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Biomedical subjects

S Y Chang

Publications and source records attributed to S Y Chang.

At least 37 records · Page 2Linked to original sources

Associations of CCR5, CCR2, and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy.

Genotype data for CCR5, CCR2, and stromal cell-derived factor 1 (SDF-1) were obtained from 354 human immunodeficiency virus type 1 (HIV-1)-positive subjects who were being treated with nucleosides. Associations with HIV-1 load, HIV syncytium-inducing (SI) phenotype, CD4 cell count, and disease progression were analyzed. No differences in HIV-1 load or CD4 cell count were observed between wild type (+) and variant genotypes. Changes from non-SI to SI viral phenotype were more frequent in heterozygotes with a 32-bp deletion (Delta32) in the CCR5 gene than in + homozygotes (40% vs. 7%; P=.01). In a multivariate analysis, heterozygous CCR5 Delta32 was associated with reduced hazard of progression (hazard ratio, 0.32; P=.02). Subjects homozygous for the SDF-1 3'A variant had more-rapid disease progression (P=.008). The SDF-1 homozygous 3'A variant was related to more-rapid disease progression, and CCR5 Delta32 was associated with reduced rates of hazard for disease progression in nucleoside-treated subjects.

Adult↗

Up-regulation of Fas ligand expression by human cytomegalovirus immediate-early gene product 2: a novel mechanism in cytomegalovirus-induced apoptosis in human retina.

Human CMV (HCMV) is an important pathogen that causes widespread diseases in immunocompromised individuals. Among the opportunistic HCMV infections, HCMV retinitis is most common in transplant recipients and AIDS patients. It often leads to blindness if left untreated. The question as to how HCMV infection causes retinal pathogenesis remains unresolved. Here, we report that viral immediate-early gene product 2 (IE2), but not IE1, up-regulates the Fas ligand (FasL) expression in HCMV-infected human retinal pigment epithelium cells. Increased secretion of FasL from virally infected cells into cultured medium was observed upon HCMV infection. The capability of such cell-free medium to induce apoptosis of Fas (CD95)-expressing Jurkat cells further implies that Fas-FasL interaction might mediate cell death in the lesion of HCMV retinitis. To support this idea, we observed augmented soluble FasL levels in vitreous from AIDS patients with HCMV retinitis as compared with that from AIDS patients without HCMV infection. In addition, by in situ hybridization and immunohistochemistry, we detected enhanced signals of FasL, the existence of viral IE Ags and apoptotic cells at the same sites in the lesion of HCMV-infected retina. These results strongly suggest that IE2 induction of FasL expression in human retina might be an important event that takes place in the early stage of infection and finally leads to visual loss in individuals affiliated with HCMV retinitis.

AIDS-Related Opportunistic Infections↗

Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain.

In mammals, specific lipids and amino acids serve as crucial signaling molecules. In bacteria, conjugates of lipids and amino acids (referred to as lipoamino acids) have been identified and found to possess biological activity. Here, we report that mammals also produce lipoamino acids, specifically the arachidonyl amino acids. We show that the conjugate of arachidonic acid and glycine (N-arachidonylglycine (NAGly)) is present in bovine and rat brain as well as other tissues and that it suppresses tonic inflammatory pain. The biosynthesis of NAGly and its degradation by the enzyme fatty acid amide hydrolase can be observed in rat brain tissue. In addition to NAGly, bovine brain produces at least two other arachidonyl amino acids: N-arachidonyl gamma-aminobutyric acid (NAGABA) and N-arachidonylalanine. Like NAGly, NAGABA inhibits pain. These findings open the door to the identification of other members of this new class of biomolecules, which may be integral to pain regulation and a variety of functions in mammals.

Alanine↗

Self-assembly and dynamics of [2]- and [3]rotaxanes with a dinuclear macrocycle containing reversible Os-N coordinate bonds.

