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Biomedical subjects

W Zhang

Publications and source records attributed to W Zhang.

At least 919 records · Page 51Linked to original sources
PubMed1997

Neuropeptide Y Y1 receptor antagonist (BIBP 3226) attenuates stress evoked tachycardia in conscious spontaneously hypertensive rats.

The effects of a novel neuropeptide Y (NPY) Y1 receptor antagonist on resting mean blood pressure (MBP) and heart rate (HR) were observed in conscious spontaneously hypertensive rats (SHR). The interference of the antagonist with cardiovascular responses to mental stress and administration of exogenous NPY were also investigated. SHR were randomly received either the NPY Y1 receptor antagonist (BIBP 3226; n = 11) or its inactive enantiomer (BIBP 3435; n = 11) as an infusion (6 mg/kg/h for 1.5 hours). Before, during, and after the infusion, rats were first stressed with a jet of air and then given a bolus injection of exogenous NPY (2 nmol/kg). There was no statistically significant difference of resting MBP and HR between the antagonist and enantiomer groups before, during, or after infusion. The stress-induced maximum increase in HR was significantly reduced during antagonist infusion (P < 0.05). The effects of exogenous NPY on both MBP and HR were significantly attenuated by antagonist infusion (P < 0.05, respectively), and the effect lasted at least 1 hour after the end of the infusion. Plasma catecholamine levels in response to stress were not significantly different between the two groups. The results suggest that endogenous NPY Y1-receptor mechanisms may be of minor importance in short-term regulation of MBP and HR in conscious adult SHR, but may be involved in the response to mental stress.

Animals↗
PubMed1997

Effects of calcium antagonist felodipine on renal sympathetic nerve activity in rats with congestive heart failure.

In order to assess the effects of dihydropyridine calcium antagonist on sympathetic nerve activity (SNA) in experimental chronic heart failure (CHF), felodipine was given to rats with CHF induced by coronary artery ligation. Anesthetized CHF (n = 7) and sham-operated (n = 9) rats were injected with a bolus dose of felodipine (20 microg/kg) and then infused with felodipine (30 microg/kg/h) for 3 hours. Control CHF rats (n = 8) were given vehicle in the same way. After felodipine treatment, mean blood pressure (MBP) rapidly decreased to 75-85 mmHg, and there was a reflex tachycardia and reflex activation of renal SNA. The heart rate (HR) had returned to baseline level after 3 hours of continuous felodipine infusion, and the SNA returned to baseline level after 2 hours of infusion. At the end of the experiment, renal SNA was 65.4 +/- 11.5% of the baseline level in CHF rats receiving felodipine (P < 0.05) and 94.1 +/- 22.8% in CHF rats receiving vehicle (P > 0.05), but there was no statistical difference between the two groups. Arterial baroreceptor sensitivity (assessed by phenylephrine infusion), which was impaired in CHF rats (-2.7 +/- 0.2 SNA%/mmHg in all CHF rats together vs. -3.6 +/- 0.4 in sham-operated rats, P < 0.5) did not differ significantly from that in sham-operated rats during felodipine infusion (-3.2 +/- 0.4 in felodipine-treated CHF rats vs. -3.7 +/- 0.6 in sham-operated rats) but deteriorated without felodipine treatment (-2.1 +/- 0.3 in CHF rats receiving vehicle, P < 0.05). The biphasic renal SNA response during felodipine infusion suggests that felodipine does not cause persistent sympathetic activation and relatively improves baroreceptor sensitivity in CHF rats.

Animals↗
PubMed1997

Effect of freezing rate on the stability of liposomes during freeze-drying and rehydration.

