Search PubMed⌕ Search

Biomedical subjects

C Zhang

Publications and source records attributed to C Zhang.

At least 127 records · Page 7Linked to original sources
PubMed2001

Calpain activity in the rat brain after transient forebrain ischemia.

Activity of the Ca(2+)-dependent protease calpain is increased in neurons after global and focal brain ischemia, and may contribute to postischemic injury cascades. Understanding the time course and location of calpain activity in the post-ischemic brain is essential to establishing causality and optimizing therapeutic interventions. This study examined the temporal and spatial characteristics of brain calpain activity after transient forebrain ischemia (TFI) in rats. Male Long Evans rats underwent 10 min of normothermic TFI induced by bilateral carotid occlusion with hypovolemic hypotension (MABP 30 mm Hg). Brain calpain activity was examined between 1 and 72 h after reperfusion. Western blot analysis of regional brain homogenates demonstrated a bimodal pattern of calpain-mediated alpha-spectrin degradation in the hippocampus, cortex, and striatum with an initial increase at 1 h followed by a more prominent secondary increase at 36 h after reperfusion. Immunohistochemical analysis revealed that calpain activity was primarily localized to dendritic fields of selectively vulnerable neurons at one hour after reperfusion. Between 24 and 48 h after reperfusion neuronal calpain activity progressed from the dorsal to ventral striatum, medial to lateral CA1 hippocampus, and centripetally expanded from watershed foci in the cerebral cortex. This progression was associated with fragmentation of dendritic processes, calpain activation in the neuronal soma and subsequent neuronal degeneration. These observations demonstrate a clear association between calpain activation and subsequent delayed neuronal death and suggest broad therapeutic window for interventions aimed at preventing delayed intracellular Ca(2+) overload and pathologic calpain activation.

Animals↗
PubMed2001

Monoclonal antibodies derived from BALB/c mice immunized with apoptotic Jurkat T cells recognize known autoantigens.

It has been postulated that post-translational modifications and relocalization of proteins during apoptosis may lead to presentation of these molecules to the immune system in such a way that normal mechanisms of tolerance are bypassed. In the present study, Jurkat cells were induced to undergo apoptosis by treatment with the chemotherapeutic agent Ara-C. BALB/c mice were then immunized with the apoptotic cells and hybridomas were generated. Using an indirect immunofluorescence assay, the monoclonal antibodies produced were screened by flow cytometry for those monoclonal antibodies demonstrating reactivity with permeabilized apoptotic Jurkat cells but not with non-permeabilized normal or apoptotic Jurkat cells. Of 281 monoclonal antibodies, 20 monoclonal antibodies with these properties were selected for further analysis. Using 32P- or 35S-metabolically labelled Jurkat cells, these selected monoclonal antibodies were screened for their ability to recognize autoantigens by immunoprecipitation and Western blotting. Well characterized autoimmune sera were then used to confirm the identity of autoantigens by immunoblotting. We demonstrate that immunization of normal mice with apoptotic Jurkat cells results in the formation of antibodies targeting multiple autoantigens or autoantigen complexes, including Ku, rRNPs, snRNPs and vimentin. These findings are consistent with the hypothesis that apoptosis can contribute to the development of autoimmunity.

Animals↗
PubMed2001

Src family kinase and adenosine differentially regulate multiple MAP kinases in ischemic myocardium: modulation of MAP kinases activation by ischemic preconditioning.

Recent studies suggest that ischemia activates Src and members of the mitogen-activated protein (MAP) kinase superfamily and their downstream effectors, including big MAP kinase 1 (BMK1) and p90 ribosomal S6 kinase (p90RSK). It has also been reported that adenosine is released during ischemia and involved in triggering the protective mechanism of ischemic preconditioning. To assess the roles of Src and adenosine in ischemia-induced MAP kinases activation, we utilized the Src inhibitor PP2 (4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and the adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (SPT) in perfused guinea pig hearts. PP2 (1 microm) inhibited ischemia-induced Src, BMK1 and JNK activation but not JAK2 and p38 activation. SPT inhibited ischemia-mediated p38 and JNK activation. These results demonstrate that Src family kinase and adenosine regulate MAP kinases by parallel pathways. Preconditioning significantly improved both recovery of developed pressure and dp/dt in isolated guinea pig hearts. Since the protective effect of preconditioning was blocked by PP2 (1 microm) and SPT (50 microm), we next investigated the regulation of Src, MAP kinases and p90RSK during preconditioning. The activity and time course of ERK1/2 was not changed, but p90RSK activation by reperfusion was completely inhibited by preconditioning. In contrast, the activation by ischemia of Src, BMK1, p38 and JNK was significantly faster in preconditioned hearts. Maximal BMK1 activation by ischemia was also significantly enhanced by preconditioning. These data suggest important roles for Src family kinases and adenosine in mediating preconditioning, and suggest specific roles for individual MAP kinases in preconditioning.