With a dinuclear macrocycle 2 that contains weak reversible OsVI-N coordinate bonds, self-assembly and equilibrium dynamics of [2]- and [3]rotaxanes have been investigated. When the macrocycle 2 was mixed together with threads 4a-e, which all contain an adipamide station but different sizes of end groups, [2]pseudorotaxane- and rotaxane-like complexes were immediately formed with large association constants of >7 x 103M(-1) in CDCl3 at 298 K. Exchange dynamics, explored by 2D-EXSY experiments, suggest that assembly and disassembly of complexes occur through two distinct pathways, slipping or clipping, and this depends on the size of the end groups. The slipping pathway is predominant with smaller end groups that give pseudorotaxane-like complexes, while the clipping pathway is observed with larger end groups that yield rotaxane-like complexes. Under the same conditions, exchange barriers (deltaG++) were 14.3 kcalmol(-1) for 4a and 16.7 kcalmol(-1) for 4d, and indicate that the slipping process is at least one order of magnitude faster than the clipping process. Using threads 13a and 13b that contain two adipamide groups, more complicated systems have been investigated in which [2]rotaxane, [3]rotaxane, and free components are in equilibrium. Concentration- and temperature-dependent 1H NMR spectroscopic studies allowed the identification of all possible elements and the determination of their relative distributions in solution. For example, the relative distribution of the free components, [2]rotaxane, and [3]rotaxane are 30, 45, and 25 %, respectively, in a mixture of 2 (2mM) and 13a (2mM) in CDCl3 at 10 degrees C. However, [3]rotaxane exists nearly quantitatively in a mixture of 2 (4 mM) and 13 a (2 mM) in CDCl3 at a low temperature - 10 degrees C.

Journal Article↗

Chiral analysis of baclofen by alpha-cyclodextrin-modified capillary electrophoresis and laser-induced fluorescence detection.

An enantioselective method for baclofen (4-amino-3-p-chlorophenylbutyric acid) based on capillary electrophoresis (CE) separation and laser-induced fluorescence (LIF) detection has been developed. Naphthalene-2,3-dicarboxaldehyde (NDA) was used for precolumn derivatization of the nonfluorescent drug. alpha-Cyclodextrin (alpha-CD) was included in the buffer as a chiral selector for the separation of NDA-labeled S-(+)- and R-(-)-baclofen. Optimal resolution and detection were obtained with an electrophoretic buffer of 50 mM sodium borate (pH 9.5) containing 7 mM alpha-CD and a He-Cd laser (lambda ex = 442 nm, lambda em = 500 nm). Combined with a simple cleanup procedure, this method can be applied to the analysis of baclofen enantiomers in human plasma. The relative standard deviation (RSD) values on peak areas of a plasma sample containing 1.0 microM racemic baclofen were 6.4 and 4.9% (n = 8) for the S-(+)- and R-(-)-enantiomer, respectively. The RSD value on migration times of both enantiomers was 0.5% (n = 8). Calibration graphs for S-(+)- and R-(-)-baclofen in plasma showed a good linearity (r > or = 0.999) in the concentration range of 0.1-2.0 microM. The limit of detection of baclofen in plasma was about 10 ng/mL.

Baclofen↗

Prenatal sonographic appearance of Beare-Stevenson cutis gyrata syndrome: two- and three-dimensional ultrasonographic findings.

Beare-Stevenson cutis gyrata syndrome is characterized by craniofacial anomalies, particularly craniosynostosis, ear defects, cutis gyrata, acanthosis nigricans, anogenit anomalies, skin tags, and prominent umbilical stump. The prenatal two- and three-dimensional ultrasonographic findings of this rare condition is reported. The detection was made at 32 weeks of gestation in a woman with polyhydramnios and fetal head anomaly. The ultrasound appearance and postnatal follow-up are presented.

Abnormalities, Multiple↗

Attenuation of Zn2+ neurotoxicity by aspirin: role of N-type Ca2+ channel and the carboxyl acid group.

