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Biomedical subjects

K S Hwang

Publications and source records attributed to K S Hwang.

At least 19 recordsLinked to original sources

Adult-to-adult living donor liver transplantation at the Asan Medical Center, Korea.

Between February 1997 and December 2001, 311 adult-to-adult living donor liver transplants (A-A LDLTs) were performed at the Asan Medical Center for patients above 20 years of age. Indications for A-A LDLT were: chronic hepatitis B (203), chronic hepatitis C (5), hepatocellular carcinoma (64), alcoholic cirrhosis (9), cryptogenic cirrhosis (4), secondary biliary cirrhosis (5), primary biliary cirrhosis (1), Wilson' s disease (2), autoimmune hepatitis (1), hepatic tuberculosis (1), cholangiocarcinoma (1), fulminant hepatic failure (14) and primary non-function of cadaveric liver graft (1). Of 311 A-A LDLTs, 36 were of medical high urgency, 20 were for acute and subacute hepatic failure, 15 were for hepato-renal syndrome and 1 was for primary non-function. Recipient age ranged from 27 to 64 years. Donor age ranged from 16 to 62 years. There was no donor mortality. Implanted liver grafts were categorized into seven types: 175 modified right lobe (MRL), 70 left lobe, 32 right lobe, 20 dual grafts, 10 left lobe plus caudate lobe, three extended right lobe and one posterior segment. In MRL, the tributaries of the middle hepatic vein were reconstructed by interpositioning a vein graft. Indication for dual graft implantation was the same as single graft A-A LDLT, and four of 20 were emergency cases. Of 20 dual grafts, 14 received two left lobes, four received a left lobe and a lateral segment, one received a right lobe and a left lobe and one received a lateral segment and a posterior segment. Graft volume ranged from 28% to 83% of the standard liver volume of the recipients. There were 33 (10.6%) in-hospital mortalities (< 4 months) among the 310 patients after 311 A-A LDLTs. Of the 36 patients receiving emergency transplants, 31 survived. These encouraging results justify the expansion of A-A LDLT in coping with increasing demands, even in urgent situations. We have aimed to introduce the establishment of the efficacy of A-A LDLT in various end-stage chronic and acute liver diseases, as well as new technical advances to overcome small graft-size syndrome by using dual-graft implantation and MRL, both of which were first developed in our department.

Adult↗

Effect of poling conditions on growth of calcium phosphate crystal in ferroelectric BaTiO3 ceramics.

Recently, ceramic materials have been given a lot of attention as candidates for implant materials, since they possess biologically favorable characteristics for osseointegration. Among them, BaTiO3 (BTO) ceramics are ferroelectric and piezoelectric after poling treatments. However, little or no information is available on the poling condition of BTO and their effect on calcium phosphate (CaP) formation. In this study, the effect of poling conditions on the formation of CaP layer was investigated. It was observed from this study that CaP was formed on negatively charged BTO surfaces. An increase in Ca/P ratio to 1.67 was observed when the poling temperature was increased above the Curie temperature. On positively charged BTO, no CaP layer was observed.

Journal Article↗

Endogenous nitric oxide inhibits neutrophil adherence to lung epithelial cells to modulate interleukin-8 release.

To investigate the effect of neutrophil adherence to epithelial cells on the release of interleukin 8 (IL-8), we measured neutrophil adherence in the presence or absence of IFN-gamma+TNF-alpha+IL-1beta (cytomix) stimulation on cultured A549 epithelial cells. The extent of neutrophil adherence to A549 epithelial cells was measured and the concomitant production of IL-8 and nitrite were assayed. The roles of adhesion molecules and nitrite in modulation of neutrophil adherence were examined by pretreatment with oversaturating ICAM-1 blocking antibody and L-NAME (1 mM), respectively. There was a time-dependent spontaneous and cytomix-induced release of IL-8 from epithelial cells, as well as a time-dependent increase in the magnitude of neutrophil adherence to epithelial cells. Stimulation of epithelial cells with cytomix induced a further increase in neutrophil adherence. Pretreatment with oversaturated ICAM-1 monoclonal antibody inhibited neutrophil adherence with or without cytomix stimulation. The inhibition of neutrophil adherence to epithelial cells with ICAM-1 monoclonal antibody or a semipermeable membrane downregulated the release of IL-8 with or without cytomix stimulation. Stimulation with cytomix decreased nitrite production. Both neutrophil adherence and L-NAME pretreatment significantly inhibited the production of nitrite. The inhibition of neutrophil adherence to epithelial cells with ICAM-1 monoclonal antibody or a semipermeable membrane upregulated nitrite production. Pretreatment with L-NAME failed to modify the spontaneous release of IL-8, but significantly enhanced the response to adherence and cytomix. In conclusion, endogenous nitric oxide may play a role in preventing neutrophil adherence to lung epithelial cells, thus modulating concomitant IL-8 release.

