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Biomedical subjects

H Liu

Publications and source records attributed to H Liu.

At least 343 records · Page 19Linked to original sources
PubMed2001

[Study of protective effect of leech, radix Salviae miltiorrhizae and its composite recipe on vascular endothelial cells in rats with blood stasis syndrome].

OBJECTIVE: To study the protective effect for Chinese medicine of promoting blood circulation and removing blood stasis (PBCRBS) on vascular endothelial cells (VEC) in rats, aiming at further research on the mechanism of blood stasis syndrome and PBCRBS. METHOD: Establishing a model of blood stasis with endothelial damage by means of giving rats an injection of adrenalin and making it swim in ice-cold water, then measuring the number of circulating endothelial cells (CEC) in whole blood and rheology. Moreover observing the change of the above indexes after the rats have taken Leech, Radix salviae miltrorrhizae (RSM) and its composite recipe for 5 days or 10 days. RESULT: It could increase the number of CEC accompanied by whole blood viscosity, fibrinogen and hematocrit in rats with blood stasis. But for groups taking Chinese medicine, the number of CEC was decreased distinctively and blood rheology was improved. CONCLUSION: The rat with blood stasis syndrome suffered from obvious injury of VEC. The Leech, RSM and its composite recipe could protect VEC.

Animals↗
PubMed2001

Effects of the HOE 694 on transient inward current and Na(+) - Ca(2+) exchange in guinea pig cardiomyocytes.

OBJECTIVE: To determine the effects of HOE 694, a new and potent Na(+)-H+ exchanger blocker, on transient inward current (It(i)) and Na(+) - Ca(2+) exchange during hypoxia-reoxygenation in guinea pig cardiomyocytes. METHODS. Cardiomyocytes were isolated from adult guinea pig ventricle. Experiment was performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure. The cells were subjected to hypoxia and reoxygenation. The ionic currents were studied with patch clamp technique. RESULTS: In the absence of HOE 694, hypoxia-reoxygenation induced It(i) in 12 of 15 experiments; but in cardiomyocytes pretreated with HOE 694 (10 approximately 50 micro mol/L), the incidence of It(i) observed during reoxygenation was reduced to 5 of 11 experiments and 3 of 10 experiments, P < 0.05 vs control respectively. The Na(+) - Ca(2+) exchange current was unaffected by HOE 694 under normoxic condition. However, when cells were pretreated with 10 micromol/L HOE 694 for 10 min, then subjected to hypoxia condition, the Na(+) - Ca(2+) exchange current significantly inhibited. CONCLUSIONS: Blockade of the Na(+)-H+ exchange by HOE 694 could reduce Ca(2+) overload upon hypoxia-reoxygenation, and inhibition of Na(+) - H+ exchange may also indirectly decrease Na(+) - Ca(2+) exchange activity during hypoxia.

Animals↗
PubMed2001

Spirochetes--the possible etiological factor of the cheilitis granulomatosa.

OBJECTIVE: To detect spirochetes in sections and to study the therapeutic effect of penicillin in cheilitis granulomatosa (CG) and Melkersson-Rosenthal syndrome (MRS) and the relationship between the spirochetes infection and CG and MRS. METHODS: Routine HE sections and Warthin-Starry special staining were carried out in 20 cases of CG and 6 cases of MRS. Meanwhile there were 9 cases of CG and 2 caes of MRS were treated by penicillin (12 000 000u, i.v., per day) for two courses (14 days). RESULTS: A kind of spirochete was discovered in the sections of all cases of the CG and MRS. The CG and MRS could be divided into two types histopathologically, that is granuloma type and interstitial inflammatory type (non-granuloma type), those morphological changes tallied with spirochetosis. After treatment by penicillin, the facial and labial swelling of the 11 cases of CG and MRS were abated. CONCLUSION: CG and MRS probably are infectious diseases caused by spirochetes.

Anti-Bacterial Agents↗
PubMed2001

[On the characteristics of velocity modulation laser spectroscopy].