Synaptically released Zn2+ ions enter into neurons primarily through voltage-gated Ca2+ channels (VGCC) or N-methyl-d-aspartate (NMDA) receptors, which can mediate pathological neuronal death. We studied the possibility (and underlying mechanisms) that aspirin, known to prevent NMDA neurotoxicity, would also attenuate Zn2+ neurotoxicity. Administration of 3 to 10 mM aspirin, in cortical cell cultures, attenuated the evolution of neuronal death following exposure to 300 microM Zn2+ for 30 min. This neuroprotective effect of aspirin was attributable to the prevention of Zn2+ ion entry. Aspirin interfered with inward currents and an increase in [Ca2+]i through VGCC and selective binding of omega-conotoxin, sensitive to N-type Ca2+ channel. The omega-conotoxins GVIA or MVIIC, the selective inhibitors of N-type Ca2+ channels, attenuated Zn2+ neurotoxicity. Aspirin derivatives lacking the carboxyl acid group did not reduce Zn2+ neurotoxicity. The present findings suggest that aspirin prevents Zn2+-mediated neuronal death by interfering with VGCC, and its action specifically requires the carboxyl acid group.

Acetylcysteine↗

Refolding and characterization of a yeast dehydrodolichyl diphosphate synthase overexpressed in Escherichia coli.

Dehydrodolichyl diphosphate synthase (DDPPs) catalyzes the sequential condensation of isopentenyl diphosphate with farnesyl diphosphate to synthesize long-chain dehydrodolichyl diphosphate, which serves as a precursor of glycosyl carrier in glycoprotein biosynthesis in eukaryotes. To perform kinetic and structural studies of DDPPs, we have expressed yeast DDPPs using Escherichia coli as the host cell. Thioredoxin and His tag were utilized to increase the solubility of the recombinant protein and facilitate its purification using Ni-nitrilotriacetic acid (NTA) column. The protein was overexpressed in E. coli but mostly existed in pellet in the absence of detergent. The low quantity of soluble DDPPs was purified using Ni-NTA, Mono Q anion-exchange, and size-column chromatographies. The protein in the pellet was solubilized with 7 M urea and purified using Ni-NTA under denaturing condition. The protein refolding was achieved via the stepwise dialysis to remove the denaturant in the presence of 6 mM beta-mercaptoethanol. Detergent n-octyl-beta-d-glucopyranoside and Triton X-100 increased the solubility of the DDPPs so that refolding can be performed at higher protein concentration. Alternatively, on-column refolding was carried out in a single step to obtain the active protein in large quantities. beta-Mercaptoethanol and Triton were both required in this quick refolding process. The kinetic studies indicated that the soluble and refolded DDPPs have comparable activities (k(cat) = 2 x 10(-4) s(-1)). Unlike its bacterial homologue, undecaprenyl diphosphate synthase, yeast DDPPs activity was not enhanced by Triton.

Alkyl and Aryl Transferases↗

First trimester diagnosis of holoprosencephaly and cyclopia with triploidy by transvaginal three-dimensional ultrasonography.

We present the prenatal three-dimensional (3D) ultrasound findings in a case of holoprosencephaly and cyclopia at 11 weeks gestation. Only holoprosencephaly with missing cyclopia were initially diagnosed because suboptimal views of the fetal face were obtained with transvaginal two-dimensional (2D) ultrasonography due to fetal position. Chromosomes identified by analysis of a fluid sample from early amniocentesis demonstrated a triploidy (69, XXX), spontaneous fetal demise occurred at 12 weeks and the pregnancy was terminated. This case demonstrated the usefulness of transvaginal 3D ultrasonography in establishing the final diagnosis.

Adult↗

Determination of the efficiency of controlled ovarian hyperstimulation in the gonadotropin-releasing hormone agonist-suppression cycle using the initial follicle count during gonadotropin stimulation.

