PubMed Health⌕ Search

Biomedical subjects

Y W Kwon

Publications and source records attributed to Y W Kwon.

At least 19 recordsLinked to original sources
PubMed2005

Vibrational characteristics of carbon nanotubes as nanomechanical resonators.

Using eigenvalue analysis of mass and stiffness matrices directly computed from atomistic simulations, natural frequencies and mode shapes of various carbon nanotubes are studied. The stiffness matrix was developed from the Tersoff-Brenner potential for carbon-carbon interactions. The computed frequencies of the radial breathing modes of a variety of armchair (n, n) nanotubes agree well with results obtained by others using different techniques. In addition, the study reveals diverse mode shapes such as accordion-like axial modes, lateral bending modes, torsional modes, axial shear modes, and radial breathing modes for a variety of single-wall, multi-wall, and bamboo-type carbon nanotubes. The effects of different constraints on the carbon nanotube ends on the computed frequencies and mode shapes have been investigated for possible applications in vibration sensors or electromechanical resonators.

Computer Simulation↗
PubMed2003

Muscle fibre size and capillarity in Korean diving women.

AIM: Effects of prolonged habitual cold-water immersion on fibre size and capillarity in vastus lateralis muscle were studied in human beings. The hypothesis tested in the present study was that cold acclimatized human skeletal muscle would have reduced muscle fibre size and higher capillarity, favouring the idea of efficacy of recruitment under cold environment. METHODS: Ten women breath-hold divers (BHDs) and 10 active women (controls CONs) participated in this study. Muscle biopsy was obtained from vastus lateralis and determined fibre type composition and capillary density. RESULTS: A major finding was that all BHDs revealed a markedly smaller cross-sectional area (CSA) in all fibre types than the CONs, or even than any other morphological data reported in previous investigations. Furthermore, mean CSA of type II fibre (range 1205-2766 microm2) was much smaller than type I fibre (2343-4327 microm2). The number of capillaries per fibre in different fibre types in the BHDs was higher than in the CONs (P < 0.001), and diffusional area was smaller in type II fibres than in type I fibres (P < 0.001). The BHDs and the CONs have similarity in the percentage of type I fibres, but type II fibre was predominant in both groups. Interestingly the proportion of type IIx fibre in the BHDs was higher (31%) than in the CONs (22%). No significant difference was found in the thigh circumference between the groups. CONCLUSION: The present study demonstrates that prolonged habitual cold-water immersion may induce a decrease in fibre size and an increase in capillarity in human skeletal muscle.

Adipose Tissue↗
PubMed2000

Insulin-like growth factor II induces interleukin-6 expression via NFkappaB activation in psoriasis.

IGF-II is known to induce the growth of keratinocytes and the level was significantly elevated in the tissue fluid of psoriatic lesion. However, the role of IGF-II in psoriasis is not well defined. Because an inflammatory cytokine, interleukin-6 (IL-6) is overexpressed in psoriatic lesions, we explored whether IGF-II has some role in psoriasis through induction of IL-6. Therefore, the expression of IL-6 was analyzed after treatment of IGF-II in primary cultured psoriatic cells and human keratinocyte cell line, HaCaT. We found that IGF-II induced the IL-6 mRNA expression significantly. To investigate the inducing mechanism of IL-6 by IGF-II, we examined the promoter activity of IL-6 and the DNA binding activity of NFkappaB, a strong regulator of IL-6. Interestingly, IL-6 promoter activity and the binding activity of NFkappaB were remarkably increased by IGF-II. Western blot data that IkappaB was reduced by IGF-II significantly suggest that NFkappaB activation by IGF-II may be mediated through the downregulation of IkappaB. Therefore, these results suggest a novel role of IGF-II in psoriasis possibly by inducing IL-6 through the activation of NFkappaB mediated by downregulation of IkappaB.

Base Sequence↗
PubMed1998

Identification of genes differentially expressed by hypoxia in hepatocellular carcinoma cells.

