Biomedical subjects

Yan Li

Publications and source records attributed to Yan Li.

At least 505 records · Page 28Linked to original sources

PubMed2004

Blood pressure in relation to three candidate genes in a Chinese population.

OBJECTIVE: In a prospective analysis of a Caucasian population, we recently found that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), alpha-adducin (Gly460Trp) and aldosterone synthase (-344C/T) jointly influence the incidence of hypertension. We therefore investigated the association between blood pressure and these three genes in a Chinese population. METHODS: We genotyped 479 Han Chinese from 125 nuclear families recruited in northern China via random sampling (approximately 75%) and at specialized hypertension clinics (approximately 25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and the quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. RESULTS: The participants included 239 (49.9%) women and 132 (27.6%) hypertensive patients, of whom 77 took antihypertensive drugs. The blood pressure, measured at the subjects' homes, averaged 126/80 mmHg. Mean values of urinary sodium, potassium and Na/K ratio were 226 mmol/day, 37 mmol/day and 6.31, respectively. In adjusted GEE analyses, systolic blood pressure was 9.3 mmHg (95% confidence interval 3.6-15.0 mmHg; P = 0.001) and 14.6 mmHg (95% confidence interval 3.4-25.8 mmHg; P = 0.01) higher in the ACE DD than II subjects among the alpha-adducin TrpTrp (n = 141) and aldosterone synthase CC (n = 33) homozygotes, respectively (P < or =0.05 for interactions of the ACE genotype with the alpha-adducin and aldosterone synthase polymorphisms). Among 40 informative offspring homozygous for the alpha-adducin Trp allele, systolic blood pressure was significantly associated with transmission of the ACE D allele (beta = 5.5 mmHg; P = 0.046). CONCLUSIONS: The ACE I/D, alpha-adducin Gly460Trp and aldosterone synthase -344C/T polymorphisms interact to influence systolic blood pressure in Chinese, suggesting that these genes might indeed predispose to hypertension, especially in an ecogenetic context characterized by a high salt intake.

Adult↗

PubMed2004

Development of RT-multiplex PCR assay for detection of adenovirus and group A and C rotaviruses in diarrheal fecal specimens from children in China.

Rotavirus, adenovirus, norovirus, sapovirus and astrovirus are considered to be significant global enteropathogens associated with sporadic cases and outbreaks of acute gastroenteritis. Therefore, a rapid and sensitive assay is preferred to screen for the presence of these viruses in diarrheal fecal specimens. In a previous study, we developed a reverse transcription single-round multiplex polymerase chain reaction (RT-smPCR) assay for the simultaneous detection of norovirus (genogroup I, genogroup II), sapovirus and astrovirus in fecal specimens (Yan et aL, 2003). Recently, we developed another RT multiplex PCR for one-step amplification of all subgenera A to F adenoviruses, and group A and C rotaviruses. In this study, a total of 207 fecal specimens collected from children with acute gastroenteritis between December 2001 and April 2003 in Yunnan Province, China were examined for the presence of adenoviruses, and group A and C rotaviruses, by RT-multiplex PCR. The detection rate of these three viruses was 55.1% (114 out of 207 specimens), among which adenovirus and group A and C rotaviruses were identified in 11, 101 and 1 fecal specimen, respectively. Furthermore, one specimen was found to be positive for co-infection with adenovirus and group A rotavirus. An epidemic of acute gastroenteritis was also identified as peaking mainly in October and November. Taken together, our results clearly indicate that this novel assay provides a potentially rapid and convenient tool for epidemiologic investigation of diarrhea caused by adenovirus and group A and C rotaviruses.

Acute Disease↗

PubMed2004

Genetic variability of the G glycoprotein gene of human metapneumovirus.