The technical properties of velocity modulation laser spectroscopy were investigated using the spectrum of A2 pi u-X2 sigma g+ (2-0) band of Meinel system of N2+. The dependence of spectral intensity on discharge current, the pressure of the gas mixture and the pump velocity of the vacuum pump were studied. Making uses of the results of these studies, the sensitivity and resolution of the spectrometer are improved by above 3 times, and economized the experimental expenses can be reduced to as 3/4 time as normal, which confirms that the results of this paper is of considerable uses.

Lasers↗
PubMed2001

[Assignments of FIR-LMR spectra of CF X 2Pi (nu = 1) and MIR-LMR spectra of NO X 2Pi (nu = 1<--0)].

According to the theories of Zeeman effect and the principle of laser magnetic resonance (LMR), a method and model for the analysis of the laser magnetic resonance spectra were developed and successfully employed to assign the FIR-LMR spectra of CF X2 Pi (nu = 1) and the MIR-LMR spectra of NO X 2Pi (nu = 1<--0). This work provided an efficient and accurate approach for primary analysis of the LMR spectra of novel radicals.

English Abstract↗
PubMed2000

Inhibition of c-Myc expression sensitizes hepatocytes to tumor necrosis factor-induced apoptosis and necrosis.

The typical proliferative response of hepatocytes to tumor necrosis factor (TNF) can be converted to a cytotoxic one by transcriptional arrest. Although NF-kappaB activation is critical for hepatocyte resistance to TNF toxicity, the contribution of other TNF-inducible transcription factors remains unknown. To determine the function of c-Myc in hepatocyte sensitivity to TNF, stable transfectants of the rat hepatocyte cell line RALA255-10G containing sense and antisense c-myc expression vectors were isolated with increased (S-Myc cells) and decreased (AN-Myc cells) c-Myc transcriptional activity. While S-Myc cells proliferated in response to TNF treatment, AN-Myc cells underwent 32% cell death within 6 h. Fluorescent microscopic studies indicated that TNF induced apoptosis and necrosis in AN-Myc cells. Cell death was associated with DNA hypoploidy and poly(ADP-ribose) polymerase cleavage but occurred in the absence of detectable caspase-3, -7, or -8 activation. TNF-induced, AN-Myc cell death was dependent on Fas-associated protein with death domain and partially blocked by caspase inhibitors. AN-Myc cells had decreased levels of NF-kappaB transcriptional activity, but S-Myc cells maintained resistance to TNF despite NF-kappaB inactivation, suggesting that c-Myc and NF-kappaB independently mediate TNF resistance. Thus, in the absence of sufficient c-Myc expression, hepatocytes are sensitized to TNF-induced apoptosis and necrosis. These findings demonstrate that hepatocyte resistance to TNF is regulated by multiple transcriptional activators.

Animals↗
PubMed2000

Effect of intrathecal galanin and its putative antagonist M35 on pain behavior in a neuropathic pain model.

There is currently some debate over a possible role of galanin in pain processing. It was recently reported that the levels of galanin in dorsal root ganglia (DRGs) seem related to development of allodynia after unilateral sciatic nerve constriction injury. In our present study, we aimed at characterizing the effect of exogenous and endogenous galanin on pain behavior in allodynic and non-allodynic rats in which the levels of galanin in DRG neurons are low and high, respectively [28]. The results show that in allodynic rats, the mechanical threshold increases dose-dependently after intrathecal (i.t.) injection of galanin, while no significant changes were observed in groups treated with the putative galanin antagonist M35 or saline. In non-allodynic rats i.t. injection of M35 induced a significant mechanical allodynic state, which did not occur after injection of galanin, bradykinin, the bradykinin fragment(2-9) or saline. The results suggest that in the present experimental paradigm exogenous galanin has an anti-allodynic effect in the allodynic rats, and that endogenous galanin has a tonic inhibitory effect in the non-allodynic group.

Analysis of Variance↗
PubMed2000

Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: the dominant role for NF-kappa B but not C/EBP beta or c-Jun.

Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) produce IL-6 and IL-8, which contribute to inflammation and joint damage. The promoters of both cytokines possess binding sites for NF-kappaB, C/EBPbeta, and c-Jun, but the contribution of each to the regulation of IL-6 and IL-8 in RA FLS is unknown. We employed adenoviral-mediated gene delivery of a nondegradable IkappaBalpha, or dominant-negative versions of C/EBPbeta or c-Jun, to determine the contribution of each transcription factor to IL-6 and IL-8 expression. Inhibition of NF-kappaB activation significantly reduced the spontaneous and IL-1beta-induced secretion of IL-6 and IL-8 by RA FLS and the IL-1ss-induced production of IL-6 and IL-8 by human dermal fibroblasts. Inhibition of C/EBPbeta modestly reduced constitutive and IL-1beta-induced IL-6 by RA FLS, but not by human dermal fibroblasts, and had no effect on IL-8. Inhibition of c-Jun/AP-1 had no effect on the production of either IL-6 or IL-8. Employing gel shift assays, NF-kappaB, C/EBPbeta, and c-Jun were constitutively activated in RA FLS, but only NF-kappaB and c-Jun activity increased after IL-1beta. The reduction of cytokines by IkappaBalpha was mediated through inhibition of NF-kappaB activation, which resulted in decreased IL-6 and IL-8 mRNA. NF-kappaB was essential for IL-6 expression, because fibroblasts in which both NF-kappaB p50/p65 genes were deleted failed to express IL-6 in response to IL-1. These findings document the importance of NF-kappaB for the regulation of the constitutive and IL-1beta-stimulated expression of IL-6 and IL-8 by RA FLS and support the role of inhibition of NF-kappaB as a therapeutic goal in RA.

Adenoviruses, Human↗
PubMed2000

Enhanced delivery of AZT to macrophages via acetylated LDL.

It is known that infected macrophages play an important role in HIV pathogenesis acting as a reservoir for dissemination of the virus to various organs. Enhanced and/or specific delivery of anti-HIV agents to infected cells is expected to improve their therapeutic index by increasing efficacy and reducing toxicity. Acetylated low density lipoproteins (AcLDL) are known to be taken up by macrophages via scavenger receptors and appear to be good carriers for targeting drug molecules to macrophages. This study investigated the delivery of 3'-azido-3'-deoxythymidine (AZT), an anti-HIV agent, to macrophages using AcLDL. Since the incorporation of AZT into AcLDL was found to be low, several derivatives of AZT including 5'-O-13-oxamyristate-AZT (5'-O-oxaMyr-AZT) have been synthesized as prodrugs. The prodrugs were incorporated into AcLDL using two different methods, namely the contact method and the microemulsion method. Our results demonstrated that the microemulsion method was more effective. The physicochemical properties of the AcLDL/prodrug complex were evaluated by electrophoresis and electron microscopy (EM). Incubation of the complex with plasma resulted in little distribution of the incorporated drug molecules from AcLDL to other components of the plasma, suggesting that the complex was quite stable. Cellular uptake studies using J774.A and U937 demonstrated that AcLDL/prodrug was taken up about 10 times more than AZT. The presence of excess AcLDL was found to inhibit the cellular uptake of AcLDL/5'-O-oxaMyr-AZT by macrophages while excess high density lipoprotein (HDL) or low density lipoprotein (LDL) was found to have little effect, suggesting that the AcLDL/prodrug complex is taken up into macrophages via the scavenger receptor.

Animals↗
PubMed2000

Ion recognition at the interface of self-assembled monolayers (SAMs) of bis-thioctic ester derivatives of oligo(ethyleneglycols).

