Biomedical subjects

M Yan

Publications and source records attributed to M Yan.

At least 19 recordsLinked to original sources

PubMed2001

The p38 MAPK pathway is involved in the IL-2 induction of TNF-beta gene via the EBS element.

As an important cytokine of the immune system, interleukin-2 (IL-2) can induce the expression of various genes, one of which is the tumor necrosis factor-beta (TNF-beta). However, the induction mechanism of TNF-beta remains to be fully explored. We have previously shown JAK-STAT pathway mediates TNF-beta gene induction upon IL-2 stimulation through an upstream -200GAS element. In this study, we further demonstrated that there is another essential -130EBS element in TNF-beta gene promoter region. Using IL-2-dependent cell line BAF/BO3beta, we found that this -130EBS element can form a specific complex with nuclear protein, which contained a novel ETS transcription factor. Furthermore, using kinase inhibitors, we revealed that p38 MAP kinase is involved in the formation of -130EBS-protein complex and the subsequent transcriptional activation of TNF-beta gene in response to IL-2 stimulation. Taken together, our results suggested that the complicated IL-2 induction of TNF-beta gene expression requires not only the activation of JAK-STAT pathway on the -200GAS element, but also the cooperation of another signal pathway on the -130EBS element.

Animals↗

PubMed2001

Local and fast relaxation phenomena after laser-induced photodetachment in a strongly electronegative rf discharge.

A one-dimensional self-consistent particle in cell/Monte Carlo method is used to study the local (at the laser impact region) and fast relaxation phenomena after laser-induced photodetachment in a strongly electronegative SiH(4)/H(2) rf discharge. The relaxation process of the local densities of the charged plasma species has been studied in association with the time evolution of the local electric field. The phenomena predicted theoretically about the relaxation processes, such as the potential well, the electrostatic oscillation, the long lasting potential structure, the distortion of the early potential perturbation on the measurement of negative ion temperature, and the depression in the positive ion density profile at the edges of the laser impact region, have been confirmed by our simulation results. Compared to the relaxation in weakly electronegative discharges, the local and even the global electric field in strongly electronegative discharges, has been weakened strongly after photodetachment. The relaxation of the local electric field lasts 100 rf cycles with the recovery of the local electron density and the local electron energy. The electrostatic oscillation exhibited as the deviation in quasineutrality, is very strong and continues over several rf cycles in our case. The large dip in the center of the positive ion density profile, observed in the experiment, is also reproduced by our model.

Journal Article↗

PubMed2001

Impaired c-Jun amino terminal kinase activity and T cell differentiation in death receptor 6-deficient mice.

During an immune response naive T helper (Th) cells differentiate into two functionally distinct subsets, Th1 and Th2, based on their cytokine secretion profile and immunomodulatory function. c-Jun amino terminal kinase (JNK) regulates Th cell differentiation by activating a transcriptional program required for cytokine production. We have recently identified a TNFR superfamily death domain-containing molecule, death receptor (DR)6, which potently activates JNK. T cells from DR6-deficient mice are substantially impaired in JNK activation. When DR6(-/-) mice were challenged with protein antigen, their T cells hyperproliferate and display a profound polarization toward a Th2 response whereas Th1 differentiation is not equivalently affected. In addition, DR6(-/)- T cells showed preference toward Th2 differentiation in vitro. The phenotype seen in the DR6(-/)- mice is not due to the apoptotic pathway. Therefore, DR6, working through JNK, rather than apoptosis, functions to attenuate the Th2 response. This is the first demonstration of a role in the activation and differentiation of Th cells by DR6 in particular and DRs in general.

Amino Acid Sequence↗

PubMed2001

Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency.