PURPOSE: In the present study we examined the effect of the freezing protocol on carboxyfluorescein (CF) retention in liposomes after freeze-drying and rehydration. METHODS: Liposomes were frozen slowly at 0.5 degree C/min, or quickly by submerging the samples in boiling nitrogen before freeze-drying. The thermal behaviour of the frozen dispersions was analysed by Modulated Temperature Differential Scanning Calorimetry (MTDSC). The dried cakes were analysed by SEM, MTDSC and FTIR. The % encapsulated CF of the (re)hydrated liposomes was determined by fluorimetry after GPC, their vesicle size was measured by the Dynamic Light scattering Technique and their bilayer transition was studied by DSC. RESULTS: Slow freezing resulted in a markedly higher CF retention after freeze-drying and rehydration as compared to quick freezing. The effect of the freezing rate depended on the lipid composition and was most pronounced for rigid liposomes. The damage caused by quick freezing did not occur after a freezing/thawing cycle. The freezing protocol did not influence the interaction between the phospholipids and the lyoprotectants (sucrose, trehalose or glucose) in the freeze-dried state. However, analysis by DSC of dipalmitoylphosphatidylcholine (DPPC): dipalmitoylphosphatidylglycerol (DPPG) = 10:1 and DPPC liposome dispersions showed that the freezing protocol affected the bilayer melting characteristics of these liposomes after freeze-drying and rehydration. CONCLUSIONS: A proper design of the freezing protocol is essential to achieve optimal stability of rigid liposomes during a freeze-drying and rehydration cycle.

Fluid Therapy↗
PubMed1997

Three-dimensional structure of the Hck SH2 domain in solution.

The hematopoietic cellular kinase (Hck) is a member of the Src family of non-receptor protein-tyrosine kinases that is expressed predominantly in granulocytes, monocytes and macrophages. Recent observations suggest that Hck may be activated in HIV-infected macrophages and in chronic myelogenous leukemia cells that express Bcr-Abl. In order to increase our understanding of the structural basis for regulation of Hck activity under normal and pathological conditions, we have solved the solution structure of the uncomplexed Hck SH2 domain using NMR spectroscopy. A novel procedure that uses intraresidue HN-H alpha distances as references for converting NOE intensities into distance restraints has been described. A total of 1757 significant experimental restraints were derived from NMR spectroscopic data including 238 medium-range and 487 long-range distance restraints and 177 torsion angle restraints. These restraints were used in a simulated annealing procedure to generate 20 structures with the program DYANA. Superimposition of residues 5-104 upon the mean coordinate set yielded an average atomic rmsd values of 0.42 +/- 0.08 A for the N,C alpha,C' atoms and 0.81 +/- 0.08 A for all heavy atoms. Rmsd values for those residues in the regions of ordered secondary structure were 0.27 +/- 0.04 A for the N,C alpha,C' atoms and 0.73 +/- 0.06 A for all heavy atoms.

Amino Acid Sequence↗
PubMed1997

Effects of hydralazine on renal sympathetic nerve activity in normal and congestive heart failure rats.

We investigated the effects of hydralazine on renal sympathetic nerve activity in anaesthetized heart failure rats. Sham-operated rats (group 1) received 0.5 mg kg-1 of hydralazine as bolus and were then infused with 0.3-0.5 mg kg-1 h-1 for 3 h intravenously. Heart failure rats received either the same regime (group 2) as group 1, or the same volume of vehicle (group 3). Heart failure rats exhibited lower mean blood pressure (P < 0.05) and elevated renal sympathetic nerve activity (P < 0.01) in the basal state. In group 2, the mean blood pressure decreased 26% after 30 min of hydralazine administration and remained lower for 3 h, with unchanged renal sympathetic nerve activity. In group 1, the mean blood pressure decreased 36%, and the heart rate and renal sympathetic nerve activity were significantly inhibited. Bilateral vagotomy did not alter renal sympathetic nerve response to hydralazine, but resulted in tachycardia. The results indicate that hydralazine, despite its profound hypotensive effect, did not activate renal sympathetic nerve activity in heart failure rats and inhibited renal sympathetic nerve activity in sham-operated rats. This inhibition was not mediated through the vagal nerve.