In order to identify genes differentially expressed under hypoxia (1% O2, 5% CO2, balance N2), we performed mRNA differential display analysis using total RNA extracted from hypoxic and normoxic HepG2, human hepatocellular carcinoma (HCC) cells. Of the differentially expressed genes by hypoxia, some of cDNA fragments were cloned and sequenced. The expression patterns of these clones by hypoxia were confirmed by Northern blot analysis and the quantitative RT-PCR. Down-regulated genes by hypoxia have homology to cDNA sequences encoding cytochrome oxidase subunit II and ADP/ATP translocase, respectively. Up-regulated gene by hypoxia was identified as Homo sapiens oscillin. Moreover, novel genes induced by hypoxia represent partial sequences of cDNAs that have not been reported or functionally identified. Up- or down-regulated expression of these genes in response to hypoxia may contribute to human hepatocarcinogenesis.

Amino Acid Sequence↗
PubMed1996

Brain-derived neurotrophic factor transiently stabilizes silent synapses on developing neuromuscular junctions.

A general feature of the developing nervous system is the activity-dependent rearrangement of genetically defined, synaptic connections. A parallel process occurs at the developing neuromuscular junction as activity-dependent synapse withdrawal reduces the initial polyneuronal innervation of individual muscle fibers to a mononeuronal innervation within the first few weeks after birth. Because members of the neurotrophin gene family influence motor neuron differentiation and survival, we examined whether or not they also influence synaptic rearrangements in neonatal muscles. We found that treatment with brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) causes the transient retention of multiple synaptic contacts on neonatal myofibers. However, the combination of both electrophysiological and histological assays revealed that the majority of such supernumerary synaptic contacts are functionally inactive or "silent." There also occurs an increase in the number of retracting axons. Because BDNF mRNA is expressed in developing muscle and the trkB tyrosine kinase receptor for BDNF is expressed by neonatal motor neurons, our results suggest that BDNF may play an endogenous role in the refinement of synaptic connectivity that occurs in skeletal muscles after birth.

Animals↗
PubMed1995

Leukemia inhibitory factor influences the timing of programmed synapses withdrawal from neonatal muscles.

We show that leukemia inhibitory factor (LIF) plays a physiological role in the programmed withdrawal of synapses from neonatal muscles. First, LIF mRNA is present in embryonic skeletal muscle and is developmentally regulated. We detect high levels of LIF mRNA at embryonic day 17 (E17) in mouse hind leg muscles. The content of LIF mRNA falls 10-fold between E17 and birth and then remains low in the neonate and adult. The decrease in LIF mRNA in skeletal muscle coincides with the end of secondary myogenesis and the completion of the adult number of myofibers. Second, treatment of the mouse tensor fascia latae (TFL), a superficial muscle of the hind leg, with LIF from birth (100 ng/day), transiently delays the withdrawal of excess inputs from polyneuronally innervated myofibers by approximately 3 days. The midpoint of the process is shifted from 7.5 +/- 10.2 +/- 0.6 days of age. LIF treatment delays synapse withdrawal by altering its timing without an appreciable effect on its rate. Third, in mice homozygous for a disruption of the LIF gene, the midpoint in the reduction of multiply innervated TFL myofibers occurs 1 day earlier, at 6.5 +/- 0.5 days of age. Muscle fiber number is unchanged in LIF null mice. Treatment with LIF does not alter the rate of neonatal growth, the number of muscle fibers in the TFL, or the reappearance of inputs that have been eliminated. Instead, LIF appears to delay maturation of the motor unit by transiently delaying the onset of synapse withdrawal. We hypothesize that this is a necessary component of a selective process that will operate simultaneously and equally on multiple, competing motor units.

Animals↗
PubMed1995

Age-dependent penetrance of disease in a transgenic mouse model of familial amyotrophic lateral sclerosis.

The mutation gly93-->ala of Cu,Zn superoxide dismutase (SOD) is found in patients with familial amyotrophic lateral sclerosis and causes motor neuron disease when expressed in transgenic mice. The progression of clinical and pathological disease was studied in a line of mice designated G1H. Clinical disease started at 91 +/- 14 days of age with fine shaking of the limbs, followed by paralysis and death by 136 +/- 7 days of age. Pathological changes begin by 37 days of age with vacuoles derived from swollen mitochondria accumulating in motor neurons. At the onset of clinical disease (90 days), significant death of somatic motor neurons innervating limb muscles has occurred; mice at end-stage disease (136 days) show up to 50% loss of cervical and lumbar motor neurons. However, neither thoracic nor cranial motor neurons show appreciable loss despite vacuolar changes. Autonomic motor neurons also are not affected. Mice that express wild-type human Cu,Zn SOD remain free of disease, indicating that mutations cause neuron loss by a gain-of-function. Thus, the age-dependent penetrance of motor neuron disease in this transgenic model is due to the gradual accumulation of pathological damage in select populations of cholinergic neurons.