BLyS (also called BAFF, TALL-1, THANK, and zTNF4), a TNF superfamily member, binds two receptors, TACI and BCMA, and regulates humoral immune responses [1-7]. These two receptors also bind APRIL [7-10], another TNF superfamily member. The results from TACI(-/-) and BCMA(-/-) mice suggest the existence of additional receptor(s) for BLyS. The TACI knockout gives the paradoxical result of B cells being hyperresponsive, suggesting an inhibitory role for this receptor [11, 12], while BCMA null mice have no discernable phenotype [13]. Here we report the identification of a third BLyS receptor (BR3; BLyS receptor 3). This receptor is unique in that, in contrast to TACI and BCMA, BR3 only binds BLyS. Treatment of antigen-challenged mice with BR3-Fc inhibited antibody production, indicating an essential role for BLyS, but not APRIL, in this response. A critical role for BR3 in B cell ontogeny is underscored by our data showing that the BR3 gene had been inactivated by a discrete, approximately 4.7 kb gene insertion event that disrupted the 3' end of the BR3 gene in A/WySnJ mice, which lack peripheral B cells.

Amino Acid Sequence↗

PubMed2001

Cobalt chloride induces PC12 cells apoptosis through reactive oxygen species and accompanied by AP-1 activation.

Reactive oxygen species (ROS) are supposed to play an important role in hypoxia- and ischemia/reperfusion-mediated neuronal injury with the characteristics of apoptosis. There are many reports showing that cobalt chloride (CoCl(2)) could mimic the hypoxic responses in some aspects including production of ROS in cultured cells. The cytotoxicity of CoCl(2) and its molecular mechanisms have yet to be elucidated. We report that CoCl(2) triggered neuronal PC12 cells apoptosis in a dose- and time-dependent manner. Apoptosis was demonstrated by morphological changes and DNA fragmentation, and was dependent on macromolecular synthesis. Apoptosis was also confirmed by the decrease of the expression of Bcl-X(L). To our knowledge, this is the first documentation of the apoptotic induction of CoCl(2) on PC12 cells. Furthermore, ROS production in PC12 cells was increased during CoCl(2) treatment. Antioxidants, which could inhibit ROS production, significantly blocked CoCl(2)-induced apoptosis, suggesting that apoptosis is mediated by ROS production. We also observed a significant increase of the DNA-binding activity of AP-1 in response to CoCl(2) and this increase was blocked by antioxidants, showing that CoCl(2)-induced apoptosis is accompanied by ROS-activated AP-1. CoCl(2)-treated PC12 cells may serve as an in vitro model for studies of molecular mechanisms in ROS-linked neuronal disorders.

Animals↗

PubMed2001

Proliferation index is related to patient age in glioblastoma.

Younger patients with glioblastomas have a significantly better prognosis than do older patients. To determine whether patient age might be related to proliferation of glioblastoma cells, glioblastomas from patients of different ages were stained with the Molecular Immunology Borstel number 1 antibody to detect proliferating cells. Younger patient age was a significant predictor of a low Molecular Immunology Borstel number 1 proliferation index (p = 0.0001). This previously unreported association favors an intrinsic difference in the type of glioblastomas that afflict younger patients.

Adolescent↗

PubMed2001

Retinoic acid administration is associated with changes in the extracellular matrix and cardiac mesenchyme within the endocardial cushion.

Retinoic acid has been associated with a number of cardiac defects, some of which seem to be related to changes in the endocardial cushions. Studies in mice and older chick embryos have suggested that these defects may be associated with a decrease in mesenchymal cell formation within the cushion. In a previous report we showed that retinoic acid lowered the number of mesenchymal cells in a culture bioassay of mesenchyme formation and that this response was due to retinoic acid modifying the production of particulate matrix from the myocardium. In this study, we have extended these observations to the embryo by implanting a retinoic acid coated bead into the embryo and examined the effect on cardiac mesenchyme formation and in the production of the particulate matrix. In all cases the addition of retinoic acid resulted in a decrease in the number of mesenchymal cells invading the endocardial cushions. In addition retinoic acid increased the production of hLAMP-1 and fibronectin but not transferrin, confirming our earlier report. Finally, we measured the volume of the cushion and calculated the cell density of both the inferior and superior cushions. The results suggest that the superior cushion is more sensitive to retinoic acid treatment than the inferior cushion. Collectively, these results support our earlier work that suggests that the mechanism of retinoic acid cardiac abnormalities involves a disruption in the production of particulate matrix from the myocardium and a subsequent decrease in cardiac mesenchyme cells that results in a malformed cardiac cushions.

