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Biomedical subjects

Y Wan

Publications and source records attributed to Y Wan.

At least 109 records · Page 6Linked to original sources

[Clinical application of TMS-MEP in spinal cord injury].

OBJECTIVE: To evaluate transcranial magnetic stimulation motor evoked potential (TMS-MEP) in the diagnosis of spinal cord injury. METHOD: 56 patients with injury of the spinal cord and cauda equina were examined using TMS-MEP and followed up. RESULT: In 21 patients with complete paralysis, TMS-MEP of bilateral tibialis anterior and gastrocnemius disappeared and paralysis did not recover. Abnormal was noted TMS-MEP and paralysis not recovered in 2 patients with injury of conus medullaris and cauda equina. Incomplete paralysis occurred in 35 patients. TMS-MEPs of more than one muscle in every patient were recorded. Paralysis and TMS-MEPs recovered in different degree in the 33 patients, in which the strength was 0 class and TMS-MEPs were abnormal in 25 target muscles before operation whereas their strength obviously recovered or even normalized after operation except two muscles. CONCLUSION: TMS-MEP is an effective method for diagnosis and prognosis of spinal cord injury.

Adolescent↗

Cytochrome P450 2E1 DraI polymorphisms in lung cancer in minority populations.

Cytochrome P4502E1 (CYP2E1) is involved in the metabolic activation of carcinogenic N-nitrosamines. This study was performed to examine whether CYP2E1 DraI polymorphisms in intron 6 are related to susceptibility to lung cancer and are associated with carcinogenetic exposure. We therefore genotyped CYP2E1 by PCR amplification of peripheral WBC DNA from 126 patients with previously untreated lung cancer (85 African Americans and 41 Mexican Americans) and 193 controls (104 African Americans and 89 Mexican Americans). Mutagen sensitivity was measured with an in vitro assay quantitating bleomycin-induced chromatid breaks in peripheral blood lymphocyte cultures. The CYP2E1 DraI DD genotype was found in 86.5% of all cases and in 74.6% of all controls (P = 0.03), in 78.1% of 41 Mexican-American cases and in 69.6% of their controls (P = 0.70), and in 90.6% of African American cases and in 78.8% of their controls (P = 0.05). The DD genotype was found to be associated with a significantly higher risk of lung cancer overall with an odds ratio (OR) of 2.4 [95% confidence interval (CI), 1.1-5.3]. This risk was significantly elevated for men and for those who had ever smoked [ORs of 3.4 (95% CI, 1.3-8.7) and 2.6 (95% CI, 1.1-6.0), respectively], but not for women and nonsmokers [ORs of 0.7 (95% CI, 0.1-3.8) and 0.9 (95% CI, 0.1-10.6), respectively]. Stratified analysis showed an interaction that seemed greater than multiplicative between cigarette smoking and the CYP2E1 DraI DD genotype. The ORs for the CYP2E1 DraI DD genotype, cigarette smoking, and both risk factors combined were 1.5, 8.5, and 22.7, respectively. The CYP2E1 DraI polymorphism and the CYP2E1 PstI polymorphism in the upstream flanking regions were significantly associated in Mexican Americans but not in African Americans. We therefore conclude that the CYP2E1 DraI polymorphism seems to be associated with lung carcinogenesis. However, a larger study is warranted to evaluate the interactions among CYP2E1 DraI DD genotype, mutagen sensitivity, and cigarette smoking.

Aged↗

Estimating the strength of genetic effects: a comparison of maximum likelihood and transmission disequilibrium methods in the study of ankylosing spondylitis.

Here we compare several methods for evaluating associations in the analysis of family data. We applied the transmission disequilibrium test (TDT), and logistic regression, familial aggregation, and segregation analyses for the study of Ankylosing Spondylitis. All methods detected effects from B27 upon susceptibility for Ankylosing Spondylitis. However, the TDT was unable to detect effects from B40 and also could not include sex as a covariate during the analysis. Conditioning or not conditioning the data for the ascertainment event led to little difference in the estimated covariate effects, although the genetic model for residual effects not due to the covariates did change. Results from these studies provide further characterization of the relationship between HLA B27, B40, and sex upon risk for developing Ankylosing Spondylitis. We also identified potential effects from further genetic susceptibility.

