PubMed Health⌕ Search

Biomedical subjects

C Q Sun

Publications and source records attributed to C Q Sun.

At least 19 recordsLinked to original sources
PubMed2005

Impedance labelless detection-based polypyrrole protein biosensor.

A simple and sensitive electrochemical immunosensor with impedance labelless detection and novel data processing method was investigated. One-step copolymerization was used to electrochemically deposit an antibody impregnated polypyrrole film on a glassy carbon electrode surface for the immunosensor. Impedance measurements provided a labelless or reporterless method to detect antibody (Ab)-antigen (Ag) interactions. Dimensionless analysis was employed to successfully process the measured impedance data. Since the method derived unit impedance change to eliminate or reduce the variation of the bulk electronic properties of Ab/polypyrrole films, the signal to noise ratio (S/N) was significantly improved for high sensitivity and specificity. Nonspecific binding effect was studied by array electrode chips and was found out that the polypyrrole electrode without antibody attachment had much stronger nonspecific binding effect than the Ab/polypyrrole electrode; incubation followed by thoroughly washing significantly reduced the nonspecific interference. 10 pg/ml detection limit and superior specificity were achieved by the method, demonstrating a highly sensitive labelless immunosensor in comparison with the detection limit of ng -microgram/ml for the reported polypyrrole based immunosensors. The electrochemical immunosensors presented in this paper, due to its simplicity, low cost, high sensitivity and superior specificity, could be an invaluable tool for clinical diagnostics and could have potential applications in drug discovery, environmental and food analysis.

Antibodies↗
PubMed2005

Impedance labelless detection-based polypyrrole DNA biosensor.

Microelectrodes were fabricated to study impedance labelless detection of DNA hybridization. The probe molecule was attached onto the platinum microelectrode surface by electrochemically copolymerizing pyrrole and the probe oligonucleotides. Measured impedance complexes showed that an electrochemical redox-reaction occurred and the electron-transfer resistance increased after DNA hybridization. It was proposed that the hybridization of DNA in the conductive polymer matrix slowed down the anionic doping/undoping process, resulting impedance changes for the target DNA detection. Impedance measurements were conducted at the complementarily hybridized probe oilgomer-attached polypyrrole film electrodes in different anionic solutions to exam the anionic effects. Results showed that higher concentration and smaller size of anions had the lower electron-transfer resistance. The results not only provide further evidence to support the detection mechanism proposed, but also offer a method to improve the signal to noise ratio for the DNA biosensor. The research also tested the specificity of the methods and experimental results, indicating good specificity of the method. A concept array chip was fabricated and used to demonstrate the capability of the labelless detection method. Nano-Molar concentrations were detected and showed fairly linear responses versus the target molecule concentrations. The method is simple and inexpensive. The technique based genosensors could have potential applications in clinical diagnosis, drug discovery, environmental and food analysis.

Base Sequence↗
PubMed2001

Beta 3 agonists. Part 1: evolution from inception to BMS-194449.

Screening of the BMS collection identified 4-hydroxy-3-methylsulfonanilidoethanolamines as full beta 3 agonists. Substitution of the ethanolamine nitrogen with a benzyl group bearing a para hydrogen bond acceptor promoted beta(3) selectivity. SAR elucidation established that highly selective beta(3) agonists were generated upon substitution of C(alpha) with either benzyl to form (R)-1,2-diarylethylamines or with aryl to generate 1,1-diarylmethylamines. This latter subset yielded a clinical candidate, BMS-194449 (35).(1)

Administration, Oral↗
PubMed2001

BMS-196085: a potent and selective full agonist of the human beta(3) adrenergic receptor.

A series of 4-hydroxy-3-methylsulfonanilido-1,2-diarylethylamines were prepared and evaluated for their human beta(3) adrenergic receptor agonist activity. SAR studies led to the identification of BMS-196085 (25), a potent beta(3) full agonist (K(i)=21 nM, 95% activation) with partial agonist (45%) activity at the beta(1) receptor. Based on its desirable in vitro and in vivo properties, BMS-196085 was chosen for clinical evaluation.

Administration, Oral↗
PubMed2001

Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1.

