Biomedical subjects

S Chung

Publications and source records attributed to S Chung.

At least 19 recordsLinked to original sources

PubMed2006

Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy.

OBJECTIVE: To compare the cognitive effects of lamotrigine vs topiramate as adjunctive therapy in adults with epilepsy. METHODS: A multicenter, double-blind, randomized, prospective study was conducted in adults with partial seizures. Lamotrigine or topiramate was introduced as an adjunctive therapy to carbamazepine or phenytoin and titrated over 8 weeks to target doses. These drugs were maintained another 8 weeks (maintenance phase) without dosage changes. The primary endpoint was change from screening to the end of the maintenance phase in a combined analysis of standardized measures of cognition (Controlled Oral Word Association Task [COWA]; Stroop Color-Word Interference; Digit Cancellation; Lafayette Grooved Pegboard, dominant hand; Rey Auditory Verbal Learning Test, delayed recall; and Symbol-Digit Modalities test). RESULTS: For the primary endpoint, cognitive performance at the end of the maintenance phase was better with lamotrigine than with topiramate (415.3 vs 315.1; p < 0.001). On the individual cognitive tests, performance was better with lamotrigine than with topiramate in mean changes from screening on the COWA (p < 0.001), Stroop Color-Word Interference (p = 0.038), and Symbol-Digit Modalities tests (p < 0.001). The treatment effect exceeded the minimum clinically important difference for the COWA and the Symbol-Digit Modalities test. Mean changes from screening in the Performance-On-Line test simulating driving skills reflected better performance with lamotrigine than with topiramate (p = 0.021). The median percentage change from baseline in seizure frequency was lower with lamotrigine than with topiramate during the escalation phase (-80% vs -100%; p = 0.028) but not during the maintenance phase (-75% vs -100%; p = 0.062). The frequencies of cognitive adverse events and of premature withdrawals related to cognitive decline were higher with topiramate than with lamotrigine (6% vs 0%; p = 0.013). CONCLUSION: Lamotrigine had significantly less impact than topiramate on measures of cognition when used as adjunctive therapy for partial seizures.

Adolescent↗

PubMed2006

Endoscopy-assisted ultrasonic surgical aspiration of axillary osmidrosis: a retrospective review of 896 consecutive patients from 1998 to 2004.

Axillary osmidrosis is a distressing and troublesome problem that causes a serious handicap in personal and social life. Many different methods have been introduced to treat axillary osmidrosis, however, they are often accompanied by marked complications. We analysed our experiences using endoscopy-assisted ultrasonic surgical aspiration in treating the axillary osmidrosis. From June 1998 to February 2004, a total of 896 patients (562 females, 334 males) were treated for axillary osmidrosis using endoscopy-assisted ultrasonic surgical aspiration. Our method was satisfactory in 815 patients (91%) and recurrence of odour occurred only in 29 (3.2%) patients. It also showed complications in 28 (3.1%) patients. Our method leaves a small inconspicuous scar and no contracture of the axillary skin after a short and comfortable recovery period and maintains normal axillary hair growth patterns. Axillary osmidrosis can be best treated by endoscopy-assisted ultrasonic surgical aspiration and this operation has many advantages with a high success rate, a low complication rate, and a rapid recovery period.

Adolescent↗

PubMed2006

Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation.

