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Biomedical subjects

C Y Chen

Publications and source records attributed to C Y Chen.

At least 37 records · Page 2Linked to original sources

Increasing relative prevalence of HSV-2 infection among men with genital ulcers from a mining community in South Africa.

OBJECTIVES: To determine the aetiology of genital ulcer disease (GUD) and its association with HIV infection in the mining community of Carletonville, South Africa, from two cross sectional surveys of consecutive men presenting with genital lesions during October 1993 to January 1994 and July to November 1998. METHODS: A multiplex polymerase chain reaction (M-PCR) assay combined with amplicon detection was used to identify DNA specific sequences of Treponema pallidum, herpes simplex virus (HSV), and Haemophilus ducreyi. A real time PCR assay was used to differentiate between HSV-1 and HSV-2. RESULTS: M-PCR detected T pallidum, HSV, and H ducreyi in 10.3%, 17.2%, and 69.4% of 232 GUD patients during 1993-4 and in 12.4%, 36.0%, and 50.5% of 186 GUD patients in 1998. The proportion of patients with more than one agent increased significantly from 7.3% (17/232) in 1993-4 to 16.7% (31/186) in 1998 (p <0.01). HSV-2 was detected in a higher proportion of ulcer specimens from HIV infected patients than in specimens from HIV uninfected patients during both time periods (1993-4: 26.2% v 6.7%, p <0.001; 1998: 42.1% v 29.6%, p >0.09). CONCLUSIONS: Based on two cross sectional surveys, 4 years apart, chancroid remained the leading cause of GUD in men who presented at the STD clinic with genital ulcers in the mining community of Carletonville, South Africa. The relative prevalence of primary syphilis has remained low. However, HSV-2 has emerged as a more significant cause of GUD and the proportion of GUD patients infected with more than one agent also increased significantly. HSV-2 DNA was detected in a significantly higher proportion of ulcer specimens from HIV positive patients than from HIV negative patients. No association was found between HIV infection status and the relative prevalence of chancroid or syphilis.

Adult↗

Use of a new fluorescence immunoassay to detect anti-dsDNA antibodies is more correlated with disease activity and complement than the ELISA method in SLE patients.

To determine whether the serum levels of anti-double strand DNA (anti-dsDNA) autoantibodies detected using a newly developed fluorescence immunoassay (FIA) in patients with systemic lupus erythematosus (SLE) correlated more with clinical parameters, such as SLE disease activity index (SLEDAI), complement and the occurrence of nephritis when compared with traditional enzyme-linked immunosorbent assay (ELISA), we prospectively collected 124 serum samples from 31 patients who had juvenile-onset SLE and were regularly monitored every 2 months at our outpatient clinic. At every visit, clinical manifestations and laboratory parameters were assessed and the SLEDAI was determined. Correlation analyses between the two different measurements of anti-dsDNA antibodies and SLEDAI, serum complement levels and the occurrence of nephritis were performed. The results showed that anti-dsDNA autoantibodies detected using both ELISA and FIA significantly correlated with SLEDAI, and significantly and inversely correlated with the serum levels of C3 and C4. FIA had significantly higher correlation with SLEDAI and C4 than did ELISA. The mean values of anti-dsDNA antibodies detected using FIA in patients with nephritis were significantly higher than in those without nephritis. In contrast, the values of anti-dsDNA antibodies detected using ELISA did not show significant differences between these two groups. We conclude that FIA had better correlation with SLEDAI, C4 and the occurrence of nephritis, and comparable correlations with C3 that were similar to the results found using ELISA. Thus, it is worthwhile developing the FIA method for clinical evaluation of disease activity in SLE patients.

Adolescent↗

Our experience with eclampsia in Singapore.