Adolescent↗

Dendritic cells transduced with an adenoviral vector encoding a model tumor-associated antigen for tumor vaccination.

Evaluation of the potential role of dendritic cells (DCs) as adjuvants for tumor vaccination has focused primarily on techniques that load DCs with peptide tumor antigens. Our aim has been to optimize the induction of antitumor immunity by enhancing the ability of DCs to present tumor-associated antigens endogenously to the afferent lymphatic system in the appropriate major histocompatibility complex (MHC)-restricted context. We have used replication-defective adenovirus vectors (Ads) to transduce DCs with various genes, including tumor antigen genes. We found that 90% of murine bone marrow derived-DCs could be infected with an Ad vector expressing the beta-galactosidase gene and still retain their physiologic and phenotypic characteristics. Furthermore, we demonstrated that transgene expression was detectable in the spleen for at least 3 days following intravenous injection of Ad-transduced DCs. Using a polyoma middle T (PymT) transgenic murine mammary carcinoma model, we have shown that a single injection of 10(5)-4 x 10(6) DCs transduced with an Ad vector expressing PymT provided complete and specific protection against tumor cell challenge in 100% of vaccinated animals. Immunization against the PymT tumor by injection with the PymT expressing Ad vector alone resulted in varying degrees of effectiveness, was highly dependent upon the route of administration, and led to significant hepatic toxicity that was not seen in mice immunized with DC transduced with the Ad vector. Our results suggest that: (i) DCs can be very efficiently modified by ex vivo Ad transduction to express tumor-specific antigens, (ii) such modified DCs appear nontoxic and stimulate a potent antitumor response.

Adenoviridae↗

Genetic evidence for a tyrosine kinase cascade preceding the mitogen-activated protein kinase cascade in vertebrate G protein signaling.

The signal transduction pathway from heterotrimeric G proteins to the mitogen-activated protein kinase (MAPK) cascade is best understood in the yeast mating pheromone response, in which a serine/threonine protein kinase (STE20) serves as the critical linking component. Little is known in metazoans on how G proteins and the MAPK cascade are coupled. Here we provide genetic and biochemical evidence that a tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Targeted deletion of tyrosine kinase Csk in avian B lymphoma cells blocks the stimulation of MAPK by Gq-, but not Gi-, coupled receptors. In cells deficient in Bruton's tyrosine kinase (Btk), Gi-coupled receptors failed to activate MAPK, while Gq-coupled receptor-mediated stimulation is unaffected. Taken together with our previous data on tyrosine kinases Lyn and Syk, the Gq-coupled pathway requires tyrosine kinases Csk, Lyn, and Syk, while the Gi-coupled pathway requires tyrosine kinases Btk and Syk to feed into the MAPK cascade in these cells. The central role of Syk is further strengthened by data showing that Syk can bind to purified Lyn, Csk, or Btk.

Agammaglobulinaemia Tyrosine Kinase↗

A transcript map encompassing the multiple endocrine neoplasia type-1 (MEN1) locus on chromosome 11q13.

