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Biomedical subjects

H B Wang

Publications and source records attributed to H B Wang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor.

Dynamic changes in chromatin structure play an important role in transcription regulation. Recent studies have revealed two mechanisms that alter chromatin structure. One involves ATP-dependent chromatin remodeling, and the other involves acetylation of the core histone tails. We have previously purified and characterized a multi-subunit protein complex, NuRD, which possesses both nucleosome remodeling and histone deacetylase activities. Despite extensive biochemical characterization of the complex, little is known about the functions of its individual components. In this study, we focused on Mi2, a component of the NuRD complex. We found that, similar to the native NuRD complex, recombinant Mi2 is a DNA-dependent, nucleosome-stimulated ATPase. Kinetic analysis of the ATP hydrolysis reaction indicated that the differential stimulation of the Mi2 ATPase by DNA and nucleosomes were primarily due to their differential effects on the turnover number of the reaction. Furthermore, we demonstrated that recombinant Mi2 is an efficient nucleosome remodeling factor when compared to that of the native NuRD complex. Our results define the biochemical function of Mi2 and set the stage for understanding the mechanism of nucleosome remodeling in a defined reconstituted system.

Adenosine Triphosphatases↗
PubMed2001

Anti-CTLA-4 antibody treatment triggers determinant spreading and enhances murine myasthenia gravis.

CTLA-4 appears to be a negative regulator of T cell activation and is implicated in T cell-mediated autoimmune diseases. Experimental autoimmune myasthenia gravis (EAMG), induced by immunization of C57BL/6 mice with acetylcholine receptor (AChR) in adjuvant, is an autoantibody-mediated disease model for human myasthenia gravis (MG). The production of anti-AChR Abs in MG and EAMG is T cell dependent. In the present study, we demonstrate that anti-CTLA-4 Ab treatment enhances T cell responses to AChR, increases anti-AChR Ab production, and provokes a rapid onset and severe EAMG. To address possible mechanisms underlying the enhanced autoreactive T cell responses after anti-CTLA-4 Ab treatment, mice were immunized with the immunodominant peptide alpha(146-162) representing an extracellular sequence of the ACHR: Anti-CTLA-4 Ab, but not control Ab, treatment subsequent to peptide immunization results in clinical EAMG with diversification of the autoantibody repertoire as well as enhanced T cell proliferation against not only the immunizing alpha(146-162) peptide, but also against other subdominant epitopes. Thus, treatment with anti-CTLA-4 Ab appears to induce determinant spreading, diversify the autoantibody repertoire, and enhance B cell-mediated autoimmune disease in this murine model of MG.

Abatacept↗
PubMed2001

Immunotoxicity of a standardized citrus polymethoxylated flavone extract.

Polymethoxylated flavones (PMFs) from citrus inhibit production of TNF-alpha and other pro-inflammatory cytokines. As TNF-alpha also modulates NK cell activity, the current studies were conducted to assess the potential for a standardized citrus PMF mixture to suppress humoral and innate immune functions. PMFs were isolated from orange peel oil using a procedure that obtained a consistent mixture of PMFs both in identity and proportion. The mixture consisted of nobiletin (30.7%), 3,3',4',5,6,7,8-heptamethoxyflavone (27.9%), trimethylscutellarein (14.5%), tangeretin (10.4%), sinensetin (5.8%), 5-demethyl-nobiletin (2.0%), hexa-O-methylquercetagetin (1.3%), 5-demethyl-tetramethylscutellarein (0.6%), and other flavonoids (2.7%). To assess the effect of the PMF mixture on humoral immune responses, female B(6)C(3)F(1) mice (n=8) were exposed to the PMF by gavage at 5, 50, 150 and 500 mg/kg/day for 28 days. On day 25, mice were sensitized to sRBC by tail vein injection and AFC response determined 4 days later. Humoral immunity was insensitive to suppression following exposure to all concentrations of the PMF mixture. Suppression of NK cell activity was observed only following 500 mg/kg/day for 28 days. Body weights were not affected by exposure to any concentration of the PMF mixture in sRBC immunized or non-immunized mice. However, in sRBC-immunized mice, higher concentrations of PMF were associated with a statistically insignificant increase in spleen weight (P>0.05). No change in spleen weight was observed in non-immunized mice. As anticipated, based on previously published in vitro observations, long-term, high-dose exposure to a standardized mixture of citrus PMFs caused a mild suppression of NK cell activity; however, humoral immunity was not sensitive to suppression at the same exposure levels.