AIM: To assess the incidence, epidemiological factors, preceding symptoms and signs, management regimens and obstetric outcomes of eclampsia in a tertiary care hospital in Singapore. METHOD: A retrospective study of all obstetric patients who suffered one or more eclamptic seizures in our hospital between January 1994 and December 1999. RESULT: There were 62 cases of eclampsia among 92,305 deliveries (6.7 per 10,000 deliveries). The incidence was highest among Indians. Those aged between 25 and 34 had the lowest incidence, while women younger than 25 or older than 34 had a significantly higher incidence. Forty (64.5%) patients had symptom or sign of impending eclampsia of which headache was the most common. Most of the patients (81.6%) who received antenatal care with us suffered their first eclamptic seizure in hospital, compared to 50% of the unbooked patients. There was one maternal death (mortality rate 1.6%), and 15 (24.2%) women had significant morbidity. There were 61 singleton pregnancies and one twin pregnancy. There were six intrauterine deaths and 57 livebirths. The perinatal mortality rate was 95.2 per 1,000 births. CONCLUSION: Eclampsia is still a major cause of maternal and foetal mortality and morbidity in Singapore. Race and age appear to be risk factors for eclampsia with Indian women and those at the extremes of reproductive age at greater risk. Antenatal care is important in reducing perinatal mortality and possibly maternal complications.

Adolescent↗

Clinical comparison of high-dose interferon-alpha2b with or without ribavirin for treatment of interferon-relapsed chronic hepatitis C.

BACKGROUND: Interferon a with ribavirin combination therapy is effective but still unsatisfactory in the treatment of patients with interferon-relapsed chronic hepatitis C. AIMS: To compare, in a randomized, double blind, placebo-controlled study, high-dose interferon-alpha2b with or without ribavirin in the treatment for interferon-relapsers. PATIENTS: A total of 52 patients with interferon-relapsed chronic hepatitis C were randomly assigned to receive 24-week treatment with interferon-alpha2b (6 MU three times per week) combined with either ribavirin (1,000 to 1,200 mg per day) or a matched placebo and then followed for an additional 24 weeks. METHODS: Hepatitis C virus RNA was detected by reverse-transcription polymerase chain reaction. For determining viral concentration, the commercial bDNA Quantiplex hepatitis C virus-RNA 2.0 assay was used. Genotyping was performed by reverse hybridization assay RESULTS: At the end of treatment, no detectable hepatitis C virus RNA levels were observed in 92% (24/26) of patients on interferon alpha2b/ribavirin and 81% (21/26) of patients on interferon alpha2b/placebo. At the end of the follow-up, a higher sustained virological response rate was seen in patients treated with interferon alpha2b/ribavirin than those treated with interferon alpha2b/placebo (69% vs 23%, p < 0.001). Patients with either initially high levels of viral concentration or with genotype 1 responded poorly. Patients who received interferon-alpha2b/ribavirin treatment and in whom no hepatitis C virus RNA was detected at 4th week after treatment had 90% chance to achieve sustained virological response. CONCLUSIONS: High-dose interferon-alpha2b plus ribavirin treatment is highly effective in interferon-relapsed patients.

Adult↗

Molecular typing of Treponema pallidum in South Africa: cross-sectional studies.

We evaluated a molecular subtyping system for Treponema pallidum for its ability to differentiate between strains obtained from male patients with primary syphilis in South Africa. Of 201 T. pallidum-positive specimens, 161 were typeable, revealing 35 subtypes. The unique subtypes identified in Durban, Cape Town, and Carletonville and the total number of subtypes suggested that the strain population was very diverse and varied geographically.

Bacterial Typing Techniques↗

A preliminary study of chromium distribution in chromium-rich brewer's yeast cell by NAA.

The purpose of this study was to assess the chromium (Cr) distribution in chromium-rich brewer's yeast cell. The chromium concentrations in the cell wall and protoplast fractions of the chromium-rich yeast were determined by neutron activation analysis (NAA). Moreover, the combined state of chromium and amino acid content in the Cr-rich brewer's yeasts was analyzed and measured. The experimental results indicate that the introduction of water-soluble chromium(III) salt as a component of the culture medium for yeasts results in a substantial amount of chromium absorbed through the cell wall by the yeast, among which 80.9% are accumulated in the protoplast. It implies that, under optimal conditions, yeasts are capable of accumulating large amounts of chromium and incorporating chromium into organic compounds.