Adenosine↗
PubMed2001

Protein folds: molecular systematics in three dimensions.

Advances in methods of structure determination have led to the accumulation of large amounts of protein structural data. Some 500 distinct protein folds have now been characterized, representing one-third of all globular folds that exist. The range of known structural types and the relatively large fraction of the protein universe that has already been sampled have greatly facilitated the discovery of some unifying principles governing protein structure and evolutionary relationships. These include a highly skewed distribution of topological arrangements of secondary-structure elements that favors a few very common connectivities and a highly skewed distribution in the capacity of folds to accommodate unrelated sequences. These and other observations suggest that the number of folds is far fewer than the number of genes, and that the fold universe is dominated by a small number of giant attractors that accommodate large numbers of unrelated sequences. Thus all basic protein folds will likely be determined in the near future, laying the foundation for a comprehensive understanding of the biochemical and cellular functions of whole organisms.

Amino Acid Motifs↗
PubMed2001

Biochemical and physiological evidence that bile acids produced and released by lake char (Salvelinus namaycush) function as chemical signals.

It has been hypothesized that faeces of juvenile lake char (Salvelinus namaycush) may contain chemical cues that mediate behaviour of conspecifics. However, our knowledge of bile acids naturally produced and released by fish is limited. Using HPLC, we fractionated bile acids produced and released by lake char and examined their stimulatory effectiveness using electro-olfactogram recordings. Taurocholic acid, taurochenodeoxycholic acid, taurooxocholanic acid, taurooxodeoxycholic acid 3alpha-sulphate, trace amounts of taurolithocholic acid and an unidentified sulphated bile steroid were found in bile and faeces. Bile acids were either taurine amidated or sulphated, or both. Lake char released an average of 4 nmol min(-1) bile acids per kilogram of body weight into their tank water. Urinary bile acids accounted for only a small portion of total bile acids released into water. Water and faeces contained higher proportion of taurochenodeoxycholic acid and sulphated bile acids (relative to taurocholic acid) than bile. The electro-olfactogram recordings demonstrated that bile acids released by lake char were detectable by their olfactory system at nanomolar concentrations, which is well below the levels of bile acids released into water. The exquisite olfactory sensitivity of lake char to water-borne bile acids released by their conspecifics is consistent with a role for these compounds as important chemical signals.

Animal Communication↗
PubMed2001

Creation of chimeric mutant axolotls: a model to study early embryonic heart development in Mexican axolotls.

The Mexican axolotl (Ambystoma mexicanum) provides an excellent model for studying heart development since it carries a cardiac lethal mutation in gene c that results in failure of contraction of mutant embryonic myocardium. In cardiac mutant axolotls (c/c) the hearts do not beat, apparently because of an absence of organized myofibrils. To date, there has been no way to analyze the genotypes of embryos from heterozygous spawnings (+/c x +/c) until stage 35 when the normal (+/c or +/+) embryos first begin to have beating hearts; mutant (c/c) embryos fail to develop normal heartbeats. In the present study, we created chimeric axolotls by using microsurgical techniques. The general approach was to transect tailbud embryos and join the anterior and posterior halves of two different individuals. The chimeric axolotl is composed of a normal head and heart region (+/+), permitting survival and a mutant body containing mutant gonads (c/c) that permits the production of c/c mutant offspring: 100% c/c offspring were obtained by mating c/c chimeras (c/c x c/c). The mutant phenotypes were confirmed by the absence of beating hearts and death at stage 41 in 100% of the embryos. Examination of the mutant hearts with electron microscopy and comfocal microscopy after immunofluorescent staining for tropomyosin showed identical images to those described previously in naturally-occurring c/c mutant axolotls (i.e., lacking organized sarcomeric myofibrils). These "c/c chimeric" axolotls provide a useful and unique way to investigate early embryonic heart development in cardiac mutant Mexican axolotls.

Ambystoma↗
PubMed2001

Retroperitoneal suppurative lymphadenitis complicating Staphylococcus aureus acute bacterial endocarditis.

