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Biomedical subjects

Qing Wang

Publications and source records attributed to Qing Wang.

At least 163 records · Page 9Linked to original sources
PubMed2002

MSH2 in contrast to MLH1 and MSH6 is frequently inactivated by exonic and promoter rearrangements in hereditary nonpolyposis colorectal cancer.

To estimate the relative frequency of mismatch repair genes, rearrangements in hereditary nonpolyposis colorectal cancer (HNPCC) families without detectable mutations in MSH2 or MLH1, we have analyzed by multiplex PCR of short fluorescent fragments MSH2, MLH1, and MSH6 in 61 families, either fulfilling Amsterdam criteria or including cases of multiple primary cancers belonging to the HNPCC spectrum. We detected 13 different genomic rearrangements of MSH2 in 14 families (23%), whereas we found no rearrangement of MLH1 and MSH6. Analysis of 31 other families, partially meeting Amsterdam criteria, revealed no additional rearrangement of MSH2. All of the MSH2 rearrangements, except one, corresponded to genomic deletions involving one or several exons. In 8 of 13 families with a MSH2 genomic deletion, the MSH2 promoter was also deleted, and the 5' breakpoint was located either within or upstream the MSH2 gene. This study demonstrates the heterogeneity of MSH2 exonic and promoter rearrangements and shows that, in HNPCC families without detectable MSH2 or MLH1 point mutation, one must consider the presence of MSH2 genomic rearrangements before the involvement of other mismatch repair genes. The simplicity and rapidity of their detection, using fluorescent multiplex PCR, led us to recommend to begin the molecular analysis in HNPCC by screening for MSH2 rearrangements.

Adaptor Proteins, Signal Transducing↗
PubMed2002

The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene.

BTG2/TIS21/PC3 protein is involved in the regulation of G1/S transition of the cell cycle by inhibiting pRb function, suggesting that BTG2/TIS21/PC3 regulation is critical for normal cell growth and proliferation. To understand the regulatory mechanisms for the expression of BTG2/TIS21/PC3 we cloned the human gene. Potential binding sites for several transcription factors were identified in the 5'-flanking region of the gene. Transient expression assays with BTG2/TIS21/PC3 promoter deletions and electrophoretic mobility shift analysis identified a major wild-type p53 response element located -74 to -122 relative to the start codon. This genomic fragment was sufficient to constitute a promoter element in the presence of p53. The BTG2/TIS21/PC3 gene is an antiproliferative gene which maps within a chromosomal segment (1q32) frequently altered in breast adenocarcinomas. However, no mutations of BTG2/TIS21/PC3 were detected in breast cancer cells, suggesting that the inactivation of this gene is not a frequent genetic event during breast carcinogenesis.

Base Sequence↗
PubMed2002

Polymorphisms and HNPCC: PMS2-MLH1 protein interactions diminished by single nucleotide polymorphisms.

Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common autosomal dominant inherited diseases. Mutations in the human mismatch repair (MMR) proteins MLH1, MSH2, MSH6, PMS1, and PMS2 have been found to co-segregate with HNPCC. The MLH1 and MSH2 proteins have been demonstrated to interact with PMS1, PMS2, and MSH6 proteins. A previous study reported that missense mutations in specific regions of MLH1 can lead to defects in protein-protein interactions with PMS2. Here we report that three missense alterations previously identified as single nucleotide polymorphisms (SNPs) in PMS2 (P511K, T597S, and M622I) cause defective protein-protein interactions with MLH1, even though the alterations are not in the previously reported interaction domain. These results suggest that an additional domain in PMS2 affects MLH1-PMS2 interaction. This study also demonstrates that SNPs can result in gene alterations that indeed have a functional effect on protein phenotype. Thus, these three SNPs may ultimately represent variants with an increased risk factor for tumorgenesis in HNPCC. This study is one of the first to use a functional assay to appraise the role of SNPs and suggests that traditional definitions of polymorphisms and mutations are in need of reconsideration.

Adaptor Proteins, Signal Transducing↗
PubMed2002

KCNQ1 and KCNH2 mutations associated with long QT syndrome in a Chinese population.