Self-assembled monolayers (SAMs) of bis-thioctic ester derivatives of oligoethylene glycols were prepared. When the number of (-CH2-CH2-O-)n units in these podands was either five or six, the corresponding SAMs showed ion binding properties and selectivities similar to those exhibited by 15-crown-5 or 18-crown-6 in aqueous solution, respectively. Impedance data for the SAMs as a function of metal ion concentrations were fitted by using a Langmuir isotherm to determine the association constants (Ka) with the different ions. The SAM derived from the n = 5 compound is selective for Na+ while that with n = 6 is selective for K+. Results presented here confirm the formation of ion recognition domains during self-assembly of acyclic polyethylene glycol derivatives on gold surfaces; this suggests that surface-confined pseudocrown ether structures are formed.

Journal Article↗
PubMed2000

The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity.

We have previously shown that members of the ELR(+) CXC chemokine family, including IL-8; growth-related oncogenes alpha, beta, and gamma; granulocyte chemotactic protein 2; and epithelial neutrophil-activating protein-78, can mediate angiogenesis in the absence of preceding inflammation. To date, the receptor on endothelial cells responsible for chemotaxis and neovascularization mediated by these ELR(+) CXC chemokines has not been determined. Because all ELR(+) CXC chemokines bind to CXC chemokine receptor 2 (CXCR2), we hypothesized that CXCR2 is the putative receptor for ELR(+) CXC chemokine-mediated angiogenesis. To test this postulate, we first determined whether cultured human microvascular endothelial cells expressed CXCR2. CXCR2 was detected in human microvascular endothelial cells at the protein level by both Western blot analysis and immunohistochemistry using polyclonal Abs specific for human CXCR2. To determine whether CXCR2 played a functional role in angiogenesis, we determined whether this receptor was involved in endothelial cell chemotaxis. We found that microvascular endothelial cell chemotaxis in response to ELR(+) CXC chemokines was inhibited by anti-CXCR2 Abs. In addition, endothelial cell chemotaxis in response to ELR(+) CXC chemokines was sensitive to pertussis toxin, suggesting a role for G protein-linked receptor mechanisms in this biological response. The importance of CXCR2 in mediating ELR(+) CXC chemokine-induced angiogenesis in vivo was also demonstrated by the lack of angiogenic activity induced by ELR(+) CXC chemokines in the presence of neutralizing Abs to CXCR2 in the rat corneal micropocket assay, or in the corneas of CXCR2(-/-) mice. We thus conclude that CXCR2 is the receptor responsible for ELR(+) CXC chemokine-mediated angiogenesis.

Administration, Topical↗
PubMed2000

Phosphorylation by cyclin-dependent protein kinase 5 of the regulatory subunit of retinal cGMP phosphodiesterase. II. Its role in the turnoff of phosphodiesterase in vivo.

Retinal cGMP phosphodiesterase (PDE) is regulated by Pgamma, the regulatory subunit of PDE, and GTP/Talpha, the GTP-bound alpha subunit of transducin. In the accompanying paper (Matsuura, I., Bondarenko, V. A., Maeda, T., Kachi, S., Yamazaki, M., Usukura, J., Hayashi, F., and Yamazaki, A. (2000) J. Biol. Chem. 275, 32950-32957), we have shown that all known Pgammas contain a specific phosphorylation motif for cyclin-dependent protein kinase 5 (Cdk5) and that the unknown kinase is Cdk5 complexed with its activator. Here, using frog rod photoreceptor outer segments (ROS) isolated by a new method, we show that Cdk5 is involved in light-dependent Pgamma phosphorylation in vivo. Under dark conditions only negligible amounts of Pgamma were phosphorylated. However, under illumination that bleached less than 0.3% of the rhodopsin, approximately 4% of the total Pgamma was phosphorylated in less than 10 s. Pgamma dephosphorylation occurred in less than 1 s after the light was turned off. Analysis of the phosphorylated amino acid, inhibition of Pgamma phosphorylation by Cdk inhibitors in vivo and in vitro, and two-dimensional peptide map analysis of Pgamma phosphorylated in vivo and in vitro indicate that Cdk5 phosphorylates a Pgamma threonine in the same manner in vivo and in vitro. These observations, together with immunological data showing the presence of Cdk5 in ROS, suggest that Cdk5 is involved in light-dependent Pgamma phosphorylation in ROS and that the phosphorylation is significant and reversible. In an homogenate of frog ROS, PDE activated by light/guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was inhibited by Pgamma alone, but not by Pgamma complexed with GDP/Talpha or GTPgammaS/Talpha. Under these conditions, Pgamma phosphorylated by Cdk5 inhibited the light/GTPgammaS-activated PDE even in the presence of GTPgammaS/Talpha. These observations suggest that phosphorylated Pgamma interacts with and inhibits light/GTPgammaS-activated PDE, but does not interact with GTPgammaS/Talpha in the homogenate. Together, our results strongly suggest that after activation of PDE by light/GTP, Pgamma is phosphorylated by Cdk5 and the phosphorylated Pgamma inhibits GTP/Talpha-activated PDE, even in the presence of GTP/Talpha in ROS.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Computer-aided design, synthesis and biological assay of p-methylsulfonamido phenylethylamine analogues.

