decreased by up to 85% after EA treatment, but mEH activities did not change. The hepatic phase II enzymes glutathione S-transferase (GST), NAD(P)H:quinone reductase [NAD-(P)H:QR] and UDP glucuronosyltransferase (UDPGT) activities increased by up to 26, 17 and 75% respectively. Assays for specific forms of GST indicated marked increases in the activities of isozymes 2-2 (190%), 4-4 (150%) and 5-5 (82%). In the rat esophageal mucosa only P450 1A1 could be detected by Western blot analysis and androstendione was the only P450 metabolite of testosterone detectable. However, there were no differences in the expression of P450 1A1, the formation of androstendione or NAD(P)H:QR activities between control and EA-fed rats in the esophagus. Although there was no significant decrease in overall GST activity, as measured with 1-chloro-2,4-dinitrobenzene (CDNB), there was a significant decrease in the activity of the 2-2 isozyme (66% of control). In vitro incubations showed that EA at a concentration of 100 microM inhibited P450 2E1, 1A1 and 2B1 activities by 87, 55 and 18% respectively, but did not affect 3A1/2 activity. Using standard steady-state kinetic analyses, EA was shown to be a potent non-competitive inhibitor of both liver microsomal ethoxyresorufin O-deethylase and p-nitrophenol hydroxylase activities, with apparent Ki values of approximately 55 and 14 microM respectively. In conclusion, these results demonstrate that EA causes a decrease in total hepatic P450 with a significant effect on hepatic P450 2E1, increases some hepatic phase II enzyme activities [GST, NAD-(P)H:QR and UDPGT] and decreases hepatic mEH expression. It also inhibits the catalytic activity of some P450 isozymes in vitro. Thus the chemoprotective effect of EA against various chemically induced cancers may involve decreases in the rates of metabolism of these carcinogens by phase I enzymes, due to both direct inhibition of catalytic activity and modulation of gene expression, in addition to effects on the expression of phase II enzymes, thereby enhancing the ability of the target tissues to detoxify the reactive intermediates.

Animals↗
PubMed1993

Prognostic significance of the proliferative potential of intracranial gliomas measured by bromodeoxyuridine labeling.

The growth potential of 174 intracranial gliomas was estimated by calculating the bromodeoxyuridine labeling index (BUdR LI). Each patient received a 30-min infusion of BUdR, 200 mg/m2, before tumor removal. Excised tumor specimens were stained immunohistochemically to determine the BUdR LI, or percentage of S-phase cells. A Cox proportional-hazards stepwise model was used to determine the correlation between the BUdR LI and survival. Among patients with glioblastomas, the BUdR LI did not improve the prediction once age was entered in the model. Among patients with malignant or low-grade astrocytomas, the BUdR LI was the best single predictor of survival. The relative predictive abilities of BUdR LI and histopathology were determined by analyzing malignant astrocytoma and glioblastomas together. Distinguishing between malignant astrocytomas and glioblastomas did not significantly improve the prediction of survival once the BUdR LI and age were entered into the model. Equations derived from the model indicate that the probability of survival is a function of age and BUdR LI in patients with glioblastoma or malignant astrocytoma, but is a function of BUdR LI alone in patients with low-grade astrocytoma. The equations also show a substantial difference in the impact of increased BUdR LI on survival among patients with glioblastoma or malignant astrocytoma and those with low-grade astrocytoma. Without highly effective treatments for specific tumor phenotypes, the survival of a patient with an intracranial glioma appears to depend strongly on the proliferative potential of the tumor. Thus, accurate estimates of the proliferative potential are important in predicting the survival of individual patients with gliomas as well as in evaluating the effectiveness of various types of treatment.

Age Factors↗