Animals↗
PubMed2001

Biosynthetic pathway to the cancer chemopreventive secoisolariciresinol diglucoside-hydroxymethyl glutaryl ester-linked lignan oligomers in flax (Linum usitatissimum) seed.

Application of stable and radioisotope precursor/tracer experiments resulted in the identification of various phenylpropanoid, monolignol, and lignan metabolites involved in the biosynthesis of the cancer chemopreventive secoisolariciresinol diglucoside (SDG; 1)-containing ester-linked "polymer(s)" in flax (Linum usitatissimum) seed. Individual analysis of size-segregated flax seed capsules at five early stages of their development provided a metabolic profile of intermediates leading to "biopolymer" biosynthesis. The use of (1)H and (13)C NMR and HRMS analyses resulted in the identification of 6a-HMG (hydroxymethyl glutaryl) SDG (17) and 6a,6a'-di-HMG SDG (18) as the two major components of the ester-linked "biopolymer(s)". Based on metabolic tracer analyses and relative radioisotopic incorporations throughout each of these five stages of seed development, a biochemical pathway is proposed from phenylalanine to SDG (1), with subsequent mono- and di-substitutions of SDG (1) with HMG CoA. These metabolites then serve as precursors for formation of the SDG-HMG ester-linked oligomers. Results from this study will facilitate future isolation and characterization of the proteins and enzymes involved in biosynthesis of the SDG-HMG ester-linked oligomers in flax seed.

Benzimidazoles↗
PubMed2001

[Non-linear compression for noises in non-contact vital signs detecting system].

A method for compressing the noises overlapping in the breath and heart signals of human beings, detected by the non-contact vital signs detecting system during the display of the waveforms in time domain, is discussed in this paper in detail. And what's more, the problem that the noise level is changed along with the increase of the gain of AD data-acquisition card and the display--gain of the software is solved by researching into the threshold of noise-level contraction in two types of circumstance in the lab, and the result of the breath and heart signal in the condition of lower noise is realized as well.

Artifacts↗
PubMed2001

[The study on non-contact detection of breathing and heartbeat based on radar principles].

The paper introduces the design of hardware and software of non-contact detection system for breathing and heartbeat in human body with radar principles and technology. The detection technology is discussed. Under conditions of the illuminating power P < 1 mW and the distance S < 10 m, the non-contact breathing and heartbeat measurement, can be in different positions and with different clothing on the subject. The results show that the system with the technology has a high sensitivity, and is harmless to the health. It is a practicable non-contact detection technology for breathing and heartbeat of human body.

Adult↗
PubMed2000

Epidermal growth factor family in rhesus monkey uterus during the menstrual cycle and early pregnancy.

This study examines immunohistochemically the presence of EGF, TGFalpha, HB-EGF, AR, and EGFR, members of the EGF family in the monkey uterus during the menstrual cycle and early pregnancy. EGF, TGFalpha, HB-EGF, AR, and EGFR were mainly localized in glandular and luminal epithelium. TGFalpha, HB-EGF, and AR staining were stronger in the glandular epithelium closer to the myometrium than in that closer to the luminal epithelium. The level of EGF, TGFalpha, HB-EGF, AR, and EGFR staining was low on days 1 and 6, and began to increase on day 9 of the menstrual cycle. A high level of EGF, and EGFR staining was maintained on days 16, 20, and 25 of the menstrual cycle. The highest levels of TGFalpha, AR, and HB-EGF staining were seen on days 16 and 20 of the menstrual cycle. In early pregnancy, a low level of EGF, TGFalpha, HB-EGF, AR, and EGFR staining appeared on days 1 and 2 of pregnancy, and then gradually increased from day 3 of pregnancy. The highest levels of EGF, TGFalpha, HB-EGF, and EGFR were detected on days 9, and 11 of pregnancy. Our data suggest that the EGF family may play a role in monkey implantation. Mol. Reprod. Dev. 55:164-174, 2000.

