Biomedical subjects

J P Zhang

Publications and source records attributed to J P Zhang.

At least 19 recordsLinked to original sources

PubMed2006

Comparative proteome analysis of rat brain and coronary microvascular endothelial cells.

The endothelium of different organs displays a remarkable heterogeneity, although it presents many common functional and morphological features. However, despite our knowledge of heterogeneity among endothelial cells from different sites, the differences between brain microvascular endothelial cells (BMEC) and coronary microvascular endothelial cells (CMEC) are poorly defined. The aim of this study was to investigate whether BMEC are distinct from CMEC at the protein level. Using the proteomic approach, we comparatively analyzed the proteome of cultured BMEC and CMEC. We reproducibly separated over 2000 polypeptides by using two-dimensional electrophoresis (2-DE) at pH range of 3-10. Using PDQuest software to process the 2-DE gel images, forty-seven protein spots were differentially expressed in the two-endothelial cells. Of these, thirty-five proteins are highly expressed in BMEC, whereas twelve proteins are highly expressed in CMEC. Fifteen proteins in BMEC and seven proteins in CMEC were identified with high confidence by matrix-associated laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS). Our data suggested that BMEC and CMEC were different in several aspects including cytokine and growth-related molecules, stress-related proteins, metabolic enzymes, signal transduction proteins and others. The identification of a set of proteins preferentially expressed in BMEC and CMEC provided new data on the heterogeneity of the endothelium.

Animals↗

PubMed2005

D(5h) C50X10: saturn-like fullerene derivatives (X=F, Cl, Br).

Based on the recently reported D(5h) C(50), the geometries and stabilities of its Saturn-like derivatives C(50)X(10) (X=F, Cl, Br) have been investigated by DFT method. Compared with C(50), the equatorial carbon atoms in C(50)X(10) have been saturated by halogens and change to sp(3) hybridization to release the large angle strain. Because the equatorial carbon atoms have been taken out of the pi system by the halogens "ring," the C(50)X(10) system has been split into two well-delocalized conjugated annulene subunits, and then the electronic stabilization has been enhanced.

Journal Article↗

PubMed2005

Protein structural deformation induced lifetime shortening of photosynthetic bacteria light-harvesting complex LH2 excited state.

Photosynthetic bacterial light-harvesting antenna complex LH2 was immobilized on the surface of TiO(2) nanoparticles in the colloidal solution. The LH2/TiO(2) assembly was investigated by the time-resolved spectroscopic methods. The excited-state lifetimes for carotenoid-containing and carotenoidless LH2 have been measured, showing a decrease in the excited-state lifetime of B850 when LH2 was immobilized on TiO(2). The possibility that the decrease of the LH2 excited-state lifetime being caused by an interfacial electron transfer reaction between B850 and the TiO(2) nanoparticle was precluded experimentally. We proposed that the observed change in the photophysical properties of LH2 when assembled onto TiO(2) nanoparticles is arising from the interfacial-interaction-induced structural deformation of the LH2 complex deviating from an ellipse of less eccentric to a more eccentric ellipse, and the observed phenomenon can be accounted by an elliptical exciton model. Experiment by using photoinactive SiO(2) nanoparticle in place of TiO(2) and core complex LH1 instead of LH2 provide further evidence to the proposed mechanism.

Bacterial Proteins↗

PubMed2004

Large-scale identification of genes required for full virulence of Staphylococcus aureus.

Gene products required for in vivo growth and survival of microbial pathogens comprise a unique functional class and may represent new targets for antimicrobial chemotherapy, vaccine construction, or diagnostics. Although some factors governing Staphylococcus aureus pathogenicity have been identified and studied, a comprehensive genomic analysis of virulence functions will be a prerequisite for developing a global understanding of interactions between this pathogen and its human host. In this study, we describe a genetic screening strategy and demonstrate its use in screening a collection of 6,300 S. aureus insertion mutants for virulence attenuation in a murine model of systemic infection. Ninety-five attenuated mutants were identified, reassembled into new pools, and rescreened using the same murine model. This effort identified 24 highly attenuated mutants, each of which was further characterized for virulence attenuation in vivo and for growth phenotypes in vitro. Mutants were recovered in numbers up to 1,200-fold less than wild type in the spleens of systemically infected animals and up to 4,000-fold less than wild type in localized abscess infections. Genetic analysis of the mutants identified insertions in 23 unique genes. The largest gene classes represented by these mutants encoded enzymes involved in small-molecule biosynthesis and cell surface transmembrane proteins involved in small-molecule binding and transport. Additionally, three insertions defined two histidine kinase sensor-response regulator gene pairs important for S. aureus in vivo survival. Our findings extend the understanding of pathogenic mechanisms employed by S. aureus to ensure its successful growth and survival in vivo. Many of the gene products we have identified represent attractive new targets for antibacterial chemotherapy.

