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Biomedical subjects

X G Zheng

Publications and source records attributed to X G Zheng.

At least 19 recordsLinked to original sources
PubMed2005

Coexistence of long-range order and spin fluctuation in geometrically frustrated clinoatacamite Cu2Cl(OH)3.

Muon spin rotation experiments are carried out on clinoatacamite, Cu2Cl(OH)3, which is a new geometrically frustrated system featuring a three-dimensional network of corner-sharing tetrahedral 3d Cu2+ spins. A long-range antiferromagnetic order occurs below 18.1 K with a surprisingly small entropy release of about 0.05Rln2/Cu. Below 6.5 K, the static long-range order transforms abruptly into a metastable state with nearly complete depolarization of muon spins which suggests strong fluctuation. The system then enters a state in which partial long-range order and spin fluctuation coexist down to the lowest experimentally attainable temperature of 20 mK. This work presents a novel system for studying geometric frustration.

Journal Article↗
PubMed2004

Novelty-seeking behavior and stress-induced locomotion in rats of juvenile period differentially related to morphine place conditioning in their adulthood.

The relationship between motor responses in a novel environment and susceptibility to place conditioning effect of psychostimulants has been reported in adult rats. However, it is in question whether this correlation could be generalized to motor activity in rats of juvenile period and place conditioning effect in their adulthood for narcotic morphine. In the present study, we tested locomotor activity in an arena open-field and the subsequent novelty-seeking behavior after adaptation process in juvenile rats (P42) and morphine (2 mg/kg) place conditioning effect 56 days later in the same rats' adulthood (P98). Our results showed that rats with high response to novelty (HRN) spent more prolonged duration in the drug-paired compartment in the place conditioning test compared with their low response counterparts (LRN), with the latter group no salient change on this measure. Moreover, rats with high response to the open-field test (HRS) expressed equally elevated duration in drug-paired side relative to their low response counterparts (LRS). The present research demonstrated that novelty-seeking behavior and locomotor activity in the open-field in rats of juvenile period differentially related to morphine place conditioning in their adulthood, with slow acquisition of morphine place conditioning effect in LRN animals.

Age Factors↗
PubMed2003

Effects of polarization on laser holography for microstructure fabrication.

We perform a kind of computer stimulation on the multi-laser-beam interference. Using this method, we picture the interference patterns and describe the influence of the polarization of lights upon the clarity of the pattern. We find out the relations between the polarization states of the lights for the case of the best pattern and provide an optimal solution of the polarization on holographic lithography technology, and experiential formulas. This kind of analysis will improve the fabrication of submicrometer periodic structure efficiently.

Journal Article↗
PubMed2000

Naphthazarin derivatives (V): formation of glutathione conjugate and cytotoxic activity of 2-or 6-substituted 5,8-dimethoxy-1,4-napthoquinones in the presence of glutathione-S-transferase, in rat liver S-9 fraction and mouse liver perfusate.

Formation of glutathione (GSH) conjugates with 2- or 6-(1-hydroxymethyl)- and 2-(1-hydroxyethyl)-DMNQ derivatives (DMNQ, 5,8-dimethoxy-1,4-naphthoquone) was carried out in phosphate buffer (pH 7.4), in the presence of glutathione-S-transferase (GST), in rat liver S-9 fraction and by perfusion, and the rates of conjugates formation were compared and correlated to cytotoxicity. The GSH conjugates of 6-(1-hydroxyalkyl)-DMNQ derivatives were formed faster than 2-(1-hydroxyalkyl)-DMNQ derivatives under all of the media, implying that steric hindrance was the cause of lowering the rate of conjugate formation of 2-substituted derivatives. For both isomers, addition of GST did not improve the reaction rate, compared with that in buffer, while the reaction in the S-9 fraction and the perfusate was accelerated to a great extent. The catalytic effect of the S-9 fraction and the perfusion on 2-isomers was greater than on 6-substituted ones, suggesting that S-9 fraction and the perfusate contain an effective system relaxing the steric hindrance of 2-(1-hydroxyalkyl)-DMNQ derivatives. Furthermore, a good correlation between the formation of the GSH conjugates and the cytotoxic activity of both naphthazarin isomers suggests that the steric hindrance is a cause of lowering the cytotoxicity of 2-isomers.