Because of their ability to proliferate and to differentiate into diverse cell types, embryonic stem (ES) cells are a potential source of cells for transplantation therapy of various diseases, including Parkinson's disease. A critical issue for this potential therapy is the elimination of undifferentiated cells that, even in low numbers, could result in teratoma formation in the host brain. We hypothesize that an efficient solution would consist of purifying the desired cell types, such as neural precursors, prior to transplantation. To test this hypothesis, we differentiated sox1-green fluorescent protein (GFP) knock-in ES cells in vitro, purified neural precursor cells by fluorescence-activated cell sorting (FACS), and characterized the purified cells in vitro as well as in vivo. Immunocytofluorescence and RT-PCR analyses showed that this genetic purification procedure efficiently removed undifferentiated pluripotent stem cells. Furthermore, when differentiated into mature neurons in vitro, the purified GFP+ cell population generated enriched neuronal populations, whereas the GFP- population generated much fewer neurons. When treated with dopaminergic inducing signals such as sonic hedgehog (SHH) and fibroblast growth factor-8 (FGF8), FACS-purified neural precursor cells responded to these molecules and generated dopaminergic neurons as well as other neural subtypes. When transplanted, the GFP+ cell population generated well contained grafts containing dopaminergic neurons, whereas the GFP- population generated significantly larger grafts (about 20-fold) and frequent tumor-related deaths in the transplanted animals. Taken together, our results demonstrate that genetic purification of neural precursor cells using FACS isolation can effectively remove unwanted proliferating cell types and avoid tumor formation after transplantation.

Animals↗

PubMed2005

The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neurons.

The A9 dopaminergic (DA) neuronal group projecting to the dorsal striatum is the most vulnerable in Parkinson's disease (PD). We genetically engineered mouse embryonic stem (ES) cells to express the transcription factors Nurr1 or Pitx3. After in vitro differentiation of Pitx3-expressing ES cells, the proportion of DA neurons expressing aldehyde dehydrogenase 2 (AHD2) increased, while the total number of DA neurons remained the same. The highest levels of AHD2 expression were observed in mouse A9 DA neurons projecting to the dorsal striatum. Furthermore, real-time PCR analyses of in vitro differentiated Pitx3-expressing ES cells revealed that genes highly expressed in A9 DA neurons were up-regulated. When transplanted into the mouse striatum, Pitx3-expressing cells generated an increased proportion of AHD2-expressing DA neurons. Contrastingly, in Nurr1-expressing ES cells, increases of all midbrain DA markers were observed, resulting in a higher total number of DA neurons in vitro and in vivo, whereas the proportion of AHD2-expressing DA neurons was not changed. Our data, using gain-of-function analysis of ES cells, suggest that Pitx3 may be important for specification and/or maintenance of A9-like neuronal properties, while Nurr1 influences overall midbrain DA specification. These findings may be important for modifying ES cells to generate an optimal cell source for transplantation therapy of PD.

Alcohol Dehydrogenase↗

PubMed2005

Widespread endoscopic mucosal resection of the esophagus with strategies for stricture prevention: a preclinical study.

BACKGROUND AND STUDY AIMS: Circumferential endoscopic mucosal resection of the esophagus is complicated by stricture formation. Prophylactic measures for avoiding such strictures have not been well studied. The aim of this preclinical study was to assess strategies for prevention of esophageal strictures in a porcine model following widespread endoscopic mucosal resection (EMR). METHODS: A total of 18 60-kg pigs were included in the study. The roles of strip width (group 1), prophylactic steroids (group 2), and prophylactic stents (group 3) in the prevention of post-mucosectomy strictures were studied. Six animals were included in each group. Esophageal mucosal resection was achieved using a novel widespread EMR technique previously described by our group. Animals in group 1 underwent partial (50% circumference) mucosal resection without prophylactic measures, while animals in the other two groups underwent circumferential mucosal resection. Animals in group 2 received 80 mg of triamcinolone injected directly into the exposed submucosal tissue (20 mg injection in four quadrants). Animals in group 3 received esophageal metal stents coated with small-intestine submucosa (SIS) that were deployed immediately post-resection. Animals were kept alive for 1 month. RESULTS: Partial and circumferential widespread EMRs were achieved in all animals. There were no procedural complications. Repeat endoscopy at 1 month showed no strictures in group 1. Only four animals were studied in group 2, owing to the high complication rate (periesophageal abscess in all animals) with one early death. Three of the surviving animals developed mild to tight strictures. In group 3, all animals developed tight strictures; however, there was early stent migration in four animals and premature stent removal in two animals because of persistent vomiting. CONCLUSIONS: Partial widespread EMR of the esophagus heals without stricture formation and does not require prophylactic intervention. The use of deep mural steroid injection following a circumferential resection does not appear to prevent strictures and may result in serious adverse events. Short-term use of esophageal stents is inadequate for stricture prevention. However, better results may be anticipated with longer term (at least 6 weeks) stent use.