Human metapneumovirus (hMPV) has been associated with respiratory illnesses like those caused by human respiratory syncytial virus (HRSV) infection. Similar to other pneumoviruses, genetic diversity has been reported for hMPV. Little information is currently available on the genetic variability of the G glycoprotein (G), which is the most variable gene in RSV and avian pneumovirus. The complete nucleotide sequences of the G open reading frame (ORF) of 24 Canadian hMPV isolates were determined. Phylogenetic analysis showed the existence of two major groups or clusters (1 and 2). All but one of the hMPV isolates that we examined belonged to cluster 1. Additional genetic variability was observed in cluster 1, which separated into two genetic subclusters. Within cluster 1 the nucleotide sequence identity for the G ORF was 74.2 to 100%, and the identity for the predicted amino acid sequence was 61.4 to 100%. The G genes of cluster 1 isolates were more divergent from the cluster 2 isolates, with 45.6 to 50.5% and 34.2 to 37.2% identity levels for the nucleotide and amino acid sequences, respectively. Sequence analysis also revealed changes in stop codon usage, resulting in G proteins of different lengths (217, 219, 228, and 236 residues). Western blot analysis with the use of hMPV-specific polyclonal antisera to each hMPV cluster showed significant antigenic divergence between the G proteins of clusters 1 and 2. These results suggest that the G protein of hMPV is continuously evolving and that the genetic diversity observed for the hMPV genes is reflected in the antigenic variability, similar to HRSV.

Amino Acid Sequence↗

PubMed2004

Ubiquitination of human T-cell leukemia virus type 1 tax modulates its activity.

Human T-cell leukemia virus type 1 (HTLV-1) encodes a 40-kDa Tax phosphoprotein. Tax is a transcriptional activator which modulates expression of the viral long terminal repeat and transcription of many cellular genes. Because Tax is a critical HTLV-1 factor which mediates viral transformation of T cells during the genesis of adult T-cell leukemia, it is important to understand the processes which can activate or inactivate Tax function. Here, we report that ubiquitination of Tax is a posttranscriptional mechanism which regulates Tax function. We show that ubiquitination does not target Tax for degradation by the proteasome. Rather, ubiquitin addition modifies Tax in a proteasome-independent manner from an active to a less-active transcriptional form.

Cysteine Endopeptidases↗

PubMed2004

Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets.

Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) is a serious emerging human infectious disease. In this report, we immunized ferrets (Mustela putorius furo) with recombinant modified vaccinia virus Ankara (rMVA) expressing the SARS-CoV spike (S) protein. Immunized ferrets developed a more rapid and vigorous neutralizing antibody response than control animals after challenge with SARS-CoV; however, they also exhibited strong inflammatory responses in liver tissue. Inflammation in control animals exposed to SARS-CoV was relatively mild. Thus, our data suggest that vaccination with rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis.

Animals↗

PubMed2004

Insertion of the beta Geo promoter trap into the Fem1c gene of ROSA3 mice.

ROSA3 mice were developed by retroviral insertion of the beta Geo gene trap vector. Adult ROSA3 mice exhibit widespread expression of the trap gene in epithelial cells found in most organs. In the central nervous system the highest expression of beta Geo is found in CA1 pyramidal cells of the hippocampus, Purkinje cells of the cerebellum, and ganglion cells of the retina. Characterization of the genomic insertion site for beta Geo in ROSA3 mice shows that the trap vector is located in the first intron of Fem1c, a gene homologous to the sex-determining gene fem-1 of Caenorhabditis elegans. Transcription of the Rosa3 allele (R3) yields a spliced message that includes the first exon of Fem1c and the beta Geo coding region. Although normal processing of the Fem1c transcript is disrupted in homozygous Rosa3 (Fem1c(R3/R3)) mice, some tissues show low levels of a partially processed transcript containing exons 2 and 3. Since the entire coding region of Fem1c is located in these two exons, Fem1c(R3/R3) mice may still be able to express a putative FEM1C protein. To this extent, Fem1c(R3/R3) mice show no adverse effects in their sexual development or fertility or in the attenuation of neuronal cell death, another function that has been attributed to both fem-1 and a second mouse homolog, Fem1b. Examination of beta Geo expression in ganglion cells after exposure to damaging stimuli indicates that protein levels are rapidly depleted prior to cell death, making the beta Geo reporter gene a potentially useful marker to study early molecular events in damaged neurons.

