Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 721 records · Page 40Linked to original sources

PubMed2000

Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population.

Recent studies have suggested that vitamin D is an important determinant of prostate cancer risk and inherited polymorphisms in the 3'-untranslated region (3'UTR) of the vitamin D receptor (VDR) gene are associated with the risk and progression of prostate cancer. This study was conducted to explore the association of VDR gene polymorphisms with prostate cancer risk in Japanese men who are considered to be much less influenced by environmental risk factors for prostate cancer. We studied 222 prostate cancer patients, 209 benign prostatic hyperplasia (BPH) patients, 128 male controls who were over 60 years old and without any evidence of prostate cancer or BPH, and 198 female controls. A PCR-RFLP method was used to determine three VDR gene polymorphisms in the 3'UTR characterized by restriction enzymes BsmI, ApaI and TaqI. In the BsmI polymorphism, heterozygosity or homozygosity for the absence of the BsmI restriction site was associated with one-third the risk of prostate cancer (P < 0.0001; odds ratio, 3.31; 95% confidence interval, 2.05-5.32) and with one-half the risk of BPH (P < 0.005; odds ratio, 2.07; 95% confidence interval, 1.33-3.22) compared with the male controls. The TaqI and ApaI polymorphisms did not show any significant association with either prostate cancer or BPH. The results indicate that the BsmI polymorphism in the VDR gene plays a significant role in protection against prostate cancer and BPH. Because of the racial difference in the strength of the linkage disequilibrium between the three polymorphisms, additional studies are required to apply the present results to other racial-ethnic groups.

3' Untranslated Regions↗

PubMed2000

DNA computing on surfaces.

DNA computing was proposed as a means of solving a class of intractable computational problems in which the computing time can grow exponentially with problem size (the 'NP-complete' or non-deterministic polynomial time complete problems). The principle of the technique has been demonstrated experimentally for a simple example of the hamiltonian path problem (in this case, finding an airline flight path between several cities, such that each city is visited only once). DNA computational approaches to the solution of other problems have also been investigated. One technique involves the immobilization and manipulation of combinatorial mixtures of DNA on a support. A set of DNA molecules encoding all candidate solutions to the computational problem of interest is synthesized and attached to the surface. Successive cycles of hybridization operations and exonuclease digestion are used to identify and eliminate those members of the set that are not solutions. Upon completion of all the multistep cycles, the solution to the computational problem is identified using a polymerase chain reaction to amplify the remaining molecules, which are then hybridized to an addressed array. The advantages of this approach are its scalability and potential to be automated (the use of solid-phase formats simplifies the complex repetitive chemical processes, as has been demonstrated in DNA and protein synthesis). Here we report the use of this method to solve a NP-complete problem. We consider a small example of the satisfiability problem (SAT), in which the values of a set of boolean variables satisfying certain logical constraints are determined.

Computing Methodologies↗

PubMed2000

Specific molecular recognition of mixed nucleic acid sequences: an aromatic dication that binds in the DNA minor groove as a dimer.

Phenylamidine cationic groups linked by a furan ring (furamidine) and related compounds bind as monomers to AT sequences of DNA. An unsymmetric derivative (DB293) with one of the phenyl rings of furamidine replaced with a benzimidazole has been found by quantitative footprinting analyses to bind to GC-containing sites on DNA more strongly than to pure AT sequences. NMR structural analysis and surface plasmon resonance binding results clearly demonstrate that DB293 binds in the minor groove at specific GC-containing sequences of DNA in a highly cooperative manner as a stacked dimer. Neither the symmetric bisphenyl nor bisbenzimidazole analogs of DB293 bind significantly to the GC containing sequences. DB293 provides a paradigm for design of compounds for specific recognition of mixed DNA sequences and extends the boundaries for small molecule-DNA recognition.

Amidines↗

PubMed2000

Epstein-Barr virus nuclear protein 2 interacts with p300, CBP, and PCAF histone acetyltransferases in activation of the LMP1 promoter.