Animals↗
PubMed1997

Effects of 1,1-dimethylguanidine administration on blood pressure, heart rate and renal sympathetic nerve activity in normotensive and spontaneously hypertensive rats.

1,1-dimethylguanidine (DMG) is an endogenous nitric oxide (NO) synthesis inhibitor. This study investigates the effects of exogenous DMG administration, in anaesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Mean blood pressure (MBP), heart rate (HR) and renal sympathetic nerve activity (SNA) were recorded in 12- to 14-week old, anaesthetized SHR and WKY. Each rat received increasing bolus injections of DMG intravenously (1.03, 2.05, 6.39, 20.45 and 51.15 mg kg-1). In separate experiments, SHR received L-arginine or D-arginine in a dose of 300 mg kg-1 followed by DMG at 6.39 mg kg-1. Thirty minutes later they received the same doses of the respective arginines followed by DMG at 20.45 mg kg-1 DMG induced dose-dependant increases in MBP in SHR and WKY. In SHR, HR increased with increasing doses of DMG (except at the near-toxic doses of 51.15 mg kg-1), whereas in WKY HR decreased with increasing doses of DMG. The net change of renal SNA ranged from -5 +/- 3 to -55 +/- 12% in SHR and from -6 +/- 8 to -66 +/- 8% in WKY. Pre-treatment with L-arginine in SHR partly inhibited the pressor effect and attenuated the inhibition of renal SNA induced by DMG, but had little effect on HR. Thus the administration of NO inhibitor DMG could alter cardiovascular function and sympathetic nerve activity, and subsequently resulted in tachycardia in SHR and bradycardia in WKY.

Animals↗
PubMed1997

Long-term expression of Fos-related antigen and transient expression of delta FosB associated with seizures in the rat hippocampus and striatum.

Systemic administration of kainic acid (KA), an analogue of glutamic acid, causes limbic seizures and pathophysiological changes in adult rats that are very similar to human temporal lobe epilepsy. One of the earliest changes in gene expression after treatment with KA is the induction of immediate-early genes. The fos and jun families are frequently studied immediate-early genes that are induced by KA. Several groups, including ours, have recently reported that a 35-kDa Fos-related antigen (FRA) is induced for a protracted time by various stimuli. It has been suggested that this FRA is delta FosB, which has a molecular mass of approximately 35 kDa. The present study characterizes the long-term expression of FRA and delta FosB after systemic treatment with KA. Immunocytochemistry and western blot analysis using an antibody that cross-reacts with all known FRAs showed that a 35-kDa FRA was induced at high levels in both the hippocampus and striatum for up to 1 month by KA. A semiquantitative PCR analysis showed that delta FosB was induced by KA, but its expression lasted for only 6 h. This result was also verified by northern blot analysis. These results suggested that the 35-kDa FRA with long-term elevated levels seen with western blot analysis and immunocytochemistry is a new species of the FRA and not delta FosB. The long-term expression of FRA in both the hippocampus and striatum may be associated with the pathophysiological changes after KA administration.

Animals↗
PubMed1997

Cytoskeletal changes in the brains of mice lacking calcineurin A alpha.

Hyperphosphorylated tau, the major component of the paired helical filaments of Alzheimer's disease, was found to accumulate in the brains of mice in which the calcineurin A alpha gene was disrupted [calcineurin A alpha knockout (CNA alpha -/-)]. The hyperphosphorylation involved several sites on tau, especially the Ser396 and/or Ser404 recognized by the PHF-1 monoclonal antibody. The increase in phosphorylated tau content occurred primarily in the mossy fibers of the CNA alpha -/- hippocampus, which contained the highest level of calcineurin in brains of wild-type mice. The CNA alpha -/- mossy fibers also contained less neurofilament protein than normal, although the overall level of neurofilament phosphorylation was unchanged. In the electron microscope, the mossy fibers of CNA alpha -/- mice exhibited abnormalities in their cytoskeleton and a lower neurofilament/microtubule ratio than those of wild-type animals. These findings indicate that hyperphosphorylated tau can accumulate in vivo as a result of reduced calcineurin activity and is accompanied by cytoskeletal changes that are likely to have functional consequences on the affected neurons. The CNA alpha -/- mice were found in a separate study to have deficits in learning and memory that may result in part from the cytoskeletal changes in the hippocampus.

