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Biomedical subjects

Z Zhao

Publications and source records attributed to Z Zhao.

At least 91 records · Page 5Linked to original sources
PubMed2000

Event-related activation in the human amygdala associates with later memory for individual emotional experience.

The role of the amygdala in enhancing declarative memory for emotional experiences has been investigated in a number of animal, patient, and brain imaging studies. Brain imaging studies, in particular, have found a correlation between amygdala activation during encoding and subsequent memory. Because of the design of these studies, it is unknown whether this correlation is based on individual differences between participants or within-subject variations in moment-to-moment amygdala activation related to individual stimuli. In this study, participants saw neutral and negative scenes and indicated how emotionally intense they found each scene. Separate functional magnetic resonance imaging responses in the amygdala for each scene were related to the participants' report of their experience at study and to performance in an unexpected memory test 3 weeks after scanning. The amygdala had the greatest response to scenes rated as most emotionally intense. The degree of activity in the left amygdala during encoding was predictive of subsequent memory only for scenes rated as most emotionally intense. These findings support the view that amygdala activation reflects moment-to-moment subjective emotional experience and that this activation enhances memory in relation to the emotional intensity of an experience.

Amygdala↗
PubMed2000

REST-VP16 activates multiple neuronal differentiation genes in human NT2 cells.

The RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress transcription of a battery of neuronal differentiation genes in non-neuronal cells by binding to a specific consensus DNA sequence present in their regulatory regions. However, REST/NRSF(-/-) mice suggest that the absence of REST/NRSF-dependent repression alone is not sufficient for the expression of these neuronal differentiation genes and that the presence of other promoter/enhancer-specific activators is required. Here we describe the construction of a recombinant transcription factor, REST-VP16, by replacing repressor domains of REST/NRSF with the activation domain of a viral activator VP16. In transient transfection experiments, REST-VP16 was found to operate through RE1 binding site/neuron-restrictive enhancer element (RE1/NRSE), activate plasmid-encoded neuronal promoters in various mammalian cell types and activate cellular REST/NRSF target genes, even in the absence of factors that are otherwise required to activate such genes. Efficient expression of REST-VP16 through adenoviral vectors in NT2 cells, which resemble human committed neuronal progenitor cells, was found to cause activation of multiple neuronal genes that are characteristic markers for neuronal differentiation. Thus, REST-VP16 could be used as a unique tool to study neuronal differentiation pathways and neuronal diseases that arise due to the deregulation of this process.

Adenoviridae↗
PubMed2000

In vitro reactivity of penicilloyl and penicillanyl albumin and polylysine conjugates with IgE-antibody.

Penicilloylated (BPO) and penicillanylated (BPA) poly-L-lysine (PLL) and human serum albumin (HSA) were prepared and characterized by penamaldate assay and proton NMR spectroscopy. The conjugates were coupled to nitrocellulose (NC) discs and cyanogen bromide activated paper discs and their in vitro reactivities with serum IgE antibodies were examined. Results showed that on paper discs, 55.3 and 83% of the sera reacted with PLL conjugates of BPO and BPA, respectively, while 41.5 and 58.1% reacted with HSA conjugates. On NC discs, HSA conjugates gave better results, 75.6 and 70.7%, respectively for BPO and BPA, compared with 38.6 and 50%, respectively for the PLL conjugates. Overall, the BPA-PLL conjugate on paper discs proved to be the most reactive preparation. Addition of the BPO-PLL paper disc preparation detected more positive sera (85.1%) and we believe that the combined use of these two specificities offers the best test for the detection of penicillin-reactive IgE antibodies.

Cyanogen Bromide↗
PubMed2000

The identification of an endonuclease that cleaves within an HuR binding site in mRNA.

Messenger RNAs (mRNAs) that contain U-rich elements are targeted for rapid decay. Selective inhibition of this decay results in a rapid increase in steady state level. Thus, this is an important regulatory step in gene expression. Previously, we have found that these mRNAs are selectively stabilized by a specific mRNA binding protein called HuR. The mechanism of action of HuR is not well understood. It has been postulated that HuR stabilizes mRNA by the displacement or inhibition of factors that specifically cleave or deadenyl-ate these mRNAs. In this paper, we report the identification and characterization of a novel endo-nuclease that cleaves within an HuR binding site in p27kip1 mRNA. The specificity of this endonuclease and its inhibition by HuR argue for it playing a role in the postranscriptional regulation of gene expression.