A transcription map of a 1200-kb region encompassing the MEN1 locus was constructed by direct cDNA selection and mapping ESTs. A total of 29 genes were mapped. Ten transcripts were identified by cDNA selection of a focused 300-kb genomic region telomeric to the MEN1 consensus region. Since many of the sequences cloned by cDNA selection also identified ESTs from the region, 19 additional RH-mapped ESTs were mapped to the entire contig region by PCR amplification of genomic clones. Nine known genes, 2 putative human homologues to mouse genes, and 18 novel transcripts map to the region. Transcripts that map to the MEN1 interval PYGM-D11S449 include SGC35223, IB1256, AA147620, ZFM1, FAU, and CAPN1. The latter 3 known genes have already been excluded as candidate MEN1 genes. The 2 putative human homologues of mouse genes Ltbp2 and Spa-1 may be candidate tumor suppressor genes, but they map telomeric to D11S449. Although both of these genes map outside the MEN1 consensus region they may play a role in sporadic endocrine tumors independent of the MEN1 gene or in other tumors, such as breast cancer, that have loss of heterozygosity within this region.

Blotting, Northern↗

Intramarrow cytokine gene transfer by adenoviral vectors in dogs.

Daily systemic administration of hematopoietic growth factors can be associated with dose-limiting systemic side effects. To overcome this, we have investigated hematopoietic cytokine gene transfer to the marrow cavity of dogs by direct intramarrow injection of adenoviral vectors. In marrow culture, replication-deficient (E1-deleted) adenoviral vectors were able to transduce marrow stromal cells, demonstrating 30-fold greater expression than from other marrow cell types. High-level (ng/ml) cytokine production from transduced stromal cells persisted for 14 days in culture. Because adenovectors could efficiently transduce marrow stromal cells in culture, we investigated if stromal cells could also be transduced in vivo following direct intramarrow vector injection. Adenovectors with genes for interleukin 6 (IL-6) and Lac Z (beta-galactosidase) were injected directly into the marrow cavity of dogs resulting in protein expression localized to within the treated marrow. To evaluate this approach further in dogs, we constructed a vector expressing biologically active canine granulocyte-macrophage colony stimulating factor (GM-CSF). 293 cells infected with ADGM-CSF demonstrated prevalent GM-CSF mRNA by Northern blot and 135 +/- 30 ng/ml of protein as measured by enzyme-linked immunosorbent assay (ELISA). In vitro bioactivity of protein expressed was confirmed by canine GM colony-forming assay (CFU-GM). In vivo high-level protein production was noted in supernatants of marrow aspirates 72 hr following direct intramarrow administration of ADGM-CSF (baseline mean +/- SEM, 27 +/- 22 ng/ml, 72-hr sample 921 +/- 461 ng/ml). A localized myeloid expansion of marrow and significant peripheral leukocytosis (neutrophilia) were noted in all ADGM-CSF-treated dogs. Peripheral blood changes lasted for up to 3 weeks in dogs following single intramarrow injection. Thus, adenoviral cytokine expression from the marrow of a single large bone (ilium) led to compartmentalized expression of growth factor and an increase of hematopoiesis sufficient to cause peripheral blood changes in a large animal model.

Adenoviridae↗

Linked markers and age at diagnosis.

This paper examines the relationship between age at diagnosis and markers linked to a disease trait using 100 replicates from Problem 2A in Genetic Analysis Workshop 10. After establishing the relationship between age and the quantitative trait used to define affection status, Q1, we evaluated the relationship between age at diagnosis and a marker which was linked with Q1. We found that the presence of an F allele at marker 15 on chromosome 5 was significantly associated with delayed age of diagnosis. When we evaluated 100 replicates, we found that the regression coefficients in the survival analyses were separated into two approximately normal distributions. The location of these distributions was solely reflective of the presence of affected individuals with the F allele in a particular replicate. In the replicates in one of the distributions, we found tremendous changes in the variance after employing survival models for dependent data. While we suggest that survival analysis of dependent data may be an important tool in investigating genotype specific alterations in age at event, the findings of this study indicate that the method used may be very sensitive to certain types of missing data.

Adult↗

Genome analysis on linkage group VI of Neurospora crassa.