Acute bacterial endocarditis is commonly caused by Staphylococcus aureus. Acute bacterial endocarditis due to S. aureus is often complicated by metastatic infection to distant organs, i.e. the central nervous system, the heart, lungs, kidneys and joints. However, metastatic lymph node involvement has not been reported. This is a case report of S. aureus acute bacterial endocarditis complicated by metastatic suppurative lymphadenitis of retroperitoneal lymph nodes. We believe this is the first reported case of suppurative lymphadenitis of the mesenteric lymph nodes secondary to S. aureus acute bacterial endocarditis.

Acute Disease↗
PubMed2001

Relationship between endogenous estrogen concentrations and serum cholesteryl ester transfer protein concentrations in Chinese women.

BACKGROUND: CETP plays an important role in HDL metabolism and in the reverse cholesterol transport pathway. METHODS: The relationship between the changes of endogenous estrogen and the concentration of cholesteryl ester transfer protein (CETP) in the serum of Chinese women was investigated. Serum concentrations of estradiol (E(2)), follicle-stimulating hormone (FSH), CETP and lipid profile were determined in 196 Chinese women (52 premenopausal with ages ranging from 18 to 40 years, 57 perimenopausal from 41 to 60 years, and 87 postmenopausal from 61 to 81 years). RESULTS: Serum CETP concentration was significantly lower in postmenopausal women compared with those in perimenopausal and premenopausal women (1.39+/-1.06, 2.36+/-1.50 and 2.31+/-1.25 mg/l, respectively, P<0.0001). Even in the women around the menopausal, CETP concentration in postmenopause was significantly lower than that in premenopause (1.93+/-1.33 vs. 3.42+/-1.35 mg/l, P<0.01). In addition, CETP concentration had a highly positive correlation with serum concentration of E(2) (r=0.243, P<0.001), while negative correlation of CETP concentration with serum concentration of FSH was found (r=-0.273, P<0.001). CONCLUSIONS: Estrogen may affect the concentration of CETP.

Adolescent↗
PubMed2001

Inhibitory effects of rosa roxburghii tratt juice on in vitro oxidative modification of low density lipoprotein and on the macrophage growth and cellular cholesteryl ester accumulation induced by oxidized low density lipoprotein.

BACKGROUND: Rosa roxburghii tratt juice (RRTJ) administration has been shown to significantly ameliorate atherosclerotic diseases in cholesterol-fed animals. However, the mechanism for the antiatherogenic effect of RRTJ is not clear. METHODS: We investigated the effects of RRTJ on in vitro oxidative modification of LDL and on LDL-induced macrophage growth and cellular cholesteryl ester (CE) accumulation. The effects of RRTJ on LDL oxidative modification were assessed by relative electrophoretic migration, thiobarbituric acid-reactive substance (TBARS) content, and the formation of conjugated dienes. The inhibition of RRTJ on oxidized LDL (Ox-LDL)-induced murine peritoneal macrophage growth was evaluated by a cell-counting assay and an MTT assay. The effect of RRTJ on Ox-LDL-induced cellular CE accumulation was examined after macrophages were incubated with Ox-LDL in the presence of RRTJ. To clarify the mechanism of the inhibitory effect of RRTJ on Ox-LDL-induced CE accumulation in macrophages, its capacity for cholesterol efflux from macrophage-derived foam cells were examined. RESULTS: We showed that RRTJ significantly reduced LDL oxidative susceptibility. In addition, RRTJ effectively suppressed Ox-LDL-induced macrophage growth and especially Ox-LDL-induced CE accumulation in murine peritoneal macrophages by promoting cellular cholesterol efflux. CONCLUSION: These results indicated that RRTJ exerted its antiatherogenic effects largely due to its ability to inhibit the oxidative modification of LDL and to suppress the formation of foam cells.

Animals↗
PubMed2001

A hypothesis on the metabolism of glyceryl trinitrate in vascular endothelial cells.

BACKGROUND: Extensive research has been conducted regarding the mechanism of action of glyceryl trinitrate (GTN). It is currently believed that GTN undergoes a thiol-dependent metabolic pathway and releases its active metabolite, nitric oxide (NO) and/or S-nitrosothiols (R-SNO). This activates guanylyl cyclase (GC) leading to the formation of cGMP, which is responsible for the relaxation of vascular smooth muscles and the inhibition of platelet aggregation. The lack of knowledge as to the precise mechanism of GTN action and the modulation of its formation has limited the prevention of tolerance to GTN. RESULTS: With cultured human vascular endothelial cells (EC), we showed that nitrite was first formed in endothelial cells whose concentration was dependent on reduced thiols. Cells preexposed to GTN significantly decreased the production of nitrite compared with cells that were not preexposed. Furthermore, we showed that thiols in cultured cells were oxidized during interaction with GTN, which correlated with the time of exposure to GTN. CONCLUSION: Nitrite is the first active intermediate of GTN metabolism in endothelial cells. The analysis of the changes of the blood nitrite and reduced thiols concentration is helpful for evaluating the vasodilatation activity of GTN during therapeutic treatments.