The long QT syndrome (LQTS) is a cardiac disorder characterized by prolongation of the QT interval on electrocardiograms (ECGs), syncope and sudden death caused by a specific ventricular tachyarrhythmia known as torsade de pointes. LQTS is caused by mutations in ion channel genes including the cardiac sodium channel gene SCN5A, and potassium channel subunit genes KCNQ1, KCNH2, KCNE1, and KCNE2. Little information is available about LQTS mutations in the Chinese population. In this study, we characterized 42 Chinese LQTS families for mutations in the two most common LQTS genes, KCNQ1 and KCNH2. We report here the identification of four novel KCNQ1 mutations and three novel KCNH2 mutations. The KCNQ1 mutations include L191P in the S2-S3 cytoplasmic loop, F275S and S277L in the S5 transmembrane domain, and G306V in the channel pore. The KCNH2 mutations include L413P in transmembrane domain S1, E444D in the extracellular loop between S1 and S2, and L559H in domain S5. The location and character of these mutations expand the spectrum of KCNQ1 and KCNH2 mutations causing LQTS. Excitement, exercises, and stress appear to be the triggers for developing cardiac events (syncope, sudden death) for LQTS patients with KCNQ1 mutations F275S, S277L, and G306V, and all three KCNH2 mutations L413P, E444D and L559H. In contrast, cardiac events for an LQTS patient with KCNQ1 mutation L191P occurred during sleep or awakening from sleep. KCNH2 mutations L413P and L559H are associated with the bifid T waves on ECGs. Inderal or propanolol (a beta blocker) appears to be effective in preventing arrhythmias and syncope for an LQTS patient with the KCNQ1 L191P mutation.

Cation Transport Proteins↗
PubMed2002

Blood pressure, cardiac, and renal responses to salt and deoxycorticosterone acetate in mice: role of Renin genes.

Several studies have demonstrated that mice are polymorphic for the number of renin genes, with some inbred strains harboring one gene (Ren-1(c)) and other strains containing two genes (Ren-1(d) and Ren-2). In this study, the effects of 1% salt and deoxycorticosterone acetate (DOCA)/salt were investigated in one- and two-renin gene mice, for elucidation of the role of renin in the modulation of BP, cardiac, and renal responses to salt and DOCA. The results demonstrated that, under baseline conditions, mice with two renin genes exhibited 10-fold higher plasma renin activity, 100-fold higher plasma renin concentrations, elevated BP (which was angiotensin II-dependent), and an increased cardiac weight index, compared with one-renin gene mice (all P < 0.01). The presence of two renin genes markedly increased the BP, cardiac, and renal responses to salt. The number of renin genes also modulated the responses to DOCA/salt. In one-renin gene mice, DOCA/salt induced significant renal and cardiac hypertrophy (P < 0.01) even in the absence of any increase in BP. Treatment with losartan, an angiotensin II AT(1) receptor antagonist, decreased BP in two-renin gene mice but not in one-renin gene mice. However, losartan prevented the development of cardiac hypertrophy in both groups of mice. In conclusion, these data demonstrate that renin genes are important determinants of BP and of the responses to salt and DOCA in mice. The results confirm that the Ren-2 gene, which controls renin production mainly in the submaxillary gland, is physiologically active in mice and is not subject to the usual negative feedback control. Finally, these data provide further evidence that mineralocorticoids promote cardiac hypertrophy even in the absence of BP changes. This hypertrophic process is mediated in part by the activation of angiotensin II AT(1) receptors.

Animals↗
PubMed2002

Cancer patients who experienced diagnostic genetic testing for cancer susceptibility: reactions and behavior after the disclosure of a positive test result.

The aim of this prospective study was to evaluate the consequences of the disclosure of a positive genetic test result to patients affected with cancer. Personal repercussions and patients' behavior with the transmission of their results to relatives were considered. We conducted semistructured interviews with 23 cancer patients identified as carriers of a cancer-predisposing mutation for hereditary breast ovarian or nonpolyposis colorectal cancers, 1 month after the disclosure of the test result. Eight patients spontaneously expressed distressed reactions ("you no longer feel cured"), and 14 patients reported at least one negative feeling (dissatisfied, discouraged, unhappy, or worried), despite expecting to be a carrier. Sixteen patients expressed concerns about the risk of developing another cancer, and 18 were concerned for their children's future, in that they may carry the mutation and develop a cancer. Although 8 patients found that disadvantages of knowing their genetic status outweighed the advantages, all but 1 did not regret having undergone genetic testing. All of the patients transmitted their results to at least one close relative. Although 6 of them expressed difficulties in being the only person who could transmit the information and 9 said it was a heavy responsibility, all except 1 did not want someone else to have to inform their families. Our results illustrate the potential negative impact of diagnostic genetic testing in patients with cancer. This includes distressed reactions and difficulties in transmitting their results to relatives. Future large-scale studies are warranted to confirm our findings.

Adaptation, Psychological↗
PubMed2002

[A novel rhodopsin E341ter mutation in patients with retinitis pigmentosa and corresponding clinical phenotype].