Abnormalities, Drug-Induced↗

PubMed2001

Alpha1A- and alpha1B-adrenoceptors are the major subtypes in human saphenous vein.

In this study we analyzed the different alpha1-adrenoceptor (AR) subtypes present in human saphenous vein (HSV) using reverse transcription polymerase chain reaction (RT-PCR), DNA-DNA hybridization analysis and functional affinities for alpha-AR antagonists. DNA-DNA hybridization analysis of RT-PCR amplification products confirmed the presence of alpha1A- and alpha1B-ARs, and low levels of alpha1D-AR in HSV. The functional results showed: (1) prazosin, the selective alpha1-AR antagonist, phentolamine, the alpha1- and alpha2-ARs antagonist, WB 4101 and 5-MU, the selective alpha1A-AR subtype antagonists were potent, competitive antagonists of noradrenaline (NA)-induced contraction (pA2 values of 11.03, 8.06, 9.02 and 8.34, respectively). (2) Alpha1-AR-induced contraction was sensitive to the alkylating effects of CEC (the alpha1B and alpha1D-AR subtypes antagonist) and (3) The selective alpha1D-AR subtype antagonist BMY displayed low affinity (pA2 values of 6.44). This indicates that the contractile response of the HSV to alpha1-AR-induced is predominantly mediated by both alpha1A and alpha1B-AR subtypes. This was also supported by the good relationship between pA2 values from the present study and reported binding affinities (pKi) values of various alpha1-AR subtype antagonists with cloned human alpha1A- and alpha1B-AR subtypes (r=0.89 and r=0.98, respectively), but not the alpha1D-AR subtype (r=0.67). Our results indicate that alpha1A- and alpha1B-ARs are the main functional and expressed receptor subtypes in HSV.

Adrenergic alpha-Antagonists↗

PubMed2001

Kinetic modeling of relaxation phenomena after photodetachment in a rf electronegative SiH4 discharge.

The global relaxation process after pulsed laser induced photodetachment in a rf electronegative SiH4 discharge is studied by a self-consistent kinetic one-dimensional particle-in-cell-Monte Carlo model. Our results reveal a comprehensive physical picture of the relaxation process, including the main plasma variables, after a perturbation up to the full recovery of the steady state. A strong influence of the photodetachment on the discharge is found, which results from an increase of the electron density, leading to a weaker bulk field, and hence to a drop in the high energy tail of the electron energy distribution function (EEDF), a reduction of the reaction rates of electron impact attachment and ionization, and a subsequent decrease of the positive and negative ion densities. All the plasma quantities related to electrons recover synchronously. The recovery time of the ion densities is about 1-2 orders of magnitude longer than that of the electrons due to different recovery mechanisms. The modeled behavior of all the charged particles agrees very well with experimental results from the literature. In addition, our work clarifies some unclear processes assumed in the literature, such as the relaxation of the EEDF, the evolution of the electric field, and the recovery of negative ions.

Journal Article↗

PubMed2001

TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice.

Interactions of the tumor necrosis factor superfamily members B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) with their receptors-transmembrane activator and CAML interactor (TACI) and B cell maturation molecule (BCMA)-on B cells play an important role in the humoral immune response. Whereas BCMA is restricted to B cells, TACI is also expressed on activated T cells; we show here that TACI-Fc blocks the activation of T cells in vitro and inhibits antigen-specific T cell activation and priming in vivo. In a mouse model for rheumatoid arthritis (RA), an autoimmune disease that involves both B and T cell components, TACI-Fc treatment substantially inhibited inflammation, bone and cartilage destruction and disease development. Thus, BLyS and/or APRIL are important not only for B cell function but for T cell-mediated immune responses. Inhibition of these ligands might have therapeutic benefits for autoimmune diseases, such as RA, that involve both B and T cells.

Animals↗

PubMed2001

Activation and accumulation of B cells in TACI-deficient mice.