Animals↗
PubMed2000

Naphthazarin derivatives (IV): synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2- or 6-acyl-5,8-dimethoxy-1, 4-naphthoquinones.

Some 2- or 6-acyl-5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives were synthesized and evaluated for inhibition of DNA topoisomerase I and cytotoxicity against L1210 cells. Compared with 2-acyl-DMNQ derivatives, 6-acyl-DMNQ compounds, bearing a higher electrophilic quinone moiety, showed a higher potency in the inhibition of DNA topoisomerase I and the cytotoxicity, implying the possible participation of electrophilic arylation in their bioactivities. Time and temperature dependence of the enzyme inhibition suggests that the arylation occurs irreversibly. Among the 6-acyl-DMNQ derivatives, the ones possessing an acyl group of an intermediate size (C(5)-C(9)) showed higher potency in their bioactivities than other derivatives. Furthermore, for the effective inhibition of DNA topoisomerase I, the size of acyl moiety of 6-acylated derivatives seems to be limited to < 12 carbon atoms.

Animals↗
PubMed1999

Naphthazarin derivatives (II): formation of glutathione conjugate, inhibition of DNA topoisomerase-I and cytotoxicity.

6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones, expressing a higher reactivity in conjugation with glutathione, showed a greater potency in the inhibition of DNA topoisomerase-I and the cytotoxicity against L1210 cells than 2-(1-hydroxyalkyl)-DMNQ derivatives, implying the participation of electrophilic arylation in the bioactivities. In further study 6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones with an alkyl group of shorter chain length (C2-C6) exerted a greater bioactivities than those with longer chain length(>C6).

Animals↗
PubMed1999

The role of CD80, CD86, and CTLA4 in alloimmune responses and the induction of long-term allograft survival.

Blocking the interaction of the CD28 costimulatory receptor with its ligands, CD80 and CD86, inhibits in vivo immune responses, such as allograft rejection, and in some instances induces tolerance. Previously, we found that CTLA4Ig, which blocks the CD28/CTLA-4 (CD152) ligands CD80 and CD86, can be used to induce transplantation tolerance to vascularized allografts. Recent data suggest that an intact CD152-negative signaling pathway is essential for induction of tolerance to nominal Ags. Here, we show that blockade of CD152 using an anti-CD152 mAb at the time of transplantation prevents the induction of long-term allograft survival by agents that target CD80 and CD86. In contrast, CD152 signals are not required for the maintenance of established graft survival. We also report for the first time that blockade of CD86 alone can induce long-term graft survival. This requires that anti-CD86 mAb is given on the day of transplantation and also depends upon an intact CD152 pathway. This result, plus experiments using CD80-deficient mice, suggests a dominant role for CD80 molecules on donor cells as the relevant ligand for CD152. We additionally find that blockade of CD152 at the time of transplantation does not interfere with the effectiveness of anti-CD154 mAbs, suggesting distinct mechanisms for inhibition of graft rejection by blocking the CD28 vs CD154 pathways.

Abatacept↗
PubMed1999

Glutathione conjugates of 2- or 6-substituted 5,8-dimethoxy-1,4-naphthoquinone derivatives: formation and structure.

Thirty-four glutathione conjugates of 5,8-dimethoxy-1,4-naphthoquinones (DMNQ) were synthesized and their structure was determined. The yield of GSH conjugate was dependent on size of alkyl group; the longer the size of alkyl group was, the lower was the yield. It was also found that the length of alkyl side chain influenced the chemical shift of quinonoid protons; the quinonoid protons of 2-glutathionyl DMNQ derivatives with R=H to propyl, 6.51-6.59 ppm vs. other ones with R=butyl to heptyl, 6.64-6.68 ppm. This was explained to be due to a folding effect of longer alkyl group. Glutathione (GSH) reacted with DMNQ derivative first to form a 1,4-adduct (2- or 3-glutathionyl-1,4-dihydroxy-5,8-dimethoxynaphthalenes) and then, the adduct was autooxidized to 2- or 3-glutathionyl-DMNQ derivatives. Moreover, GSH reduced DMNQ derivatives to their hydrogenated products. It was suggested that such an organic reaction might play an important role for a study of metabolism or toxicity of DMNQ derivatives in the living cells.