Aging↗
PubMed1994

Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.

Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Systemic injections of ciliary neurotrophic factor induce sprouting by adult motor neurons.

The ability of ciliary neurotrophic factor (CNTF) to induce sprouting by undamaged adult motor neurons was studied in gluteal muscles of adult ICR mice. Low doses of CNTF (0.02 mg kg-1 day-1) only induced sprouting in gluteus muscles that were beneath the site of injection, whereas high doses of CNTF (0.4-1.2 mg kg-1 day-1) acted systemically to induce motor neuron sprouting. We found little difference between the type or quality of sprouting induced by CNTF compared with muscle paralysis. Both stimuli induced sprouts of the same length, although muscle paralysis tended to induce more sprouts per end-plate. Paralysis also induced more nodal sprouting than did CNTF, but both were weaker stimuli for nodal sprouting than was partial denervation. In addition to its effects on motor neuron sprouting, high doses of CNTF induced loss of up to 36% of the body weight of treated mice. The substantial wasting caused by CNTF indicates that the factor has potent cachectic activity.

Animals↗
PubMed1993

Rat cardiac calcium channels and their relationships with beta-adrenergic and muscarinic receptors in hypothyroidism.

Thyroid hormone deficiency is associated with changes in the cardiovascular system. No one has reported the measures of both atrial and ventricular calcium channel density and function, in association with measures of negative and positive channel modulators, in hypothyroid hearts. Hormonally-induced modulation of calcium channels has clinical significance in the development and application of therapeutic agents in dysthyroid states. We thyroidectomized male rats and sham-operated euthyroid controls, in order to measure radioligand binding to ventricular and atrial membrane Ca2+ channels ([3H]-isradipine), beta-adrenoceptors ([125I]-iodocyanopindolol) and atrial muscarinic receptors ([3H]-quinuclidinyl benzilate) and related these data to contraction and heart rate responses to isoproterenol, carbachol and calcium. When data from hypothyroid tissues were compared to those of controls, the densities of calcium channels increased 50% in ventricles, but no differences were seen in atrial homogenates. In both atria and ventricles, beta-adrenoceptors decreased modestly with no change in affinity. Atrial muscarinic receptor density was also unchanged. Dose response curves of left atrial contractions showed: decreased sensitivity (increased EC50 value) but equal maximal responsiveness to extracellular calcium; an increased carbachol sensitivity (decreased EC50 value); and no significant difference in isoproterenol response. Comparisons of within-individual preparation ratioed EC50 values confirm the changed calcium and carbachol sensitivities. Heart-rate dose response curves displayed: increased maximal heart rate responsiveness to calcium associated with increased EC50 values; isoproterenol sensitivity was decreased nearly 3-fold. There was no significant difference in heart rate response to carbachol; however, ratioed values of carbachol and calcium EC50s were significantly different. These data are consistent with a tissue-level state of enhanced negative chronotropism and inotropism occurring in hypothyroid myocardia. We also confirm an earlier controversial finding of increased calcium channel density in ventricles from hypothyroid rats.

Animals↗
PubMed1993

Continuous versus intermittent nitroglycerin administration in experimental heart failure: vascular relaxation and radioligand binding to adrenoceptors and ion channels.