Buffers↗
PubMed2001

Pharmacokinetics of testosterone after percutaneous gel or buccal administration.

OBJECTIVE: To determine the pharmacokinetics of testosterone following its administration using transdermal gel or buccal lozenges. DESIGN: Pilot study. SETTING: University-based hospital. PATIENT(S): Ten bilaterally oophorectomized women. INTERVENTION(S): Daily micronized testosterone gel (1 mg) and testosterone propionate lozenge (1 mg). MAIN OUTCOME MEASURE(S): Total testosterone, androstenedione, dihydrotestosterone, 3alpha-androstanediol glucuronide, and sex hormone-binding globulin were measured in serum by specific radioimmunoassays; free testosterone levels were also calculated. RESULT(S): Before treatment, serum testosterone levels in the groups using the lozenge and gel were 16 +/- 4.0 and 20 +/- 6.0 ng/dL, respectively. Mean maximum testosterone levels obtained with the lozenge occurred 1 hour after administration on days 1 (692 +/- 236 ng/dL) and 14 (836 +/- 309 ng/dL) of treatment and fell precipitously thereafter. In contrast, testosterone levels obtained with the gel showed a prolonged rise reaching maximal levels of 97 +/- 78 and 100 +/- 60 ng/dL after 18 hours. The serum level patterns of free testosterone, dihydrotestosterone, and 3alpha-androstanediol glucuronide were similar to the corresponding total testosterone levels. CONCLUSION(S): Administration of testosterone lozenge by buccal absorption produced a rapid and brief elevation of testosterone levels, with levels reaching upper limits of the male range. In contrast, transdermal testosterone gel absorption resulted in a prolonged elevation of testosterone levels, which were in the hyperandrogenic female range but resembled steady state pharmacokinetics.

Absorption↗
PubMed2001

Elastic and plastic behavior of plasma-sprayed hydroxyapatite coatings on a Ti-6Al-4V substrate.

A novel approach that combines the indentation tests with nonlinear finite element modeling (FEM) is proposed to estimate the elastic/plastic constitutive relation of plasma-sprayed hydroxyapatite (HA) coatings on a Ti-6Al-4V substrate. The Ramberg-Osgood constitutive equation can well describe the deformation behavior of plasma-sprayed HA coating on Ti-6Al-4V. A reasonable estimation for the elastic modulus of the HA coatings is given, based on the fact that the coating consists of a crystalline phase, an amorphous phase and pores. The Ramberg-Osgood equations of the coatings indicate that the post-treatment increases both resistance to elastic and plastic deformation, but no effect on strain hardening behavior. The post-treatment, however, could reduce the resistance to coating/substrate separation. The influence of titanium substrate becomes more significant with decreasing coating thickness and increasing indentation load because the plasma-sprayed HA coatings exhibit much less resistance to indentation deformation than does Ti-6Al-4V.

Alloys↗
PubMed2001

Effect of cholecystokinin-8 microinjection into ventral tegmental area on dopamine release in nucleus accumbens of rats: an in vivo voltammetric study.

1. Effects of microinjection of cholecystokinin-8 (CCK-8) into the rat ventral tegmental area were studied on dopamine (DA) release from nucleus accumbens (Acb), using fast cyclic voltammetry and carbon fibre microelectrode. 2. DA release was evoked by electrical stimulation of the medial forebrain bundle (MFB). DA release from Acb was increased with increasing intensity or frequency of electrical stimulation in a dose-dependent manner and was inhibited by microinjection of CCK-8 (0.5 microg/kg) into the ventral tegmental area. 3. The release of DA was clearly reduced at all the intensities (0.25, 0.5, 0.75 and 1.0 mA) tested following CCK injection into the VTA, which was statistically significant (P<0.05). But the reduced percentage of DA release did not show significant changes between the data obtained with stimuli of different intensities (P>0.05). 4. While no change could be found with the stimuli of 10Hz, the DA release was significantly suppressed by injection of CCK-8 at the other three frequencies tested (50 Hz, 100 Hz and 250 Hz). Furthermore, although the differences in the reduced amounts of DA release obtained at 50 Hz, 100 Hz and 250 Hz were statistically significant, the reduced percentage seemed to be not closely related to the frequency applied (P>0.05). 5. These results indicate that CCK-8 is involved in the regulation of midbrain DA neurotransmission, and thereby implicated in disorders, such as Parkinson's disease, that involve malfunctions of the basal ganglion DA neuronal systems.