Antigens, Surface↗
PubMed2000

Resistance and some enzyme activities in Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae) in relation to carbon dioxide enriched atmospheres.

Two populations (S-1 and S-2) of the psocid, Liposcelis bostrychophila Badonnel were exposed to carbon dioxide enriched atmospheres. Carbon dioxide resistance developed at steady rates in these two populations during this study period. Selection with 35 and 55% CO(2) resulted in resistance development as expressed by LT(50). Resistance increased steadily under continuous selection to 4.6- and 5.3-fold by generation F(30) for S-1 and S-2, respectively. Throughout the selection process, the slopes of regression lines were always lower than that of the control. The results of biochemical assays showed that the activities of carboxyl esterase (CarE) and superoxide dismutase (SOD) in vitro increased in the selection process. Exposure to higher CO(2) content (HCC) resulted in a gradual decrease in CarE activity in both selected and control populations. Although the induction effect of CO(2) on SOD was brief, the induction times for the S-1 and S-2 were greater than those of the control. The elevated catalase (CAT) activity in association with resistance development was also evident, but no statistical correlation was found between CAT activity and HCC resistance. No significant differences were found in acid phosphatase and alkaline phosphatase activities in both selected and control populations during this study. This study demonstrated that high CarE and SOD activities were positively correlated to CO(2) resistance.

Journal Article↗
PubMed2000

Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1.

The CC chemokine receptor-1 (CCR1) is a prime therapeutic target for treating autoimmune diseases. Through high capacity screening followed by chemical optimization, we identified a novel non-peptide CCR1 antagonist, R-N-[5-chloro-2-[2-[4-[(4-fluorophenyl)methyl]-2-methyl-1-piperazinyl ]-2-oxoethoxy]phenyl]urea hydrochloric acid salt (BX 471). Competition binding studies revealed that BX 471 was able to displace the CCR1 ligands macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES, and monocyte chemotactic protein-3 (MCP-3) with high affinity (K(i) ranged from 1 nm to 5.5 nm). BX 471 was a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca(2+) mobilization, increase in extracellular acidification rate, CD11b expression, and leukocyte migration. BX 471 demonstrated a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors. Pharmacokinetic studies demonstrated that BX 471 was orally active with a bioavailability of 60% in dogs. Furthermore, BX 471 effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis. This study is the first to demonstrate that a non-peptide chemokine receptor antagonist is efficacious in an animal model of an autoimmune disease. In summary, we have identified a potent, selective, and orally available CCR1 antagonist that may be useful in the treatment of chronic inflammatory diseases.

Administration, Oral↗
PubMed2000

Vasopressin increases [Ca(2+)](i) in differentiated astrocytes by activation of V1b/V3 receptors but has no effect in mature cortical neurons.

Vasopressin (AVP) plays an important role in regulation of astrocytic, but not neuronal, water content and cell volume during hydro-osmotic challenge. To investigate the intracellular mechanism(s) signaling this response, [Ca(2+)](i) was measured fluorometrically in cultured cerebrocortical astrocytes and neurons, obtained from neonatal and fetal mouse brains, and matured during the culturing period. In astrocytes, [Ca(2+)](i) increased with an EC(50) of between 10(-10) and 10(-9) M AVP, the maximum increase was approximately 100 nM, and the response was independent of extracellular Ca(2+), identifying the receptor as being of the V1b/V3 subtype. In contrast, AVP had no effect on [Ca(2+)](i) in cortical neurons. This cellular difference is consistent with the ability of AVP to increase water permeability in astrocytes but not in neurons.

Animals↗
PubMed2000

Peripheral NMDA and non-NMDA receptors contribute to nociception: an electrophysiological study.