Amino Acids↗

[Changes of serum soluble tumor necrosis factor receptor I in patients with rheumatic fever].

OBJECTIVE: To study the changes and the effects of soluble tumor necrosis factor receptor I (sT-NFR I) in patients with rheumatic fever, and to find out the laboratorial marker of clinic activity in patients with rheumatic fever. METHODS: The serum concentrations of sTNFR I in 16 patients with ARF, 16 patients with chronic inactive rheumatic heart disease (CRHD) and 15 healthy controls were measured by methods of ELISA and the relationship between sTNFR I and ESR or CRP were studied. RESULTS: The sTNFR I serum concentrations in patients with ARF (3.92 +/- 1.28) ng.ml-1 were significantly higher than those with CRHD (1.43 +/- 0.66) ng.ml-1 and healthy controls (1.06 +/- 0.42) ng.ml-1 (all P < 0.01). The serum concentrations of sTNFR I in patients with CRHD were almost the same with those in healthy controls (P > 0.05); Their positive correlation was significantly observed between sTNFR I and CRP(P < 0.001), and wasn't observed between sTNFR I and ESR. CONCLUSION: The Patients with ARF have high serum levels of sTNFR I. It may be used as the laboratorial marker in the clinic assessment of activity in patients with rheumatic fever.

Adolescent↗

AU binding proteins recruit the exosome to degrade ARE-containing mRNAs.

Inherently unstable mammalian mRNAs contain AU-rich elements (AREs) within their 3' untranslated regions. Although found 15 years ago, the mechanism by which AREs dictate rapid mRNA decay is not clear. In yeast, 3'-to-5' mRNA degradation is mediated by the exosome, a multisubunit particle. We have purified and characterized the human exosome by mass spectrometry and found its composition to be similar to its yeast counterpart. Using a cell-free RNA decay system, we demonstrate that the mammalian exosome is required for rapid degradation of ARE-containing RNAs but not for poly(A) shortening. The mammalian exosome does not recognize ARE-containing RNAs on its own. ARE recognition requires certain ARE binding proteins that can interact with the exosome and recruit it to unstable RNAs, thereby promoting their rapid degradation.

3' Untranslated Regions↗

Practical asymmetric synthesis of a selective endothelin A receptor (ETA) antagonist.

[structure: see text]. A practical, chromotography-free asymmetric synthesis was developed for the large scale preparation of an endothelin receptor antagonist 2. This synthesis includes a new efficient process for the preparation of 6-bromo-2,3-dihydrobenzofuran, a stereoselective conjugate addition of an aryllithium followed by stereospecific addition of the Grignard reagent of the top aryl bromide, and an aminophosphate-mediated sterospecific intramolecular enolate alkylation, which led to the formation of the five-membered ring bearing three contiguous asymmetric centers.

Antihypertensive Agents↗

Different risks of symptomatic brain necrosis in NPC patients treated with different altered fractionated radiotherapy techniques.