Animals↗
PubMed2001

Ran GTPase: a master regulator of nuclear structure and function during the eukaryotic cell division cycle?

Ran is an abundant GTPase that is highly conserved in eukaryotic cells and has been implicated in many aspects of nuclear structure and function, especially determining the directionality of nucleocytoplasmic transport during interphase. However, cell-free systems have recently shown that Ran plays distinct roles in mitotic spindle assembly and nuclear envelope (NE) formation in vitro. During spindle assembly, Ran controls the formation of complexes with importins, the same effectors that control nucleocytoplasmic transport. Here, we review these advances and discuss a general model for Ran in the coordination of nuclear processes throughout the cell division cycle via common biochemical mechanisms.

Active Transport, Cell Nucleus↗
PubMed2001

Type I interferons and limitin: a comparison of structures, receptors, and functions.

The type I interferon (IFN) family includes IFN-alpha, IFN-beta, IFN-pi, and IFN-tau. These molecules are clustered according to sequence homologies, use of the same cell surface receptor, and similar functions. IFN-alpha and IFN-beta have a globular structure composed of five a-helices. Their receptors, IFNAR1 and IFNAR2, belong to the class II cytokine receptor family for a-helical cytokines. Information about structure-function relationships between these and other IFNs is being provided by comparative sequence analysis, reference to a prototypic three-dimensional structure, analysis with monoclonal antibodies, construction of hybrid molecules and site directed mutagenesis. While much remains to be done, it should someday be possible to understand differences among IFNs in terms of how they interact with their corresponding receptors. Our recently identified IFN-like molecule, limitin, has weak sequence homology to IFN-alpha, IFN-beta, and IFN-omega and displays its biological functions through the same IFN-alpha/beta receptors. While limitin has antiproliferative, immunomodulatory, and antiviral effects like IFN-alpha and IFN-beta, it is unique in lacking influence on myeloid and erythroid progenitors. Further analysis of this functionally unique cytokine should be informative about complex IFN-receptor interactions. Furthermore, a human homologue or synthetic variant might be superior for clinical applications as an IFN without myelosuppressive properties.

Amino Acid Sequence↗
PubMed2001

Reactions of electron-deficient alkynes and allenes under phosphine catalysis.

The development of some new synthetic reactions derived from nucleophilic addition of phosphines to electron-deficient carbon-carbon triple bonds is described. These reactions show that the phosphine plays the role of a nucleophile as well as an excellent leaving group. The central problem is to generate a 1,3-dipole from alkynoates or allenoates (2,3-butadienoates) by interaction with various phosphines. This study illuminates the unusual phenomena and shows how this understanding allows control of the reaction.

Journal Article↗
PubMed2001

A comparison of enamelin and amelogenin expression in developing mouse molars.

Amelogenin and enamelin are structural proteins in the enamel matrix of developing teeth. The temporal and spatial patterns of enamelin expression in developing mouse molars have not been characterized, while controversy remains with respect to amelogenin expression by odontoblasts and cementoblasts. Here we report the results of in situ hybridization analyses of amelogenin and enamelin expression in mouse molars from postnatal days 1, 2, 3, 7, 9, 14, and 21. Amelogenin and enamelin mRNA in maxillary first molars was first observed in pre-ameloblasts on the cusp slopes at day 2. The onsets of amelogenin and enamelin expression were approximately synchronous with the initial accumulation of predentin matrix. Both proteins were expressed by ameloblasts throughout the secretory, transition, and early maturation stages. Enamelin expression terminated in maturation stage ameloblasts on day 9, while amelogenin expression is still detected in maturation stage ameloblasts on day 14. No amelogenin expression was observed in day 21 mouse molars. Amelogenin and enamelin RNA messages were restricted to ameloblasts. No expression was observed in pulp, bone, or along the developing root. We conclude that amelogenin and enamelin are enamel-specific and do not directly participate in the formation of dentin or cementum in developing mouse molars.

Ameloblasts↗