The Epstein-Barr virus (EBV) nuclear protein 2 (EBNA2) and herpes simplex virion protein 16 (VP16) acidic domains that mediate transcriptional activation now are found to have affinity for p300, CBP, and PCAF histone acetyltransferases (HATs). Transcriptionally inactive point mutations in these domains lack affinity for p300, CBP, or PCAF. P300 and CBP copurify with the principal HAT activities that bind to EBNA2 or VP16 acidic domains through velocity sedimentation and anion-exchange chromatography. EBNA2 binds to both the N- and C-terminal domains of p300 and coimmune-precipitates from transfected 293T cells with p300. In EBV-infected Akata Burkitt's tumor cells that do not express the EBV encoded oncoproteins EBNA2 or LMP1, p300 expression enhances the ability of EBNA2 to up-regulate LMP1 expression. Through its intrinsic HAT activity, PCAF can further potentiate the p300 effect. In 293 T cells, P300 and CBP (but not PCAF) can also coactivate transcription mediated by the EBNA2 or VP16 acidic domains and HAT-negative mutants of p300 have partial activity. Thus, the EBNA2 and VP16 acidic domains can utilize the intrinsic HAT or scaffolding properties of p300 to activate transcription.

Acetyltransferases↗

PubMed2000

Cloning and neuronal expression of a type III newt neuregulin and rescue of denervated, nerve-dependent newt limb blastemas by rhGGF2.

Urodele amphibians are the only vertebrates that can regenerate their limbs throughout their life. The critical feature of limb regeneration is the formation of a blastema, a process that requires an intact nerve supply. Nerves appear to provide an unidentified factor, known as the neurotrophic factor (NTF), which stimulates cycling of blastema cells. One candidate NTF is glial growth factor (GGF), a member of the neuregulin (NRG) growth factor family. NRGs are both survival factors and mitogens to glial cells, including Schwann cells. All forms of NRGs contain an EGF-like domain that is sufficient to activate NRG receptors erbB2, erbB3, and erbB4. To investigate the involvement of neuregulin in newt limb regeneration, we cloned and characterized one neuregulin isoform, a neuregulin with a cysteine-rich domain (CRD-NRG), from newt (Notophthalmus viridescens) spinal cord. Results of in situ hybridization showed that the newt CRD-NRG is highly expressed in dorsal root ganglia and spinal cord neurons that innervate the limbs. We also demonstrated the biological activity of recombinant human GGF2 (rhGGF2) in urodele limb regeneration. When rhGGF2 was injected into denervated, nerve-dependent axolotl blastemas, the labeling index (LI) of blastema cells was maintained at a level near to that of control, innervated blastemas, whereas without rhGGF2 the LI decreased significantly. In another experiment, rhGGF2 was delivered into denervated, nerve-dependent blastemas either by direct infusion into blastemas or by injection into the intraperitoneal cavity. The denervated blastemas were rescued into a regeneration response.

Ambystoma mexicanum↗

PubMed2000

Loss of expression of the DRR 1 gene at chromosomal segment 3p21.1 in renal cell carcinoma.

Consistent deletion of DNA sequences in chromosomal band 3p21 observed in a variety of human tumors suggests the presence of one or more tumor suppressor genes within this region. Previously, we reported on the construction of two distinct cosmid contigs and our identification of several new genes within 3p21.1. In our search for tumor suppressor genes from this region, we have cloned a gene that we have called DRR 1 (downregulated in renal cell carcinoma). The gene was first mapped to 3p21.1 by fluorescence in situ hybridization analysis. Further analysis of yeast artificial chromosome clones in 3p14.2-p21.1 refined its localization. DRR 1 spans about 10 Kb of genomic DNA with a 3.5-Kb mature transcript. The putative protein encoded by this gene is 144 amino acids and includes a nuclear localization signal and a coiled domain. The gene showed loss of expression in eight of eight renal cell carcinoma cell lines, one of seven ovarian cancer cell lines, one of one cervical cancer cell line, one of one gastric cancer cell line, and one of one non-small-cell lung cancer cell line. Southern blot analysis did not show any altered bands, indicating that gross structural changes or deletions did not cause the loss of expression. This gene was also found to have reduced expression in 23 of 34 paired primary renal cell carcinomas. Mutational analysis detected three polymorphic sites within the gene, but no point mutations were identified in the 34 primary tumors. However, we did detect base substitutions in 4 of 12 cell lines that had undetectable expression of the gene. We also transfected the gene into DRR 1-negative cell lines and observed clear growth retardation. Our results suggest that loss of expression of the DRR 1 gene may play an important role in the development of renal cell carcinoma and possibly other tumors. Genes Chromosomes Cancer 27:1-10, 2000.