The tumor necrosis factor (TNF)-related ligand B lymphocyte stimulator (BLyS) binds two TNF receptor family members, transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI) and B cell maturation molecule (BCMA). Mice that are transgenic for BLyS show B cell accumulation, activation and autoimmune lupus-like nephritis. The existence of at least two distinct BLyS receptors raises the question of the relative contribution of each to B cell functions. We therefore generated mice that were deficient in TACI. TACI-/- mice showed increased B cell accumulation and marked splenomegaly. Isolated TACI-/- B cells hyperproliferated and produced increased amounts of immunoglobulins in vitro. In vivo antigen challenge resulted in enhanced antigen-specific antibody production. Thus, TACI may play an unexpected inhibitory role in B cell activation that helps maintain immunological homeostasis.

Animals↗

PubMed2001

A linear-time algorithm for computing inversion distance between signed permutations with an experimental study.

Hannenhalli and Pevzner gave the first polynomial-time algorithm for computing the inversion distance between two signed permutations, as part of the larger task of determining the shortest sequence of inversions needed to transform one permutation into the other. Their algorithm (restricted to distance calculation) proceeds in two stages: in the first stage, the overlap graph induced by the permutation is decomposed into connected components; then, in the second stage, certain graph structures (hurdles and others) are identified. Berman and Hannenhalli avoided the explicit computation of the overlap graph and gave an O(nalpha(n)) algorithm, based on a Union-Find structure, to find its connected components, where alpha is the inverse Ackerman function. Since for all practical purposes alpha(n) is a constant no larger than four, this algorithm has been the fastest practical algorithm to date. In this paper, we present a new linear-time algorithm for computing the connected components, which is more efficient than that of Berman and Hannenhalli in both theory and practice. Our algorithm uses only a stack and is very easy to implement. We give the results of computational experiments over a large range of permutation pairs produced through simulated evolution; our experiments show a speed-up by a factor of 2 to 5 in the computation of the connected components and by a factor of 1.3 to 2 in the overall distance computation.

Algorithms↗

PubMed2001

The ataxia-telangiectasia gene product may modulate DNA turnover and control cell fate by regulating cellular redox in lymphocytes.

The ATM kinase, when activated postnatally, exerts multiple functions to prevent the onset of ataxia-telangiectasia (AT). Using freshly isolated thymocytes from Atm-/- mice that were under stress during postnatal differentiation, we noted that thiol redox activity, as indicated by reduction of the tetrazolium MTS, and DNA turnover activity, as indicated by incorporation of [(3)H]thymidine into DNA, were both greatly increased compared with activities in thymocytes from Atm+/+ mice. This increased thymidine incorporation could be suppressed by the thiol N-acetylcysteine. In primary noncycling splenocytes, mitogens proportionally increased both the rate of [(3)H]thymidine incorporation and the rate of reduction of MTS. The mitogen-induced activities in splenocytes were not affected by ATM but were suppressed by the calcineurin-dependent inhibitor FK-506, which has no effect on these activities in thymocytes. These findings suggest that increased [(3)H]thymidine incorporation and reducing power indicate increased cell cycling in mitogenically stimulated splenocytes, whereas these two indicators represent increased FK-506-independent DNA turnover activities in thymocytes. Thus, a primary function of ATM is to activate the redox-sensitive checkpoint required for down-regulation of DNA turnover activities in developing lymphocytes. Cell-cycling checkpoints in undamaged quiescent lymphocytes are not activated by ATM with mitogenic stimulation. ATM may suppress abnormal DNA turnover and the resultant oncogenesis by regulating cellular thiol redox pathways.

Acetylcysteine↗

PubMed2001

A new implementation and detailed study of breakpoint analysis.

Phylogenies derived from gene order data may prove crucial in answering some fundamental open questions in biomolecular evolution. Yet very few techniques are available for such phylogenetic reconstructions. One method is breakpoint analysis, developed by Blanchette and Sankoff for solving the "breakpoint phylogeny." Our earlier studies confirmed the usefulness of this approach, but also found that BPAnalysis, the implementation developed by Sankoff and Blanchette, was too slow to use on all but very small datasets. We report here on a reimplementation of BPAnalysis using the principles of algorithmic engineering. Our faster (by 2 to 3 orders of magnitude) and flexible implementation allowed us to conduct studies on the characteristics of breakpoint analysis, in terms of running time, quality, and robustness, as well as to analyze datasets that had so far been considered out of reach. We report on these findings and also discuss future directions for our new implementation.