Antibodies, Monoclonal↗

Structure and dynamics of dense monolayers of no adsorbed on Rh(111) in equilibrium with the gas phase in the Torr pressure range.

Using scanning tunneling microscopy, we show the phase transition between new structures of NO on Rh(111) in equilibrium with the gas phase near 300 K, in the Torr pressure range. Two phases with (2 x 2) and (3 x 3) periodicity transform into each other as the pressure and temperature change around the equilibrium P-T line. By measuring P and T at coexistence, we determined the heat of adsorption in the (3 x 3) structure. From the phase boundary dynamics, the activation energy barrier between phases were estimated. The results demonstrate that unique information can be obtained from high-pressure and high-temperature studies.

Journal Article↗

Interleukin-5 in growth and differentiation of blood eosinophil progenitors in asthma: effect of glucocorticoids.

1. There are increased numbers of circulating CD34(+) progenitor cells for eosinophils in patients with atopic asthma, with a further increase following allergen exposure or spontaneous worsening of asthma. We investigated the expression of IL-5 and IL-5Ralpha receptor in circulating CD34(+) progenitor cells in allergic asthmatics and the effects of corticosteroids. 2. Using double-staining techniques, up to 50% of CD34(+) cells expressed intracellular IL-5, and by RT - PCR, there was significant expression of IL-5 mRNA. When cultured in a semi-liquid methylcellulose medium, there were more eosinophil colony-forming units grown from asthmatic non-adherent mononuclear cell depleted of T cells in the presence of the growth factors GM-CSF, SCF and IL-3, but not of IL-5. 3. An anti-IL-5Ralpha receptor antibody and an anti-sense IL-5 oligonucleotide reduced the number of eosinophil colony forming units. No IL-5 mRNA or protein expression on T cells was observed in asthmatics or normal subjects. In the presence of growth factors including IL-5, there were significantly greater colony numbers with eosinophilic lineage grown from either asthmatics or normal subjects. 4. Dexamethasone (10(-6) M) suppressed IL-5 mRNA and protein expression in CD34(+) cells, and reduced eosinophil colony-forming units in asthmatics, but not in normal subjects. Dexamethasone did not change the expression of IL-5Ralpha on CD34(+) cells. 5. We conclude that there is increased expression of IL-5 on blood CD34(+) cells of patients with asthma and that this expression may auto-regulate eosinophilic colony formation from these progenitor cells. Corticosteroids inhibit the expression of IL-5 in circulating CD34(+) progenitor cells.

Adult↗

The interaction between intrathecal neostigmine and GABA receptor agonists in rats with nerve ligation Injury.

UNLABELLED: Nerve ligation injury may produce a pain syndrome that includes tactile allodynia. Reversal effects on tactile allodynia have been demonstrated after the intrathecal administration of gamma-aminobutyric acid (GABA) receptor agonists or cholinesterase inhibitors in rats. We examined the drug interactions between neostigmine and muscimol or baclofen in a rat model of nerve ligation injury. Rats were prepared with tight ligation of the left L5-6 spinal nerves and chronic intrathecal catheter implantation. Tactile allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hindpaw. Thresholds for paw withdrawal were assessed. Neostigmine (0.3-10 microg), muscimol (0.1-10 microg), and baclofen (0.1-3.0 microg) were administered to obtain the dose-response curve and the 50% effective dose (ED(50)). Fractions of ED(50) values were administered intrathecally to establish the ED(50)s of drug combinations (neostigmine-muscimol and neostigmine-baclofen). The drug interactions were performed. Intrathecal neostigmine, muscimol, baclofen, and their combinations produced a dose-dependent increase in withdrawal threshold of the lesioned hindpaw. Both analyses revealed a synergistic interaction for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination was additive. These results suggest that the activation of both muscarinic and GABA(A) receptors is required for synergistic interaction. IMPLICATIONS: This study indicates that drug interaction is synergistic for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination is additive. In a rat model of nerve ligation injury, neostigmine, muscimol, baclofen, and their combinations provide an antagonism on touch-evoked allodynia at the spinal level.

Animals↗

An analysis of drug interaction between morphine and neostigmine in rats with nerve-ligation injury.