Animals↗

PubMed2003

Hyperacute lung rejection in the pig-to-human model. 2. Synergy between soluble and membrane complement inhibition.

BACKGROUND: The role of complement in hyperacute lung xenograft rejection has not been elucidated. The present study evaluates the effect of complement (C) C3/C5 convertase inhibition on hyperacute rejection of pig lung by human blood. METHODS: In an established ex-vivo model, lungs from pigs heterozygous for human decay accelerating factor (hDAF), non-transgenic littermate control pigs, or farm-bred pigs were perfused with fresh human blood that was either unmodified or treated with soluble complement receptor type 1 (sCR1: TP10, 100 microg/ml). RESULTS: Non-transgenic lungs from littermate controls had a median survival time of 35 min (range 5 to 210; P = 0.25 vs. farm-bred piglets: median 5 min, range 5 to 10). Lungs expressing hDAF survived for a median of 90 min (range 10 to 161; P = 0.5 and 0.01 vs. littermate and farm-bred controls, respectively), with sCR1, whereas hDAF (-) lungs failed by 35 min (range 6 to 307), hDAF (+) lungs survived for 330 min (range 39 to 577) [P = 0.002 vs. farm-bred; P = 0.08 vs. hDAF (-); P = 0.17 vs. sCR1/hDAF (-)]. The rise in pulmonary vascular resistance (PVR) at 5 min was blunted only by hDAF (+) with sCR1 (0.26 +/- 0.2 vs. 0.5 to 0.7 mmHg/ml/min for other groups). Plasma C3a and sC5b-9 and tissue deposition of C5b-9 were dramatically diminished using sCR1, and further decreased in association with hDAF. Histamine and thromboxane were produced rapidly in all groups. CONCLUSION: Complement plays an important role in lung HAR. However, even potent inhibition of C3/C5 convertase, both membrane bound in lung and by a soluble-phase inhibitor in the blood, does not prevent activation of inflammatory responses known to be particularly injurious to the lung. Our findings implicate a role for innate immune pathways resistant to efficient complement regulation. The role of anti-species antibody, coagulation pathway dysregulation, and additional environmental or genetic influences remain to be defined.

Acute Disease↗

PubMed2002

Activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB in tumour necrosis factor-induced eotaxin release of human eosinophils.

The CC chemokine eotaxin is a potent eosinophil-specific chemoattractant that is crucial for allergic inflammation. Allergen-induced tumour necrosis factor (TNF) has been shown to induce eotaxin synthesis in eosinophils. Nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK) have been found to play an essential role for the eotaxin-mediated eosinophilia. We investigated the modulation of NF-kappaB and MAPK activation in TNF-induced eotaxin release of human eosinophils. Human blood eosinophils were purified from fresh buffy coat using magnetic cell sorting. NF-kappaB pathway-related genes were evaluated by cDNA expression array system. Degradation of IkappaBalpha and phosphorylation of MAPK were detected by Western blot. Activation of NF-kappaB was determined by electrophoretic mobility shift assay. Eotaxin released into the eosinophil culture medium was measured by ELISA. TNF was found to up-regulate the gene expression of NF-kappaB and IkappaBalpha in eosinophils. TNF-induced IkappaBalpha degradation was inhibited by the proteasome inhibitor N-cbz-Leu-Leu-leucinal (MG-132) and a non-steroidal anti-inflammatory drug sodium salicylate (NaSal). Using EMSA, both MG-132 and NaSal were found to suppress the TNF-induced NF-kappaB activation in eosinophils. Furthermore, TNF was shown to induce phosphorylation of p38 MAPK time-dependently but not extracellular signal-regulated kinases (ERK). Inhibition of NF-kappaB activation and p38 MAPK activity decreased the TNF-induced release of eotaxin from eosinophils. These results indicate that NF-kappaB and p38 MAPK play an important role in TNF-activated signalling pathway regulating eotaxin release by eosinophils. They have also provided a biochemical basis for the potential of using specific inhibitors of NF-kappaB and p38 MAPK for treating allergic inflammation.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

[Family support and quality of life among hemodialysis patients].