Algorithms↗

PubMed2001

Effects of micromolar concentrations of manganese, copper, and zinc on alpha1-adrenoceptor-mediating contraction in rat aorta.

To determine the influences of the Mn, Cu, and Zn on alpha1-adrenoceptor (AR)-mediated vasoconstriction, we investigated their effects on vasoconstriction produced by the alpha1-AR agonist phenylephrine in isolated rings of rat thoracic aorta. The cumulative concentration-contraction curves for phenylephrine were obtained in the absence and presence of Mn (0.3, 1, 3 microM), Cu (1, 10, 16 microM), and Zn (0.3, 1, 10 microM). Mn, Cu, and Zn each inhibited phenylephrine-mediated contraction in a dose-dependent manner. The maximal phenylephrine-induced contraction was significantly reduced by the pretreatment of the arterial rings with 10 and 16 microM Cu (p<0.05). The results suggest that variations in the plasma concentrations of metal might lead to changes in alpha1-AR-mediated constrictive response.

Adrenergic alpha-1 Receptor Agonists↗

PubMed2001

[Studies on inhibiting activities of five antitumour drugs to human cancer cell in vitro with MTT assay].

The inhibiting activities of five antitumour drugs including "An ke su" to human cancer cell lines coming from 19 patients were measured in vitro with MTT assay, which can provide proper antitumor agents for clinical chemotherapy. The evaluation rate of medicine sensitivity is 89.47%, which is same as the result of clinical therapy. This method indicates the response of tumour cells to "An Ke Su" and other agents. Being simple, sensitive and rapid, it proves to be valuable in clinical therapy.

Antineoplastic Agents↗

PubMed2001

[Effects of different varieties and sowing dates on development stages of wheat].

The effects of different sowing dates and varieties on development stages of wheat were studied in this paper. The results showed that the emergence of tiller was mainly regulated by the ecological factors rather than the genetic effect. For winter-type variety(Jing 411), most variable growth duration throughout the entire growth cycle occurred from tillering to jointing. In contrast, the timing of single ridge stage was determined by genotypic effect rather than ecological factors. Single ridge to double ridge stage was most sensitive to vernalization progress. For spring sowing of winter-type variety, the vernalization process could last till floral primordium differentiation stage. The corresponding relationships existed between phenological and spike development stages in different sowing dates, although a little variable. Winter-type variety had more ecologically variable leaf primoudia, due to its stronger vernalization requirement. For winter-type variety, the primordium numbers of reproductive organs were not apparently related to the GDD accumulated prior to vernalization completion, while for spring-type variety(Yangmai 158), the numbers of different apex primordia including vegetative and reproductive organs were significantly related to the accumulated GDD during the entire phenological stages as well as before anther separation stage.

Triticum↗

PubMed2001

[Different serum lipid adjustment drugs for the treatment of hyperlipidemic fatty liver].

OBJECTIVE: To research the effect of different serum lipid adjustment drugs, Simvastatin and Fenofibrate, on hyperlipidemic fatty liver. METHODS: The rat models of hyperlipidemic fatty liver induced by high fat diet were treated with Fenofibrate and Simvastatin respectively to investigate the change of the liver index, liver function, the serum and liver lipid, MDA, and pathologic histology. RESULTS: The liver index and the content of triglyceride (TC1.80 +/-0.20/2.10+/-0.33), total cholesterol (TG 0.76+/-0.18/1.09+/-0.31), MDA both in the serum and the liver in the model group were significantly higher than those in control group. Slight or moderate hepatic steatosis was observed in model group. Fenofibrate decreased serum triglyceride, total cholesterol, and MDA both in serum and liver significantly, but increased the ALT, ALP, liver index, liver lipids, and finally leading to severe hepatic steatosis. Simvastatin lowered the level of lipid and MDA both in serum and liver, and liver histology was improved nearly to normal. Moreover, little side effect on the liver was observed. CONCLUSIONS: Simvastatin can be applied for prevention and treatment of hyperlipidemic fatty liver safely and effectively, while Fenofibrate can not.

Animals↗