Amphiregulin↗
PubMed2000

Role for interferon-gamma in rat strains with different susceptibility to experimental autoimmune myasthenia gravis.

Experimental autoimmune myasthenia gravis (EAMG) is caused by autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular postsynaptic membrane and represents an animal model of myasthenia gravis in human. Recent studies highlighted the roles of TH1 cytokines (IFN-gamma, IL-12), rather than TH2 cytokines (IL-4), in the pathogenesis of EAMG by using homozygous (-/-) knockout mice with an EAMG-susceptible genetic background. To further evaluate a role for IFN-gamma, we injected recombinant rat IFN-gamma (rrIFN-gamma) at the time of immunization with AChR in complete Freund's adjuvant to EAMG-susceptible Lewis rats and EAMG-resistant Wistar Furth (WF) rats. RrIFN-gamma enhanced Lewis rat EAMG. The exacerbated muscular weakness was associated with higher levels of anti-AChR IgG and enhanced TNF-alpha responses. Anti-AChR IgG antibody levels were augmented to a similar extent as in Lewis rats, however, the identical immunization and IFN-gamma injection induced only mild and transient EAMG in WF rats due to the default TH3 phenotype development and inherent low TH1 responses. We conclude that IFN-gamma plays a major role in the pathogenesis of EAMG in the Lewis rat, but fails to break disease resistance in the WF rat.

Animals↗
PubMed2000

Cell movement is guided by the rigidity of the substrate.

Directional cell locomotion is critical in many physiological processes, including morphogenesis, the immune response, and wound healing. It is well known that in these processes cell movements can be guided by gradients of various chemical signals. In this study, we demonstrate that cell movement can also be guided by purely physical interactions at the cell-substrate interface. We cultured National Institutes of Health 3T3 fibroblasts on flexible polyacrylamide sheets coated with type I collagen. A transition in rigidity was introduced in the central region of the sheet by a discontinuity in the concentration of the bis-acrylamide cross-linker. Cells approaching the transition region from the soft side could easily migrate across the boundary, with a concurrent increase in spreading area and traction forces. In contrast, cells migrating from the stiff side turned around or retracted as they reached the boundary. We call this apparent preference for a stiff substrate "durotaxis." In addition to substrate rigidity, we discovered that cell movement could also be guided by manipulating the flexible substrate to produce mechanical strains in the front or rear of a polarized cell. We conclude that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion.

3T3 Cells↗
PubMed2000

Natural killer cells determine the outcome of B cell-mediated autoimmunity.

Natural killer (NK) cells can affect the outcome of adaptive immune responses. NK cells, but not NK1.1+T cells, were found to participate in the development of myasthenia gravis (a T cell-dependent, B cell- and antibody-mediated autoimmune disease) in C57BL/6 mice. The requirement for NK cells was reflected by the lack of a type I helper T cell response and antibodies to the acetylcholine receptor in both NK1.1+ cell-depleted and NK cell-deficient IL-18-/- mice. These findings establish a previously unrecognized link between NK cells and autoreactive T and B cells.

Amino Acid Sequence↗
PubMed2000

Cloned piglets born after nuclear transplantation of embryonic blastomeres into porcine oocytes matured in vivo.

Nuclear transplantation in the pig is more difficult than in other domestic animals and only one embryonic nuclear transplantation (NT) pig has been born to date. In this study, reconstituted porcine embryos were produced by electrofusion of blastomeres from in vivo four-cell embryos to enucleated in vivo or in vitro matured (IVM) oocytes. Nuclear transfer using cumulus cells as nuclear donors was also conducted. When blastomeres were used as donors, the electrofusion rate was significantly higher in oocytes matured in vivo (91.5%) than in those matured in vitro (66.1%) (p < 0.01). After fusion, the NT embryos reconstituted from in vivo matured oocytes developed to blastocysts at a rate of 10.3% after culture in rabbit oviducts for up to 5 days, while only 5.9% of the NT embryos reconstructed from in vitro matured oocytes developed to blastocyst stage. Electrofusion rate of cumulus cell nuclei with enucleated IVM oocytes was lower (47.6%) and only 1.5% (2/136) of the reconstituted eggs developed in vitro to morula stage, and 1.9% developed to blastocysts when cultured in the ligated rabbit oviducts. Transfer of 94 embryos reconstructed by blastomere NT with in vivo matured oocytes to five synchronous recipients resulted in the birth of two cloned piglets. No piglet was born following transfer to two recipients of embryos (n = 39) derived from NT with in vitro matured oocytes. The results demonstrate that in vivo matured oocytes are better recipients than those matured in vitro for pig cloning.