Chromatography, Thin Layer↗
PubMed1999

Stable restoration of the sarcoglycan complex in dystrophic muscle perfused with histamine and a recombinant adeno-associated viral vector.

Limb-girdle muscular dystrophies 2C-F represent a family of autosomal recessive diseases caused by defects in sarcoglycan genes. The cardiomyopathic hamster is a naturally occurring model for limb-girdle muscular dystrophy caused by a primary deficiency in delta-sarcoglycan. We show here that acute sarcolemmal disruption occurs in this animal model during forceful muscle contraction. A recombinant adeno-associated virus vector encoding human delta-sarcoglycan conferred efficient and stable genetic reconstitution in the adult cardiomyopathic hamster when injected directly into muscle. A quantitative assay demonstrated that vector-transduced muscle fibers are stably protected from sarcolemmal disruption; there was no associated inflammation or immunologic response to the vector-encoded protein. Efficient gene transduction with rescue of the sarcoglycan complex in muscle fibers of the distal hindlimb was also obtained after infusion of recombinant adeno-associated virus into the femoral artery in conjunction with histamine-induced endothelial permeabilization. This study provides a strong rationale for the development of gene therapy for limb-girdle muscular dystrophy.

Animals↗
PubMed1998

2-(1-Oxyalkyl)-1,4-dioxy-9,10-anthraquinones: synthesis and evaluation of antitumor activity.

Fourty eight derivatives of 2-(1-oxyalkyl)-1,4-dioxy-9,10-anthraquinone were synthesized, and their antitumor activity was evaluated. On the whole, 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones (DHAQ = 1,4-dihydroxy-9,10-anthraquinone) showed stronger cytotoxic activity against L1210 cells than 2-(1-hydroxyalkyl)-1,4-dimethoxy-9,10-anthraquinones(DMAQ = 1,4-dimethoxy-9,10-anthraquinone), implying that free hydroxy groups at C-1 and C-4 of the anthraquinone structure are necessary for the cytotoxic activity. The bioactivity of 2-(1-hydroxyalkyl)-DHAQ derivatives differed according to the size of alkyl group at C-1; while the elongation of alkyl group over 7 carbon atoms failed to enhance the bioactivity, the derivatives possessing alkyl moiety of 1-6 carbon atoms showed an increase in the cytotoxicity and the antitumor activity in Sarcoma-180; 2-hydroxymethyl-DHAQ (ED50, 15 micrograms/ml; T/C, 125%), 2-(1-hydroxyethyl)-DHAQ(1.9 micrograms/ml; 139.2%), 2-(1-hydroxypropyl)-DHAQ (7.2 micrograms/ml; 135.1%), 2-(1-hydroxybutyl)-DHAQ (10.2 micrograms/ml; 125.3%), 2-(1-hydroxypentyl)-DHAQ (23.7 micrograms/ml; 110.1%), and 2-(1-hydroxyhexyl)-DHAQ (58 micrograms/ml; 108%). Next, 2-(1-Hydroxyalkyl)-DHAQ derivatives were acetylated to produce 2-(1-acetoxyalkyl)-DHAQ analogues. Although the acetylation somewhat enhanced the cytotoxicity, but not the antitumor action. In addition, the presence of phenyl group at C-1' enhanced the cytotoxicity and the T/C value, compared to alkyl groups of same size; 2-(1-hydroxy-1-phenyl)-DHAQ (ED50, 5.6 micrograms/ml; T/C, 137%).

Acetylation↗
PubMed1998

Naphthazarin derivatives: synthesis, cytotoxic mechanism and evaluation of antitumor activity.

