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Biomedical subjects

X Wang

Publications and source records attributed to X Wang.

At least 163 records · Page 9Linked to original sources
PubMed2004

Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation.

Plasmid vectors have been widely used for DNA vaccines and gene therapy. Following intramuscular injection, the plasmid that persists is extrachromosomal and integration into host DNA, if it occurs at all, is negligible. However, new technologies for improving DNA delivery could increase the frequency of integration. In the present study, we tested the effect of electroporation on plasmid uptake and potential integration following intramuscular injection in mice, using a plasmid containing the mouse erythropoietin gene. Electroporation increased plasmid tissue levels by approximately six- to 34-fold. Using a quantitative gel-purification assay for integration, electroporation was found to markedly increase the level of plasmid associated with high-molecular-weight genomic DNA. To confirm integration and identify the insertion sites, we developed a new assay - referred to as repeat-anchored integration capture (RAIC) PCR - that is capable of detecting rare integration events in a complex mixture in vivo. Using this assay, we identified four independent integration events. Sequencing of the insertion sites suggested a random integration process, but with short segments of homology between the vector breakpoint and the insertion site in three of the four cases. This is the first definitive demonstration of integration of plasmid DNA into genomic DNA following injection in vivo.

Animals↗
PubMed2004

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate.

The Kazakh inhabitants living in Barkol pasture of northeast China belong to a genetic isolate characterized by ethnically homogeneous and a communal pastoral lifestyle. To investigate whether the polymorphisms in the G-protein beta-3 subunit (GNB3) gene and angiotensin-converting enzyme (ACE) gene are associated with essential hypertension (EH), we carried out a case-control study of 290 hypertensive subjects and 244 normotensive (NT) controls randomly selected from Kazakh populations of Barkol. A previous medical history of diabetes and hypertension, and body mass index (BMI) was recorded. Plasma glucose, triglyceride, and cholesterol were measured. The insertion/deletion (I/D) polymorphism of the ACE gene and the C825T polymorphism of the GNB3 gene were determined by the polymerase chain reaction (PCR) technique. The distributions of genotypes and alleles for the two polymorphisms did not differ significantly between the case and control populations, and odds ratio of EH related to the ACE gene D allele and GNB3 gene T allele was not significantly different from 1.0. Logistic regression analysis shows the variation at the GNB3 and ACE did not have any statistically significant synergistic effect on blood pressure (BP). Stratification of NT and untreated hypertensives according to I/D polymorphism of ACE gene and C825T polymorphism of GNB3 gene disclosed no significant difference across genotypes with respect to BMI, glucose, triglyceride, cholesterol, systolic and diastolic BP. In conclusion, the polymorphisms in the GNB3 gene and ACE gene, solely or combined, did not confer a significantly increased risk for the development of EH in the Kazakh isolate of northeast China.

Adult↗
PubMed2004

Interleukin 1alpha (IL-1alpha) induced activation of p38 mitogen-activated protein kinase inhibits glucocorticoid receptor function.

Previous studies have demonstrated that interleukinalpha (IL-1alpha) inhibits glucocorticoid receptor (GR) nuclear translocation and dexamethasone (Dex)-induced gene transcription. Given that IL-1alpha is a potent activator of the p38 mitogen-activated protein kinase (MAPK) signal transduction pathway and p38 MAPK has been associated with reduced GR function, we examined the role of p38 MAPK in IL-1alpha-mediated inhibition of GR function in mouse fibroblast cells stably transfected with a GR-mediated reporter gene construct (LMCAT cells). Treatment of LMCAT cells with IL-1alpha (1000 U/ml) for 24 h inhibited Dex (50 nM)-induced GRE-CAT activity by approximately 35%. When cells were cotreated for 24 h with IL-1alpha plus SB-203580 (0.5-1 microM), a selective p38 inhibitor, IL-1alpha's inhibitory effect on GR function as determined by Dex-induced GRE-CAT activity was reversed. Using gel mobility shift assay, SB-203580 was also found to reverse IL-1alpha inhibition of GR-GRE binding. Further confirming the role of p38 pathways, pretreatment of LMCAT cells with antisense oligonucleotides targeted to p38 MAPK completely abrogated IL-1alpha inhibition of Dex-induced GRE-CAT activity. Taken together, these results demonstrate that activation of p38 MAPK pathways are involved in IL-1alpha-mediated inhibition of GR function. In addition, these findings extend the intracellular targets of p38 to include the GR and indicate that p38 inhibitors may have special utility in immunologic and/or neuropsychiatric disorders associated with impaired GR-mediated feedback inhibition.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families.

