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Biomedical subjects

Xin Zhou

Publications and source records attributed to Xin Zhou.

At least 37 records · Page 2Linked to original sources

Phenol quaternary ammonium derivatives: charge and linker effect on their DNA photo-inducible cross-linking abilities.

We report here that phenol derivatives with two and four quaternary ammoniums were synthesized and their abilities to bind and cross-link DNA were investigated. Thermal denaturizing studies indicated that derivatives possess similar DNA binding abilities and gel electrophoresis revealed that more charges (series B) and electronic donation substitute linkers (like -S-) dramatically increase the DNA cross-linking abilities.

Cross-Linking Reagents↗

A dielectric polymer with high electric energy density and fast discharge speed.

Dielectric polymers with high dipole density have the potential to achieve very high energy density, which is required in many modern electronics and electric systems. We demonstrate that a very high energy density with fast discharge speed and low loss can be obtained in defect-modified poly(vinylidene fluoride) polymers. This is achieved by combining nonpolar and polar molecular structural changes of the polymer with the proper dielectric constants, to avoid the electric displacement saturation at electric fields well below the breakdown field. The results indicate that a very high dielectric constant may not be desirable to reach a very high energy density.

Journal Article↗

Evidence for the formation of the (Ph3P)2Pt complex of 3,7-dimethyltricyclo[3.3.0.03,7]oct-1(5)-ene, the most highly pyramidalized alkene in a homologous series. Isolation and X-ray structure of the product of the ethanol addition to the complex.

[reaction: see text] Attempts to isolate the (Ph(3)P)(2)Pt complex of the highly pyramidalized olefin 3,7-dimethyltricyclo[3.3.0.0(3,7)]oct-1(5)-ene 2 by generation of 2 in the presence of (Ph(3)P)(2)PtC(2)H(4), followed by crystallization of the complex (2-Pt) from THF-ethanol, resulted in the isolation of the adduct of 2-Pt with ethanol (5). Calculations confirm that addition of alcohol across the C1-C5 bond is more favorable in 2-Pt than in the corresponding (Ph(3)P)(2)Pt complexes of less pyramidalized olefins, despite the stronger Pt-C bonds in 2-Pt.

Journal Article↗

Mechanism of altered TNF-alpha expression by macrophage and the modulatory effect of Panax notoginseng saponins in scald mice.

AIM: To explore the mechanism of altered tumor necrosis factor-alpha (TNF-alpha) expression by peritoneal macrophages (PMPhi) and Panax notoginseng saponins (PNS) modulation in light of NF-kappaB signal transduction in severely scalded mice. METHODS: Eighteen percent total body surface area (TBSA) full-thickness scalded mice were used. PMPhi was collected at different time intervals (0, 2, 6, 12, 24 and 48 post-burn hour (PBH)) separately. The following parameters were measured: TNF-alpha mRNA and IL-10 mRNA expression (reverse transcription-polymerase chain reaction, RT-PCR), protein kinase C (PKC) activity (isotope incorporation analysis), NF-kappaB activity (electrophoretic mobility shift assay, EMSA), IkappaB-alpha expression (Western blot). RESULTS: After scald, increased expression of TNF-alpha mRNA of PMPhi peaked at 12 PBH. Meanwhile, expression of IL-10 mRNA dropped to the lowest level at 12 PBH. NF-kappaB activity was markedly activated and reached its peak at 2 PBH. Membrane PKC activity was up-regulated after scald and showed a positive correlation with the change of TNF-alpha mRNA. Expression of IkappaB-alpha first decreased at 2 PBH and then increased to high level at 24 PBH. When 12 PBH was chosen as the time point for in vitro intervention with the application of specific NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC), PKC inhibitor H-7 and PNS, both TNF-alpha mRNA expression and NF-kappaB activity decreased significantly. CONCLUSIONS: These results indicate that abnormal expression of TNF-alpha mRNA of macrophages might be regulated by PKC-NF-kappaB signaling following severe burn. PNS might play an anti-inflammatory effect by inhibiting NF-kappaB activity and TNF-alpha mRNA expression.

Animals↗

Arylamine N-acetyltransferase aggregation and constitutive ubiquitylation.