OBJECTIVE: Sixty chronic renal failure patients who had received hemodialysis for 3 months or longer were interviewed with the Quality of Life Questionnaire and Social Support from Family Scale. The results were that the hemodialysis patients had a lower of quality of life and there was a positive correlation between family support and the patients' quality of life. The results suggest that both the patients' condition and their family background should be estimated so as to improve the quality of life of the chronic renal failure patients who had been received hemodialysis.

Adolescent↗

PubMed2001

Structure of C-phycocyanin from Spirulina platensis at 2.2 A resolution: a novel monoclinic crystal form for phycobiliproteins in phycobilisomes.

The crystal structure of C-phycocyanin from the cyanobacterium S. platensis has been determined at 2.2 A resolution. The crystals belong to the monoclinic crystal form, which has not been previously reported for phycobiliprotein structures. The structure was solved using the molecular-replacement method with a final R value of 18.9% (R(free) = 23.7%) after model building and refinement. In the crystals used for the study, the C-phycocyanin hexamers formed by face-to-face association of two trimers are arranged in layers rather than in columns. Three different kinds of packing between adjacent hexamers in the layer were compared. The tight packing of two adjacent hexamers formed by four trimers in the asymmetric unit brings beta155 PCB chromophores close together, so it is possible that lateral energy transfer takes place through the beta155-beta155 route.

Amino Acid Sequence↗

PubMed2001

Crystal structure of R-phycocyanin and possible energy transfer pathways in the phycobilisome.

The crystal structure of R-phycocyanin from Polysiphonia urceolata (R-PC-PU) at 2.4 A is reported. The R-PC-PU crystal belongs to space group P4(3)2(1)2 with cell parameters a = 135.1 A, c = 210.0 A, and alpha = beta = gamma = 90 degrees. The structure was determined by molecular replacement. The crystallographic R-factor of the refined model is 0.189 (R(free) = 0.239). Comparison of the microenvironment of chromophore beta 155 in R-PC-PU and in C-PC from Fremyolla diphosiphon (C-PC-FD) reveals that their spectral differences may be caused by their different alpha 28 residues. In the R-PC-PU crystal structure, two (alpha beta)(3) trimers assemble face to face to form a hexamer, and two such hexamers assemble in two novel side-to-side arrangements. Possible models for the energy transfer from phycoerythrin to phycocyanin and from phycocyanin to allophycocyanin are proposed based on several phycobiliprotein crystal structures.

Algal Proteins↗

PubMed2001

Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction.

Recent studies in transgenic mice have demonstrated that PTH-related protein (PTHrP), signaling through the type 1 PTH/PTHrP receptor (PTHR1), regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Recently, it has been shown that loss-of-function mutations in the PTHR1 gene result in a rare, lethal form of dwarfism known as Blomstrand chondrodysplasia. These patients suffer from severe defects in endochondral bone formation, but abnormalities in breast and tooth development have not been reported. To ascertain whether PTHrP signaling was important to human breast and tooth development, we studied two fetuses with Blomstrand chondrodysplasia. These fetuses lack nipples and breasts. Developing teeth were present, but they were severely impacted within the surrounding alveolar bone, leading to distortions in their architecture and orientation. Compatible with the involvement of PTHR1 and PTHrP in human breast and tooth morphogenesis, both were expressed within the developing breasts and teeth of normal human fetuses. Therefore, impairment of the PTHrP/PTHR1 signaling pathway in humans is associated with severe abnormalities in tooth and breast development. In addition to regulating human bone formation, this signaling pathway is also necessary for the normal development of the human breast and tooth.

Breast↗

PubMed2001

Transient absorption from the 1Bu+ state of all-trans-beta-carotene newly identified in the near-infrared region.