Animals↗

PubMed2005

Hospital planning for acts of terrorism and other public health emergencies involving children.

In today's world the increased potential of terrorist attacks places unique burdens and consequences on health care workers. Hospitals and hospital personnel must now be prepared to react immediately to such events. They must also implement, in advance, policies to protect their own health care personnel while providing care to victims. In this review, we discuss the four major forms of mass casualty terrorism (biological, chemical, nuclear, and thermomechanical) including clinical signs and symptoms for each, the impact on health care personnel, and special considerations for children. We will then outline key principles of hospital preparation with regard to paediatrics in anticipation of such emergencies.

Child↗

PubMed2005

Social support and sexually transmitted disease related healthcare utilisation in sexually experienced African-American adolescents.

OBJECTIVE: To determine whether adolescents' perceived social support predicts future utilisation of sexually transmitted disease (STD) related health care. METHODS: A longitudinal study of African-American adolescents ages 12-18 recruited from a random sample of households in the San Francisco Bay area in which baseline data were collected by telephone and follow up data were collected by telephone or in-home audio computer assisted self interview. At baseline, participants were asked about their sexual behaviours, STD history, and social support. At follow up 14-18 months later, participants were asked whether they, while asymptomatic, had sought STD related medical care within the past year. RESULTS: Asymptomatic sexually experienced adolescents who talked to their closest friend almost every day were more likely to have had STD related health care in the past year (odds ratio (OR) = 1.38; 95% confidence interval (CI) 1.09, 1.76). Closeness to female and male parents/guardians and participation in extracurricular activities were not associated with utilisation of STD related health care within the past year. After controlling for age and sex, sexually experienced adolescents who talked to or saw their closest friend almost every day were more likely to have had STD related health care within the past year (OR = 1.35; 95% CI = 1.08 to 1.70). CONCLUSIONS: These findings suggest that friends have an impact on the seeking of confidential healthcare services, such as care for STDs.

Adolescent↗

PubMed2004

Modulation of delayed rectifier potassium channel by protein kinase C zeta-containing signaling complex in pheochromocytoma cells.

Voltage-dependent delayed rectifier K(+) (Kv) channels are fundamental components in the regulation of neuronal excitability. We found that nerve growth factor (NGF) treatment of PC12 cells induced a hyperpolarizing shift of the Kv current activation curve by about 15 mV. This effect was similar to the effect of the modulatory subunit, Kv beta, on the cloned Kv channel, and required the activity of protein kinase C (PKC)zeta. Since NGF treatment of PC12 cells is known to increase the expression of p62 protein, which binds both to Kv beta and to PKC zeta, our results are consistent with the model in which p62 functions as a physical link in the assembly of signaling complex, PKC zeta-p62-Kv channel. In agreement with this model, the transient expression of p62 induced the same change in the Kv current activation curve as NGF, and the suppression of p62 expression inhibited the effect of NGF. The amount of bound Kv beta to p62 was increased by NGF treatment. These results suggest that the increased p62 protein induces the formation of the signaling complexes, enabling PKC zeta to modulate Kv channels. Thus, this may constitute a new way of modulating Kv channel activities.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Purification and characterization of a lipopeptide produced by Bacillus thuringiensis CMB26.