Nox1, a homologue of gp91phox, the catalytic moiety of the superoxide (O(2)(-))-generating NADPH oxidase of phagocytes, causes increased O(2)(-) generation, increased mitotic rate, cell transformation, and tumorigenicity when expressed in NIH 3T3 fibroblasts. This study explores the role of reactive oxygen species (ROS) in regulating cell growth and transformation by Nox1. H(2)O(2) concentration increased approximately 10-fold in Nox1-expressing cells, compared with <2-fold increase in O(2)(-). When human catalase was expressed in Nox1-expressing cells, H(2)O(2) concentration decreased, and the cells reverted to a normal appearance, the growth rate normalized, and cells no longer produced tumors in athymic mice. A large number of genes, including many related to cell cycle, growth, and cancer (but unrelated to oxidative stress), were expressed in Nox1-expressing cells, and more than 60% of these returned to normal levels on coexpression of catalase. Thus, H(2)O(2) in low concentrations functions as an intracellular signal that triggers a genetic program related to cell growth.

Animals↗
PubMed2001

A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors.

A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.

Administration, Oral↗
PubMed2001

Accumulation of mitochondrial DNA deletions in the malignant prostate of patients of different ages.

It has been shown that mitochondrial DNA (mtDNA) deletion mutations accumulate with age in many tissues of the body. However, to date no one has shown that these deletions occur in the malignant prostate. Therefore, we hypothesize that such deletions do occur in the prostate and increasingly so with advanced age. To test this hypothesis, DNA was isolated from 34 radical prostatectomy specimens, and the entire mitochondrial genome (16.5kb) was amplified using long range PCR (LXPCR). The LXPCR products were visualized by gel electrophoresis, and the presence of low molecular weight (<16kb) bands was considered evidence of large mtDNA deletions. In order to show that these lower molecular weight LXPCR bands were not simply PCR artifact, we also digested mtDNA from a subset of the same patients and did Southern analysis with a mtDNA probe. Southern blots confirmed the existence of large deletions in every sample tested. Furthermore, several of the specific deletions identified by LXPCR were also seen in the Southern blots. From the LXPCR data, we found that as the age of the specimen increased, so did the average number of low molecular weight bands (i.e. deletions). In particular, one prominent band was seen at 1.2kb and became more consistent with advanced age.

Adult↗
PubMed2001

[The comparison of genetic divergences and its relationships to heterosis revealed by SSR and RFLP markers in rice (Oryza sativa L.)].

Genetic divergences of 57 entries from 6 ecotypes of rice were surveyed by PCR analysis with 48 pairs of SSR and by Southern analysis by 50 RFLP probes. It was indicated that SSR markers detected polymorphism efficiently in comparison to RFLP markers, considering the allele numbers per locus and average gene diversity. Among all of 1,596 pairs, 1,452 pairs of genetic distances based on SSR data (GDSSR) were higher than the genetic distance based on RFLP data (GDRFLP) by average of 0.2492. The average GDSSR of entries within indica subspecies was 0.5483, but GDRFLP was only 0.2776. And the GDSSR and GDRFLP of entries with japonica subspecies were 0.577, 0.2405 respectively. The average GDSSR between varieties of interspecies was 0.8074, and the average GDRFLP was 0.7310. It is suggested that the GDSSR between varieties of introspecies or interspecies are higher than that of GDRFLP. The analysis of correlation between GDSSR and GDRFLP of any entry with other 56 entries indicated that the correlation coefficient for typical Indica or Japonica varieties were higher, but lower for Indica-like or Japonica-like materials. It was also found that the relationships between genetic distance based on these two kinds of markers and the yield of hybrid performance were not significant, but most of the correlation coefficient between heterosis and GDRFLP or GDSSR arrived at highly significant level.

Genetic Variation↗
PubMed2001

[QTL analysis of anther length and ratio of stigma exsertion, two key traits of classification for cultivated rice (Oryza sativa L.) and common wild rice (O. rufipogon Griff.)].

A genetic map including 120 RFLP markers covering 1418.2 cM has been constructed using a BC1 population derived from a cross between common wild rice (Oryza rufipogon Griff.) from Dongxiang, Jiangxi Province, China, and an elite Indica variety Guichao 2. The linkage orders and genetic distances of markers in this map are consistent with the map constructed by Rice Genome Program of Japan except the markers of short arm of Chromosome 1. The QTLs analysis of anther length and ratio of stigma exsertion, two key traits of classification for cultivated rice and common wild rice indicated that there are two QTLs controlling anther length located at the region of C424-G39 of Chromosome 2, and C2807-C1263 of Chromosome 9 respectively. It was also found that there are two QTLs controlling ratio of stigma exsertion, and located at the region of C2289-R1553 of Chromosome 5 and G1149-R1963 of Chromosome 8 respectively. The detected QTLs affecting the key traits of classification for wild rice and cultivated rice will be useful for study of molecular evolution mechanism of cultivated rice.