The present study investigated the effects of peripheral administration of N-methy-D-aspartate (NMDA) and non-NMDA receptor antagonists on C-fiber evoked responses of the spinal dorsal horn neurons in the spinalized rats. When DL-2-amino-5-phosphonovaleric acid (AP5) (10 mM, 1 mM, 0.1 mM, 20 microl) or 6, 7-dinitroquinoxaline-2, 3-dione (DNQX) (1 mM, 0.1 mM, 0.01 mM, 20 microl) was subcutaneously injected into the receptive field on the hindplantar region, C-fiber evoked responses of the dorsal horn neurons were profoundly inhibited in a dose-dependent manner. Three hours after subcutaneous injection of carrageenan into the ipsilateral hindpaw, NMDA and non-NMDA antagonist-induced inhibition of C-fiber evoked responses was more potent than that in the normal rat (Student's t-test, p < 0.05). In the carragenan-treated rats, DNQX-induced inhibition was stronger than AP-5-induced one (Student's t-test, p < 0.05). The results suggest that peripheral NMDA and non-NMDA receptors are involved in mediating excitation of nociceptors.

2-Amino-5-phosphonovalerate↗
PubMed2000

Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors.

Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-100-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography studies suggest that the 2-substituent may have a conformational effect favoring the extended binding conformation.

Anticoagulants↗
PubMed2000

Expression of sulfoglucuronyl (HNK-1) carbohydrate and its binding protein (SBP-1) in developing rat cerebellum.

Sulfoglucuronyl carbohydrate (SGC) is expressed on several glycoproteins of the immunoglobulin superfamily of cell-adhesion molecules. Developmental expression of SGC and its binding protein, SBP-1, was studied in the rat cerebellum by immunocytochemistry to understand the function of SBP-1 and the significance of its interaction with SGC. During early postnatal development (postnatal day (PD) 3-10) SBP-1 was strongly expressed in the granule neurons of the external and internal granule cell layers (EGCL and IGCL). This expression declined by PD 15, and disappeared in the adult. Between PD 3 and 15, SGC was expressed in cellular processes surrounding the granule neurons in the IGCL, and it also declined and disappeared with development. SGC expression, however, continued in Purkinje cells and their dendrites in the molecular layer in adults. The expressions of SBP-1 and SGC were developmentally regulated and appeared to be chronologically co-ordinated with granule neuron migration from EGCL to IGCL. High magnification confocal microscopy showed that SBP-1 was primarily localized in nuclei and plasma membranes of granule neurons, whereas SGC in the IGCL was localized on neuronal plasma membranes, dendrites and glial processes, but not in cell soma. The relative localization of SBP and SGC was confirmed by cellular and subcellular markers in vivo and with dissociated cerebellar cells in culture. It is proposed that SBP-1 on plasma membranes of granule neurons interacts with SGC on the surrounding processes and membranes and this interaction could provide a potential mechanism for guidance and cell signaling, in the processes of granule neuron migration and differentiation.

Aging↗
PubMed2000

A role for the A3 adenosine receptor in determining tissue levels of cAMP and blood pressure: studies in knock-out mice.

Adenosine administration has been reported to lower blood pressure by activating specific membrane receptors. The rat and human heart and aorta have been previously found to express both A2-type adenosine receptors, which activate adenylyl cyclase, and A3 adenosine receptors (A3AR), which inhibit adenylyl cyclase. In the current study, we used A3 adenosine receptor (A3AR) knock-out mice to examine the hypothesis that the relative levels of the A2-type adenosine receptors and A3AR determine the steady-state levels of cAMP in the cells and may affect blood pressure. We found that the A3AR knock-out mice express normal levels of the A1- and A2-type adenosine receptors. In situ hybridization demonstrated that the level of A3AR is high in the vascular smooth muscle layer of aortas derived from wild-type mice, but is not detectable in the knock-out mice. The steady-state level of cAMP is elevated in the aorta and heart of knock-out mice, as compared to wild-type mice, but is not altered in platelets, where A3AR is not expressed naturally. A3AR knock-out mice possess a blood pressure comparable to this in wild-type mice. However, when challenged with adenosine, the knock-out mice display a further increase in cAMP levels in the heart and vascular smooth muscle and a significant decrease in blood pressure, as compared to wild-type mice. In contrast, the effect of adenosine on ADP-induced platelet aggregation is similar in both types of mice. These studies indicate that the A3AR affects the steady-state level of cAMP in the tissues where it is naturally expressed, and that it influences the blood pressure in response to adenosine.

Adenosine↗
PubMed2000

[Effect of homocysteine on the proliferation and differentiation of rat embryo midbrain cell].

