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Biomedical subjects

Z Xu

Publications and source records attributed to Z Xu.

At least 289 records · Page 16Linked to original sources
PubMed1999

[Study on syntheses and spectroscopic property of complexes of quinoxaline-2,3-dicarboxamide with transition metals].

Three new solid complexes of transition metal Co(II), Ni(II) and Cu(II) with quinoxaline-2,3-dicarboxamide were synthesized, and the composition of the complexes was confirmed to be M(Qxda)2Cl2 [M = Co(II), Ni(II), Cu(II)] by elemental analysis, molar conductance and thermal analysis. The coordination pattern and structure were discussed by infrared spectra, electronic spectra.

English Abstract↗
PubMed1999

[Determination of potassium, sodium, chromium and nickel in 11 Chinese traditional medicines by FAAS].

Four metallic elements in 11 Chinese traditional medicines such as potassium, sodium, chromium and nickel were determined by flame atomic absorption spectrophotometer. The results showed that there are rich metal elements, but the contents are different in 11 Chinese traditional medicines, providing useful data for discussing relations between trace elements in Chinese traditional medicines and the cure for CHD.

Chromium↗
PubMed1999

[Determination of 11 metal elements in niuhuang jiangya wan by atomic absorption spectrophotometer].

Eleven metal elements in niuhuang jiangya wan, including sodium, calcium, magnesium, potassium, iron, chromium, manganese, nickel, cadmium, copper and zinc, were determined by flame atomic absorption spectrophotometer. The results showed that there are rich metal elements in niuhuang jiangya wan and provided useful data for discussing the relation between trace elemtnts in niuhuang jiangya wan and cure for high blood pressure.

Drugs, Chinese Herbal↗
PubMed1998

GroEL/GroES: structure and function of a two-stroke folding machine.

Recent structural and functional studies have greatly advanced our understanding of the mechanism by which chaperonins (Cpn60) mediate protein folding, the final step in the accurate expression of genetic information. Escherichia coli GroEL has a symmetric double-toroid architecture, which binds nonnative polypeptide substrates on the hydrophobic walls of its central cavity. The asymmetric binding of ATP and cochaperonin GroES to GroEL triggers a major conformational change in the cis ring, creating an enlarged chamber into which the bound nonnative polypeptide is released. The structural changes that create the cis assembly also change the lining of the cavity wall from hydrophobic to hydrophilic, conducive to folding into the native state. ATP hydrolysis in the cis ring weakens it and primes the release of products. When ATP and GroES bind to the trans ring, it forms a stronger assembly, which disassembles the cis complex through negative cooperativity between rings. The opposing function of the two rings operates as if the system had two cylinders, one expelling the products of the reaction as the other loads up the reactants. One cycle of the reaction gives the polypeptide about 15 s to fold at the cost of seven ATP molecules. For some proteins, several cycles of GroEL assistance may be needed in order to achieve their native states.

Adenosine Triphosphate↗
PubMed1998

Non-NMDA receptor antagonist-induced drinking in rat.

Glutamate has been implicated in the central control of mechanisms that maintain body fluid homeostasis. The present studies demonstrate that intracerebroventricular (i.c.v.) injections of the non-N-methyl-d-aspartate (NMDA) receptor antagonists 6, 7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) induce drinking in rats. The dipsogenic effect of i.c.v. DNQX was antagonized by the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The water intake induced by DNQX was also blocked by pretreatment with a NMDA receptor antagonist, MK-801, but not by angiotensin type 1 (AT1) or acetylcholine muscarinic receptor antagonists (losartan and atropine). The results indicate that non-NMDA receptors may exert a tonic inhibitory effect within brain circuits that control dipsogenic activity and that functional integrity of NMDA receptors may be required for the non-NMDA receptor antagonists to induce water intake.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

Interaction of Ionic Species and Fine Solids with a Low Energy Hydrophobic Surface from Contact Angle Measurement.