Amino Acid Sequence↗

PubMed2000

Petrochemical exposure and menstrual disturbances.

BACKGROUND: An exploratory, cross-sectional retrospective study was conducted to examine the effects of benzene exposure on menstrual problems. METHODS: The study was based on a survey administered to over 3,000 women who worked in a large petrochemical company in Beijing, China. An abnormal menstrual cycle length (AMCL), defined as an average menstrual cycle length of greater than 35 days or less than 21 days, is the major outcome of interest. RESULTS: After 7 years of benzene exposure, the adjusted odds ratio of having AMCL for each additional 5 years of exposure was 1.71 (95% CI 1.27-2.31). Feeling stressed at work was also an important predictor. CONCLUSIONS: This study suggests a significant association of benzene exposure and perceived stress with menstrual disturbance. A prospective study is needed to confirm this finding.

Adult↗

PubMed2000

Test-retest reliability of combined sensory index: implications for diagnosing carpal tunnel syndrome.

When compared to single nerve conduction tests, the combined sensory index (CSI) has been shown previously to have superior sensitivity and specificity for diagnosing carpal tunnel syndrome. The CSI is the sum of (1) median-ulnar ring finger antidromic latency difference at 14 cm (ring-diff); (2) median-radial thumb antidromic latency difference at 10 cm (thumb-diff); and (3) median-ulnar midpalmar orthodromic latency difference at 8 cm (palm-diff). To evaluate the reliability of single nerve conduction tests (ring-diff, thumb-diff, and palm-diff) vs. a combined summary variable (CSI), we conducted a prospective study during which the same investigator performed test and retest sessions on one hand of 32 subjects. Results showed that the CSI had the highest test-retest reliability (Spearman rho = 0.95), when compared with ring-diff, thumb-diff, and palm-diff (Spearman rho = 0.67, 0.75, and 0.74, respectively). Therefore, we propose the use of the CSI as not only an accurate but also a reliable method for diagnosing carpal tunnel syndrome.

Adult↗

PubMed2000

Optimizing the number of tests for carpal tunnel syndrome.

The combined sensory index (CSI), the sum of three latency differences, median-ulnar across the palm (palmdiff), median-ulnar to the ring finger (ringdiff), and median-radial to the thumb (thumbdiff), has higher sensitivity and reliability for carpal tunnel syndrome than individual tests. The objective in this study was to develop an approach that minimizes testing but maximizes accuracy. We retrospectively studied 300 hands. There were endpoints for individual tests that confidently predicted the CSI; for ranges between these endpoints, further testing was required. These ranges were: palmdiff 0-0.3 ms; ringdiff 0.1-0.4 ms; and thumbdiff 0.2-0.7 ms. One may use a strategy in which more tests are performed when results are in these ranges. This approach can allow accurate diagnosis with fewer tests when values are extreme, yet uses the greater diagnostic power of more tests when values are midrange.

Adult↗

PubMed2000

Seasonality of matings and births in captive Sichuan golden monkeys (Rhinopithecus roxellana).

This study, based on three years of mating behavior observations and 10 years of birth records, reveals that Sichuan golden monkeys in captivity displayed a marked seasonality of mating behavior and births. The peak of matings occurred around October, and births occurred in March-June. The birth peak followed the mating peak by six to seven months. This seasonal cycle of matings and births was similar to observations made in the wild, where both temperature and food resources were favorable in spring. The time delay between peaks of matings and births was the approximate length of gestation, which implies that mating behavior was concentrated during the period of conception. We suggest that the peak of births in captive Sichuan golden monkeys occurred during the time of year with the most favorable environmental conditions, and the peak of matings corresponded with the period of conception.

Animals↗

PubMed2000

Translocation of P53-regulated laminin receptors in pro-apoptotic microcircumstance of human vasculogenesis inhibition.

It is not clear what type of cells will inhibit vasculogenesis and under what circumstances. Here we examined the human spontaneous abortion villi and discovered that cells in the vasculogenesis-inhibited environment appear to be pro-apoptotic as indicated by strong staining of bak. In particular, an increasing laminin receptor (LNR) expression in cytoplasm and on apical membrane, being most likely mediated by p53 because of coexpression, was observed in the pro-apoptotic syncytiotrophoblasts. The transcriptional increase and translocation of the receptors to the cytoplasm and apical membrane may be used as a pathological marker, indicating a change of the structure and function of integrins in the non-vasculogenesis micro-environment.