Two chromosome walks covering 420 and 110 kb on the left arm of linkage group VI (LGVIL) of Neurospora crassa were purscrooued with the goal of cloning carotenogenic loci. Complementation analysis with clones isolated in the 420-kb walk allowed identification of the yellow-1 (ylo-1) gene which is essential for Neurospora carotenogenesis. We have physically located a second gene, unknown-13 (un-13), between the cross-pathway control-1, (cpc-1) and ylo-1 loci. Cloning of a second potential carotenogenic locus, vivid (vvd), from our walks was attempted using screening of Northern blots with radiolabeled DNA fragments from walk clones to identify gene transcripts. The radiolabeled DNA fragments were used to clone complementary DNA isolates representing an additional four genes in the two walks.

Carotenoids↗

A permutation test for the robust sib-pair linkage method.

The robust sib-pair method introduced by Haseman & Elston (1972) is one of the most widely circulated allele-sharing methods for linkage analysis. The procedure evaluates linkage by significance testing of a regression coefficient and, hence, a standard t-test has traditionally been applied despite known violations of the statistical assumptions underlying the test. We present a permutation based reference distribution for the estimate of the regression coefficient that is motivated by genetic principles rather than by standard regression testing procedures. The permutation test approximates Mendelian co-segregation under the null hypothesis of no linkage, making it a very natural approach. Theory and simulations show that the conventional t-test approximates the permutation test quite well, even when dependent sib pairs are used for analysis. These results thus indirectly address concerns over the t-test. To illustrate the permutation test using real data we applied the procedure to two lipoprotein systems that have been well characterized.

Animals↗

Optimal seat suspension design based on minimum "simulated subjective response".

This work addresses a method for improving vertical whole body vibration isolation through optimal seat suspension design. The primary thrusts of this investigation are: (1) the development of a simple model that captures the essential dynamics of a seated human exposed to vertical vibration, (2) the selection and evaluation of several standards for assessing human sensitivity to vertical vibration, and (3) the determination of the seat suspension parameters that minimize these standards to yield optimal vibration isolation. Results show that the optimal seat and cushion damping coefficients depend very much on the selection of the vibration sensitivity standard and on the lower bound of the stiffnesses used in the constrained optimization procedure. In all cases, however, the optimal seat damping obtained here is significantly larger (by than a factor of 10) than that obtained using existing seat suspension design methods or from previous optimal suspension studies. This research also indicates that the existing means of assessing vibration in suspension design (ISO 7096) requires modification.

Automobile Driving↗

[A study on histogenesis of gastrointestinal stromal tumors].

OBJECTIVE: The purpose of this study was to consider the histogenesis of gastrointestinal stromal tumors (GIST). METHOD: 36 cases of GIST were studied by light microscopy, histochemical and immunohistochemical techniques. RESULTS: In 15 cases of small intestine spindle cell tumors, various sized eosinophilic globules were observed between the tumor cells and were designated as skeinoid fibers, which stained blue with Masson's trichrome and strongly PAS-positive. The positive rate by immunohistochemical methods for S-100 protein and desmin were 44.44% and 8.33% respectively. The immunoexpression of tumor cells was unrelated to their differentiation. CONCLUSION: Complex immunophenotypes of GIST suggest primitive mesenchymal origin, and small intestine stromal tumors (SIST) are mostly neurogenic which may have been derived from neurilemmal cells or autonomous nerve tissue of the small intestine.

Adult↗

[Studies on programmed cell death induced by amsacrine and expression of bcl-2 in leukemia cell lines].

OBJECTIVE: To study programmed cell death (PCD) in two human acute myelocytic leukemia cell lines in different differentiated phases, NB4(AML3) and HL-60(AML2). METHODS: PCD cells were detected microscopically, DNA electrophoretically and flow cytometrically. Expression of bcl-2 gene was examined by immunohistochemistry staining. RESULTS: Exposed to 1-20 micrograms/ml m-AMSA for 6-12 h, morphological changes in NB4 cells were more evident than in HL-60 cells. Internucleosomal fragmentation(DNA ladders) was more marked in NB4 than in HL-60 cells. Flow cytometric analysis indicated that the number of PCD cells in NB4 cells was more than that in HL-60 cells. HL-60 cells had significantly higher mean bcl-2 level than NB4 cells. CONCLUSION: The high bcl-2 level in HL-60 cells may be related to their comparatively low sensitivity to m-AMSA-induced PCD.