PURPOSE: To report our observation of excessive temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients treated with 160 cGy b.i.d. radiotherapy technique. During the same period, patients treated with 120 cGy b.i.d. have not shown a similar tendency. Our experience may be useful for designing unconventional radiotherapy regimens for NPC patients. METHODS AND MATERIALS: During the period from October 1991 to January 1998, 81 M0, previously untreated NPC patients completed altered fractionated radiotherapy. Seventy patients were treated with the hyperfractionated technique, and 11 were treated using the accelerated-hyperfractionated scheme. Hyperfractionated radiotherapy was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. A minimum tumor dose of 8000 cGy was the standard dose over an 8-week period. With the accelerated-hyperfractionated scheme, 160 cGy was given twice daily, also with an interval of 6 h. The minimum tumor dose ranged between 6840 and 7640 cGy, with 7 of the 11 patients receiving 7000 cGy. The arrangement of portals was the same for both regimens. The follow-up period for patients alive was from 32 to 102 months with a median of 61 months for the hyperfractionated patients. For the accelerated-hyperfractionated group, it ranged from 67 to 82 months with a median of 72 months. No patient was lost to follow-up. RESULTS: At the time of analysis, 49 of the 70 patients in the hyperfractionated group were alive. In the accelerated group, 8 of the 11 patients were alive. The estimated radiation dose to the temporal lobe for the hyperfractionated group was 6000-7440 cGy with a median of 7080 cGy. For the accelerated-hyperfractionated group, the dose range was 4480-6700 cGy with a median of 6400 cGy. Of the 70 patients treated with hyperfractionated radiotherapy, none developed symptomatic brain necrosis, despite the higher total dose to the temporal lobe in general. In contrast, 3 of the 11 (27%) patients irradiated using the accelerated-hyperfractionated regimen suffered from temporal lobe necrosis at 16, 19, and 40 months after completion of radiotherapy. CONCLUSION: An excessive incidence of temporal lobe necrosis was noted when an accelerated-hyperfractionated regimen with 160 cGy b.i.d. was used in NPC patients with a median brain dose of 6400 cGy. There has been no such event in patients treated using a hyperfractionated regimen with 120 cGy and a median brain dose of 7000 cGy. The real causes of this discrepancy are not known. However, a high sensitivity of the human brain to a change in fraction size may play a role.

Adolescent↗

Identification and characterization of a high-affinity zinc uptake system in Neisseria gonorrhoeae.

A search of the gonococcal genome database using the known zinc-binding protein (znuA) sequences from Escherichia coli and Haemophilus influenzae identified an open reading frame encoding a putative gonococcal ZnuA. The consensus amino acid sequence of this open reading frame possessed a characteristic 30-amino acid histidine-rich metal-binding motif (repetitive HDH sequence) containing 43% histidine and 37% aspartic acid and glutamic acid. Subsequently, two adjacent open reading frames with homology to E. coli and H. influenzae znuB and znuC were located upstream of znuA. When partially purified from sonicated cell-free supernatants by CM-Sepharose chromatography, the mature gonococcal ZnuA had an estimated molecular mass of 38 kDa by SDS-PAGE. The presence of a DNA sequence encoding a 19-amino acid signal peptide and the solubility of the mature ZnuA suggested that this protein was located in the periplasm. Inactivation of the Neisseria gonorrhoeae F62 znuA by insertional mutagenesis resulted in a mutant that had a growth rate lower than that of the wild-type parent strain and that required high concentrations of ZnCl2 (> or = 200 microM) for optimal growth. Using a chemically defined agar medium, the gonococcal ZnuA mutant grew only in the presence of Zn(2+), whereas Mg(2+), Ca(2+), Ni(2+), Fe(2+), Cu(2+), Mn(2+) and Cd(2+) had either no effect or were growth inhibitory.

Amino Acid Sequence↗

Enhancement of the immunity to foot-and-mouth disease virus by DNA priming and protein boosting immunization.

Subunit vaccination is effective in eliciting humoral responses to a variety of viral antigens, however, it has not generated persistent protective immunity to foot-and-mouth disease virus (FMDV). In this study, we observed that priming mice with a DNA plasmid encoding VP1 of the FMDV O/Taiwan/97 capsid protein followed by boosting with a VP1 peptide conjugate (P29-KLH) resulted in production of not only high titers of antibodies but also antibodies with FMDV neutralizing activities. Moreover, the mice immunized in this manner cleared the virus from their sera in FMDV challenge experiments. Mice subjected to DNA plasmid priming and P29-KLH protein boosting had relatively higher ratio of IgG2a/IgG1 than those primed and boosted with P29-KLH conjugate. Addition of an oligodeoxynucleotide (ODN) containing immunostimulatory cytosine-phosphate-guanosine (CpG) motifs to P29-KLH conjugate also induced a higher ratio of IgG2a/IgG1 and significantly higher titer of neutralizing antibodies. These results indicate that treating animals with DNA plasmids priming and FMDV antigen(s) boosting may elicit immunity to FMD and this immune response may be augmented by CpG ODN.

Amino Acid Sequence↗

Ligand preorganization in metal ion complexation: molecular mechanics/dynamics, kinetics, and laser-excited luminescence studies of trivalent lanthanide complex formation with macrocyclic ligands TETA and DOTA.