Animals↗
PubMed1997

An essential tryptophan residue of green crab (syclla serrata) alkaline phosphatase.

The tryptophan residues in green crab (scylla serrata) alkaline phosphatase (EC 3.1.3.1) have been modified by N-bromosuccinimide (NBS). The modification of five tryptophan residues leads to complete loss of enzymatic activity. With the increase of NBS concentration, both the absorption at 278 nm and the fluorescence emission intensity at 335 nm of the modified enzyme decreased markedly indicating the modification of tryptophan residues. Quantitative treatment of the data (Tsou, Sci. Sinica 1962, 11, 1535-1558) shows that among the tryptophan residues modified, one is essential for its catalytic activity. The presence of the substrate markedly protects the modification of tryptophan residues as well as the inactivation, suggesting that the essential tryptophan residue is situated at the active site of this enzyme.

Alkaline Phosphatase↗
PubMed1997

p53-dependent response in UV-induced transformation.

Cells carrying different numbers of copies of wild-type p53 were transformed by UV irradiation. Putative dense foci were analyzed for their growth behavior in low serum and for anchorage-independence. A correlation was found between number of copies of wild-type p53 gene and transformation frequency: cells with more copies of p53 gene were more resistant to transformation by UV. The p53 in the transformed clones was shown to be wild-type at the protein level. A single DNA base change was detected between GenBank data and our normal and transformed cells; this pre-existing single base difference is probably due to the differences between the strains of mice from which the cells were derived.

Animals↗
PubMed1997

Liver involvement in epidemic haemorrhagic fever: in situ hybridization, immunohistochemical and pathological studies.

In the present study, liver biopsy specimens from 37 patients with epidemic haemorrhagic fever (EHF) were investigated by using light and electron microscopy, immunohistochemistry for the EHF virus envelope protein G2 and in situ hybridization (ISH) for EHF viral RNA. Immunostaining and in situ hybridization were both positive, and a few of the aetiological agents, the EHF virus (EHFV) particles, were found individually within the dilated Golgi cisternae and vesicles, and the dilated rough endoplasmic reticulum of the hepatocyte. The pathological alterations of the liver cells infected with EHFV were: hepatocellular degeneration, cytoplasmic vacuolation, and spotty necrosis; moreover, zonal necrosis was present and adjacent to the narrowed and occluded sinusoids. In degenerated and spotty necrotic cells, the positive signals from of ISH for EHFV RNA and those from immunostaining for the virus protein were both stronger than those in the zonal liver cell necrosis area. The results showed that hepatocellular degeneration and spotty necrosis might be directly related to the virus and its duplication inside the liver cells, while the zonal necrosis was ischaemic and thought to be caused by microcirculation dysfunction.

Adolescent↗
PubMed1997

Primary structure and functional analysis of the soluble transducer protein HtrXI in the archaeon Halobacterium salinarium.

Signal transduction in the archaeon Halobacterium salinarium is mediated by a family of 13 soluble and membrane-bound transducers. Here, we report the primary structure and functional analysis of one of the smallest halobacterial putative transducers, HtrXI. Hydropathy plot analysis of the primary structure predicts no membrane-spanning segments in HtrXI. The fractionation of the H. salinarium proteins confirmed that HtrXI is a soluble protein. Capillary assay with an HtrXI deletion mutant and a complemented strain revealed that this soluble transducer is involved in Asp and Glu taxis. In vivo analysis of the methylesterase activity of the htrXI-1 deletion mutant suggests that HtrXI plays an important role in the adaptation of the chemotactic responses to His, Asp, and Glu, which are attractants for halobacteria. Stimulation by Asp and Glu causes demethylation of HtrXI and of another putative transducer, HtrVII. But addition of His to halobacterial cells increases HtrXI methylation together with that of other putative transducers. In the absence of HtrXI, stimulation by either Glu or His does not decrease or increase the methylation of any putative transducers. Therefire, the HtrXI transducer appears to have a complex role in chemotaxis signal transduction.