Interactions of ionic species, (organic and inorganic) precipitates, and fine solids with a low energy hydrophobic surface were examined using a model system of paraffin wax in aqueous solutions. Contact angle measurement was used to evaluate the interactions between paraffin wax and testing variables. No changes in contact angle were observed with various types of metal and metal hydroxyl ions, metal hydroxyl precipitates, fine silica, and alumina powders, suggesting weak or absence of interactions between these species and paraffin wax. At pH <9, the presence of amine reduced the contact angle, but no pH dependence on contact angle was observed for a given amine concentration. A sharp decrease in contact angle was observed at higher pHs, where precipitates of amine molecules formed probably on wax surfaces. In the presence of lauric acid, on the other hand, contact angles reduced at a pH below 8, due to the formation of precipitates, but the reduction was less significant, compared with the reduction by amine precipitates. At high pHs, adding lauric acid did not show any effect on the measured contact angles. The significant effect of fine solids on contact angle was observed only when the solids were made hydrophobic by adsorbed surfactants. The present study further demonstrated that both the thermodynamic criteria and the interactions among substrate/solids/surfactants/metal ions must be considered in identifying the effect of different factors on the wettability of low energy hydrophobic surfaces. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Evidence that Hsc70 negatively modulates the activation of the heme-regulated eIF-2alpha kinase in rabbit reticulocyte lysate.

The role of the heat-shock cognate protein, Hsc70, in regulating the activity of the heme-regulated eIF-2alpha kinase (HRI) in hemin-supplemented rabbit reticulocyte lysate (RRL) in response to heat and oxidative stress was examined and compared with the effect of Hsc70 on HRI activation in response to heme deficiency. Hsc70 suppressed eIF-2alpha phosphorylation and maintained the guanine nucleotide exchange activity of eIF-2B in heme-deficient RRL and in hemin-supplemented RRL exposed to elevated temperatures (42 degrees C), denatured protein (reduced carboxymethylated bovine serum albumin, RCM-BSA), oxidized glutathione or Hg2+. The ability of Hsc70 to inhibit HRI activation was mediated through its ability to inhibit the hyper-autophosphorylation of transformed HRI, which causes the hyperactivation of HRI. Maintenance of protein-synthesis rate was observed to be an unreliable indicator of the ability of Hsc70 to suppress HRI activation in response to stress. While Hsc70 completely reversed protein synthesis inhibition caused by Hg2+. Hsc70 only partially reversed translational inhibition caused by oxidized glutathione (GSSG) or heat shock. The inability of Hsc70 to fully protect protein synthesis from inhibition induced by heat shock or GSSG was due to inability of Hsc70 to protect eIF-4 E from heat-induced dephosphorylation, and its inability to protect translational elongation from GSSG-induced inhibition, respectively. Activation of HRI in heat-shocked hemin-supplemented lysate correlated with a marked decrease in the pool of Hsc70 that was available to bind RCM-BSA and the loss of the interaction of Hsc70 with HRI. These observations indicate that heat shock induced the accumulation of a sufficient quantity of Hsc70 binding substrates (e.g., denatured protein) to sequester Hsc70 and inhibit the ability of Hsc70 to suppress HRI activation. Our results indicate that Hsc70 not only negatively modulates the activation of HRI in heme-deficienct RRL, but also in hemin-supplemented RRL in response to heat and oxidative stress.

Animals↗
PubMed1998

LMA1 binds to vacuoles at Sec18p (NSF), transfers upon ATP hydrolysis to a t-SNARE (Vam3p) complex, and is released during fusion.

Vacuole fusion requires Sec18p (NSF), Sec17p (alpha-SNAP), Ypt7p (GTP binding protein), Vam3p (t-SNARE), Nyv1p (v-SNARE), and LMA1 (low Mr activity 1, a heterodimer of thioredoxin and I(B)2). LMA1 requires Sec18p for saturable, high-affinity binding to vacuoles, and Sec18p "priming" ATPase requires both Sec17p and LMA1. Either the sec18-1 mutation and deletion of I(B)2, or deletion of both I(B)2 and p13 (an I(B)2 homolog) causes a striking synthetic vacuole fragmentation phenotype. Upon Sec18p ATP hydrolysis, LMA1 transfers to (and stabilizes) a Vam3p complex. LMA1 is released from vacuoles in a phosphatase-regulated reaction. This LMA1 cycle explains how priming by Sec18p is coupled to t-SNARE stabilization and to fusion.