PURPOSE: Our purpose was to evaluate the relationship between the initial follicle count during gonadotropin stimulation after gonadotropin-releasing hormone (GnRH) agonist suppression and the efficiency of controlled ovarian hyperstimulation (COH) in patients receiving treatment with assisted reproductive technologies (ARTs). METHODS: A total of 338 COH procedures in 291 couples was performed with cycles that reached the stage of oocyte retrieval. The ovarian antral follicle number was measured using transvaginal ultrasonography at the folliculometry during gonadotropin stimulation by GnRH agonist suppression in patients undergoing ARTs. Controlled ovarian hyperstimulation was accomplished using GnRH agonist down-regulation combined with FSH and menotropin stimulation. The characteristics of oocytes after retrieval and embryos after in vitro culture and the pregnancy rates were assessed. RESULTS: The procedures performed included 195 ET cycles, 129 TET cycles, and 14 incomplete cycles. The treatment cycles were divided into four categories according to the antral follicle number (i.e., < or = 5, 6-10, 11-15, and > or = 16) at the first folliculometry to evaluate the influence of various factors. The antral follicle count correlated significantly with the patient age, dosage of gonadotropins, serum estradiol concentration, number of antral follicles (> or = 13 mm) while receiving hCG injections, number of oocytes retrieved, and, later, number of embryos transferred. There was a trend toward an increasing number of pregnancies per cycle as the number of antral follicles increased (14.7, 26.5, 44, and 45%, respectively). CONCLUSIONS: We were able to predict the efficiency of COH and outcome of ARTs based on the follicle count during the first folliculometry during gonadotropin stimulation after GnRH agonist suppression. The results of the folliculometry significantly predicted the ovarian response to COH and the outcome of ARTs in the current treatment cycle.

Adult↗

Detection of chromosomal alterations in bladder cancer by comparative genomic hybridization.

OBJECTIVES: To characterize which genomic alterations occur in bladder cancers of different grades and stages, and to evaluate the prognostic implication of chromosomal imbalances. Materials and methods Twelve transitional cell carcinoma cell lines were used to study chromosomal aberrations, using comparative genomic hybridization to examine metaphase cells. RESULTS: There was a mean of 6.0 aberrations per tumour with 4.9 gains and 1.08 deletions per tumour cell line. The mean number of aberrations was the same in grade 2 and 3 tumours. High-stage (>/= T2) carcinomas had markedly more genomic gains than had low-stage (T1) tumours, with 7.2 gains and 1.3 deletions per >/= T2 tumour, and 2.7 gains and 0.8 deletions per T1 tumour, although the difference was not statistically significant. The most frequent changes were gains of chromosome 1 (seven), 9 and 16 (six), and losses of chromosomes 14 (three), 21 and Y (two). The changes 1p+, 3p+, 9q+, 14p-, 16q+ and Yp- were significantly more frequent in low-grade tumours, with 1p+, 3p+ and Yq- the most frequent in stage T1 tumours, and 16p+, 9q+ and 13q- the most frequent in stage >/= T2 tumours. Conclusion These findings indicate several genomic regions in chromosomes 1, 9, 14 and 16 that may carry genes for the development and progression of bladder cancers.

Carcinoma, Transitional Cell↗

Hematometra of the rudimentary horn of a unicornuate uterus resulting from cesarean section.

A 30-year-old woman complained of increasing dysmenorrhea and progressive right lower-quadrant pain after cesarean section. A pelvic mass was observed and subsequently a congenital müllerian anomaly was diagnosed upon serial examination. We report the first apparent case of hematometra of the rudimentary horn of a unicornuate uterus resulting from cesarean section.

Adult↗

The nonlinearity and related band strength of carbon monoxide when applied in ambient air measurement using open long-path Fourier transform infrared spectrometry.

The accuracy of CO concentration determination by open-path Fourier transform infrared (FTIR) spectrometry has been re-evaluated in detail. The evaluation focuses on the correction of the calibration curve--the integrated intensity of a standard spectrum--that is used as a comparison spectrum when doing quantitative analysis of CO. Results show that the calibration curve (with 0.5 cm(-1) or 1 cm(-1) resolution) is apparently inclined to be nonlinear under standard conditions, and that the threshold point of nonlinearity is approximately 0.1 atm-cm. Two commercial FTIR field monitoring systems have been used to investigate the nonlinearity trend. The experimental method consists of using open-path FTIR systems in combination with nondispersive infrared (NDIR) monitors to establish the calibration curve in a semi-closed corridor The results have been double-checked using closed-cell dynamic equilibrium systems. When the optical density is larger than a certain value, the curves begin to bend, and when the optical density approaches zero, the band strength is around 178 +/- 3 atm(-1) cm(-2) and 173 +/- 2 atm(-1) cm(-2), respectively, for 0.5 and 1 cm(-1) resolution at standard temperature and pressure (STP). These values are quite different from other published data that have been acquired by the pressurized method or by high-resolution (<0.006 cm(-1)) spectrometers. It is thought that a higher accuracy is achieved when these new calibration results are used to quantify the CO concentration. The error in concentration determination within 0.1 optical density is less than 2%, and that in the higher optical density region is less than 5%.