Amino Acid Sequence↗
PubMed1997

Amino termini of histones H3 and H4 are required for a1-alpha2 repression in yeast.

The Saccharomyces cerevisiae alpha2 repressor controls two classes of cell-type-specific genes in yeast through association with different partners. alpha2-Mcm1 complexes repress a cell-specific gene expression in haploid alpha cells and diploid a/alpha cells, while a1-alpha2 complexes repress haploid-specific genes in diploid cells. In both cases, repression is mediated through Ssn6-Tu1 corepressor complexes that are recruited via direct interactions with alpha2. We have previously shown that nucleosomes are positioned adjacent to the alpha2-Mcm1 operator under conditions of repression and that Tupl interacts directly with histones H3 and H4. Here, we examine the role of chromatin in a1-alpha2 repression to determine if chromatin is a general feature of repression by Ssn6-Tup1. We find that mutations in the amino terminus of histone H4 cause a 4- to 11-fold derepression of a reporter gene under a1-alpha2 control, while truncation of the H3 amino terminus has a more modest (3-fold or less) effect. Strikingly, combination of the H3 truncation with an H4 mutation causes a 40-fold decrease in repression, clearly indicating a central role for these histones in a1-alpha2-mediated repression. However, in contrast to the ordered positioning of nucleosomes adjacent to the alpha2-Mcm1 operator, nucleosomes are not positioned adjacent to the a1-alpha2 operator in diploid cells. Our data indicate that chromatin is important to Ssn6-Tup1-mediated repression but that the degrees of chromatin organization directed by these proteins differ at different promoters.

Chromatin↗
PubMed1997

Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity.

LIM-homeodomain proteins direct cellular differentiation by activating transcription of cell-type-specific genes, but this activation requires cooperation with other nuclear factors. The LIM-homeodomain protein Lmx1 cooperates with the basic helix-loop-helix (bHLH) protein E47/Pan-1 to activate the insulin promoter in transfected fibroblasts. In this study, we show that two proteins originally called Lmx1 are the closely related products of two distinct vertebrate genes, Lmx1.1 and Lmx1.2. We have used yeast genetic systems to delineate the functional domains of the Lmx1 proteins and to characterize the physical interactions between Lmx1 proteins and E47/Pan-1 that produce synergistic transcriptional activation. The LIM domains of the Lmx1 proteins, and particularly the second LIM domain, mediate both specific physical interactions and transcriptional synergy with E47/Pan-1. The LIM domains of the LIM-homeodomain protein Isl-1, which cannot mediate transcriptional synergy with E47/Pan-1, do not interact with E47/Pan-1. In vitro studies demonstrate that the Lmx1.1 LIM2 domain interacts specifically with the bHLH domain of E47/Pan-1. These studies provide the basis for a model of the assembly of LIM-homeodomain-containing complexes on DNA elements that direct cell-type-restricted transcription in differentiated tissues.

Amino Acid Sequence↗
PubMed1997

Endothelin-activated calcium signaling in enteric glia derived from neonatal guinea pig.