Abortion, Spontaneous↗

PubMed2000

An iterative fitting procedure for the determination of longitudinal NMR cross-correlation rates.

We present a method to measure (15)N-(1)H dipolar/(15)N CSA longitudinal cross-correlation rates in protonated proteins. The method depends on the measurement of four observables: the cumulative proton-proton cross relaxation rates, the (15)N R(1) relaxation rate, the multiexponential decay of 2N(Z)H(N)(Z) spin-order, and multiexponential buildup of 2N(Z)H(N)(Z) spin-order. The (15)N-(1)H dipolar/(15)N CSA longitudinal cross-correlation rate is extracted from these measurements by an iterative fitting procedure to the solution of differential equations describing the coupled relaxation dynamics of the z-magnetization of the (15)N nucleus, the two-spin-order 2N(Z)H(N)(Z), and a two-spin-order term 2N(Z)H(Q)(Z) describing the interaction with remote protons. The method is applied to the microbial ribonuclease binase. The method can also extract longitudinal cross-correlation rates for those amide protons that are involved in rapid solvent exchange. The experiment that serves for extracting proton-proton cross-relaxation rates is a modification of 3D (15)N-resolved NOESY-HSQC. The experiment restores the solvent magnetization to its equilibrium state during data detection for all phase cycling steps and all values of NOE mixing times and is recommended for use in standard applications as well.

Hydrogen↗

PubMed2000

Polymorphisms in the CBS gene associated with decreased risk of coronary artery disease and increased responsiveness to total homocysteine lowering by folic acid.

Elevated total plasma homocysteine (tHcy) is an established risk factor for the development of vascular disease and neural tube defects. Total homocysteine levels can be lowered by folic acid supplements but individual response is highly variable. In this case-control study, involving 142 coronary artery disease (CAD) patients and 102 controls, we have typed six genetic polymorphisms in three homocysteine metabolizing genes and examined their relationship to the incidence of CAD, tHcy levels, and lowering of tHcy levels in response to folic acid supplementation. We found that two single nucleotide polymorphisms in the cystathionine beta synthase (CBS) gene, 699C --> T and 1080T --> C, are associated with decreased risk of CAD and increased responsiveness to the tHcy lowering effects of folic acid. Individuals homozygous for 699T were significantly underrepresented in CAD patients as compared to controls (4.9% vs 17.3%, P = 0.0015), as were individuals homozygous for the 1080C (29.6% vs 44.2%, P = 0.018). Additionally, 699T and 1080C homozygous individuals were the most responsive to folate supplementation. 699T homozygotes lowered tHcy levels 13.6% on average, compared to 4.8% lowering in 699C homozygotes (P = 0.009), while 1080C homozygotes lowered 12.9% compared to just 2.7% for 1080T homozygotes (P = 0.005). The two polymorphisms in CBS are third codon changes and would not be predicted to affect the underlying protein. However, there is strong linkage disequilibrium between these two positions, suggesting that they may also be linked to other as yet unidentified polymorphisms within the CBS gene. These observations suggest that specific CBS alleles are a risk factor for the development of vascular disease and that genetic information could be predictive of individual response to folic acid supplementation.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2000

Sustained expression of therapeutic level of factor IX in hemophilia B dogs by AAV-mediated gene therapy in liver.

We demonstrate that a single intraportal vein injection of a recombinant adeno-associated virus (rAAV) vector encoding canine factor IX (cFIX) cDNA under the control of a liver-specific enhancer/promoter leads to a long-term correction of the bleeding disorder in hemophilia B dogs. Stable expression of the therapeutic level of cFIX (5% of normal level) was detected in the plasma of a dog injected with an AAV vector at a dose of 4.6 x 10(12) particles/kg for over 7 months. Both whole-blood clotting time (WBCT) and activated partial thromboplastin time (aPTT) of the treated dogs have been greatly decreased since the treatment. No anti-canine factor IX antibodies have been detected in the treated animals. Importantly, no bleeding has been observed in the dog that expresses a therapeutic level of cFIX for 7 months following vector administration. Moreover, no persistent significant hepatic enzyme abnormalities were detected in the treated dogs. Thus, a single intraportal injection of a rAAV vector expressing cFIX successfully corrected the bleeding disorder of hemophilia B dogs, supporting the feasibility of using AAV-based vectors for liver-targeted gene therapy of genetic diseases.