UNLABELLED: Intrathecal neostigmine reverses mechanical allodynia in humans and animals. The efficacy of morphine in a neuropathic pain state is still controversial. This study examines the antiallodynic interaction between morphine and neostigmine in a rat model of neuropathic pain. Rats were prepared with tight ligation of left L5-6 (fifth and sixth lumbar) spinal nerves and chronic intrathecal catheter implantation. Mechanical allodynia was measured by using application of von Frey hairs to the left hindpaw. Morphine (1, 3, 10, and 30 microg) and neostigmine (0.3, 1, 3, and 10 microg) were administered intrathecally to obtain the dose-response curves and the 50% effective dose (ED(50)) for each drug. ED(50) values and fractions of the ED(50) values (1/2, 1/4, and 1/8) were administered intrathecally in an equal dose ratio to establish the ED(50). Isobolographic and fractional analyses for the drug interaction were performed. Intrathecal morphine produced a moderate antagonism of the tactile allodynia. A morphine-neostigmine combination produced a dose-dependent increase in withdrawal threshold of the lesioned hind paw with reduced side effects. Both analyses revealed a synergistic interaction after the coadministration of morphine and neostigmine. These experiments suggest that the antiallodynic action of a morphine-neostigmine combination is synergistic at the spinal level. IMPLICATIONS: This study indicates that, by using both isobolographic and fractional analyses, the antiallodynic effect of intrathecal morphine and neostigmine is synergistic when coadministered intrathecally. In a rat model of neuropathic pain, the intrathecal morphine produced a moderate antagonism on touch-evoked allodynia at the spinal level.

Analgesics, Opioid↗

Do patients know which healthcare professionals are doctors?

Using an anonymous questionnaire survey this study aimed to determine patients' knowledge of professional qualifications and which healthcare professionals are required to have undergone medical school training. Four hundred patients were questioned equally distributed between four general practices in Roehampton, London. The mean age of the sample was 43 y. Gender ratio was skewed with 31% men and 63% women (6% missing data). Amongst the three professional groups, just over 50% scored correctly. Almost 25% of respondents failed to correctly identify the listed doctors and medical non-doctors. The mean score of incorrectly identified alternative practitioners was 13%. There were significant age-related differences for scores, identified by chi-square and trend analysis, with the younger groups scoring better. Patients were largely unsure in identifying professional qualifications. It is concluded that confusion exists amongst patients as to which health-workers are doctors. Listing of professional qualifications does not help in clarifying this. Health-workers whose work involves invasive procedures or drug therapy are more likely to be thought of as medically qualified doctors. This confusion appears not to exist with alternative practitioners. Given the growing regard to appropriate and useful skill mix of health professionals (patients are increasingly seen in the first instance by non-doctors, eg nurse practitioners), it would seem appropriate that patients are made fully aware of who they are consulting.

Adolescent↗

The antiallodynic effects of intrathecal cholinesterase inhibitors in a rat model of neuropathic pain.

BACKGROUND: This study determined the effect of intrathecally administered cholinesterase inhibitors, edrophonium and neostigmine, on nerve injury-induced, touch-evoked allodynia and identified the pharmacologic characteristics of this action. METHODS: Rats were prepared with tight ligation of the left L5 and L6 spinal nerves and with lumbar intrathecal catheters fitted for long-term monitoring. Edrophonium (3, 10, 30, or 100 microg) or neostigmine (0.3, 1, 3, or 10 microg) was administered intrathecally. Tactile allodynia and motor weakness were assessed. To evaluate the pharmacologic characteristics of the activity, a muscarinic receptor antagonist or a nicotinic receptor antagonist was administered intrathecally before edrophonium or neostigmine was injected. To compare the action of subtype antagonists, the M1 muscarinic receptor antagonist pirenzepine, the M2 antagonist methoctramine, the M3 antagonist 4-DAMP (diphenylacetoxy-N-methypiperidine), and the M4 antagonist tropicamide were administered intrathecally before cholinesterase inhibitors were injected. RESULTS: Intrathecal edrophonium or neostigmine produced a dose-dependent antagonism of the touch-evoked allodynia. Neostigmine resulted in a moderate effect on motor weakness at doses of 3 and 10 microg. Pretreatment with intrathecal atropine but not mecamylamine yielded a complete antagonism of the effects of the cholinesterase inhibitors. In addition, antiallodynia produced by edrophonium (100 microg) was reversed by pretreatment with methoctramine, 4-DAMP, tropicamide, and pirenzepine. In the neostigmine (10 microg) group, only the M1 antagonist pirenzepine had a moderate effect on reversal of increased allodynic threshold. CONCLUSIONS: These experiments suggest that intrathecal edrophonium or neostigmine produces an antagonism on touch-evoked allodynia at the spinal level in a rat model of neuropathic pain and that the antiallodynic action of cholinesterase inhibitors is probably mediated by a spinal muscarinic system, especially at the M1 receptor subtype.