The enzyme catechol-o-methyltransferase (COMT) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of COMT with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP rs4680, which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs rs737865-rs4680-rs165599, was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that COMT gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects.

Alleles↗
PubMed2004

Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by Gly.

Prothrombin deficiency is a rare bleeding disorder inherited as an autosomal recessive trait. In this study, we reported a Chinese family with hereditary prothrombin deficiency. The proposita had a prolonged activated partial thromboplastin time (APTT, 71.6 s) and prothrombin time (PT, 28.0 s). The coagulation factors activities were normal except that prothrombin coagulation activity was markedly reduced, and the prothrombin antigen level was moderately decreased. Nucleotide sequencing of amplified DNA revealed a novel mutation, Glu (GAG) to Gly (GGG) at residue 29, which normally undergoes gamma-carboxylation within the Gla domain of prothrombin. The proposita was identified as homozygous, while her father, mother and maternal grandmother were heterozygous for the mutation. Gla29 has been demonstrated as one of the key residue for Ca2+-binding, membrane interaction and biological activity of prothrombin.

Amino Acid Substitution↗
PubMed2004

Assessment of genetic, antigenic and pathotypic criteria for the characterization of IBDV strains.

The aim of this work was the selection and comparison of representative infectious bursal disease virus (IBDV) strains. Nine strains of IBDV, isolated at different times and from different geographic regions of Europe and China, were characterized. Batches of all strains were prepared following standardized protocols and checked for the absence of contaminating viruses. Criteria used for their characterization were: (i) the nucleotide sequence of the VP2 variable region, (ii) binding to a panel of neutralizing monoclonal antibodies in antigen capture enzyme-linked immunosorbent assays, and (iii) virulence in specific pathogen free chickens after infection with a standardized number of median embryo infective doses. Based on the first two criteria, two of nine strains were classified as classical virulent (cv) IBDV (F52/70, Cu-1wt), and five as very virulent (vv) IBDV (849VB, 96108, HK46, GX, Harbin). Remarkably, although a clear-cut difference was demonstrable between European cvIBDV (F52/70 and Cu-1wt) and vvIBDV (849VB and 96108) strains, there was a continuum in the pathogenicity of Chinese vvIBDVs. Our results indicate the probable existence of differences in virulence within IBDV lineages determined on the basis of antigenic typing using monoclonal antibodies and the alignment of the VP2 sequences. This indicates limitations in the analysis of IBDV pathotypes based on the VP2 variable region and emphasizes that these criteria may not be sufficient for the classification of IBDV strains.

Amino Acid Sequence↗
PubMed2004

Chemical-chemical interaction between cyanogenic toxicants and aldehydes: a mechanism-based QSAR approach to assess toxicological joint effects.

A QSAR approach was proposed to assess toxicological joint effects based on the mechanism of chemical-chemical interactions between cyanogenic toxicants and aldehydes. It has been observed that the chemical-chemical interaction between cyanogenic toxicants and aldehydes resulted in the formation of carbanion intermediates, and therefore this interaction led to different toxicological joint effects between cyanogenic toxicants and aldehydes. Analysis of this chemical-chemical interaction showed that the formation of carbanion intermediate highly depended on the charge of the carbon atom in the -CHO of aldehydes and this of the carbon atom (C*) in the carbochain of cyanogenic toxicant. By using the Hammett Constant (sigma(p)) to measure the charge of carbon atom in the -CHO of aldehydes, a mechanism-based QSAR approach (M = 0.316 - 4.386sigma(p) with r2 = 0.933, SE = 0.082, F = 55.389, p = 0.002, M = sum of toxic units) was proposed to assess the toxicological joint effects between alpha-hydroxy-isobutyronitrile and individual aliphatic aldehydes. Another one (M = 0.978 - 0.720sigma(p) with r2 = 0.852, SE = 0.152, F = 40.148, p = 0.0001) was also proposed to assess the toxicological joint effects between alpha-hydroxy-isobutyronitrile and individual aromatic aldehydes. Lastly, by using the charge of carbon atom (C*) in the carbochain of cyanogenic toxicant, a mechanism-based QSAR model (M = -0.161 - 7.721C* with r2 = 0.847, SE = 0.227, F = 27.657, p = 0.003) was derived to assess toxicological joint effects between p-nitrobenzaldehyde and cyanogenic toxicants.

Aldehydes↗
PubMed2004

A novel lectin with a fibrinogen-like domain and its potential involvement in the innate immune response of Armigeres subalbatus against bacteria.