Air Pollutants↗

Chest wall thickness measurements and the dosimetric implications for male workers in the south Korean uranium industry.

Using ultrasound techniques, the Human Monitoring Laboratory has measured chest wall thicknesses of a group of male workers at the Korea Atomic Energy Research Institute. A site-specific biometric equation has been developed for these workers, who are somewhat smaller than other workers reported in the literature. Chest wall thickness is an important modifier on lung counting efficiency. These data have been put into the perspective of the ICRP recommended dose limits for occupationally exposed workers: 100 mSv in a 5-year period with a maximum of 50 mSv in any one year. For measured chest wall thicknesses of 1.9 cm to 4.1 cm and a 30 min counting time, the achievable MDAs for natural uranium in the KAERI lung counter vary from 6.6 mg to 13.2 mg. These values are close to, or even exceed, the predicted amounts of natural uranium that will remain in the lung (absorption type M and S) after an intake equal to the Annual Limit on Intake corresponding to a committed dose of 20 mSv. This paper shows that the KAERI lung counter probably cannot detect an intake of Type S natural uranium in a worker with a chest wall thickness equal to the average value (2.7 cm) under routine counting conditions.

Adult↗

Identification of human immunodeficiency virus type 1 subtype C Gag-, Tat-, Rev-, and Nef-specific elispot-based cytotoxic T-lymphocyte responses for AIDS vaccine design.

The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occurring in southern Africa. It is caused by HIV-1 subtype C (HIV-1C). In this study we present the identification and analysis of cumulative cytotoxic T-lymphocyte (CTL) responses in the southern African country of Botswana. CTLs were shown to be an important component of the immune response to control HIV-1 infection. The definition of optimal and dominant epitopes across the HIV-1C genome that are targeted by CTL is critical for vaccine design. The characteristics of the predominant virus that causes the HIV-1 epidemic in a certain geographic area and also the genetic background of the population, through the distribution of common HLA class I alleles, might impact dominant CTL responses in the vaccinee and in the general population. The enzyme-linked immunospot (Elispot) gamma interferon assay has recently been shown to be a reliable tool to map optimal CTL epitopes, correlating well with other methods, such as intracellular staining, tetramer staining, and the classical chromium release assay. Using Elispot with overlapping synthetic peptides across Gag, Tat, Rev, and Nef, we analyzed HIV-1C-specific CTL responses of HIV-1-infected blood donors. Profiles of cumulative Elispot-based CTL responses combined with diversity and sequence consensus data provide an additional characterization of immunodominant regions across the HIV-1C genome. Results of the study suggest that the construction of a poly-epitope subtype-specific HIV-1 vaccine that includes multiple copies of immunodominant CTL epitopes across the viral genome, derived from predominant HIV-1 viruses, might be a logical approach to the design of a vaccine against AIDS.

AIDS Vaccines↗

Metabolism of chiisanoside from Acanthopanax divaricatus var. albeofructus by human intestinal bacteria and its relation to some biological activities.

The metabolic pathway of chiisanoside isolated from leaves of Acanthopanax divaricatus var. albeofructus (Araliaceae) by human intestinal bacteria and by the protein fraction of leaves of this plant were investigated, and the cytotoxic and anti-rotaviral activities of chiisanoside and its metabolite, chiisanogenin, were assayed. Chiisanogenin was produced as a main metabolite, when chiisanoside were incubated for 15 h with human intestinal bacteria. This metabolic pathway proceeded more potently with the protein fraction than with human intestinal bacteria. The in vitro cytotoxicity of chiisanogenin was superior to that of chiisanoside. H+/K+ ATPase was more potently inhibited by chiisanogenin than by chiisanoside. However, the anti-rotaviral activity of chiisanoside was more potent than that of chiisanogenin.

Animals↗