Arylamine N-acetyltransferases (NAT1 and NAT2) acetylate and detoxify arylamine carcinogens. Humans harboring certain genetic variations within the NAT genes exhibit increased likelihood of developing various cancer types, especially urinary bladder cancer. Such DNA polymorphisms result in protein products with reduced cellular activity, which is proposed to be due to their constitutive ubiquitylation and enhanced proteasomal degradation. To identify the properties that lead to the reduced cellular activity of certain NAT variants, we introduced one such polymorphism into the human NAT1 ortholog hamster NAT2. The polymorphism chosen was human NAT1*17, which results in the replacement of R64 with a tryptophan residue, and we demonstrate this substitution to cause hamster NAT2 to be constitutively ubiquitylated. Biophysical characterization of the hamster NAT2 R64W variant revealed that its overall protein structure and thermostability are not compromised. In addition, we used steady-state kinetics experiments to demonstrate that the R64W mutation does not interfere with NAT catalysis in vitro. Hence, the constitutive ubiquitylation of this variant is not caused by its inability to be acetylated. Instead, we demonstrate this mutation to cause the hamster NAT2 protein to aggregate in vitro and in vivo. Importantly, we tested and confirmed that the R64W mutation also causes human NAT1 to aggregate in cultured cells. By using homology modeling, we demonstrate that R64 is located at a peripheral location, which provides an explanation for how the NAT protein structure is not significantly disturbed by its mutation to tryptophan. Altogether, we provide fundamental information on why humans harboring certain NAT variants exhibit reduced acetylation capabilities.

Amino Acid Sequence↗

Expression of PEA3 and lack of correlation between PEA3 and HER-2/neu expression in breast cancer.

The ETS protein PEA3 functions as a transcription factor to regulate gene expression. Although members of the ETS family have been reported to be involved in tumor progression, ectopic expression of PEA3 has been shown to suppress tumor formation. Despite several studies demonstrated frequent expression of PEA3 and its high association with HER-2/neu and have suggested a potential role of PEA3 in breast cancer, contradictory result has shown that the PEA3 was associated with better survival rate in breast cancer. In the current study, we address this discrepancy by examining the expression of PEA3 and HER-2/neu on 289 archived breast cancer tumor tissues and their correlation with clinicopathologic factors and prognosis. The staining of PEA3 was further validated by in situ hybridization for PEA3 mRNA. We found PEA3 was positive in 22.2% (64/289) of all cases and only 25.6% (21/82) of HER-2/neu-overexpressing cases showed co-expression of PEA3. In contrast to HER-2/neu, PEA3 expression was not correlated with prognosis or major clinicopathologic factors, except for a negative correlation with lymphovascular permeation ( p=0.007). This study demonstrates that PEA3 expression is not correlated with HER-2/neu expression in breast cancer tumor tissues, nor is it associated with adverse clinicopathologic factors or prognosis.

Adult↗

Enantioselective determination of dencichine in rabbit plasma by high-performance liquid chromatography-electrospray mass spectrometry.

An analytical method was developed for the determination of enantiomers of dencichine in plasma. Sample extraction from plasma was achieved by a solid-phase extraction (SPE) procedure using a C(18) cartridge, with carbocisteine as the internal standard. Plasma was deproteinized using inorganic acid and derivatizated before the SPE. Chiral separation of dencichine enantiomers was achieved by pre-column derivatization using o-phthaldialdehyde (OPA) and the chiral thiol N-isobutanoyl-L-cysteine (NIBC) to form diastereoisomeric isoindole derivatives that were separable by ODS column using a gradient solvent programme. The column eluent was monitored using mass spectrometry (MS). The conditions of MS detection were optimized, and selected ion monitoring was used to selectively detect D-dencichine and its arrangement isomer. High sensitivity and selectivity were obtained using this method. The limit of detection was determined to be 10 ng/ml for D-dencichine and 8 ng/ml for L-dencichine in plasma. The linearity was demonstrated over a wide range of concentrations, from 0.5 to 50 microg/ml for both enatiomers. The intra- and inter-day precision (C.V.), studied at four concentrations, was less than 7.0%. No interferences from endogenous amino acids and isomers of dencichine were found. The method was suitable for pharmacokinetic studies of dencichine enantiomers.

Amino Acids, Diamino↗

Childhood injuries from motor vehicle-pedestrian collisions in Wuhan, The People's Republic of China.