Alanine Transaminase↗

PubMed2000

Effect of c-myc antisense oligodeoxynucleotides on hypoxia-induced proliferation of pulmonary vascular pericytes.

To study the effect of c-myc antisense oligodeoxynucleotides (ODNs) on proliferation of pulmonary vascular pericytes (PC) induced by hypoxia, cell culture, dot hybridization using probe of digoxigenin-11-dUTP-labeled cDNA, 3H-thymidine incorporation, immunocytochemical technique and image analysis methods were used to observe the effect of c-myc antisense ODNs on expression of c-myc gene and proliferating cell nuclear antigen (PCNA), and 3H-thymidine incorporation of PC induced by hypoxia. The results showed that hypoxia could significantly enhance the expression of c-myc and PCNA (P < 0.01), and elevate 3H-thymidine incorporation of PC (P < 0.01), but antisense ODNs could significantly inhibit the expression of c-myc and PCNA (P < 0.05), and 3H-thymidine incorporation of PC (P < 0.01). It was suggested that hypoxia could promote the proliferation of PC by up-regulating the expression of c-myc gene, but c-myc antisense ODNs could inhibit hypoxia-induced proliferation of PC by downregulating the expression of c-myc gene.

Animals↗

PubMed2000

Separation of CD34 positive cells and determination of surface homing antigen.

To study the differences in homing potential between bone marrow cells and umbilical blood cells, CD34 positive cells were obtained from bone marrow (BM) and umbilical blood (UB) by the direct cell separation with domestic immunomagnetic beads. The expression of the two adhesion molecules CD11a/CD18 and CD44 were examined. After separation, CD34 positive cells accounted for 51%-82% of the harvested cells and dye-resistance rate was 82%-88%. The expression of CD11a/CD18 and CD44 on the surfaces of UB cells was 49.6% +/- 10.2% and 37.7% +/- 10.3% respectively. On BM cells they were 50.2% +/- 6.2% and 34% +/- 13.3% respectively. There were no significant differences in the expression of these two molecules. It was concluded that the cell separation method with domestic immunomagnetic beads was effective and the stem cells from UB could serve as an alternative source for transplantation.

Antigens, CD34↗

PubMed2000

Screening of novel epilepsy-related genes and isolation and identification of cDNAs.

Twenty cDNA differential fragments were isolated from the hippocampus of rats in epileptic state using mRNA differential display technique. Four fragments were sequenced and compared with the known sequences in the Genebank, which showed that ERG8, ERG11, ERG12 had no significant identity to any known sequences; ERG14 had 64%-69% identity to microtubulin-associated protein of the rat. Because the differential expression of these genes was caused by epilepsy inducer coriaria lactone (CL) and anti-epilepsy drug MK-801 and ERG8 might be a novel candidate epilepsy gene; ERG11 and ERG12 might be novel candidate anti-epilepsy genes. Since the microtubulin-associated protein is closely associated with the collateral sprouting of mossy fibers in the hippocampus of seizured rat, the high expression of ERG14 in the early stage of epilepsy might predict the growth of axon and formation of synapse.

Animals↗

PubMed2000

Restrictive effect of puerarin on myocardial infarct area in dogs and its possible mechanism.

To evaluate the protective effect of puerarin on ischemic myocardium in dogs with acute myocardial infarction (AMI) and to reveal its possible mechanism, 10 dogs were randomly divided into puerarin group (group G) and control group (group C). AMI model was established in all dogs. Puerarin or saline was administered over a period of 21 days. Coronary angiography was performed before and after ligation of coronary artery. Eight hemorheological parameters were examined before and 22 days after the operation. The infarct area and vessel density of myocardium were assessed. The infarct area in group G was smaller than that in group C. Angiography 2 h and 22 d after ligation of coronary artery revealed significant augmentation of collateral vessels in group G as compared with control group. The platelet aggregation and the blood viscosity were increased during AMI when compared with control phase, and the increased indexes during AMI would be inhibited when puerarin were given. Capillaries and distribution vessel density in ischemic zone on day 22 showed statistically significant augmentation in group G as compared with control group. Puerarin might improve the opening and formation of coronary collateral circulation, and might inhibit the increase of platelet aggregation and the blood viscosity during AMI, and thereby improve microcirculation and restrict myocardial infarct area.

Animals↗