OBJECTIVE: To detect rhodopsin (RHO) mutation in Chinese families with autosomal dominant retinitis pigmentosa (ADRP) and study on the association of RHO gene mutations with clinical phenotype. METHODS: Twenty-seven members from 13 Chinese families with ADRP and 30 normal subjects were recruited. The complete coding regions of the rhodopsin gene were amplified with polymerase chain reaction (PCR) and then DNA single-strand conformation polymorphism (SSCP) technique was used to screen RHO gene mutations. When a variant band was observed after the SSCP electrophoresis, the variant band was analyzed by sequencing PCR-amplified DNA. All subjects were examined clinically by slit-lamp, direct funduscopy, Goldmann kinetic perimetry, Humphrey threshold perimetry and electroretinogram. RESULTS: Nine affected subjects and 2 boys (11 and 9 years old respectively) in one pedigree among 13 families were found to have three DNA single strand bands by SSCP analysis. Results of assaying sequence showed the 11 members were heterozygous for rhodopsin E341ter mutation. The codon 341 is changed from GAG to TAG, resulting in a stop codon mutation. Thirty normal controls and unaffected subjects in this family were the wild type of RHO gene. Affected individuals reported night blindness in the second decade, showed optic atrophy, vessel attenuation and a few bone spicule-like pigments in the peripheral retina. The impairment of visual acuity was relatively severe, loss of peripheral visual field was greatly considerable after 30 years of age, rod and cone ERG were not detectable in the second decade, and only slight cone response was left. CONCLUSIONS: The natural history of RP in this family begins with a loss of rod function, progresses to involve the cone system, and leads eventually to a severe loss of visual function. A novel rhodopsin gene mutation E341ter is responsible for a Chinese family with ADRP.

Adult↗
PubMed2002

[Study on intervention and comparison of rational use of antibiotics on perioperative period of clean incision and clean-defiled incision].

OBJECTIVE: To explore a set of scientific evaluation and intervention methods on perioperatur period which fits for China's situation, and to promote the development of rational drug use. METHODS: Two would tertiary general hospitals were selected and separated in to intervention group and control group. Intervention was carried out and compared at the same period on inpatient surgical cases of thryroidectomy, mastectomy, cholescystectomy, and hysteromyomectomy plus appendix. RESULTS: The average drug costs was decreased from 1 601.27 yuan to 1 489.59 yuan and the average antibiotics use from 740.20 yuan to 352.03 yuan (P < 0.01) in the intervention group pre and post intervention. There was a remarkable improvement on the rationality of antibiotics use in intervention group, from 31.35% to 91.81% (P < 0.01) pre and post intervention, implemented in the hospital. CONCLUSION: It is practicable and effective to implement rational drug use where intervention was carried out, since it plays an active role on promoting safely, effectively and economic antibiotic use in China.

Anti-Bacterial Agents↗
PubMed2002

[Dynamics of forage supplement and nutrition requirements of grazing sheep in alpine grasslands].

The dynamics of forage supply and nutrition requirements of sheep were monitored for a whole year under alpine grassland conditions in Sunan County, Gansu Province. The digestion and metabolism of grazed sheep were determined in different seasons. The results showed that the DE(9.76 MJ), CP(21.53%) and the ratio of crude protein to digestible energy (22.06 g.MJ-1) of forage were the highest in Spring, while the herbage dry matter yield and dry matter intake (60.51 +/- 3.42 g.W0.75kg-1.d-1) by grazed sheep were the lowest. Supplementary DM especially in energy should be provided. The ratio of crude protein to digestible energy was 17.62 g.MJ-1 in Summer, and was somewhat higher. The nitrogen utility of the forage would be improved, if energy feed was supplemented. Both the quality and quantity of forage produced in grasslands in Autumn could meet the sheep requirement. Whereas during Winter, neither forage yield nor nutritive value was sufficient for sheep, and the contents of the DE and CP of forage were the lowest in the year, which were 4.30 MJ and 4.63%, respectively. The nitrogen metabolism of sheep was negative. Therefore, DM, especially DE and CP, should be supplemented. To improve the conditions, it was necessary to develop seasonal animal husbandry, and combine the subsystems into coupling systems.

Agriculture↗
PubMed2002

[Preliminary study of chromosome aberrations in pituitary adenoma].