Animals↗

PubMed2004

Reduction in p48-ISGFgamma levels confers resistance to interferon-alpha2a in MHCC97 cells.

OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in China and, due to the limited efficacy of currently available therapies, is responsible for a large number of deaths. IFN-alpha therapy has shown promise in the treatment of various forms of human cancer and is considered in the treatment of HCC. Previous results from our group showed that high doses of IFN-alpha exert a significant antiproliferative effect on MHCC97 human xenografts in nude mice, but not on MHCC97 cells when tested in vitro. Here we present experiments designed to characterize the molecular mechanism underlying the defective response of MHCC97 cells to IFN-alpha. Elucidation of the mechanism underlying the defective response of MHCC97 to IFN-alpha may help to explain and possibly to overcome clinical failures of this form of tumor therapy. METHODS: IFN-alpha(2a) was administered between 3,000 and 10,000 IU/ml, a range strongly inhibiting proliferation in other cell lines. Gene expression profiles of MHCC97 cells were obtained before and after treatment with IFN-alpha(2a) using cDNA microarray analysis. The transcriptional activity of relevant genes responding to IFN-alpha(2a) in the cDNA microarray experiments was confirmed by RT-PCR and Northern blot analysis. Transient transfection with an expression vector was used to restore p48-ISGFgamma (IRF9) protein levels. Cell proliferation was evaluated using the MTT assay. RESULTS: Although IFN-alpha treatment caused the activation of several signal transduction pathways in MHCC97 cells, the lack of an antiproliferative effect was found to mainly derive from a defect in the activation of the transcription factor ISGF3 required for Jak/STATS signaling. We show that the defect in ISGF3 activation is mainly caused by the absence of one of its essential components, the protein p48-ISGFgamma from MHCC97 cells. Indeed, transient expression of p48-ISGFgamma restores sensitivity to IFN-alpha(2a). Although the mRNA levels of p48-ISGFgamma were normal in MHCC97 cells, mutations could be detected in the gene coding for the protein. We hypothesize, therefore, that these mutations alter the message or protein stability, leading to the reduced protein levels observed. CONCLUSION: Our results confirm the important role of Jak/STATS signaling in the antiproliferative effects of IFN-alpha in tumor cells and indicate that defects in ISGF3 can cause resistance to IFN-alpha(2a) treatment.

Antineoplastic Agents↗

PubMed2004

Anti-tussive activity of benproperine enantiomers on citric-acid-induced cough in conscious guinea-pigs.

The anti-tussive effect of the R-(+)- and S-(-)-enantiomers of benproperine was evaluated and compared with that of the racemate on cough induced by 7.5% citric acid in conscious guinea-pigs. All the three compounds, intraperitoneally administered 1.5 h before the test, significantly inhibited citric-acid-induced cough. The ID50 values (effective doses for 50% inhibition) (with 95% confidence intervals) were 16.1 (9.1-28.4), 23.3 (11.2-48.6), 25.4 (11.7-55.1) mg kg(-1) for the number of coughs in the 3 min of challenge, and 11.9 (5.3-26.6), 13.5 (5.6-32.4), 19.2 (12.8-28.9) mg kg(-1) for the number of coughs in the 5 min immediately after the challenge, for (+/-)-benproperine, R-(+)-benproperine and S-(-)-benproperine, respectively. These findings suggest that the use of either enantiomer does not show any advantage over the racemate with regard to their anti-tussive effect.

Animals↗

PubMed2004

Life-threatening human metapneumovirus pneumonia requiring extracorporeal membrane oxygenation in a preterm infant.

We present the first report in the literature of a child with human metapneumovirus pneumonia who required extracorporeal membrane oxygenation for survival. This was a 3-month-old premature boy from British Columbia, Canada, who developed severe respiratory failure, experienced failure of high-frequency oscillatory mechanical ventilation, and required extracorporeal membrane oxygenation support for 10 days. This case illustrates the importance of including this newly discovered pathogen among the causes of childhood pneumonia.