Mosquitoes have an efficient cellular innate immune response that includes phagocytosis of microbial pathogens and encapsulation of metozoan parasites. In this study, we describe a novel lectin in the mosquito, Armigeres subalbatus (aslectin or AL-1). The 1.27 kb cDNA clone for the AL-1 gene (AL-1) encodes a 279 deduced amino acid sequence that contains a C-terminal fibrinogen-like domain. AL-1 is transcribed in all life stages. AL-1 mainly exists in the haemolymph of adult female mosquitoes, and is upregulated following both Escherichia coli and Micrococcus luteus challenge. AL-1 specifically recognizes N-acetyl-d-glucosamine and is able to bind both E. coli and M. luteus. These results suggest that AL-1 might function as a pattern recognition receptor in the immune response in Ar. subalbatus.

Amino Acid Sequence↗
PubMed2004

Systolic pressure and the myogenic response of the renal afferent arteriole.

The transmission of elevated blood pressure to the glomerulus and pressure-induced glomerular injury play central roles in the pathogenesis of kidney disease and its progression to end-stage renal failure. The renal afferent arteriole sets the pre-glomerular resistance and pressure-induced or 'myogenic' afferent arteriolar vasoconstriction is a primary mechanism protecting the glomerulus from the damaging effects of hypertension. The systolic pressure, being the highest level of pressure attained and most frequent pressure oscillation impacting on the renal vasculature, potentially represents the most damaging component of the blood pressure. Indeed, recent studies indicate that elevations in systolic blood pressure are more closely linked to kidney disease than are elevations in diastolic pressure. However, the current view, derived from dynamic studies of autoregulation, is that the renal vasculature responds passively to pressure signals presented at rates exceeding the myogenic operating frequency (0.2-0.3 Hz in the rat). Thus existing concepts do not explain the mechanisms that normally protect the kidney from elevations in the systolic pressure which are presented at the heart rate (6 Hz in the rat). A recent study from our laboratory addressed this issue. Using a modelling approach and direct measurements of myogenic responses, we found that the afferent arteriole is able to sense and appropriately adjust tone in response to changes in systolic pressure, presented at the heart rate. Key kinetic attributes allowing this vessel to respond in this manner appear to be a very short delay in activation, an unusually rapid rate of vasoconstriction and a longer delay in vasodilation. The present review summarizes this work and presents recent findings addressing the determinants of the myogenic vasoconstriction in the afferent arteriole.

Animals↗
PubMed2004

Application of electrospray ionization mass spectrometry in rapid typing of fengycin homologues produced by Bacillus subtilis.

AIMS: To rapidly type the fengycin homologues produced by Bacillus subtilis strains with electrospray ionization/collision-induced dissociation (ESI/CID) mass spectrometry. METHODS AND RESULTS: Fengycin homologues produced by Bacillus subtilis JA were analysed. When each homologue was subjected to ESI/CID analysis, ions representing characteristic fragmentations were detected. These ions can help to identify the homologues; even homologues of the same nominal mass can be discriminated by their ESI/CID spectra. Based on the CID results, fengycin homologues can be correctly assigned. CONCLUSIONS AND SIGNIFICANCE OF THIS STUDY: ESI/CID leads to rapid detection and structural characterization of fengycin homologues or lipopeptides with similar properties. It will be very useful in studying the regulatory expression of these peptides.

Bacillus subtilis↗
PubMed2004

Stress and dysmenorrhoea: a population based prospective study.

BACKGROUND: Dysmenorrhoea is the most common gynaecological disorder in women of reproductive age. Despite the association between stress and pregnancy outcomes, few studies have examined the possible link between stress and dysmenorrhoea. AIMS AND METHODS: Using a population based cohort of Chinese women, the independent effect of women's perceived stress in the preceding menstrual cycle on the incidence of dysmenorrhoea in the subsequent cycle was investigated prospectively. The analysis included 1160 prospectively observed menstrual cycles from 388 healthy, nulliparous, newly married women who intended to conceive. The perception of stress and the occurrence of dysmenorrhoea in each menstrual cycle were determined from daily diaries recorded by the women. RESULTS: After adjustment for important covariates, the risk of dysmenorrhoea was more than twice as great among women with high stress compared to those with low stress in the preceding cycle (OR = 2.4; 95% CI 1.4 to 4.3). The risk of dysmenorrhoea was greatest among women with both high stress and a history of dysmenorrhoea compared to women with low stress and no history of dysmenorrhoea (OR = 10.4, 95% CI 4.9 to 22.3). Stress in the follicular phase of the preceding cycles had a stronger association with dysmenorrhoea than stress in the luteal phase of the preceding cycles. CONCLUSION: This study shows a significant association between stress and the incidence of dysmenorrhoea, which is even stronger among women with a history of dysmenorrhoea.