The molecular mechanics and dynamics calculations, kinetics, and laser-excited luminescence studies were carried out for trivalent lanthanide (Ln(3+)) complexes of macrocyclic polyaminopolycarboxylate ligands TETA and DOTA (where TETA is 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid and DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to further understand the observed thermodynamic, kinetic, and structural properties and to examine how ligand preorganization affects metal ion complexation. Excitation spectroscopy (emission monitored at 614.0 nm) of the (7)F(0) --> (5)D(0) transition of Eu(3+) was used to study the aqueous properties of the Eu(3+)-TETA system. A stopped-flow spectrophotometric method was used to study the formation kinetics of the aqueous Ce(3+)-TETA/DOTA systems in the pH range 6.1-6.7. Molecular mechanics calculation results are consistent with the proposed mechanism of Ln(DOTA)(-) formation, i.e., formation of a carboxylate O-bonded precursor, followed by metal ion moving into the preformed macrocyclic cavity. For Ln(TETA)(-) formation, at least two carboxylate O-bonded intermediates have been predicted and Ln(3+) ion assisted reorganization of the TETA ligand is present. The calculated bond distances and overall structures of Ln(DOTA)(-) and Ln(TETA)(-) were in agreement with the single-crystal and solution NMR structural data. The origin of the difference in thermodynamic stability of Ln(DOTA)(-) and Ln(TETA)(-) complexes and the corresponding formation intermediates is mainly due to the differences in water-occupancy energy (i.e., whether there is an apical coordinated water molecule), the ligand strain energy, and the cation-ligand interaction energy. Kinetic studies revealed that the formation rates of the Ce(TETA)(-) complex are smaller at lower pH and temperature but become greater at higher pH and temperature, as compared to those of the Ce(DOTA)(-) complex. This is attributed to the lanthanide ion and both mono- and di-hydroxide ion assisted TETA conformational reorganization and higher kinetic activation parameters. The presence of a di-hydroxide ion assisted intermediate rearrangement pathway could make the Ce(TETA)(-) complex formation rate faster at higher pH, and the higher activation barrier makes Ce(TETA)(-) complex formation rate slower at lower pH, as compared to those of the Ce(DOTA)(-) complex.

Journal Article↗

Expression in Pichia pastoris and characterization by circular dichroism and NMR of rhodostomin.

Rhodostomin (Rho) is a snake venom protein isolated from Calloselasma rhodostoma. Rho is a disintegrin that inhibits platelet aggregation by blocking the binding of fibrinogen to the integrin alpha(IIb)beta3 of platelets. Rho produced in Escherichia coli inhibited platelet aggregation with a K(I) value of 263 nM. Although functional, Rho produced in E. coli is misfolded based on our 2D and 3D NMR studies. In order to correct the folding problem, Rho was expressed in Pichia pastoris. The recombinant Rho expressed in P. pastoris inhibited platelet aggregation with a resulting K(I) value of 70 nM. This is the same potency as that of native Rho. CD analysis showed that the secondary structures of Rho are pH-independent and contain 3.5-7.9% alpha-helix, 48.2-50.5% beta-structures, and 42.3-47% coil. The sequential assignment and structure analysis of Rho were obtained using 2D and 3D 15N-edited NMR spectra. These results provide the first direct evidence that highly disulfide-bonded disintegrin can be expressed in P. pastoris with the correct fold. This evidence may serve as the basis for exploring the structure and function relationships as well as the dynamics of disintegrin and its variants.

Amino Acid Sequence↗

Disposition of polychlorinated dibenzo-p-dioxins, dibenzofurans, and non-ortho polychlorinated biphenyls in pregnant long evans rats and the transfer to offspring.