Adenosine Triphosphatases↗
PubMed1998

Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1.

Amyotrophic lateral sclerosis (ALS) involves motor neuron degeneration, skeletal muscle atrophy, paralysis, and death. Mutations in Cu,Zn superoxide dismutase (SOD1) are one cause of the disease. Mice transgenic for mutated SOD1 develop symptoms and pathology similar to those in human ALS. To understand the disease mechanism, we developed a simple behavioral assay for disease progression in mice. Using this assay, we defined four stages of the disease in mice expressing G93A mutant SOD1. By studying mice with defined disease stages, we tied several pathological features into a coherent sequence of events leading to motor neuron death. We show that onset of the disease involves a sharp decline of muscle strength and a transient explosive increase in vacuoles derived from degenerating mitochondria, but little motor neuron death. Most motor neurons do not die until the terminal stage, approximately 9 weeks after disease onset. These results indicate that mutant SOD1 toxicity is mediated by damage to mitochondria in motor neurons, and this damage triggers the functional decline of motor neurons and the clinical onset of ALS. The absence of massive motor neuron death at the early stages of the disease indicates that the majority of motor neurons could be rescued after clinical diagnosis.

Amyotrophic Lateral Sclerosis↗
PubMed1998

In-frame elimination of exon 10 in Cftrtm1Unc CF mice.

Cystic fibrosis (CF) is a severe autosomal-linked inherited disease in humans. Transgenic CF animals play a crucial role in the study of molecular mechanisms underlying disease pathology. In the present study, CFTR mRNA expression was examined in different tissues from one CF mouse model that contains a disruption in exon 10 sequence of the CF transmembrane conductance regulator (CFTR) gene. Multiple tissue samples were collected from new-born normal (+/+), homozygous (-/-), and heterozygous (+/-) mice and compared for their CFTR mRNA expression. Total RNA samples were prepared from eight different tissues (nasal mucosa, trachea, lung, colon, intestine, pancreas, liver, gonads, and brain) and then analyzed by reverse transcription polymerase chain reaction (RT-PCR) amplification. A 329-bp fragment comprising exon 9 through exon 11 of the CFTR gene was amplified from all tissues of the normal mouse. In contrast, a 137-bp fragment was observed in tissue samples from homozygous CF mice. Both the 329-bp and 137-bp fragments were detected in samples from heterozygous mice. Direct sequencing analysis of the amplified fragments showed an exon 9-exon 11 splice junction, indicating that the entire exon 10 sequence was eliminated from homozygous CF mice. RT-PCR analysis of the 3' end of CFTR mRNA showed the presence of a 682-bp, exon 20-24 fragment in -/- and +/- mice. These results demonstrate that an alternately spliced CFTR mRNA is produced in this CF 'knock-out' mouse. A semi-quantitative comparison of the wild-type and exon 10 minus CFTR (CFTR-E10) mRNA in heterozygote animals indicated that less (but a detectable amount) mutant CFTR mRNA was present in all organs tested. There was, however, a significant reduction of CFTR-E10 mRNA in the liver and the pancreas. Since the deletion of exon 10 is in-frame, the significance of the CFTR-E10 mRNA in terms of CFTR protein and function requires further analysis.

Animals↗
PubMed1998

Arachidonic acid-sensitive A-currents and multiple Kv4 transcripts are expressed in chick ciliary ganglion neurons.

A-currents (IA) of chick ciliary ganglion (CG) neurons were blocked reversibly by arachidonic acid and a non-metabolizable analog of arachidonic acid, 5,8,11,14-eicosatetraynoic acid. Inhibition of IA by both lipids was observed in whole-cell recordings and in excised inside-out patches, suggesting that Kv4 (Shal) subunits contribute to functional IA channels in CG neurons. Consistent with this, Kv4.2 and Kv4.3 cDNAs were isolated by RT-PCR from chick CG neurons.

Animals↗
PubMed1998

DNA minor groove binding-directed poisoning of human DNA topoisomerase I by terbenzimidazoles.