Animals↗

cAMP-dependent enhancement of dihydropyridine-sensitive calcium channel availability in hippocampal neurons.

Dihydropyridine-sensitive calcium channels can be strongly modulated by cAMP-dependent phosphorylation. This modulation takes the form of increased channel availability in cardiac myocytes (for review, see McDonald et al., 1994) and has been suggested to be essential for voltage-dependent facilitation in adrenal chromaffin cells (Artalejo et al., 1992) and skeletal muscle (Sculptoreanu et al., 1993b). To determine the role of cAMP-dependent phosphorylation on dihydropyridine-sensitive calcium channels in hippocampal neurons, we have used both single-channel and whole-cell recording techniques and have examined the effects of the membrane-permeable cAMP analog 8-(4-chlorophenylthio) (CPT)-cAMP and the protein kinase inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and N-[2-(p-bromocinnamyl-amino)ethyl]-5-isoquinolinesulfonamide (H-89). Hippocampal neurons contain two kinds of dihydropyridine-sensitive calcium channel activity: Ls and Lp (Kavalali and Plummer, 1994). The Ls channel closely resembles the cardiac L-type channel, whereas the Lp channel shows a novel low-voltage form of voltage-dependent potentiation (). 8-CPT-cAMP increased the availability of both the Ls and Lp channels and caused a parallel increase in Lp channel reopenings at the repolarization potential that result from voltage-dependent potentiation. This effect was completely blocked by the broad spectrum kinase inhibitor H-7 and by the protein kinase A-specific inhibitor H-89. The two inhibitors, however, did not disrupt baseline potentiation of the Lp channel, suggesting that cAMP-dependent protein kinase activity can enhance Ls and Lp channel activity but is not required for voltage-dependent potentiation in hippocampal neurons.

Animals↗

Arterial and venous blood sampling in pharmacokinetic studies: bumetanide in rabbits.

The pharmacokinetics of bumetanide were evaluated simultaneously using both arterial and venous plasma data in 4 rabbits after a rapid 5 sec intravenous (iv) bolus dosing. Initial arterial to venous concentration ratios at 5 sec after injection were the highest with the values of 1410, 246, 4.25, and 351 for rabbits 1-4, respectively. Both curves decayed paralleling each other at the terminal phase with the higher venous levels than the arterial levels by 21.6, 48.2, 17.0, and 47.9% for rabbits 1-4, respectively. An exponential term with a negative coefficient was used to account for the short and steep rising phase of venous plasma levels after injection. Detailed analysis showed apparent volume of distribution at steady state (VSS) and mean residence time (MRT) values calculated from venous plasma data were higher than those form arterial plasma data. A plot of 1/Q (urine flow rate) versus 1/CLR (renal clearance) of bumetanide yielded a straight line in 4 rabbits, indicating that the CLR of bumetanide is urine flow dependent in rabbits.

Animals↗

Molecular cloning and characterization of the ryanodine receptor/junctional channel complex cDNA from skeletal muscle sarcoplasmic reticulum.

Major progress has been made in elucidating the calcium release mechanism involved in excitation-contraction coupling. The ryanodine receptor of sarcoplasmic reticulum has been isolated and found to be morphologically identical to the foot structure, which is involved in the junctional association of terminal cisternae with the transverse tubule. The foot structure also contains the calcium release channel itself. For this reason, we refer to the foot structure as the junctional channel complex (JCC). The JCC consists of an oligomer of a single high molecular weight protein. Although progress has been made in characterizing important aspects of the structure and function of the JCC, further understanding of the JCC protein subunit awaits the molecular cloning of the JCC. We report on the isolation of cDNA clones encoding portions of the JCC from rabbit fast-twitch skeletal muscle and its tissue distribution and expression. The large size and lack of solubility of the JCC protein posed particular challenges to cloning this molecule. Among these was the necessity to develop techniques for partially digesting the JCC protein subunit with endoproteases in the presence of detergent. With this approach we obtained partial amino acid sequences from regions of the JCC and designed oligonucleotide primers and probes to synthesize and screen cDNA libraries. The rabbit skeletal muscle JCC mRNA encodes an approximately 16-kilobase mRNA present in skeletal, heart, and aortic smooth muscle, as determined by RNA blot analysis with a 700-base-pair cDNA probe. Whereas the JCC mRNA appears to be relatively abundant in adult rabbit fast-twitch skeletal muscle, it is much less abundant in heart and smooth muscle. The JCC mRNA in BC3H1 (a myoblast cell line) is reversibly regulated by growth factors in a manner similar to muscle-specific contractile protein genes.