OBJECTIVES: To examine motor vehicle-pedestrian collision injuries resulting in hospitalisation among children admitted into Wuhan Children's Hospital, The People's Republic of China. METHODS: From the 1993 to 2004 inpatient data of Wuhan Children's Hospital, we identified injury cases from motor vehicle traffic crashes among children aged 18 years or less using the discharge diagnosis defined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). We examined characteristics of injuries from motor vehicle traffic crashes (ICD-9-CM = E810-E819) and then calculated the proportion of injuries from motor vehicle-pedestrian collisions (ICD-9-CM = E814) among all hospitalisations for childhood injuries (ICD-9-CM = 800-959). The trend of injuries from motor vehicle-pedestrian collisions from 1993 to 2004 was described. RESULTS: Of the 12,939 injuries resulting in hospitalisation among children admitted into Wuhan Children's Hospital during 1993-2004, a total of 528 injuries were caused by motor vehicle traffic crashes. The majority of the injured children in motor vehicle traffic crashes were males (59.3%). In comparison with other traffic injuries, a higher proportion of motor vehicle-pedestrian collisions occurred among children aged 12-15 years. Motor vehicle-pedestrian collision injuries resulted in significantly longer lengths of stay in the hospital than other motor vehicle traffic injuries (19.4 days versus 14.3 days, respectively; t-test = 2.59, p-value < 0.05). The percentage of motor vehicle-pedestrian collision injuries among all hospitalisations for childhood injuries increased significantly from 1.6% (95% confidence interval [CI] = 1.2-2.1) in 1993 to 3.1% (95% CI = 2.7-3.6) in 2004 (p < 0.05). CONCLUSIONS: Hospitalisations for injuries from motor vehicle-pedestrian collisions at this large children's hospital increased significantly in the past decade. These data underscore the need for additional research and a major concerted effort to prevent motor vehicle-pedestrian collisions among children in China.

Accidents, Traffic↗

The E23K polymorphism in Kir6.2 gene and coronary heart disease.

BACKGROUND: The G to A mutation in the Kir 6.2, the ATP-sensitive potassium channel subunit, resulted a glutamate (E) to lysine (K) substitution at codon 23, and the A allele was shown to have a relationship with high risk to type 2 diabetes in previous study. Their role in coronary heart disease (CHD) has not been evaluated. We hypothesized that the polymorphism would be associated with increased susceptibility to CHD. METHODS: The E23K gene polymorphism of Kir6.2 gene was analyzed by PCR-restriction site polymorphism (PCR-RSP) methods in 101 controls and 119 CHD patients. Serum lipids and C reactive protein concentrations were measured in all subjects. RESULTS: Among the CHD patients, the frequency of the G allele was higher (63.4% vs. 56.9%, P>0.05) and the frequency of the A allele was lower (36.6% vs. 43.1%, P>0.05) than among controls. No significant differences were found in allele frequencies between CHD and controls (P>0.05), but there were significant differences in GG and combined (GA+AA) genotypes frequencies (42.0% vs. 28.7%, and 58.0% vs. 71.3%, P<0.050). CONCLUSIONS: The E23K gene polymorphism in Kir6.2 gene appeared to be related to high susceptibility to CHD.

Base Sequence↗

Combined effects of apoE-CI-CII cluster and LDL-R gene polymorphisms on chromosome 19 and coronary artery disease risk.

OBJECTIVE: To investigate associations of gene polymorphisms of the apoE-CI-CII gene cluster and the LDL-R gene on coronary artery disease (CAD) and their interactions with alcohol drinking and smoking in the Chinese Han population. METHODS: A questionnaire survey of the behaviors of smoking and drinking, dietary patterns and anamnesis was conducted among 203 patients of CAD, aged 65.0 +/- 11.1 years, and 365 controls, aged 63.6 +/- 12.0 years. Peripheral blood samples were colleted and the total DNA was extracted. The apoE genotypes were identified by multiplex amplification refractory mutation system (multi-AMRS), the apoCI promoter polymorphisms and AvaII polymorphisms of the apoCII and LDL-R gene were detected by using PCR-RFLP. Pairwise linkage disequilibrium coefficients (D, D') were estimated by the LINKAGE program. The interactions between genes with alcohol drinking and smoking were analyzed by using multivariate logistic regression models. RESULTS: The differences of systolic/diastolic blood pressure, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations, smoking and drinking were significant between subjects with CAD and controls. The frequencies of apoE gene epsilon 3/4 genotype (25.9%) and epsilon 4 (13.9%) in CAD were significantly higher than those in controls (12.5% and 6.9%, respectively, p < 0.05). A significant difference was also found for the apoCI locus, the frequencies of H2 allele were 20.5% in the CAD and 11.3% in the control. Linkage disequilibrium coefficient D' was 0.672 (p < 0.01) between apoE and apoCI genes. Significant differences for a deficit of epsilon 3-H1-T1 and excess of epsilon 4-H2-T1 was found in CAD by estimation of the haplotype frequencies. After control for possible confounding factors, the multivariate logistic analysis showed that epsilon 4, H2 allele, smoking and drinking were risk factors of CAD. A significant interaction among epsilon 4, H2 and smoking was observed (OR 18.3, 95% CI: 2.35-150.81, p < 0.05), it was a multiplicative model. An additive model was shown among epsilon 4, H2 and drinking (OR12.7, 95% CI: 2.8-58.6, p < 0.05). CONCLUSION: The results suggested that both apoE and apoCI on chromosome 19 were the susceptibility locus for CAD, their linkage disequilibrium should be responsible for the development of CAD. Drinking and smoking enhance the genetic predisposition to CAD.