Adult↗
PubMed2004

Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.

Analysis of Variance↗
PubMed2004

Probing the self-assembly and the accompanying structural changes of hydrophobin SC3 on a hydrophobic surface by mass spectrometry.

The fungal class I hydrophobin SC3 self-assembles into an amphipathic membrane at hydrophilic-hydrophobic interfaces such as the water-air and water-Teflon interface. During self-assembly, the water-soluble state of SC3 proceeds via the intermediate alpha-helical state to the stable end form called the beta-sheet state. Self-assembly of the hydrophobin at the Teflon surface is arrested in the alpha-helical state. The beta-sheet state can be induced at elevated temperature in the presence of detergent. The structural changes of SC3 were monitored by various mass spectrometry techniques. We show that the so-called second loop of SC3 (C39-S72) has a high affinity for Teflon. Binding of this part of SC3 to Teflon was accompanied by the formation of alpha-helical structure and resulted in low solvent accessibility. The solvent-protected region of the second loop extended upon conversion to the beta-sheet state. In contrast, the C-terminal part of SC3 became more exposed to the solvent. The results indicate that the second loop of class I hydrophobins plays a pivotal role in self-assembly at the hydrophilic-hydrophobic interface. Of interest, this loop is much smaller in case of class II hydrophobins, which may explain the differences in their assembly.

Air↗
PubMed2004

Factors associated with serum leptin in patients with chronic kidney disease.

BACKGROUND AND AIMS: Serum leptin levels are elevated in patients with kidney failure. Data on the associations of serum leptin and on the relationship of leptin with both kidney function and inflammation, are limited in patients with reduced glomerular filtration rate (GFR). We evaluated the independent associations of serum leptin in patients with reduced GFR. MATERIAL AND METHODS: Serum leptin and C-reactive protein (CRP) were measured in samples from 798 participants of the Modification of Diet in Renal Disease Study. Multivariable analysis was used to evaluate the independent effects of kidney function and CRP on leptin levels. RESULTS: Median (interquartile range) of serum leptin was 9.1 ng/ml (14.0). Female gender, higher percent body fat, higher insulin levels, older age, lower GFR and higher CRP were associated with higher serum leptin levels and explained 51% of the variability in the logarithm of serum leptin levels. After adjusting for the other variables, a 10 ml/min/1.73 m2 lower GFR was associated with 6% higher mean serum leptin levels. Percent body fat and gender, explained 45% of the variability in serum leptin levels. CONCLUSIONS: Level of kidney function and CRP are associated with serum leptin in patients with reduced GFR. However, there is a stronger association between serum leptin and indices of body fat and gender in patients in the earlier stages of chronic kidney disease. 50% of the variability remains unexplained in patients with reduced GFR.

Body Mass Index↗
PubMed2004

From hemorheology to vascular mechanobiology: An overview.

Almost all of the cells of the human body are subjected to mechanical stresses. In endothelial cells, mechanical stresses can vary from some milli-Pascal (shear stress) to one ore more Pascal (hydrostatic pressure). Now it is know that mechanical stresses have a decisive part cellular physiology. However, if the main biological effects of mechanical stress are well related, the mechanisms allowed the relation between mechanical stress to physiological phenomenon remain nearly unknown (mechanotransduction phenomenon). In this work, through personal results and published works, the authors considers all the effects of mechanical stresses and the possible hypothesis.

Blood Vessels↗
PubMed2004

Effect of back-pressure on absorption efficiency of impingers used for air sampling.

The gas-liquid absorption method, using an impinger as an extracting device, is the most common method for quantifying most gaseous pollutants. The performance of conventional impingers was studied, and several modified impingers were tested. It was found that the sampling efficiency varied from impinger to impinger, which resulted from back-pressure differences between impingers. The back-pressure of ten tested impingers ranged between 160 mm to 520 mm water gage when a 50 mL absorbing solution was used, which caused the ammonia concentration coefficients of variations to be up to 15%. It was also verified that an open bubble distribution tube could be used to eliminate back-pressure variations between impingers. Nearly identical back-pressure (44 +/- 4 mm water gage) could be obtained. This modification can improve measurement repeatability significantly and reduce the coefficient of variation of measurements to 1.2%. With this modification to the impingers, greater accuracy, repeatability and comparison of results can be achieved in the measurement of gaseous pollutants in air.

Adsorption↗