Class III antiarrhythmic agents selectively delay the effective refractory period (ERP) and increase the transmembrance action potential duration (APD). Based on our previous studies, a set of 17 methylsulfonamido phenylethylamine analogues were investigated by 3D-QSAR techniques of CoMFA and CoMSIA. The 3D-QSAR models proved a good predictive ability, and could describe the steric, electrostatic and hydrophobic requirements for recognition forces of the receptor site. According to the clues provided by this 3D-QSAR analysis, we designed and synthesized a series of new analogues of methanesulfonamido phenylethylamine (VIa-i). Pharmacological assay indicated that the effective concentrations of delaying the functional refractory period (FRP) 10ms of these new compounds have a good correlation with the 3D-QSAR predicted values. It is remarkable that the maximal percent change of delaying FRP in microM of compound VIc is much higher than that of dofetilide. The results showed that the 3D-QSAR models are reliable.

Animals↗
PubMed2000

Indomethacin prevents the L-NAME-induced increase in plasma levels of oxytocin in dehydrated rats.

Inhibiting NO synthase (NOS) with N(G)-nitro-L-arginine methyl ester (L-NAME, 250 microg/5 microl of artificial cerebrospinal fluid (aCSF)) injected intracerebroventricularly (i.c.v.) increased already enhanced levels of oxytocin, but not vasopressin, in conscious adult male Sprague-Dawley rats dehydrated for 24 h. Intracerebroventricular pretreatment with indomethacin (200 microg/5 microl aCSF), an inhibitor of cyclo-oxygenase, but not with losartan (25 microg/5 microl aCSF), an antagonist of angiotensin II (ANG II) AT(1)-receptor subtype, nearly prevented the elevation in oxytocin levels after L-NAME. Thus, NO inhibits prostaglandin (but not ANG II) mediated the modulatory actions of NO on oxytocin secretion from the hypothalamo-neurohypophysial system (HNS) during water deprivation.

Angiotensin II↗
PubMed2000

Preparation and Catalytic Properties of Amphiphilic Copolymer-Stabilized Platinum Metals Colloids.

Several metal colloids stabilized by an amphiphilic copolymer, poly(1-vinylpyrrolidone-co-acrylic acid) (abbreviated as PVPAA), were prepared by refluxing alcohol-water mixed solutions of the corresponding metal precursors. They had small particle sizes and narrow size distributions. Their catalytic activity was tested by hydrogenation of cyclooctene, 1-dodecene, and ortho-chloronitrobenzene (o-CNB). With the introduction of nickel(II) ions to a PVPAA-stabilized platinum catalytic system, selective hydrogenation of o-CNB to ortho-chloroaniline (o-CAN) with 97.1% selectivity and 100% conversion was obtained. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Allosteric silencing of activating function 1 in the 4-hydroxytamoxifen estrogen receptor complex is induced by substituting glycine for aspartate at amino acid 351.