Chromosome Mapping↗
PubMed2000

[A study of the genetic diversity of common wild rice (O. rufipogon Griff.) and cultivated rice (O. sativa L.) by RFLP analysis].

The genetic diversity of cultivated rice and common wild rice from 10 countries in Asia were evaluated by RFLP analysis using 44 probes of single copy. We used the parameters such as proportion of polymorphic loci (P), average number of alleles per locus (A), average number genotype per locus (Ng), degree of heterozygate per locus (Ho) and average gene diversity (Hs) showing genetic diversity. It is indicated that the common wild rice from China has the largest genetic diversity in the 10 countries, and the secondary is the common wild rice from India. The results also showed that the genetic diversity in Chinese common wild rice is larger than the genetic diversity in common wild rice of South and Southeast Asia. The average gene diversity (Hs) of South Asian wild rice is higher than Southeast Asian wild rice, while the parameters value of proportion of polymorphic loci (P), average number of alleles per locus (A) and average number genotype per locus (Ng), Southeast Asian wild rice is higher than South Asian wild rice. It is found that the genetic diversity in cultivated rice is obviously lower than in common wild rice. In the detected 44 loci, the number of polymorphic loci on O. sativa is as the same as 3/4 in O. rufipogon, the number of alleles in O. sativa is as the same as 60% in O. rufipogon, the number of genotype in O. sativa is as same as 1/2 in O. rufipogon. In O. sativa, the genetic diversity of indica is larger than that of japonica. O. rufipogon from China have highest value in degree of hetrozygate per locus (Ho), and Ho of wild rice is as two times as cultivated rice. It is showed that in the proceeding of wild rice evolved into cultivated rice, Ho and number of alleles was reduced, and the genetic diversity was decreased.

Genetic Variation↗
PubMed1998

The effect of pH on the inhibition of bacterial growth by physiological concentrations of butyric acid: implications for neonates fed on suckled milk.

Butyric acid is released from milk by pre-intestinal lipases during suckling. It is also known to inhibit bacterial growth. To investigate whether butyric acid may be a significant factor in controlling bacterial growth in the stomach of pre-weaned animals, the ability of butyric acid to inhibit growth of selected bacteria was tested over physiological ranges of pH and butyric acid concentrations. Six enteric and environmental strains of bacteria were used: two strains of Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, Enterococcus faecalis, and Enterococcus casseliflavus. At pH 4.5 and 5.0, the growth of all organisms was significantly inhibited in the presence of butyrate, and in some cases growth was completely arrested. At pH 6.0, butyric acid did not affect bacterial growth until the concentration reached 40 mM. The maximum concentration of butyric acid available in cow's milk after incubation with pre-gastric lipase is approximately 16 mM, which would be sufficient to prevent growth of the organisms tested at pH values occurring in the stomach. Therefore, butyric acid inhibition of bacterial growth may explain in part, the role of pre-intestinal lipases in young animals' natural defenses against bacteria in ingested food prior to weaning.

Animals↗
PubMed1997

Dual metalloprotease inhibitors: mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral endopeptidase.

A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiated urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency and duration of action, compound 1a (BMS-186716) was advanced into clinical development for the treatment of hypertension and congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Aminodiol HIV protease inhibitors. Synthesis and structure-activity relationships of P1/P1' compounds: correlation between lipophilicity and cytotoxicity.

A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1' were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1' phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (10l, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.

Amines↗
PubMed1992

New hydroxyethylamine HIV protease inhibitors that suppress viral replication.