AIMS: To isolate an antagonist for use in the biological control of phytopathogenic fungi including Colletotrichum gloeosporioides, then to purify and characterize the biocontrol agent produced by the antagonist. METHODS AND RESULTS: Bacteria that exhibited antifungal activity against the causative agent pepper anthracnose were isolated from soil, with Bacillus thuringiensis CMB26 showing the strongest activity. A lipopeptide produced by B. thuringiensis CMB26 was precipitated by adjusting the pH 2 with 3 n HCl and extracted using chloroform/methanol (2:1, v/v) and reversed-phase HPLC. The molecular weight was estimated as 1447 Da by MALDI-TOF mass spectrometry. Scanning electron and optical microscopies showed that the lipopeptide has activity against Escherichia coli O157:ac88, larvae of the cabbage white butterfly (Pieris rapae crucivora) and phytopathogenic fungi. The lipopeptide had cyclic structure and the amino acid composition was L-Glu, D-Orn, L-Tyr, D-allo-Thr, D-Ala, D-Val, L-Pro, and L-Ile in a molar ratio of 3:1:2:1:1:2:1:1. The purified lipopeptide showed the same amino acid composition as fengycin, but differed slightly in fatty acid composition, in which the double bond was at carbons 13-14 (m/z 303, 316) and there was no methyl group. CONCLUSION: A lipopeptide was purified and characterized from B. thuringiensis CMB26 and found to be similar to the lipopeptide fengycin. This lipopeptide can function as a biocontrol agent, and exhibits fungicidal, bactericidal, and insecticidal activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Compared with surfactin and iturin, the lipopeptide from B. thuringiensis CMB26 showed stronger antifungal activity against phytopathogenic fungi. This lipopeptide is a candidate for the biocontrol of pathogens in agriculture.

Amino Acids↗

PubMed2004

Following-up for HIV test results: what limits return in an STD clinic population?

HIV testing is routinely performed in sexually transmitted disease (STD) clinics, but many tested do not follow up for results. We analysed data on STD clinic patients undergoing HIV testing between 1994-1998 who tested HIV-negative to describe characteristics associated with 'non-return' for results. Among 31,777 patients testing HIV-negative, male gender (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.19, 1.33), age <30 years (OR 1.72, 95% CI 1.43, 1.82), and a diagnosis of gonorrhoea at the testing visit (OR 1.72, 95% CI 1.43, 1.82) were all independently associated with 'non-return.' Presentation to clinic specifically for HIV testing (OR 0.70, 95% CI 0.63, 0.77) or reporting a partner with HIV (OR 0.63, 95% CI 0.53, 0.74) were factors independently protective against 'non-return.' Operational changes to improve test results notification, or enhanced counselling at the initial test visit, particularly focusing on young men with gonorrhoea, may optimize prevention outcomes in this high risk population.

Adult↗

PubMed2002

Free radical scavenging effect of Diospyros kaki, Laminaria japonica and Undaria pinnatifida.

Diospyros kaki folium, Laminaria japonica thallus and Undaria pinnatifida thallus have been used traditionally in Korea to promote maternal health. The scavenging activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals of the methanol extracts of these plants were investigated. The extract of D. kaki was found to be the most potent, with an IC(50) value of 0.11 mg/ml.

Biphenyl Compounds↗

PubMed2002

Biofiltration of ammonia gas with sponge cubes coated with mixtures of activated carbon and zeolite.

Removal of ammonia gas was investigated using a biofilter system packed with small cubes of polyurethane sponge that were coated with a powder mixture of activated carbon and natural zeolite. Experimental tests and measurements include removal efficiency, pH, metabolic products of ammonia and kinetic analysis. A removal efficiency over 90% can be obtained with ammonia concentrations below 150 ppm and at contact times above 23 sec.The ammonia adsorbing power of the present biocarrier can protect the biofilter system from a high ammonia shock loading in the feed. The maximum removal rate, Vm, obtained from the kinetic analysis is 8.47 g N (kg carrier)(-1) day(-1) and the saturation constant Ks is 50.36 ppm. Nitrite is produced dominantly during the entire experiments. The cell number of nitrifying bacteria is 1.58 x 10( cell (g carrier)(-1). The present synthetic bio-carrier is considered to be one of the best among bio-carriers that have been used for the biofiltration of ammonia.