The active metabolite of tamoxifen, 4-hydroxytamoxifen (4-OHT), is used in the laboratory for mechanistic studies of antiestrogen action. This compound binds to the estrogen receptor alpha (ER) and silences activating function 2 (AF2) in the ligand binding domain, but activating function 1 (AF1) at the other end of the ER remains constitutive and is considered to be ligand independent. Amino acid D351 in the ligand binding domain appears to be critical for interactions with the antiestrogenic side chain of antiestrogens. We have devised an assay to evaluate the biological activity of 351 mutant ERs and antiestrogens at the transforming growth factor alpha (TGFalpha) gene in situ (J. I. MacGregor Schafer et al., Cancer Res., 59: 4308-4313, 1999). The substitution of glycine for aspartate at position 351 results in the conversion of the 4-OHT:ER complex from estrogen-like to completely antiestrogenic. In cells stably expressing D351G ER, the ER retains responsiveness to estradiol (E2) and also retains antiestrogenic responsiveness to both raloxifene and ICI 182,780. The relative binding affinity of E2 for D351G ER (0.77 +/- 0.17 x 10(-9) M) is comparable with wild-type ER (0.42 +/- 0.08 x 10(-9) M). In addition, the D351G ER retains the ability to bind SRC-1 in the presence of E2, thus D351G ER AF2 activity has not been compromised. We also used a cell line stably expressing an ER with a triple mutation in helix 12 (D538A, E542A, and D545A) that ablated AF2 activity, which resulted in decreased effects of E2, suggesting that both AF1 and AF2 activity are required for maximal estrogen activity in MDA-MB-231 cells. Interestingly, the triple mutation also completely reduced the estrogen-like actions of 4-OHT. We propose that a specific mutation at amino acid 351 can allosterically silence AF1 in the 4-OHT:ER complex by either preventing the binding of coactivators or encouraging the binding of a corepressor molecule. We suggest that the 4-OHT-specific site responsible for estrogen-like actions can be referred to as AF2b. This binding site would consist of at least four carboxylic acids at amino acids 351 and 538, 542 and 545 in helix 12 to permit coactivator docking for gene activation. The AF2b site is distinct from AF2 for E2 action. Further studies will provide insight into the estrogen-like actions of tamoxifen in select tissues and breast tumors and identify a significant mechanism of drug resistance to tamoxifen.

Allosteric Regulation↗
PubMed2000

Expression of phosphodiesterase 4D (PDE4D) is regulated by both the cyclic AMP-dependent protein kinase and mitogen-activated protein kinase signaling pathways. A potential mechanism allowing for the coordinated regulation of PDE4D activity and expression in cells.

Multiple families of cyclic nucleotide phosphodiesterases (PDE) have been described, and the regulated expression of these genes in cells is complex. Although cAMP is known to control the expression of certain PDE in cells, presumably reflecting a system of feedback on cAMP signaling, relatively little is known about the influence of non-cAMP signaling systems on PDE expression. In this study, we describe a novel mechanism by which activators of the protein kinase C (PKC)-Raf-MEK-ERK cascade regulate phosphodiesterase 4D (PDE4D) expression in vascular smooth muscle cells (VSMC) and assess the functional consequences of this effect. Whereas a prolonged elevation of cAMP in VSMC resulted in a protein kinase A (PKA)-dependent induction of expression of two PDE4D variants (PDE4D1 and PDE4D2), simultaneous activation of both the cAMP-PKA and PKC-Raf-MEK-ERK signaling cascades blunted this cAMP-mediated increase in PDE4D expression. By using biochemical, molecular biological, and pharmacological approaches, we demonstrate that this PDE4D-selective effect of activators of the PKC-Raf-MEK-ERK cascade was mediated through a mechanism involving altered PDE4D mRNA stability and markedly attenuated the cAMP-mediated desensitization that results from prolonged activation of the cAMP signaling system in cells. The data are presented in the context of activators of the PKC-Raf-MEK-ERK cascade having both short and long term effects on PDE4D activity and expression in cells that may influence cAMP signaling.

3',5'-Cyclic-AMP Phosphodiesterases↗