Continuous nitroglycerin (NTG) administration causes pharmacologic tolerance in humans and animals, whereas intermittent dosing is capable of avoiding or reducing tolerance development. The mechanism of NTG-induced hemodynamic tolerance may involve specific vascular desensitization and/or neurohormonal compensation. We compared effects of long-term (10 days) NTG administration (continuous or intermittent 12 h on/12 h off transdermal dosing, 10 micrograms/min) to rats with congestive heart failure (CHF) on radioligand binding from selected tissues. Tension responses in isolated blood vessels, plasma renin activity (PRA), plasma Na+ and K+ concentrations were also determined. The maximal binding values (Bmax) for [3H]glyburide and [3H]PN 200 110 in homogenates of left ventricle, right ventricle, and brain were not significantly different after NTG administration (continuous or intermittent), as compared with control. Intermittent, but not continuous, NTG caused significant increases in beta-adrenoceptor densities in the left ventricle, as judged by [3H]dihydroalprenolol binding (Bmax values: intermittent NTG 34.5 +/- 4.8, continuous NTG 24.4 +/- 2.6, placebo control 20.9 +/- 2.9 fmol/mg protein); Kd values for all ligands were not significantly altered by NTG administration. Both intermittent and continuous NTG increased the vascular contractile response to phenylephrine in isolated rat thoracic aorta. Slight reductions (two- to four-fold shifts in EC50 values) in thoracic aorta relaxant response to NTG were observed in both treatment groups as compared with control. Intermittent and continuous NTG administration caused selective changes in beta-adrenoceptor density and vascular response. These changes may contribute partly to the phenomenon of pharmacologic tolerance after chronic nitrate administration.

Administration, Cutaneous↗
PubMed1992

Effect of an homologous series of aliphatic alcohols on neuronal and smooth muscle voltage-dependent Ca2+ channels.

The acute inhibitory actions of alcohol on K(+)-stimulated 45Ca2+ uptake into synaptosomes shows regional variation in sensitivity throughout the brain, suggesting the possibility of a selective action on a specific Ca2+ channel subtype. This was examined by comparing the effects of a homologous series of aliphatic alcohols on synaptosomal Ca2+ channels with their actions on K(+)-stimulated Ca2+ channels in guinea-pig intestinal longitudinal muscle, which have been demonstrated to be of the L-type. K(+)-stimulated contraction of and [3H]nitrendipine binding to smooth muscle were both inhibited by the alcohols at similar concentrations, with the potency increasing with chain length. In synaptosomes, however, K(+)-stimulated 45Ca2+ uptake was 5-30 times more sensitive to the inhibitory actions of alcohol than were [3H]nitrendipine and [125I]omega-conotoxin binding. These observations suggest that K(+)-stimulated 45Ca2+ uptake is mediated by a non-L non-N type channel which is more sensitive to the acute effects of alcohols. This is supported by the observation that K(+)-stimulated 45Ca2+ uptake which is insensitive to L- and N-channel antagonists was inhibited by funnel web spider venom.

Alcohols↗
PubMed1992

Synthesis and muscarinic receptor activity of ester derivatives of 2-substituted 2-azabicyclo[2.2.1]heptan-5-ol and -6-ol.

Radioligand binding affinities of four new muscarinic antagonists and six potential muscarinic agonists which possess the 2-alkyl-2-azabicyclo[2.2.1]heptane ring system have been determined in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations to examine the selectivity for subtypes of muscarinic receptor. The efficacies of the potential muscarinic agonists were determined by the ratio of binding affinities against [3H]QNB and [3H]Oxo-M. Four muscarinic antagonists which have the 2,2-diphenylpropionate side chain at either the C5 (5-endo or 5-exo) or the C6 (6-endo or 6-exo) positions did not discriminate between the subtypes of muscarinic receptors. The 2,2-diphenylpropionate 5-endo substituted compound was the most potent, showing affinities between 4.23 x 10(-10) and 1.18 x 10(-9) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. The rank order of ester potency was 5-endo greater than 5-exo greater than 6-endo greater than 6-exo. A molecular modeling study based on the pharmacophore developed for azaprophen was used to account for the relative potency of these antagonists. Six potential muscarinic agonists which have acetoxy groups in the C5 or C6 position with an N-methyl or N-benzyl substituent did not discriminate subtypes of muscarinic receptors and had affinities between 6.63 x 10(-6) and 4.76 x 10(-5) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. exo-2-Methyl-5-acetoxy-2-azabicyclo[2.2.1]heptane was the most efficacious partial agonist.

Animals↗
PubMed1992

Synthesis of 2-(3-substituted-1,2,4-oxadiazol-5-yl)-8-methyl-8-azabicyclo [3.2.1]octanes and 2 alpha-(3-substituted-1,2,4-oxadiazol-5-yl)-8-methyl-8- azabicyclo[3.2.1]oct-2-enes as potential muscarinic agonists.