BACKGROUND & OBJECTIVE: Pituitary adenoma is one of the most common intracranial benign tumor. This study was designed to seek the most suitable method for cytogenetic study of pituitary adenoma(PA), and then to analyze the genetic change of PA cell. METHODS: Twenty-five samples of primary PA were examined by R-banding through direct preparation(DP) and short-term culture(STC) to analyze genomic alterations. RESULTS: A karyotype of 17 samples was identified in 25 PAs by using the DP, whereas there was a karyotype of 21 samples by using the STC. An abnormal clonal karyotype was observed in 11 samples processed by the DP, however only 3 of 25 samples when processed by the STC. The common chromosomal alterations included gains of chromosomes X(6/25), 7(4/25), 8(2/25), 5(2/25) as well as losses of chromosomes 11(5/25), 9(4/25), 13(3/25), and the latter was observed predominantly in invasive PAs. CONCLUSIONS: DP is one of the most suitable methods for the cytogenetic study of PA. There were multiple regions of chromosomes with copy number changes in PA including gains of chromosomes X, 7, 8, and losses of chromosomes 11, 9, 13. However, structural chromosome aberrations are not common. The loss of chromosome and the abnormality of structure may have some correlation with the biologic behavior of PA.

Adenoma↗
PubMed2002

[Gene frequency of 12 characters in 5 nationalities in inner mongolia].

The gene frequency of 12 characters was reported in Ewenki, Oroqen, Daur, Mongol and Han nationalities in Inner Mongolia, and compared among these nationalities. The result indicated that the difference of Mongoloid fold among nationalities was significant, followed by the Folding tongue, while the difference of Handedness and Nasal profile was relatively insignificant.

English Abstract↗
PubMed2002

[Determination of acetochlor and oxyfluorfen by capillary gas chromatography].

A method is described for the determination of acetochlor and oxyfluorfen by capillary gas chromatography with FID and an SE-30 capillary column (60 m x 0.53 mm i. d., 1.5 microm), using dibutyl phthalate as the internal standard. The standard deviations for acetochlor and oxyfluorfen concentration(mass fraction) were 0.44% and 0.47% respectively. The relative standard deviations for acetochlor and oxyfluorfen were 0.79% and 0.88% and the average recoveries for acetochlor and oxyfluorfen were 99.3% and 101.1% respectively. The method is simple, rapid and accurate.

Chromatography, Gas↗
PubMed2000

CEK2, a Novel MAPK from Candida albicans Complement the Mating Defect of fus3/kss1 Mutant.

A novel MAPK(mitogen-activated protein kinase) gene, CEK2(Candida albicans extracellular signal-regulated kinase 2), was isolated by screening the Candida albicans library based on oligonucleotide probe hybridization and degenerated PCR. The CEK2 gene is 1 119 bp in length, and coding for a 373 aa protein. The CEK2 shares 56% homology with CEK1 from Candida albicans, 55 % homology with FUS3 from S. cerevisiae. From the deduced amino acid sequence, the Cek2 protein contains a conserved ATP binding site and a Ser/Thr kinase activity signal and a conserved TEY sequence was located at L(12) region. In vitro kinase activity assay showed Cek2 could phosphorylate MBP(myelin bovine protein) but not histone H1. CEK2 gene could complement the fus3/kss1 mutant and underwent mating signal induction by a tester strain, but CEK1 gene could not complement with the fus3/kss1 mutant. CEK2 is therefore a FUS3 homolog in Candida albicans.

Journal Article↗
PubMed1999

Expression of Inducible Nitric Oxide Synthase Gene in Neuronal Cells Mediated by Retrovirus Vector.

The role of an inducible nitric oxide synthase (iNOS)expression in the mechanisms of opioid tolerance and dependence was investigated. A recombinant retroviral expression vector containing a cDNA fragment of iNOS was transfected into the neuroblastomaxglioma NG108-15 cells by lipofectamine gene transferring technique. G418-resistant clones were selected and were named NG-LNCXiNOS cells. Using Southern blot, PCR amplification for Neo gene, RT-PCR and Western blot analysis, NG-LNCXiNOS cells were confirmed to have an integral exogenous iNOS gene which was being transcribed and translated into protein. NADPH-diaphorase (NADPH-d) histochemical staining and immunohistochemical staining with iNOS-specific antibody demonstrated that high-level expression of iNOS protein was present in the cytoplasm of NG-LNCXiNOS cells. The catalytic activity and NO( )(2) content in supernatant medium were obviously enhanced in iNOS gene-transfected cells. The results show that the biochemical and pharmacological properties of the recombinant enzyme were similar to those of native enzyme. The recombinant enzyme activity was completely dependent on NADPH and failed to be stimulated by the addition of calcium and calmodulin. Chelating agents failed to decrease its activity. NOS inhibitors could markedly reduce NO( )(2) production at a concentration-dependent manner. The expression of iNOS gene was involved in the up-regulation of NO-cGMP signal transduction cascade. Therefore, an iNOS gene-modified neuronal cell line was successfully established, offering an excellent model system for seeking and screening new drugs to treat opioid tolerance and dependence.