Extracorporeal Membrane Oxygenation↗

PubMed2004

Primary and secondary prevention of stroke by antihypertensive drug treatment.

Hypertension is the most powerful risk factor for stroke. Antihypertensive drug treatment reduces the incidence of stroke. In a meta-analysis of actively controlled trials, calcium-channel blockers, including (-8%; p = 0.07) or excluding verapamil (-10%; p = 0.02), as well as angiotensin Type 1 receptor blockers (-24%; p = 0.0002) resulted in better stroke prevention than the old drugs (diuretics or beta-blockers), whereas the opposite trend was observed for angiotensin-converting enzyme inhibitors (+10%; p = 0.03). An overview of six trials conducted in patients with a history of cerebrovascular disease demonstrated that blood pressure-lowering therapy reduced stroke recurrence by 25% (p = 0.004). A meta-regression analysis showed that within-trial differences in systolic blood pressure accounted for the prevention of stroke in most trials. This finding was corroborated by the recently published Valsartan Antihypertensive Long-term Use Evaluation trial.

Antihypertensive Agents↗

PubMed2004

Resistance of Glycine species and various cultivated legumes to the soybean aphid (Homoptera: Aphididae).

The soybean aphid, Aphis glycines Matsumura, is a new pest of soybean, Glycine max (L.) Merr., in North America. It has become widespread on soybean in North America since it was first identified in the Midwest in 2000. Species of Rhamnus L. (buckthorn) are the primary hosts of A. glycines, and soybean is known as a secondary host. There is limited information about the secondary host range of A. glycines. Aphid colonization on various legume hosts was compared in choice experiments. Aphid colonization occurred on species in the genus Glycine Wild. No colonization occurred on Lablab purpureus (L.) Sweet, Lens culinaris Medik, Phaseolus vulgaris L., Pisum sativum L., or species of Vicia L. and Vigna Savi. Colonization was limited or aphids were transient on species of Medicago L., Phaseolus L., and Trifolium L. There were significant differences in aphid colonization among Medicago truncatula accessions with numbers ranging from 7 to 97 aphids per plant. Six Glycine soja Sieb. & Zucc. accessions were as resistant as G. max accessions to A. glycines; these may represent novel sources of A. glycines resistance not found in G. max. Antibiosis was found to play a large role in the expression of resistance in three of the G. soja accessions. Results of this study indicated that G. max and G. soja were the best secondary hosts of A. glycines; however, its secondary host range may include other leguminous species. Therefore, A. glycines did not seem to have a highly restricted monophagous secondary host range.

Animals↗

PubMed2004

Novel avian influenza H7N3 strain outbreak, British Columbia.

Genome sequences of chicken (low pathogenic avian influenza [LPAI] and highly pathogenic avian influenza [HPAI]) and human isolates from a 2004 outbreak of H7N3 avian influenza in Canada showed a novel insertion in the HA0 cleavage site of the human and HPAI isolate. This insertion likely occurred by recombination between the hemagglutination and matrix genes in the LPAI virus.

Amino Acid Sequence↗

PubMed2004

Human illness from avian influenza H7N3, British Columbia.

Avian influenza that infects poultry in close proximity to humans is a concern because of its pandemic potential. In 2004, an outbreak of highly pathogenic avian influenza H7N3 occurred in poultry in British Columbia, Canada. Surveillance identified two persons with confirmed avian influenza infection. Symptoms included conjunctivitis and mild influenzalike illness.

Adolescent↗

PubMed2004

Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: Results of a randomized controlled clinical trial.