In order to determine the potential mechanisms by which HCY may exerts its teratogenic effects, a micromass culture for rat embryo midbrain cell was used to reveal the differentiation and proliferation of the cell under different HCY doses (0-10 mmol/L). The results showed that with increased concentration of HCY, the promotion effect changed into inhibition. The concentration inhibiting the formation of differentiated foci by 50% of the control was 4.3 mmol/L, and 2.3 mmol/L when S9 was added. It had an inhibition effects on proliferation in the testing scope. The result suggested that HCY obviously inhibited more cell differentiation than proliferation. The teratogenic hazard of HCY may play an important role in the occurrence of neural tube defects.

Animals↗
PubMed2000

Programmed cell death in the developing heart: regulation by BMP4 and FGF2.

Programmed cell death, or apoptosis, plays an important role in embryonic development. To provide new insights into the role of programmed cell death in cardiac development, we examined the hearts of the murine embryos from E9.5 to postnatal day 3. Using terminal transferase-mediated dUTP nick end-labeling assays, apoptosis was detected in the endocardial cushions and myocardium from E11.5 to postnatal day 3 (P3). In the ventricular myocardium, more apoptotic cells were observed in the left than right ventricles throughout embryonic and early postnatal development. Apoptosis was also present in the trabeculae and papillary muscles of the ventricles. In the outflow tract, cell death was present in the endocardial cushions before they fuse to form the conotruncal septum (E11.5-E12. 5) and reached a peak intensity when the conotruncal septum formed (E13.5). In the atrioventricular (AV) endocardial cushions, cell death was detected in the fusion seam of the cushion tissues at E12. 5 and E13.5 during AV septation. When the patterns of apoptosis were compared with patterns of cell division, we found that programmed cell death occurred in the areas in the endocardial cushions and trabeculae where rates of cell proliferation were low. We also found that programmed cell death was regulated by the growth factors, BMP4 and FGF2, in vitro. BMP4 induced, whereas FGF2 inhibited, apoptosis in both endocardial cushions and ventricular myocardium. Overall, our observations show that there is apoptosis in the regions where fusion or remodeling of tissues occurs. We also show that cardiac programmed cell death can be influenced by growth factors.

Animals↗
PubMed2000

Interleukin 2-induced antinociception partially coupled with mu receptor.

The present study was designed to investigate the involvement of mu receptor in interleukin 2-induced antinociception. Intraplantar injection of human recombinant interleukin 2 (rIL-2) (1. 5x10(4) U) significantly enhanced pain threshold as measured by paw withdrawal latencies (PWLs) to noxious radiant heat in normal rats. After administration of rIL-2, PWLs were also markedly increased in morphine-tolerant and chronic constriction injury (CCI)-operated rats, which have been proven morphine-insensitive. rIL-2-induced antinociception in both morphine-tolerant and CCI-operated rats was significantly lower than that in normal rats. rIL-2 antinociception was partially blocked by naloxone (1 mg/kg i.p.) in normal rats but remained unchanged in the CCI group. Our results suggest that the use of rIL-2 in human medical practice may be extended for its effectiveness in relief of neuropathic pain induced by CCI. Here we infer that mu receptor plays an critical role in IL-2-induced antinociception and that there are also some other receptors involved in this process.

Analgesics↗
PubMed2000

A novel gene is transcribed in the chicken alpha-globin gene domain in the direction opposite to the globin genes.

A novel gene transcribed in the direction opposite to that of the globin genes was found in the chicken alpha-globin gene domain. Northern hybridisation with single-stranded riboprobes revealed that a 4.5-kb poly(A)+ RNA is transcribed in antisense polarity with respect to the globin genes. The transcription unit encoding this RNA seems to overlap the entire cluster of alpha-globin genes and extends at least 15 kb upstream from pi, the first of the alpha-globin genes. This new transcript shows partial sequence homology with that encoded by the human "-14" gene. An oligonucleotide based on part of a restriction fragment of chicken DNA that is 80% homologous to exon 4 of the human "-14" gene hybridises with a 4.5-kb RNA molecule. In situ hybridisation of globin-antisense probes, that detect polyribosomal mRNAs of 1.7 and 2.5 kb on Northern blots, shows these "antisense" transcripts to be present in the cytoplasm. The 4.5-kb RNA is absent in polyribosomal poly(A)+ RNA and may, hence, represent a nuclear pre-mRNA transcribed from the chicken gene that is homologous to the human "-14" gene. The expression of this gene is not specific to erythroid cells; analogous transcripts were also detected in poly(A)+ RNA extracted from a chicken lymphoblastoma cell line (HP50). Taken together, these data allow us to postulate the existence in the chicken genome of a novel gene, for which we suggest the name "ggPRX" in analogy to the murine mProx1, a gene identified in the upstream region of the alpha-globin gene domain in mice.