Journal Article↗
PubMedDate not supplied

Lysophosphatidylcholine promotes cholesterol efflux from mouse macrophage foam cells via PPARgamma-LXRalpha-ABCA1-dependent pathway associated with apoE.

Formation of macrophage-derived foam cells is a hallmark in earlier stages of atherosclerosis (AS). Increased cholesterol efflux from macrophage foam cells promote atherosclerotic regression. In the present study, lysophosphatidylcholine (LPC) promoting cholesterol efflux from macrophage foam cells was observed, and the mechanism underlying the action was investigated. Macrophage foam cells from mice were incubated with different concentrations of LPC (10, 20, 40, 80 microM), and the free cholesterol in medium increased but total intracellular cholesterol decreased. At the same time, the expression of PPARgamma, LXRalpha, ABCA1 was enhanced in a dose-dependent manner. The treatment of macrophage foam cells with 40 microM LPC for 12, 24 and 48 h promoted cellular cholesterol efflux in a time-dependent manner, meanwhile expression of PPARgamma, LXRalpha, ABCA1 was also raised respectively. Addition of different specific inhibitors of PPARgamma (GW9662), LXRalpha (GGPP), ABCA1 (DIDS) to the foam cells significantly suppressed LPC-induced cholesterol efflux. Also treatment with specific inhibitors of PPARgamma or LXRalpha decreased ABCA1 mRNA and protein expressions. LPC (40 microM)-induced cholesterol efflux was significantly lower in macrophage foam cells from apoE deficient mice than from normal C57BL/6J mice. In contrast, 10 microg apoAI-induced cholesterol efflux from foam cells remained in apoE deficient mice. The present results indicate that LPC promotes cholesterol efflux from macrophage foam cells via a PPARgamma-LXRalpha-ABCA1-dependent pathway. Furthermore, apoE may be involved in this process.

ATP Binding Cassette Transporter 1↗
PubMedDate not supplied

Inter-species comparison of 7-hydroxycoumarin glucuronidation and sulfation in liver S9 fractions.

UDP glycosyltransferases (UGTs) and sulfotransferases (SULTs) are phase II enzymes that interact with a number of xenobiotics in humans and animals. Species differences in enzymatic characteristics have seldom been investigated. Liver S9 fractions are commonly used for studying phase II metabolism in vitro. The objective of this study was to characterize the UGT and SULT activities in liver S9 fractions from various species including humans, monkeys, dogs, and rats. A single substrate, 7-hydroxycoumarin (7-HC), at several concentrations was incubated at 37 degrees C with the S9 reaction matrices along with necessary cofactors. The rate of formation of two metabolites, 7-HC-glucuronide (7-HC-G) and 7-HC-sulfate (7-HC-S), was determined with Liquid Chromatography/Tanderm Mass Spectrometry (LC/MS/MS). Apparent Km and Vmax values were calculated for each species. For the UGTs, the apparent Km and Vmax for 7-HC-G formation varied greatly among different species, with dog UGTs having both the highest Km and Vmax values. In contrast to UGTs, the Km for 7-HC-S formation showed no significant difference among humans, monkeys, and rats (approximately 3 microM). However, the Km in dog was 8.7 microM. Species differences with respect to phase II metabolism must be carefully considered when selecting an in vitro model system to study various aspects of drug metabolism.

Animals↗
PubMedDate not supplied

Molecular perspectives on p97-VCP: progress in understanding its structure and diverse biological functions.

The 97-kDa valosin-containing protein (p97 or VCP) is a type-II AAA ( ATPases associated with a variety of activities) ATPases, which are characterized by possessing two conserved ATPase domains. VCP forms a stable homo-hexameric structure, and this two-tier ring-shaped complex acts as a molecular chaperone that mediates many seemingly unrelated cellular activities. The involvement of VCP in the ubiquitin-proteasome degradation pathway and the identification of VCP cofactors provided us important clues to the understanding of how this molecular chaperone works. In this review, we summarize the reported biological functions of VCP and explore the molecular mechanisms underlying the diverse cellular functions. We discuss the structural and biochemical studies, and elucidate how this sophisticated enzymatic machine converts chemical energy into the mechanical forces required for the chaperone activity.

Adenosine Triphosphatases↗