The rate of the GSH conjugate formation, the inhibition of DNA topoisomerase-I and the cytotoxic activity against L1210 cells of the naphthoquinones showed the same order; 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) > 6-(1-hydroxyethyl)-DMNQ > 2-(1-hydroxyethyl)-DMNQ; the steric hindrance of the substituents, particularly 2-substutuent, in reacting with cellular nucleophiles must be the main cause for lowering the bioactivities. Acetylation of 2-(1-hydroxyethyl)-DMNQ producing 2-(acetyloxyethyl)-DMNQ potentiated the bioactivities; 2-(1-hydroxyethyl)-DMNQ did not react with GSH and the enzyme, and showed ED50 of 0.680 microgram/ml, whereas the values of 2-(1-acetyloxyethyl)-DMNQ were the conjugate formation of 0.14 microM, IC50 value of 81 microM for the enzyme inhibition and ED50 of 0.146 microgram/ml for the cytotoxcity. Furthermore, the acetylation 2-(1-hydroxyethyl)-DMNQ (T/C, 119%) enhanced the T/C values for the mice bearing S-180 tumor [T/C of 2-(1-acetyloxyethyl)-DMNQ, 276%]. It was assumed that the difference in bioactivities ensued by acetylation was based on the mechanism of the so-called bioreductive alkylation.

Acetylation↗
PubMed1997

Donor antigen is necessary for the prevention of chronic rejection in CTLA4Ig-treated murine cardiac allograft recipients.

BACKGROUND: Optimal activation of T cells requires two signals: antigen engagement through the T cell receptor and a costimulatory signal. Previous studies have shown that blockade of the CD28:B7 costimulatory pathway using the soluble fusion protein CTLA4Ig can prevent acute rejection of organ and tissue allografts; however, long-term engraftment has not been seen universally. This study was undertaken to define the role of donor antigen in inducing long-term allograft survival in CTLA4Ig-treated recipients. METHODS: A murine cardiac allograft model was employed using BALB/c donors and C57BL/6 recipients. Additional donor antigen in the form of donor splenocytes was given at the time of transplantation. Recipients were treated with a single dose of CTLA4Ig 2 days after transplantation. RESULTS: We find that a single dose of CTLA4Ig prolongs cardiac allograft survival, but permanent engraftment is not observed unless the recipients receive an injection of donor-type splenocytes. Treatment of the donor cells with CTLA4Ig does not by itself prolong allograft survival, which indicates the need for systemic treatment of the recipient. Allografts from animals not receiving donor cells show classic histologic changes of chronic rejection, and most cease function from 1 to 4 months after transplantation. Lethal irradiation of the donor cells does not appreciably affect their ability to prevent late allograft loss. CONCLUSIONS: Donor cells are required to synergize with CTLA4Ig and prevent late cardiac allograft loss in the murine system. The fact that pretreatment of the donor cells alone is not effective suggests a role for antigen presentation by recipient antigen-presenting cells in the initiation of rejection. As lethal irradiation of the donor cells does not affect their ability to promote long-term engraftment, our data suggest that long-term microchimerism is not required to prevent chronic rejection in this model.

Abatacept↗
PubMed1997

The role of donor and recipient B7-1 (CD80) in allograft rejection.

Blockade of CD28-mediated T cell costimulatory signals produces effective immunosuppression of a variety of T cell-dependent in vivo immune responses, including autoimmune disorders and transplant rejection. The soluble fusion protein CTLA4Ig, which competitively blocks CD28 ligands B7-1 and B7-2, can prevent allograft and xenograft rejection and in some circumstances induce transplantation tolerance. To determine the relative roles of B7-1 and B7-2 in graft rejection, we have performed islet and cardiac allografts with normal and B7-1(-/-) mice in conjunction with selective blocking reagents. We found that the absence of B7-1 on donor or recipient tissues leads to a slight prolongation of islet allograft survival, but has minimal or no effect on cardiac allograft survival. Allograft function is further prolonged in the islet model when both donor and recipient lack B7-1, although cardiac allograft survival is not prolonged. In the cardiac model, treatment with CTLA4Ig induces long term survival in B7-1(-/-) recipients regardless of donor status. In contrast, anti-B7-2 mAb leads to indefinite allograft survival only when the recipient and donor both lack B7-1, indicating that even in the absence of available B7-2, B7-1 molecules on the donor or recipient cells alone are sufficient to induce graft rejection. These data also indicate that B7-1 and B7-2 are the only CD28 ligands relevant to cardiac allograft rejection in mice.

Animals↗
PubMed1996

Costimulatory function and expression of CD40 ligand, CD80, and CD86 in vascularized murine cardiac allograft rejection.