Animals↗
PubMed2000

Tumor necrosis factor receptor-1 is critically involved in the development of experimental autoimmune myasthenia gravis.

Tumor necrosis factor receptor-1 (TNFR1, CD120a) has been implicated in the pathogenesis of several experimental models of T cell-mediated autoimmune disorders, but its role in antibody-mediated autoimmune diseases has not been addressed. Experimental autoimmune myasthenia gravis (EAMG), an autoantibody-mediated T cell-dependent neuromuscular disorder, represents an animal model for myasthenia gravis in human. To investigate the role of TNFR1 in the pathogenesis of EAMG, TNFR1(-/-) and wild-type mice were immunized with TORPEDO: acetylcholine receptor (AChR) in complete Freund's adjuvant. TNFR1(-/-) mice failed to develop EAMG. Lymphoid cells from TNFR1(-/-) mice produced low amounts of T(h)1 (IFN-gamma, IL-2 and IL-12)-type cytokines, but elevated levels of T(h)2 (IL-4 and IL-10)-type cytokines compared with lymphoid cells of wild-type mice. Accordingly, the levels of anti-AChR IgG2 antibodies were severely reduced and the level of anti-AChR IgG1 antibodies were moderately reduced. Co-injection of recombinant mouse IL-12 with AChR in adjuvant restored T cell responses to AChR and promoted development of EAMG in TNFR1(-/-) mice. These results demonstrate that the TNF/TNFR1 system is required for the development of EAMG. The lack of a functional TNF/TNFR1 system can, at least in part, be substituted by IL-12 at the stage of initial priming with AChR and adjuvant.

Animals↗
PubMed2000

Leukemia inhibitory factor, leukemia inhibitory factor receptor, and glycoprotein 130 in rhesus monkey uterus during menstrual cycle and early pregnancy.

This goal of this study was to examine immunohistochemical distribution of leukemia inhibitory factor (LIF), LIF receptor (LIFR), and glycoprotein (gp) 130 in rhesus monkey uterus during the menstrual cycle and early pregnancy. Pregnancy rate was significantly reduced in the control group from 66.7% (12 of 18) to 22.2% (4 of 18) with an injection of goat anti-human recombinant LIF immunoglobulin G into the uterine lumen on Day 8 of pregnancy. LIF was mainly localized in glandular and luminal epithelium. LIF immunostaining during the luteal phase was stronger than it was during the proliferative phase. LIF staining gradually increased from Day 3 of pregnancy and reached its highest level on Day 9. LIFR was mainly localized in the glandular and luminal epithelium. LIFR staining during the luteal phase was stronger than it was during the proliferative phase. LIFR staining began to increase from Day 3 of pregnancy and reached a high level on Days 9 and 11. Gp130, a signal-transducing receptor component of LIF, was mainly localized in the glandular epithelium. A high level of gp130 was found on Days 16 and 20 of menstrual cycle, and from Days 5 to 11 of pregnancy. These results suggest that LIF may play an important role in monkey implantation, as it does in mice.

Animals↗
PubMed2000

Substrate flexibility regulates growth and apoptosis of normal but not transformed cells.