Amino Acid Sequence↗

Modulation of ryanodine-induced Ca2+ release in amphibian skeletal muscle.

We examined effects of ryanodine on tension in intact and skinned amphibian skeletal muscle. 100 microM ryanodine (RY) alone in the frog Ringer's solution (FR) produced tension in the intact muscle reaching its peak by 1 h; 10 min treatment with RY augmented depolarization-induced tension and prevented a subsequent caffeine-induced contraction. In contrast, RY in Ca2+-free FR was unable to produce tension, after which caffeine produced irreversible tension. In skinned fibers, RY at pCa 6.5 produced tension and abolished a subsequent caffeine-induced contraction; while Ry in 2 mM EGTA did not produce tension. These data indicate that RY, in the presence of CA2+, releases CA2+ from the SR resulting in subsequent depletion of CA in the SR.

Alkaloids↗

Effect of dB-c-AMP and forskolin on the 45Ca influx, net Ca uptake and tension in rabbit aortic smooth muscle.

The effects of dibutyril-adenosine-3',5'-cyclic monophosphate (dB-c-AMP) and forskolin on aortic tension and 45Ca influx were measured. dB-c-AMP reduced both the rate of force development and the maximal tension achieved in solutions containing various K+ concentrations. Stimulated 45Ca influx was also reduced, however, to a lesser extent than was the tension. Forskolin showed more marked effects of a similar nature. Thus, both these agents which increase intracellular c-AMP caused a rightward shift in the curve expressing force (ordinate) as a function of Ca2+ influx (abscissa). Consequently, we found that dB-c-AMP stimulated more net Ca to be taken up by sarcoplasmic reticulum (SR) at the same influx rate. The conclusion that c-AMP produced these effects by stimulating Ca uptake into the superficial SR was supported by the finding that dB-c-AMP increased the amount of Ca taken up into a caffeine releasable fraction.

Animals↗

Ryanodine modulation of 45Ca efflux and tension in rabbit aortic smooth muscle.

The effects of ryanodine on isometric tension development, net cellular Ca content and 45Ca efflux were measured in the isolated rabbit aorta. Pretreatment of the tissue with 10 microM ryanodine for 30 min reduced the norepinephrine (NE)-induced tension of the aortic rings bathed in the absence of extracellular Ca2+ in parallel with a reduction in the NE-stimulated 45Ca efflux. Ryanodine alone caused a delayed moderate increase in 45Ca efflux, slowly increasing the fractional loss from 0.02/min to 0.03/min, without any increase in tension. The increased 45Ca efflux was accompanied by a decrease in the net cellular Ca content. When ryanodine and NE were administered in sequence during 45Ca efflux, we found a quantitative correlation between the ryanodine induced loss of 45Ca and the inhibition of the NE-induced 45Ca release. We conclude that the inhibition of the NE-induced contraction by 10 microM ryanodine is the result of depletion of Ca from intracellular stores rather than inhibition of Ca2+ release.

Alkaloids↗

Effects of the Ca agonist Bay K8644 on 45Ca influx and net Ca uptake into rabbit aortic smooth muscle.

We examined the effects of Bay K8644 and external K+ on isolated rings of rabbit aorta. Previous evidence has suggested that the Ca channel agonist, Bay K8644, preferentially opens the potential-sensitive Ca2+ channels (PSCs) rather than receptor-operated Ca2+ channels (ROCs). Bay K8644 stimulated 45Ca influx, net Ca gain and contractile tension were measured as a function of extracellular K+ concentration. Although Bay K8644 induced little tension at 5 mM K+ (PSS), Ca2+ influx was stimulated from a resting value of 12 mumol X kg-1 X min-1 (0.02 pmol X cm-2 X s-1) to 17 mumol X kg-1 X min-1 while the total Ca content increased by 95 mumol X kg-1. This net Ca gain was reversed by 50 mM caffeine. As the external K+ was increased from 5 to 80 mM, the Bay K8644 stimulation of influx and contraction first increased and then decreased. The data are explained in terms of a calcium entry model consisting of membrane Ca2+ channels in series with a subplasmalemmal barrier consisting of superficial sarcoplasmic reticulum (SR).

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