Animals↗
PubMed2000

Expression of Dlx genes during the development of the murine dentition.

The mammalian Dlx homeobox gene family has been shown to play multiple roles in tooth development, but a detailed comparison of the expression pattern of all members throughout tooth development has been lacking. We provide such an analysis for the six known murine Dlx genes. The expression patterns for these genes allow a refinement of previously proposed models for the role of Dlx genes in tooth type specification and raise the possibility of roles for subsets of these genes in tooth initiation, morphogenesis (enamel navel formation, enamel knot induction, cervical loop growth), and enamel formation. The relationship of Dlx gene expression to their genomic organization suggests coordinate regulation of linked genes at early stages but regulatory differences at later stages.

Animals↗
PubMed2000

Comparative study of AMP579 and adenosine in inhibition of neutrophil-mediated vascular and myocardial injury during 24 h of reperfusion.

OBJECTIVE: The purpose of this study was to compare protective effects of AMP579 and adenosine (Ado) at reperfusion (R) on inhibition of polymorphonuclear neutrophil (PMN) activation, PMN-mediated injury to coronary artery endothelium, and final infarct size. METHODS: In anesthetized dogs, 1 h of left anterior descending coronary artery occlusion was followed by 24 h R and drugs were administered at R. Control (n=8, saline control), AMPI (n=7, AMP579, 50 microg/kg i.v. bolus followed by 3 microg/kg/min for 2 h), AMPII (n=7, AMP579, 50 microg/kg i.v. bolus), AMPIII (n=7, AMP579, 3 microg/kg/min i.v. for 2 h), and Ado (n=7, adenosine, 140 microg/kg/min i.v. for 2 h). RESULTS: AMP579 in vitro directly inhibited superoxide radical (O(-)(2)) generation (nM/5x10(6) PMNs) from PMNs dose-dependently (from 17+/-1* at 10 nM to 2+/-0.2* at 10 microM vs. activated 30+/-2). However, inhibition of O(-)(2) generation by Ado at each concentration was significantly less than for AMP579. The IC(50) value for AMP579 (0.09+/-0.02 microM) on O(-)(2) generation was significantly less than that of Ado (3.9+/-1. 1 microM). Adherence of unstimulated PMN to postischemic coronary artery endothelium (PMNs/mm(2)) was attenuated in AMPI and AMPIII vs. Control (60+/-3* and 58+/-3* vs. Control 110+/-4), while Ado partially attenuated PMN adherence (98+/-3*). Accordingly, endothelial-dependent vascular relaxation was significantly greater in AMPI and AMPIII vs. Ado. At 24 h R, myocardial blood flow (MBF, ml/min/g) in the area at risk (AAR), confirmed by colored microspheres, in AMPI and AMPIII was significantly improved (0.8+/-0. 1* and 0.7+/-0.1* vs. Control 0.3+/-0.04). Infarct size (IS, TTC staining) in AMPI and AMPIII was significantly reduced from 38+/-3% in Control to 21+/-4%* and 22+/-3%*, respectively, confirmed by lower plasma creatine kinase activity (I.U./g protein) in these two groups (27+/-6* and 32+/-2* vs. 49+/-3). Cardiac myeloperoxidase activity (MPO, Abs/min) in the AAR was significantly reduced in AMPI and AMPIII vs. Control (36+/-11* and 35+/-10* vs. 89+/-10). However, changes in MBF, IS and MPO were not significantly altered by Ado. CONCLUSIONS: These data suggest that continuous infusion of AMP579 at R is more potent than adenosine in attenuating R injury, and AMP579-induced cardioprotection involves inhibition of PMN-induced vascular and myocardial tissue injury. *P<0.05 vs. Control.

Adenosine↗