AIM: To study the effects of perioperative administration of cimetidine (CIM) on peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODS: Forty-nine GI cancer patients were randomized into treatment group, who took CIM in perioperative period, and control group, who did not take the drug. The treatment was initiated 7 days before operation and continued for 10 days after surgery. At baseline examination before operation, on the 2nd and 10th postoperative days, total T lymphocytes, T helper cells, T suppressor cells, and NK cells in peripheral blood were measured respectively by immunocytochemical method using mouse-anti human CD(3), CD(4), CD(8) and CD(57) monoclonal antibodies. Blood samples from 20 healthy volunteers were treated in the same way as normal controls. Surgical specimens were examined during routine histopathological evaluation for the presence of TIL in tumor margin. Immunohistochemical study was performed to measure the proportion of T and B lymphocytes in TIL population. T and B lymphocytes were detected respectively using mouse-anti-human CD(3) and CD(20) monoclonal antibodies. RESULTS: In comparison with normal controls, both the treatment and control groups had decreased T cells, T helper cells and NK cells at baseline. In control group, total T cells, T helper cells and NK cells declined continuously with the disease progression and the decrease became more obvious after operation. From baseline to the 2nd postoperative day, the proportion of total T cells, T helper cells, and NK cells went down from 60.5+/-4.6% to 56.2+/-3.8%, 33.4+/-3.7% to 28.1+/-3.4%, and 15.0+/-2.8% to 14.2+/-2.2%, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative day, the treatment group had significantly higher percentages of total T cells, T helper cells and NK cells than control group. Moreover, CIM treatment also boosted TIL response, as was reflected by findings that 68% (17/25) of the patients in treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL responses (P<0.01). CONCLUSION: Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity induced by tumor burden and surgical maneuver. The drug could also boost TIL responses to tumor. These effects suggest that the drug be used as an immunomodulator for GI cancer patients.

Adjuvants, Immunologic↗

PubMed2004

[Migration and invasion of human hepatocellular carcinoma mediated by lung extracts].

BACKGROUND & OBJECTIVE: Invasion and metastasis are obstacles to successful treatment of hepatocellular carcinoma. Lung is the most common site of distant metastasis from hepatocellular carcinoma. In in vitro chemoinvasion assay that different tissue extracts from mice were used to induce human hepatocellular carcinoma cells with different metastatic potentials, lung extracts show the strongest inducing activity. This study was designed to investigate the mechanism of migration and invasion in human hepatocellular carcinoma with highly metastatic potential mediated by lung extracts from mice. METHODS: The changes of cytoskeleton were tested using F-actin polymerization assay and flow cytometry (FCM). Correlation between matrix metalloproteinas-9 and F-actin was analyzed by fluorescence double staining in human hepatocellular carcinoma MHCC97-H cells induced by lung extracts. RESULTS: When MHCC97-H cells were incubated with serum-free medium or spleen extracts, the cells showed elongated or polygonal morphology. When MHCC97-H cells were incubated with lung extracts, the formation of lamelliopodia or filopodia became more and more obvious and distinct as time increasing. Results of FCM showed that 1.9-fold increase in intracellular F-actin within 30s after MHCC97-H cells were incubated with lung extracts. Confocal laser scan microscopy of MHCC97-H cells stimulated in suspension showed intense F-actin staining in the periphery of the cells and redistribution of F-actin towards a leading edge. MMP-9 and F-actin were mainly localized in the perinuclear pool when the cells were incubated with serum-free medium. After stimulation with lung extracts, MMP-9 and F-actin were localized at the front of extending pseudopodia of MHCC97-H cells. CONCLUSION: The mechanism that lung extracts promote migration and invasion of MHCC97-H may correlate with the pseudopodia formation and reorganization of MMP-9. Lung extracts may contribute to organ-specific metastasis of hepatocellular carcinoma.

Animals↗

PubMed2004

[Expression and purification of recombinant N-terminal protein of SARS S1 subunit expressed in E. Coli].