The synthesis of analogues of AcSerLeuAsn[Phe-HEA-Pro]IleValOMe (1, JG-365; where HEA stands for the hydroxyethylamine unit 2), a tight-binding inhibitor of HIVP, are reported. Systematic modification of the P3 and P3' regions of the inhibitors has led to smaller HIVP inhibitors that inhibit viral replication in HIV-infected and SIV-infected cell cultures. Six aliphatic and/or aromatic derivatives were prepared by replacing residues in the P3 regions of BocLeuAsn[Phe-HEA-Pro]IleValOMe. Aromatic side chains at P3 gave better inhibitors than aliphatic side chains. The better inhibitors in this series contained a beta-naphthylalanine or a biphenyl unit at P3. A second series of HIVP inhibitors were obtained by converting the P3 group into acyl groups. CbzAsn[Phe-HEA-Pro]IlePheOMe and Qua-Asn-[Phe-HEA-Pro]-Ile-Phe-OMe (where Qua = quinolin-2-ylcarbonyl) are potent HIVP inhibitors with Ki values equal to 1.0 and 0.1 nM, respectively. The inhibition constants were determined by using the continuous fluorometric assay developed by Toth and Marshall. The activities of the protease inhibitors for inhibition of SIV replication were determined in vitro using CEM x 174 cells. Inhibition of HIV infection was determined essentially as reported by Pauwels and co-workers. The anti-HIV assay was carried out in culture using CEM cells (a CD4+ lymphocyte line) infected with virus strain HTLV-IIIb with a multiplicity of infection of 0.1. Several analogues inhibited the cytopathic effect at concentrations of 0.1-0.8 microgram/mL. These results establish that good inhibitors of HIV protease that inhibit viral replication in infected lymphocytes in in vitro cell assays can be obtained from JG-365 when the AcSerLeu unit is replaced by aromatic acyl derivatives.

Amino Acid Sequence↗
PubMed1991

Convergence of somatosensory and baroreceptive inputs onto parabrachio-subfornical organ neurons in the rat: an electrophysiological study.

Electrophysiological characteristics were described for neurons of the parabrachial nucleus (PBN) which receive baroreceptive and somatosensory inputs in the rat. Following focal electrical stimulation in the ipsilateral caudal nucleus of the tractus solitarii (NTS), the firing rates of these neurons were increased in 94 (55.6%), and decreased in 38 (22.5%). Fifty-three (54.5%) of 97 PBN neurons tested were excited, and 11 (11.3%) inhibited in response to contralateral common peroneal nerve (CPN) stimulation. Of these neurons, 52 were found to respond to both caudal NTS and CPN stimulation. Effects of subfornical organ (SFO) stimulation were also examined in 151 of 169 parabrachial neurons. 13 (7.7%) were activated antidromically and were located in the lateral division of the PBN, while 34 (22.5%) were affected orthodromically. Stimulation of the caudal NTS resulted in both a fall in the heart rate and changes of PBN neuronal firing rates. Similar effects were elicited by activating peripheral baroreceptors by the administration of phenylephrine, an alpha-adrenergic agonist. These results strongly indicate that: (1) the lateral PBN is involved in central cardiovascular control; (2) somatosensory and baroreceptive messages may converge onto some PBN neurons; and (3) some PBN neurons may relay baroreceptive information from the caudal NTS to the SFO.

Action Potentials↗
PubMed1990

Synthesis, conformation, and immunosuppressive activities of three analogues of cyclosporin A modified in the 1-position.

The syntheses of three new cyclosporin A (CsA) analogues that contain novel MeBmt derivatives in the 1-position are described. The MeBmt analogue that contains an additional methyl group on C4, (2S,3R,6E)-4,4-dimethyl-3-hydroxy-2-(N-methylamino)-6-octenoic acid (MeBm2t), was synthesized in four steps beginning with the reaction of Pmz-Sar-OtBu with (4E)-2,2-dimethyl-4-hexenal. The C4 desmethyl analogue of MeBmt, (2S,3R,6E)-3-hydroxy-2-(N-methylamino)-6-octenoic acid (MeBth), was synthesized in nine steps by a route based on the Sharpless chiral epoxidation procedure. The alkynyl derivative of MeBmt, (2S,3R,4R)-4-methyl-3-hydroxy-2-(N-methylamino)-6-octynoic acid (MeByt), was synthesized by a modification of the procedure described by Tung et al. for the synthesis of MeBmt. Each MeBmt analogue was protected as the N,O-acetonide and coupled with the hexapeptide Abu-Sar-MeLeu-Val-MeLeu-Ala-OBzl. The resulting heptapeptide was deprotected and coupled with Fmoc-D-Ala-MeLeu-MeLeu-MeVal-OH. The resulting undecapeptides were deprotected and cyclized to give the corresponding CsA analogues. Conformational analysis by 1D and 2D NMR methods was carried out for each analogue in chloroform, and the results are compared with the corresponding solution conformations of CsA and dihydrocyclosporin. The immunosuppressive activities of each analogue, determined in concanavalin A stimulated thymocytes, are lower than obtained for CsA. The results establish the important effect the methyl group and the double bond in MeBmt have on the solution conformation of the 1-position residue in CsA and on immunosuppressive activity.

Cyclosporins↗