Amsacrine↗

[Method of mRNA differential display and its application in life science].

The changes of mRNA expression level control cell function. Many factors such as individual development, cell proliferation and differentiation, and even apoptosis, physiological stimuli, and drug treatment will change the level of gene expression. Comparisons of gene expression in different cell types provide the underlying information for analyzing the molecular and cellular mechanisms of the physiological processes. A method of mRNA differential display is developed recently, providing a powerful and useful tool, which can efficiently and rapidly isolate the genes that display a difference in transcription. These genes may play important role in cell function.

Animals↗

[Environmental pollution, human exposure and its health effect of sodium pentachlorophenate in schistosomiasis prevalent area].

Sodium pentachlorophenate (Na-PCP) has been used in China for years as an molluscacide to kill oncomelania, which is an intermediate host of Schistosome. To evaluate the effects of its long-term successive usage on environment, human exposure and health, studies were carried out in Sichuan, Jiangxi, Jiangsu and Fujian provinces, with a time gap of more than one month between sample collection and last spray of Na-PCP. Results indicated that PCP contents in surface water, soil, sediment, animals and plants were significantly higher in studied areas than in control areas. The daily intake and the content in urine of PCP were also sigificantify higher in studied areas. But, there was no difference on physical and biochemical examinations except that a 22%-28% decrease of blood cholinesterase activity was found in studied areas. The health effect of impurities in Na-PCP, dioxins and furans, was assessed and discussed.

Animals↗

Tyrosine kinases in activation of the MAP kinase cascade by G-protein-coupled receptors.

The mitogen-activated protein kinase (MAPK) signalling cascade is a prominent cellular pathway used by many growth factors, hormones and neurotransmitters to regulate physiological responses. Although activation of the MAPK pathway by receptors with tyrosine kinase activity is well defined, the mechanism used by heterotrimeric G-protein-coupled receptors to activate this pathway is less clear. Here we show that in cells deficient in the Src-related tyrosine kinase Lyn, stimulation of MAPK kinase and MARPK by Gq-coupled m1 muscarinic acetylcholine receptors (mAChR) is blocked, whereas Gi-coupled m2 mAChR-mediated stimulation is unaffected. In cells deficient in the tyrosine kinase Syk, both m1 and m2 mAChRs failed to stimulate MAPK kinase and MAPK. This result indicates that Syk is essential for the Gi-coupled pathway and that Lyn and Syk are necessary for the Gq-coupled pathway.

Animals↗

Factors accounting for different responses of pulmonary and cerebral vessels to hypoxia.

The roles of sympathicus, sensory neuropeptides (SNP), cyclooxygenase metabolites (COX-M), lipoxygenase metabolites (LOX-M), endothelium derived relaxing factor (EDRF), reactive oxygen (ROS) and potassium channels (PC) in the hypoxic pulmonary vasoconstriction (HPV) and hypoxic cerebral vasodilation (HCVD) were investigated in intact rats, rabbits and dogs. The results showed that during hypoxia, the excitation of sympathicus caused a constriction of both pulmonary and cerebral vessels, while SNP, EDRF and the opening of voltage sensitive PC caused the dilation of both of them; LOX-M mediated HPV and HCVD, COX-M might serve as their modulators; the blockade of ATP sensitive PC induced by hypoxia mediated HPV, but had no effect on HCVD; the reduction of O2-. in the lung might potentiate HPV, however, O2-. remained unchanged in brain during hypoxia. It is suggested that the alterations of LOX-M, ROS and the ATP sensitive PC are the factors accounting for the difference in the response of pulmonary and cerebral vessels to hypoxia.

Animals↗