Radioligand binding affinities of seven muscarinic receptor ligands which possess an oxadiazole ring side chain have been determined in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations to determine the selectivity for subtypes of muscarinic receptor. The ratios of binding constants in brain membranes were measured as an indicator of potential agonist activity against [3H]QNB and [3H]Oxo-M. These muscarinic ligands did not discriminate the subtypes of muscarinic receptors. Six muscarinic ligands which have a 3-amino- or 3-methyl-1,2,4-oxadiazol-5-yl groups attached to the 8-methyl-8-azabicyclo[3.2.1]oct-2-ene or 8-methyl-8-azabicyclo[3.2.1]octane head group show binding constants between 2.04 x 10(-6) and 1.79 x 10(-5) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. 1-Methyl-2-[3-amino-1,2,4-oxadiazol-5-yl]piperidine shows low binding constants of approximately 10(-4) M in rat heart and rat brain. (1R,5S)-2-[3-Amino-1,2,4-oxadiazol-5-yl]-8-methyl-8-azabicyclo- [3.2.1]oct-2-ene [(1R,5S)-17] was the most active compound.

Animals↗
PubMed1991

Interactions of local anesthetics with neuronal 1,4-dihydropyridine binding sites.

A series of local anesthetics competed with 1,4-dihydropyridine [3H]PN 200,110 binding to synaptosomes from guinea pig cerebral cortex synaptosomes. Dibucaine (10(-3)M) increased the dissociation rate of bound [3H]PN 200,110 consistent with an indirect, rather than competitive, interaction between local anesthetics and the 1,4-dihydropyridine site. The binding activities were compared to those previously available for local anesthetic competition with [3H]batrachotoxinin benzoate binding at a Na+ channel site. A linear correlation was observed between the two sets of activities with significantly higher activities being exhibited at the Na+ channel site. This relationship is consistent with the significant structural homologies exhibited between Na+ and Ca2+ channels.

Anesthetics, Local↗
PubMed1991

Chiral aspects of drug action at ion channels: a commentary on the stereoselectivity of drug actions at voltage-gated ion channels with particular reference to verapamil actions at the Ca2+ channel.

Ion channels may be considered as pharmacological receptors possessing specific drug binding sites with defined structure-activity relationships. Accordingly drug binding to ion channels is stereoselective. Interpretation of this stereoselectivity may be complex because of the existence of differences in affinity and access to different channel states. Such state-dependent interactions may give rise to quantitative and qualitative differences in stereoselectivity. The implications of such differences are reviewed for drug action at Na+, K+ and Ca2+ channels. Detailed attention is paid to the actions of verapamil enantiomers in the cardiovascular system where activities differ in vascular and cardiac tissues because of state-dependent interactions and stereoselective first-oass metabolism.

Animals↗
PubMed1991

Molecular level model for the agonist/antagonist selectivity of the 1,4-dihydropyridine calcium channel receptor.

Crystal structures of the 1,4-dihydropyridine (1,4-DHP) calcium channel activators Bay K 8643 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-nitrophenyl)-pyridine-5-carboxy lat e], Bay O 8495 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-trifluoromethylphenyl)-pyridine-5- carboxylate], and Bay O 9507 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(4-nitrophenyl)-pyridine-5-carboxy lat e] were determined. The conformations of the 1,4-DHP rings of these activator analogues of Bay K 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate] do not suggest that their activator properties are as strongly correlated with the degree of 1,4-DHP ring flattening as was indicated for members of the corresponding antagonist series. The solid state hydrogen bonding of the N(1)-H groups of the activators is not, unlike that of their antagonist counterparts, to acceptors that are directly in line with the donor. Rather, acceptor groups are positioned within +/- 60 degrees of the N(1)-H bond in the vertical plane of the 1,4-DHP ring. Previously determined structure-activity relationships have indicated the importance of this N(1)-H group to the activity of the 1,4-DHP antagonists. Based on these observations, a model is advanced to describe the 1,4-DHP binding site of the voltage-gated Ca2+ channel and its ability to accommodate both antagonist and activator ligands.

Calcium Channel Agonists↗