We have employed a broad range of spectroscopic, calorimetric, DNA cleavage, and DNA winding/unwinding measurements to characterize the DNA binding and topoisomerase I (TOP1) poisoning properties of three terbenzimidazole analogues, 5-phenylterbenzimidazole (5PTB), terbenzimidazole (TB), and 5-(naphthyl[2,3-d]imidazo-2-yl)bibenzimidazole (5NIBB), which differ with respect to the substitutions at their C5 and/or C6 positions. Our results reveal the following significant features. (i) The overall extent to which the three terbenzimidazole analogues poison human TOP1 follows the hierarchy 5PTB > TB >> 5NIBB. (ii) The impact of the three terbenzimidazole analogues on the superhelical state of plasmid DNA depends on the [total ligand] to [base pair] ratio (rbp), having no effect on DNA superhelicity at rbp ratios < or = 0.1, while weakly unwinding DNA at rbp ratios > 0.1. This weak DNA unwinding activity exhibited by the three terbenzimidazoles does not appear to be correlated with the abilities of these compounds to poison TOP1. (iii) Upon complexation with both poly(dA).poly(dT) and salmon testes DNA, the three terbenzimidazole analogues exhibit flow linear dichroism properties characteristic of a minor groove-directed mode of binding to these host DNA duplexes. (iv) The apparent minor groove binding affinities of the three terbenzimidazole analogues for the d(GA4T4C)2 duplex follow a qualitatively similar hierarchy to that noted above for ligand-induced poisoning of human TOP1-namely, 5PTB > TB > 5NIBB. In the aggregate, our results suggest that DNA minor groove binding, but not DNA unwinding, is important in the poisoning of TOP1 by terbenzimidazoles.

Animals↗
PubMed1998

Antagonistic roles of neurofilament subunits NF-H and NF-M against NF-L in shaping dendritic arborization in spinal motor neurons.

Dendrites play important roles in neuronal function. However, the cellular mechanism for the growth and maintenance of dendritic arborization is unclear. Neurofilaments (NFs), a major component of the neuronal cytoskeleton, are composed of three polypeptide subunits, NF-H, NF-M, and NF-L, and are abundant in large dendritic trees. By overexpressing each of the three NF subunits in transgenic mice, we altered subunit composition and found that increasing NF-H and/or NF-M inhibited dendritic arborization, whereas increasing NF-L alleviated this inhibition. Examination of cytoskeletal organization revealed that increasing NF-H and/or NF-M caused NF aggregation and dissociation of the NF network from the microtubule (MT) network. Increasing NF-H or NF-H together with NF-M further reduced NFs from dendrites. However, these changes were reversed by elevating the level of NF-L with either NF-H or NF-M. Thus, NF-L antagonizes NF-H and NF-M in organizing the NF network and maintaining a lower ratio of NF-H and NF-M to NF-L is critical for the growth of complex dendritic trees in motor neurons.

Animals↗
PubMed1998

Effects of intracerebroventricular dizocilpine (MK801) on dehydration-induced dipsogenic responses, plasma vasopressin and c-fos expression in the rat forebrain.

This study determines the interaction between glutamate receptors and dehydration-induced drinking, vasopressin (AVP) release, plasma osmolality and c-fos expression in the brain of conscious rats. The NMDA receptor antagonist dizocilpine (100 nmol infused into the cerebral ventricles) suppressed drinking following either 22 h water deprivation or intragastric injection of hypertonic saline (1.5 M), attenuated the increased plasma vasopressin induced by dehydration, but had no effects on peripheral hyperosmolality caused by either water deprivation or injections of hypertonic saline. Dizocilpine had no inhibitory effects on feeding after 24 h food deprivation. Dizocilpine also suppressed c-fos expression induced by dehydration in the median preoptic nucleus (MPN), the supraoptic and paraventricular nuclei (SON and PVN), but did not influence c-fos expression in the subfornical organ (SFO). The non-NMDA receptor antagonists CNQX (400 nmol) or DNQX (60 nmol) affected neither the animals' drinking nor c-fos expression induced by dehydration. Double staining showed that suppression of c-fos expression following dizocilpine occurred in the NMDA R1 receptor containing neurons in the hypothalamus. These results suggest that the NMDA-type glutamate receptors may be involved in dehydration induced dipsogenic and neuroendocrinological responses. They complement our earlier findings that dizocilpine also attenuates drinking and c-fos expression following intraventricular infusions of angiotensin II.