The ability of guinea pig enteric glia to respond to endothelins was examined using fura 2-based digital microscopy in glial cells derived from guinea pig taenia coli. Each isoform of endothelin (ET-1, ET-2, ET-3) evoked dose-dependent and equipotent increases in intracellular Ca2+ concentration ([Ca2+]i) and in percentage of cells responding, 4alaEt-1, an ETB receptor agonist, elicited similar [Ca2+]i increments. BQ-788, an ETB antagonist, inhibited [Ca2+]i responses to endothelin. Preincubation of glia with U-73122 a phospholipase C inhibitor, abolished the [Ca2+]i response to ET-3 exposure. Thapsigargin also eliminated ET-3-evoked Ca2+ signaling. The inositol 1,4,5-trisphosphate (IP3) receptor antagonist heparin, introduced into glial cells by radio frequency electroporation, blocked [Ca2+]i responses to ET-3 (100 nM) in 63% of glia. Sustained elevation in [Ca2+]i was abolished by removal of Ca2+ from the buffer and inhibited 85. -3% by Ni2+ (1 mM). Preincubation of glia with 100 nM phorbol 12-myristate 13-acetate (24 h) also inhibited sustained increments in [Ca2+]i by 87%. The presence of IP3 receptors in enteric glia was confirmed by immunofluorescent confocal microscopy.

Animals↗
PubMed1997

Role of free apolipoprotein A-I in cholesterol efflux. Formation of pre-alpha-migrating high-density lipoprotein particles.

This article characterizes products formed by the interaction of purified apolipoprotein (apo) A-I and human fibroblasts. Fibroblasts were incubated with different concentrations of purified apoA-I (1 to 30 micrograms/mL) in tissue culture medium for different periods of time (0 to 24 hours). The medium was then characterized by one- (agarose) and two-dimensional (agarose: polyacrylamide nondenaturing gradient gel) electrophoresis. At any given concentration of apoA-I, the rate of cellular cholesterol efflux appeared linear over 24 hours. Incubating purified apoA-I with fibroblasts for 4 hours, we detected five pre-alpha lipoproteins with particle sizes between 114 and 684 kDa. Formation of pre-alpha lipoproteins was concentration-dependent. At low concentrations (below 5 micrograms/mL apoA-I), all purified apoA-I (with pre-beta mobility) was converted to pre-alpha lipoproteins. At higher concentrations (greater than 5 micrograms/mL apoA-I), more apoA-I remained with pre-beta mobility. The pre-alpha lipoproteins were characterized by colocalization of apoA-I particles with 14C-cholesterol and 32P-phospholipids. Results showed that the pre-alpha particle of lowest molecular weight contained phospholipid and apoA-I but no cholesterol. The remaining pre-alpha particles contained all three substances. When pre-alpha particles were subjected to ultracentrifugation, all particles floated at d < 1.21 g/mL with some of the smallest phospholipid apoA-I only particles being present in the d > 1.21 g/mL fraction. Based on these results, we postulated that in the first stages of reverse cholesterol transport, pre-alpha lipoproteins are formed by the interaction of lipid free apoA-I and peripheral cells.

Apolipoprotein A-I↗
PubMed1997

Evidence for muscarinic 3 receptor mediated ion transport in HT29 cells studied by X-ray microanalysis.

Changes in elemental content in response to muscarinic drugs in HT29 cells were investigated by X-ray microanalysis. Acetylcholine (ACh) and carbachol (Cch), both agonists binding to muscarinic receptors, induced a decrease of the intracellular Cl and K content. This agrees with the notion that these agonists induce electrolyte and water secretion. Atropine, a non-selective antagonist of muscarinic receptors, inhibited the decrease in K and Cl caused by ACh and Cch, and instead caused an increase of the Cl and K concentrations. A similar inhibition was found in the case of the selective muscarinic 3 receptor antagonist P-F-HHSiD. In contrast, the selective muscarinic 2 receptor antagonist AF-DX 116 did not inhibit Cch-activated secretion of K and Cl. A slight inhibition of ACh induced ion secretion was seen, but this inhibition was weak compared to that caused by P-F-HHSiD. Treatment with U-73122, an inhibitor of phospholipase C, blocked ACh or Cch induced ion secretion. These results suggest that ACh and Cch stimulated secretion of Cl and K is mediated by muscarinic 3 receptors via the inositol-1,4,5-trisphosphate (IP3) dependent pathway.

Acetylcholine↗