OBJECTIVE: To express and purify the recombinant N-terminal protein of SARS virus S1 subunit and to study its role in SARS immune response. METHODS: The gene encoding N-terminal 334 amino acid residuals of SARS virus S1 subunit was cloned and expressed in E. Coli. After purification, the recombinant protein was identified by anti-SARS positive sera from recovered SARS patients. The sera from health donors, which were collected before the out-break of SARS, were used as negative control in the study. RESULTS: Sequencing analysis confirmed that the desired DNA sequence in recombinant plasmid was correct and had the same sequence of natural N-terminal of SARS virus S1 subunit. The molecular weight of recombinant fusion protein is about 64 000. The recombinant S1 protein could react with three antibody positive samples from recovered SARS patients, which showed specific bands at 64 000, but not with the control samples according to results of western blot. CONCLUSION: The recombinant N-terminal protein of SARS virus S1 subunit displays specific reaction with SARS antibody and may provide a good tool for further research of immune response to SARS virus.

Blotting, Western↗

PubMed2004

[The inhibiting effect of niflumic acid on airway hyperresponsiveness in asthmatic mice].

OBJECTIVE: To evaluate the inhibiting effect of niflumic acid (NFA), an inhibitor of calcium-activated chloride channel (ClCa) on airway epithelium, on the airway hyperresponsiveness in asthmatic mice. METHODS: BALB/c mice were randomly divided into an asthma group (A group), a NFA prevention asthmatic group (B group) and a sham-challenged group (C group). The airway pressure time index (APTI) and the content of ET-1 and NO in bronchoalveolar lavage fluid (BALF) in all groups were measured. With the isolated tracheal rings with integral epithelium or epithelium removed from the asthma group (A(1) group and A(2) group) and the sham-challenged group (C(1) group and C(2) group), the contractile responsiveness of various rings to methacholine (mACh) was examined, and its change was observed when the rings were exposed to NFA beforehand. RESULTS: Compared with A group (1.62 +/- 0.14), the APTI in B group (1.21 +/- 0.07) was reduced remarkably (P < 0.01), and the contents of ET-1 [(103 +/- 9) ng/L] and NO [(48.5 +/- 3.2) micromol/L] in BALF of A group were significantly higher than those in B group, [(53 +/- 5) ng/L, (23.7 +/- 2.5) micromol/L (P < 0.01), respectively]. The ratios of maximum contractility in A(1), A(2), C(1) and C(2) groups were (3.79 +/- 0.44), (2.15 +/- 0.21), (1.26 +/- 0.14) and (2.06 +/- 0.18), respectively. The contractility of A(1) group was highest among all groups (all P < 0.01), but could be effectively decreased by NFA. CONCLUSIONS: By inhibiting the special ClCa on the airway epithelium, NFA can inhibit the production of ET-1 and NO by epithelium and thus exert preventive effect on airway hyperresponsiveness in asthma.

Animals↗

PubMed2004

[Effects of oxidized low-density lipoprotein on expression of type A scavenger receptor in human mesangial cells].

OBJECTIVE: To explore the regulational effect of oxidized low-density lipoprotein (Ox-LDL) on expression of type A scavenger receptor (SR-A) in human mesangial cells (HMC). METHODS: HMC line (HMCL) with high expression of SR-A (HMCL-SRA) was established after stable transfection of expressive vector with cDNA encoding SR-A. Uptake of Ox-LDL by HMCL was evaluated using Oil Red "O" staining. SR-A mRNA expression was examined using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: More uptake of Ox-LDL was observed in the HMCL-SRA than that in the untransfected HMCL. Ox-LDL could induce SR-A mRNA expression in HMC in a dose-dependent manner, and reached a peak level after 24 h of stimulation. After 24 h of stimulation with Ox-LDL at the dose of 10, 50 and 100 micrograms/ml, SR-A mRNA expression was up-regulated to 1.35, 1.83 and 2.30-fold of controls, respectively. However, LDL had no effect on the expression of SR-A. CONCLUSIONS: It suggests that SR-A be a major binding receptor to uptake Ox-LDL in HMC. Ox-LDL may promote the progression of chronic renal diseases through up-regulation of SR-A.

Cells, Cultured↗