Animals↗
PubMed1998

Central renin injections: effects on drinking and expression of immediate early genes.

This study investigated the drinking response and the expression of Fos- and Egr-1-immunoreactivity (Fos-ir; Egr-1-ir) in the brain induced by endogenous angiotensin generated by intracerebroventricular (i.c.v.) injection of renin. Renin induced Fos-ir in the subfornical organ (SFO), median preoptic (MnPO), supraoptic and paraventricular nuclei (SON and PVN), area postrema (AP), nuclei of the solitary tract (NTS) and lateral parabrachial nuclei (LPBN). Renin-induced Egr-1-ir exhibited a similar pattern of distribution as that observed for Fos-ir. The dose of i.c.v. renin that induced expression of immediate early gene (IEG) product immunoreactivity also produced vigorous drinking. When renin-injected rats were pretreated with captopril, an angiotensin converting enzyme inhibitor, drinking was blocked. With the same captopril pretreatment, both Fos- and Egr-1-ir in the SFO, MnPO, SON, PVN, AP and LPBN were also significantly reduced.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Humanization and pharmacokinetics of a monoclonal antibody with specificity for both E- and P-selectin.

E- and P-selectin (CD62E and CD62P) are cell adhesion molecules that mediate leukocyte-endothelial cell and leukocyte-platelet interactions and are involved in leukocyte recruitment during inflammation. We previously developed a murine mAb, EP-5C7 (or mEP-5C7), that binds and blocks both E- and P-selectin. When used in humans, murine mAbs have short circulating half-lives and generally induce potent human anti-mouse Ab responses. We therefore engineered a humanized, complementarity determining region-grafted version of mEP-5C7 incorporating human gamma4 heavy and kappa light chain constant regions (HuEP5C7.g4). HuEP5C7.g4 retains the specificity and avidity of mEP-5C7, binding to human E- and P-selectin but not to human L-selectin, and blocking E- and P-selectin-mediated adhesion. Surprisingly, when administered to rhesus monkeys, HuEP5C7.g4 was eliminated from the circulation very rapidly, even faster than the original murine Ab. To isolate the cause of the short serum half-life of HuEP5C7.g4, several Ab variants were constructed. A chimeric IgG4 Ab was made by replacing the humanized V regions with murine V regions. A humanized IgG2 Ab, HuEP5C7.g2, was also made by replacing the human gamma4 with a gamma2 constant region. Results from pharmacokinetic studies in rhesus monkeys demonstrated that the chimeric IgG4 is also rapidly eliminated rapidly from serum, similar to the humanized IgG4 Ab, while the humanized IgG2 Ab displays a long circulation half-life, typical of human Abs.

Amino Acid Sequence↗
PubMed1998

A novel fiber-optic pH sensor incorporating carboxy SNAFL-2 and fluorescent wavelength-ratiometric detection.

A fiber-optic pH sensor was prepared using the self-referencing fluorescent pH probe carboxy seminaphtho-fluorescein (SNAFL-2). The ratio of the emission from the base form of this dye and the emission near the isoemissive point is insensitive to variations in the excitation intensity and photobleaching. The carboxy SNAFL-2 and a photoaffinity crosslinker, 4-azido-2,3,5,6-tetrafluorobenzoic acid, succinimidyl ester, were attached onto poly(acrylamide-co-vinylamine) to form a hydrophilic functional membrane for the fiber-optic sensor. Photo crosslinking was used to create a crosslinked pH-sensing membrane and covalently bind the membrane onto the surface of the PMMA optical fiber. The fluorescent properties of the membrane-fiber conjugate have been determined. The membrane is stable, and the pH sensor shows a fast response time and excellent resolution in a wide pH range of 3 to 11.

Biocompatible Materials↗