Adult↗

Isolation of multiple cell-binding ligands from different phage displayed-peptide libraries.

A technical challenge in the development of biosensor devices for cancer detection and diagnosis is the identification of ligands that recognize cancer cells with high affinity and specificity. Furthermore, it is unlikely that one cell-binding ligand will provide sufficient biological information, thus, multiple ligands for a given cancer type will be needed for confident clinical diagnosis. Biopanning of phage displayed peptide libraries is a route to isolation of specific cell-binding reagents. A potential approach towards isolation of multiple ligands for a single cell type is to pan against the same cell type using different peptide libraries. Here we report the synthesis of a new 20-mer peptide-phage library and its use to select a peptide that binds to the large cell lung carcinoma cell line, H1299. The isolated phage clone binds H1299 cells 80 times better than a control phage and can distinguish between H1299 and normal control cells. The phage clone also binds to the lung pleura epidermoid cell line, Calu-1 but not to all lung carcinoma cell lines. The peptide is functional outside the context of the phage and tetramerization of the peptide on a trilysine core improves the affinity of the peptide. The tetrameric peptide can be used to deliver a fluorescent quantum dot to H1299 cells. Unexpectedly, the peptide shares sequence similarity to a previously isolated H1299-binding peptide isolated from a different 20-mer peptide library. Data suggests that the two peptides target the same cellular receptor. Our results imply that cell-based biopanning can isolate cell-binding ligands that may be of utility for cancer diagnosis, and isolation of cell-targeting peptides from different peptide libraries can expand the repertoire of cell-binding reagents.

Amino Acid Sequence↗

Variation of mitochondrial gene and the association with type 2 diabetes mellitus in a Chinese population.

Mitochondrial DNA (mtDNA) variants have been implicated in many diseases including diabetes mellitus. To explore whether these genetic variants contribute to the susceptibility for type 2 diabetes mellitus (T2DM) in a Chinese population, a total of 184 T2DM cases and 279 matched healthy controls were recruited. PCR restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing were used to determine the variants of mtDNA (including T16189C, G3316A, T3394C, A14693G, A3243G and C1310T). Some of them were further analyzed by mfold or tRNA-scan-SE software. A homoplastic A14693G, for the first time, was found in 4 of 184 Chinese cases, the frequency of A14693G and T3394C was 2.17% and 2.72%, respectively, in patients but not in the controls. Secondary structure prediction revealed that there were obvious conformational changes in T3394C mutant ND1 versus wild type and A14693G mutant tRNA(Glu) protein versus wild type, providing additional clues to the disease pathogenesis although A3243G and C1310T mutations were not detected in any patients in the two groups. The 16189 variant among type 2 diabetes was more prevalent than in controls (36.9% versus 28.7%, P=0.039), and stepwise multiple regression analysis showed that the 16189 variant was an independent factor contributing to HOMA-IR (R(2)=0.043, P=0.037). Our results suggest that the mutations of T3394C and A14693G may contribute to genetic predisposition to T2DM, with the T16189C variant being associated with insulin resistance.

Asian People↗

Practical application of fluorescent quantitative PCR on Trisomy 21 in Chinese Han population.