Pharmacokinetic properties of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDFs), and non-ortho biphenyls (PCBs) play a critical role in their relative toxicity. The present study examined the transfer of these chemicals to offspring and placenta. Pregnant Long Evans rats received 0.0 (control), 0.05, 0.2, 0.8, and 1.0 microg/kg of dioxin toxic equivalence (TEQ) by oral gavage on the 15th gestational day (GD 15), using a dosing mixture that contained 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), octachlorodibenzofuran (OCDF), 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) in ratios approximating that in food. Rats were euthanized on GD 16, GD 21, and postnatal day 4 (PND 4). The chemical concentrations in fetus, pup, placenta, and maternal liver, serum, and adipose tissue were determined using gas chromatography/high-resolution mass spectrometry. A dose-dependent increase in hepatic sequestration was seen with TCDD, PeCDD, 4-PeCDF, OCDF, PCB 126, and PCB 169, and the transfer to offspring was reduced at higher doses. 4-PeCDF, PeCDD and PCB 126 showed higher liver affinity than TCDD. TCDF, 1-PeCDF, and PCB 77 were metabolized rapidly. On GD 16, TCDD and the three PCBs reached equilibration between the fetus and placenta, but this did not occur with PeCDD and 4-PeCDF until GD 21, according to the lipid-based concentrations. Offspring compartments received more of the dosed compounds lactationally than transplacentally (7-28% versus 0.5-3%). The behavior of each congener was dose-dependent; therefore, extrapolation of high-dose experimental data should be used with caution.

Adipose Tissue↗

The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women.

Lung cancer is the leading cause of cancer death in Taiwanese women since 1982. High lung cancer mortality ratio of male:female in Taiwan (2:1) was observed, although less than 10% of female lung cancer patients are smokers. Until now, the etiological factor remains unknown. We hypothesize that high-risk human papillomavirus (HPV) 16/18 may be associated with lung cancer development based on high prevalence of p53 negative immunostainings in female lung tumors compared with that of male lung tumors. In this study, 141 lung cancer patients and 60 noncancer control subjects were enrolled to examine whether HPV 16/18 DNA existed in lung tumor and normal tissues by nested PCR and in situ hybridization (ISH), respectively. The concordant detection of HPV 16 and 18 DNA between nested PCR and ISH method was 73 and 85.5%, respectively. Our data showed that 77 (54.6%) of 141 lung tumors had HPV 16/18 DNA compared with 16 (26.7%; P = 0.0005) of 60 noncancer control subjects. In addition, ISH data showed that HPV 16/18 DNA was uniformly located in lung tumor cells, but not in the adjacent nontumor cells. When study subjects were stratified by gender, age, and smoking status, nonsmoking female lung cancer patients who were older than 60 years old had significantly high prevalence of HPV 16/18 infection. The odds ratio of HPV 16/18 infection of nonsmoking female lung cancer patients is much higher at 10.12 (95% confidence interval, 3.88-26.38) compared with 1.98 (95% confidence interval, 0.84-4.76) of nonsmoking male lung cancer patients. This result strongly suggests that HPV infection is associated with lung cancer development of nonsmoking female lung cancer patients. The high prevalence of HPV 16/18 infection may explain to a certain extent why Taiwanese women nonsmokers had a higher lung cancer mortality rate.

Female↗

Effects of nickel chloride on human platelets: enhancement of lipid peroxidation, inhibition of aggregation and interaction with ascorbic acid.

This study was undertaken to examine the effects of nickel (Ni) on human platelet function. In a (concentration-dependent manner, Ni significantly inhibited the function of platelet aggregation induced by collagen. The phenomenon of lipid peroxidation was involved as Ni significantly increased malondialdehyde (MDA) levels with reduction in platelet reduced glutathione (GSH) and alpha-tocopherol content. Further, platelet thromboxane B2, formation was markedly inhibited and the levels of cyclic AMP were significantly elevated by Ni. Treatment with ascorbic acid (Vit C) significantly lowered the levels of MDA and increased the content of alpha-tocopherol and reduced GSH. Vit C also significantly increased platelet aggregation and thromboxane B2 when coincubated with Ni. Data show that Ni is toxic as evidenced by lipid peroxidative damage and inhibition of human platelet aggregation, but that ascorbic acid provides protection, at least partially, against this metal.

Ascorbic Acid↗