Recent data implicates a role for the CD40-CD40 ligand (CD40L) pathway in graft rejection. One potential mechanism is direct costimulation of T cells through CD40L. Alternatively, the ability of CD40 stimulation to induce CD80 (B7-1) and CD86 (B7-2) expression on antigen-presenting cells (APCs) has led to the hypothesis that the role of CD40-CD40L interactions in transplant rejection might be indirect, i.e., to promote the costimulatory capacity of APCs. Here, we have used a murine vascularized cardiac allograft model to test this hypothesis. Treatment of the recipients with donor splenocytes and a single dose of anti-CD40L mAb induces long-term graft survival (> 100 days) in all animals. This is associated with marked inhibition of intragraft Th1 cytokine [interferon gamma and interleukin (IL) 2] and IL-12 expression with reciprocal up-regulation of Th2 cytokines (IL-4 and IL-10). In untreated allograft recipients, CD86 is strongly expressed on endothelial cells and infiltrating mononuclear cells of the graft within 24 hr. In contrast, CD80 expression is not seen until 72 hr after engraftment. Anti-CD40L mAb has no detectable effect on CD86 up-regulation, but almost completely abolishes induction of CD80. However, animals treated with anti-CD80 mAb or with a mutated form of CTLA4Ig (which does not bind to CD86) rejected their cardiac allografts, indicating that blockade of CD80 alone does not mediate the graft-prolonging effects of anti-CD40L mAb. These data support the notion that the role of CD40-CD40L in transplant rejection is not solely to promote CD80 or CD86 expression, but rather that this pathway can directly and independently costimulate T cells. These data also suggest that long-term graft survival can be achieved without blockade of either T cell receptor-mediated signals or CD28-CD86 engagement.

Animals↗
PubMed1994

T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28.

The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7-1 and B7-2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7-1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7-1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7-1, or vector-only transfected CHO cells. These procedures confirmed that a B7-1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7-1 expression on lymphocytes, B7-3, as defined by anti-BB-1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7-1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.

Animals↗
PubMed1994

T cell receptor stimulation, but not CD28 costimulation, is dependent on LFA-1-mediated events.

Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge. In this manuscript we specifically examine the role of two accessory molecules, CD28 and LFA-1, in modulating the T cell proliferative response to a variety of stimuli. We demonstrate that the proliferation induced by staphylococcal enterotoxins A and B in combination with CD28 costimulation is dependent on LFA-1-mediated events. This requirement for LFA-1 is independent of T cell-accessory cell adhesion. Similarly, an allogeneic mixed lymphocyte reaction, which has previously been shown to be a CD28-dependent response, can be inhibited by blockade of LFA-1. This suggests LFA-1 plays an essential role in these responses, either by enhancing intercellular adhesion or by an independent signal transduction event. In contrast, when the primary activating stimulus is delivered by immobilized anti-CD3 antibody or by PMA, and the secondary stimulus by either alpha-CD28 or cell-bound CD28 ligand B7, there is no requirement for LFA-1. In addition, we demonstrate that cross-linking of LFA-1 with immobilized monoclonal antibody, or engagement of LFA-1 with ICAM-1 expressed on the surface of a CHO cell, provide an insufficient costimulus for T cell proliferation initiated by enterotoxin, immobilized alpha-CD3 or phorbol ester. Our data suggests that LFA-1, in contrast to CD28, functions not as a costimulatory molecule, but serves primarily to modulate the signal delivered through the T cell receptor.

Animals↗
PubMed1994

[Comparison of the ultrastructural and clinical studies on myocardium in patients with congenital heart disease].

Right ventricle myocardium of 25 cases of tetralogy of Fallot and 11 cases of ventricle septal defect were studied by both light and electron microscopy. Normal human myocardium from 4 cases were used as the control. The resulting data indicate that the mean muscle diameter correlated significantly with the course of disease, mean pressure of right ventricle and diameter of ventricle septal defect. In 6 cases with congenital heart disease, the myocardium was atrophic and presented with 2 types of ultrastructural features: accumulation of Z-line material or hyperplasia of the mitochondria. The significance of these ultrastructural findings in congenital heart disease is discussed.

Heart Septal Defects, Ventricular↗