OBJECTIVE: To apply the fluorescent quantitative PCR method on the detection of Trisomy 21 by D21S11 locus and make a foundation for rapid prenatal diagnosis of Trisomy 21. METHODS: About 409 controls (39 amniotic fluid samples and 370 peripheral blood samples) and 35 patients (4 amniotic fluid samples and 31 peripheral blood samples) with Trisomy 21 were tested using fluorescent quantitative PCR by amplification of DNA fragment on D21S11 STR locus. The results were compared with conventional cytogenetic analysis to confirm the utility of this method. And the allele frequency distributions of D21S11 STR locus were analyzed. RESULTS: The 95% reference interval of fluorescent intensity ratios of peak heights of PCR products amplified from two alleles on D21S11 locus ranged from 0.84 to 1.42 (1.13 +/- 0.29) in heterozygous controls. About 19 out of 35 patients showed a "diallelic" pattern and their height ratio of fluorescent peaks of PCR products amplified from two alleles in patients with "diallelic" patterns were all outside of the 95% reference range of controls. The PCR products of DNA from 12 patients presented the third allele. No sample with the "monoallelic" pattern was found. Four chimeras diagnosed by cytogenetic method could not be diagnosed by this method. There were 17 and 11 alleles found in controls and patients, respectively. About 343 out of 409 controls were heterozygous and the heterozygosity was 83.86%. We did not find any significant differences in the frequency distributions of alleles on D21S11 locus between controls and patients. But there were significant differences in the frequency distributions of alleles on D21S11 locus between controls and patients. But there were significant differences in the frequency distributions of alleles on D21S11 locus among different populations. CONCLUSIONS: The fluorescent quantitative polymerase chain reaction method was rapid, accurate, and only small amount of starting material was needed, it could be applied in rapid prenatal diagnosis of Trisomy 21. D21S11 was a good marker with high heterozygosity for the screening of Trisomy 21. And the frequency distributions of alleles on D21S11 locus were significantly related to ethnic background.

Amniotic Fluid↗

Ultrasound-guided hydrostatic reduction of intussusceptions by saline enema: a review of 5218 cases in 17 years.

BACKGROUND: The aim of this study was to evaluate the results of ultrasound (US)-guided hydrostatic reduction (UGSED) of intussusceptions in pediatric patients by saline enema. METHODS: Five thousand two hundred eighteen pediatric patients with intussusceptions treated by UGSED from October 1985 to October 2002 were reviewed retrospectively. RESULTS: The success rate of reduction in 5218 patients was 95.5%. Two hundred thirty-seven patients (4.5%) underwent surgery. Colonic perforation occurred in 9 patients (0.17%). Two infants suffered from milk aspiration because of vomiting during the hydrostatic enema reduction. There was no mortality. CONCLUSIONS: UGSED of intussusceptions avoids radiation exposure. It is reliable and safe. It has high success rate and minimal complications. It is a perfect method for the nonoperative treatment of pediatric intussusception and can be widely used as routine therapy.

Catheterization↗

Mutation p.Arg954Trp of KIF21A causes congenital fibrosis of the extraocular muscles in a Chinese family.

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. In this study, we identified a Chinese family with CFEOMI for four generations. Linkage analysis mapped the causative gene of the family to 12q with a Lod score 2.1 for polymorphic marker D12S85, where KIF21A is located. Direct DNA sequence analysis identified a 2860C-->T change in exon 21, resulting in a tryptophan substitution for arginine in codon 954 of KIF21A. SSCP (single-stranded conformational polymorphism) analysis showed that mutation p.Arg954Trp of KIF21A co-segregated with the affected members, but was absent in the unaffected individuals in the family and 150 normal controls. Our results indicate that mutation p.Arg954Trp of the KIF21A is the genetic basis of the Chinese family with CFEOM1.

Amino Acid Substitution↗

Complex notation for the dielectric response of ferroelectric materials beyond the small sinusoidal fields.

For the polarization response beyond the small field range, Rayleigh's law has been introduced in the past to describe the field-dependent behavior (with loss) of ferroelectric materials with some success. We examine the relationship between Rayleigh's law and the complex dielectric constant notation that has been used widely in the scientific and engineering community; and we show that a modified complex notation can describe the field-dependent dielectric response with loss in the small and medium field range quite well. In addition, the modified complex notation easily can include a field independent dielectric loss that is, in fact, present in all the dielectric materials. The results also show that the alternating current (AC) field response is still predominantly linear with the amplitude and phase of the complex coefficient changing with the applied field amplitude.

Letter↗