Ammonia↗

PubMed2002

Gamma-linolenic acid in borage oil reverses epidermal hyperproliferation in guinea pigs.

As dietary sources of gamma-linolenic acid [GLA; 18:3(n-6)], borage oil (BO; 24-25 g/100 g GLA) and evening primrose oil (PO; 8-10 g/100 g GLA) are efficacious in treating skin disorders. The triglycerol stereospecificity of these oils is distinct, with GLA being concentrated in the sn-2 position of BO and in the sn-3 position of PO. To determine whether the absolute level and/or the triglycerol stereospecificity of GLA in oils affect biological efficacy, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut oil (HCO) diet for 8 wk. Subsequently, guinea pigs were fed diets of PO, BO or a mixture of BO and safflower oil (SO) for 2 wk. The mixture of BO and SO (BS) diet had a similar level of GLA as PO but with sn-2 stereospecificity. As controls, two groups were fed SO and HCO for 10 wk. Epidermal hyperproliferation was reversed by all three oils in the order of BO > BS > PO. However, proliferation scores of group PO were higher than of the normal control group, SO. The accumulations of dihomo-gamma-linolenic acid [DGLA; 20:3(n-6)], an elongase product of GLA, into phospholipids and ceramides, of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent antiproliferative metabolite of DGLA, and of ceramides, the major lipid maintaining epidermal barrier, in the epidermis of group BO were greater than of groups BS and PO. Group BS had higher levels of DGLA, 15-HETrE and ceramides than group PO. With primary dependence on absolute levels, our data demonstrate that the antiproliferative efficacy of GLA in the epidermis is preferably exerted from sn-2 stereospecificity of GLA in BO.

Acanthosis Nigricans↗

PubMed2001

Mechanistic insight into the inactivation of carboxypeptidase A by alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid, a novel type of irreversible inhibitor for carboxypeptidase A with no stereospecificity.

On the basis of the active site topology and enzymic catalytic mechanism of carboxypeptidase A (CPA), a prototypical zinc-containing proteolytic enzyme, alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (1), was designed as a novel type of mechanism-based inactivator of the enzyme. All four possible stereoisomers of the inhibitor were synthesized in an enantiomerically pure form starting with optically active aspartic acid, and their CPA inhibitory activities were evaluated to find that surprisingly all of the four stereoisomers inhibit CPA in a time dependent manner. The inhibited enzyme did not regain its enzymic activity upon dialysis. The inactivations were prevented by 2-benzylsuccinic acid, a competitive inhibitor that is known to bind the active site of the enzyme. These kinetic results strongly support that the inactivators attach covalently to the enzyme at the active site. The analysis of ESI mass spectral data of the inactivated CPA ascertained the conclusion from the kinetic results. The values of second-order inhibitory rate constants (k(obs)/[I](o)) fall in the range of 1.7-3.6 M(-1) min(-1). The lack of stereospecificity shown in the inactivation led us to propose that the ring cleavage occurs by the nucleophilic attack at the 2-position rather than at the 5-position and the ring opening takes place in an addition-elimination mechanism. The tetrahedral transition state that would be generated in this pathway is thought to be stabilized by the active site zinc ion, which was supported by the PM3 semiemprical calculations. In addition, alpha-benzyl-2-oxo-1,3-oxazolidine-5-acetic acid (18), a structural isomer of 1 was also found to inactivate CPA in an irreversible manner, reinforcing the nucleophilic addition-elimination mechanism. The present study demonstrates that the transition state for the inactivation pathway plays a critical role in determining stereochemistry of the inactivation.

Carboxypeptidases↗

PubMed2001

Nitric oxide directly activates large conductance Ca2+-activated K+ channels (rSlo).