One of the hallmarks of oncogenic transformation is anchorage-independent growth (27). Here we demonstrate that responses to substrate rigidity play a major role in distinguishing the growth behavior of normal cells from that of transformed cells. We cultured normal or H-ras-transformed NIH 3T3 cells on flexible collagen-coated polyacrylamide substrates with similar chemical properties but different rigidity. Compared with cells cultured on stiff substrates, nontransformed cells on flexible substrates showed a decrease in the rate of DNA synthesis and an increase in the rate of apoptosis. These responses on flexible substrates are coupled to decreases in cell spreading area and traction forces. In contrast, transformed cells maintained their growth and apoptotic characteristics regardless of substrate flexibility. The responses in cell spreading area and traction forces to substrate flexibility were similarly diminished. Our results suggest that normal cells are capable of probing substrate rigidity and that proper mechanical feedback is required for regulating cell shape, cell growth, and survival. The loss of this response can explain the unregulated growth of transformed cells.

3T3 Cells↗
PubMed2000

Comparison of the viscoelastic properties of normal hepatocytes and hepatocellular carcinoma cells under cytoskeletal perturbation.

The viscoelastic properties of both hepatocytes and hepatocellular carcinoma (HCC) cells were measured by means of a micropipette aspiration technique. Experimental results were analyzed with a three-element standard linear solid model, in which an elastic element, K1, is in parallel with a Maxwell element composed of another elastic element, K2, in series with a viscous element, mu. Further, we investigated the relevance of viscoelastic properties of these two types of cells to the cytoskeleton structures by treating cells with three cytoskeletal perturbing agents, namely cytochalasin D (CD), colchicine (Col) and vinblastine (VBL). The results showed that the elastic coefficients, but not viscous coefficient of HCC cells (K1 = 103.6 +/- 12.6 N m-2, K2 = 42.5 +/- 10.4 N m-2, mu = 4.5 +/- 1.9 Pa s, n = 30), were significantly higher than the corresponding values for hepatocytes (K1 = 87.5 +/- 12.1 N m-2, K2 = 33.3 +/- 10.3 N m-2, mu = 5.9 +/- 3.0 Pa s, n = 24). Upon treatment with CD, the viscoelastic coefficients of both hepatocytes and HCC cells decreased uniformly, with magnitudes for the decrease in elastic coefficients of HCC cells (K1: 68.7 to 81.7 N m-2, 66.3 to 78.9%; K2: 34.5 to 37.1 N m-2, 81.2 to 87.3%) larger than those for normal hepatocytes (K1: 42.6 to 49.8 N m-2, 48.7 to 56.9%; K2: 17.2 to 20.4 N m-2, 51.7 to 61.3%). There was a smaller decrease in the viscous coefficient of HCC cells (2.0 to 3.4 Pa s, 44.4 to 75.6%) than that for hepatocytes (3.0 to 3.9 Pa s, 50.8 to 66.1%). Upon treatment with Col and VBL, the elastic coefficients of hepatocytes generally increased or tended to increase while those of HCC cells decreased. The differences in either the pattern or the magnitude of the effect of cytoskeletal perturbing agent on the viscoelastic properties between HCC cells and hepatocytes might possibly reflect differences in the state of the cytoskeleton structure and function, or in the cells' sensitivity to perturbing agent treatment between these two types of cells. Changes in the viscoelastic properties of cancer cells might well affect tumor cell invasion and metastasis as well as interactions between tumor cells and their micro-mechanical environments.

Carcinoma, Hepatocellular↗
PubMed2000

[The regulating mechanism of anti-fungicides on mouse oocyte development].

AIM: To study the mechanism of the effect of gonadotropin-induced oocyte maturation. METHODS: Mouse oocytes were cultured in HX-medium, and the effects of amphotericin B and ketoconazole on resumption of meiosis of mouse oocyte were examined. RESULTS: 1. FSH(10-200 IU/L) induced a dose-dependent manner of oocytes maturation in CEO. A maximum increase in GVBD was observed with 25-50 IU/L FSH. 2. Amphotericin tericim B (0.025-2.5 micrograms/L) caused significant increases in GVBD in CEO, which mimicked the function of FSH. 3. Ketoconazole (10(-7)-10(-3) mol/L) inhibited the effect of FSH on resumption of meiosis, but no effect on oocyte spontaneous maturation. CONCLUSION: Amphotericin B and ketoconazole are able to affect mouse oocyte maturation, and indicates that they have a regulation on FSH-induced synthesis of meiosis-activating sterol.

Amphotericin B↗