We investigated whether nitric oxide (NO) directly activates the cloned alpha-subunit of large conductance Ca2+-activated K+ (Maxi-K) channels from rat brain (rSlo), expressed either in HEK293 cells or Xenopus oocytes. In inside-out patches, the application of S-nitroso-N-acetylpenicillamine (SNAP), a NO-releasing compound, reversibly activated the channel shifting the voltage dependent activation curve of the macroscopic Maxi-K current to the left by about 15 mV. Pretreatment of the patches with N-ethylmaleimide to alkylate free sulfhydryl groups did not prevent the effect of SNAP, suggesting that NO may directly interact with the channels. These results suggest that Maxi-K channels might be one of the physiological targets of NO in the brain.

Animals↗

PubMed2001

Electron transfer and stability of the cytochrome b6f complex in a small domain deletion mutant of cytochrome f.

The lumen segment of cytochrome f consists of a small and a large domain. The role of the small domain in the biogenesis and stability of the cytochrome b(6)f complex and electron transfer through the cytochrome b(6)f complex was studied with a small domain deletion mutant in Chlamydomonas reinhardtii. The mutant is able to grow photoautotrophically but with a slower rate than the wild type strain. The heme group is covalently attached to the polypeptide, and the visible absorption spectrum of the mutant protein is identical to that of the native protein. The kinetics of electron transfer in the mutant were measured by flash kinetic spectroscopy. Our results show that the rate for the oxidation of cytochrome f was unchanged (t(12) = approximately 100 micros), but the half-time for the reduction of cytochrome f is increased (t(12) = 32 ms; for wild type, t(12) = 2.1 ms). Cytochrome b(6) reduction was slower than that of the wild type by a factor of approximately 2 (t(12) = 8.6 ms; for wild type, t(12) = 4.7 ms); the slow phase of the electrochromic band shift also displayed a slower kinetics (t(12) = 5.5 ms; for wild type, t(12) = 2.7 ms). The stability of the cytochrome b(6)f complex in the mutant was examined by following the kinetics of the degradation of the individual subunits after inhibiting protein synthesis in the chloroplast. The results indicate that the cytochrome b(6)f complex in the small domain deletion mutant is less stable than in the wild type. We conclude that the small domain is not essential for the biogenesis of cytochrome f and the cytochrome b(6)f complex. However, it does have a role in electron transfer through the cytochrome b(6)f complex and contributes to the stability of the complex.

Animals↗

PubMed2001

Beta-amyloid peptide induces the expression of voltage dependent outward rectifying K+ channels in rat microglia.

Upregulation of voltage-dependent outward rectifying K+ (Kv) channels has been reported in activated microglia. Since beta-amyloid peptide (A beta) is known to activate microglia, we tested whether the exposure of cultured rat microglia to A beta fragment 25-35 (A beta 25-35) induced the Kv current. A beta 25-35 in 5-200 nM concentration range significantly increased Kv current density, while there was small change in inward rectifying K+ current density. The full length A beta peptide (A beta 1-42) also increased Kv current. However, the control peptide, A beta 35-25, did not induce Kv current. Most of the Kv current induced by A beta was specifically blocked by the presence of antisense deoxyoligonucleotides against Kv1.3, and Kv1.5. Thus, it is concluded that we have identified Kv1.3 and Kv1.5 as the channel types expressed in A beta-treated microglia.

Alzheimer Disease↗

PubMed2001

Modulation of large conductance calcium-activated potassium channels from rat hippocampal neurons by glutathione.

We have investigated the modulation of neuronal large conductance Ca2+-activated K+ channels by glutathione. Single channel recordings were made from cultured neonatal rat hippocampal neurons by using excised inside-out patch clamp method. Glutathione, a physiological sulfhydryl specific reducing reagent, increased channel activities in concentration dependent manner with half activation concentration of 710 microM. Conversely, oxidized form of glutathione inhibited channel activities with half inhibition concentration of 520 microM. Our results provide direct evidence that when neuronal large conductance Ca2+-activated K+ channels are exposed to reducing or oxidizing environments, channel activities are increased or decreased in opposite directions due to the redox modification. This may constitute an important regulatory mechanism of neuronal Ca2+-activated K+ channel activities.

Animals↗