We have attempted subpicosecond time-resolved absorption spectroscopy of all-trans-beta-carotene in organic solvents in the 820-1060 nm region and found novel transient absorption features which lived in subpicosecond time scales. A first component that appeared immediately after excitation showed a lifetime of 190 +/- 10 fs in n-hexane in agreement with the 1Bu+ lifetime that had been determined by fluorescence upconversion spectroscopy (195 +/- 10 fs). (Kandori et al. [1994] J. Am. Chem. Soc. 116, 2671-2672.) Therefore, this component is assigned to a transient absorption from the 1Bu+ state.

Carbon Disulfide↗

PubMed2001

Antifibrotic effects of matrine on in vitro and in vivo models of liver fibrosis in rats.

AIM: To study the antifibrotic effects of matrine in vitro a nd in vivo. METHODS: Rat hepatic stellate cell HSC-T6 and mouse fibroblast cell NIH3T3 proliferation stimulated with serum and platelet-derived growth factor (PDGF) was measured b y crystal violet staining assay. Collagen synthesis stimulated with serum and transforming growth factor beta1 (TGF-beta1) was determined by [3H]proline incorporation. Liver fibrosis was induced by carbon tetrachloride (CCl4) in rats an d evaluated with plasma hyaluranic acid level and hepatic hydroxyproline content. RESULTS: Matrine (1-2 mmol/L) markedly reduced serum-driven proliferation and collagen synthesis of HSC-T6 cells as well as NIH3T3 cells. PDGF-driven proliferative activity and TGF-beta1-driven collagen synthesis in HSC-T6 cel ls were attenuated by matrine (0.25-2 mmol/L) in a concentration-dependent manner. In vivo matrine (50 mg/kg and 100 mg/kg) significantly decreased serum hyaluranic acid levels and hepatic hydroxyproline contents in rats treated with CCl4. CONCLUSION: Inhibition of PDGF and TGF-beta1 actions on hepatic stellate cell by matrine might provide a possible mechanism of its antifibrotic activities.

3T3 Cells↗

PubMed2001

Matrine inhibits production and actions of fibrogenic cytokines released by mouse peritoneal macrophages.

AIM: To study the effects of matrine (Mat) on production and actions of fibrogenic cytokines from mouse peritoneal macrophages. METHODS: Mouse peritoneal macrophages were primed with calcimycin 1 micromol/L for 8 h then elicited by lipopolysaccharides (LPS) 100 microg/L for 6 h to induce fibrogenic cytokines. Proliferative and collagen stimulating activity in the macrophage culture supernatants was determined by crystal violet staining assay and [3H]-proline incorporation assay using rat hepatic stellate HSC-T6 cell or mouse fibroblast NIH3T3 cell. Transforming growth factor beta (TGFbeta) activity was measured by [3H]-thymidine incorporation assay using Mv-1-Lu mink lung epithelial cell. RESULTS: Mat (0.5-2 mmol/L) was shown to significantly inhibit LPS-induced collagen stimulating activities and TGFbeta production (P < 0.01) whereas did not inhibit proliferative activities induced by macrophages. Macrophage conditioned medium (MCM)-driven proliferation and collagen synthesis of HSC-T6 cells as well as NIH3T3 cells were attenuated by Mat (0.5-2 mmol/L) in a concentration-dependent manner. CONCLUSION: Antifibrotic effects of Mat on hepatic stellate cells may be related to reduction of fibrogenic cytokine production and blockade of their actions.

Alkaloids↗

PubMed2001

Effect of genistein and quercetin on proliferation, collagen synthesis, and type I procollagen mRNA levels of rat hepatic stellate cells.

AIM: To study the effects of genistein (GE) and quercetin (QU) on proliferation, collagen synthesis, and procollagen messenger RNA (mRNA) expression of rat hepatic stellate cell line HSC-T6 cells. METHODS: Cell proliferation was measured by crystal violet staining assay. Collagen synthesis was determined by [3H]proline incorporation assay. Type I mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: GE (25 - 70 micromol/L) and QU (6.25 - 50 micromol/L) concentration-dependently reduced serum-driven HSC-T6 cell proliferation and collagen synthesis associated with a suppression of type I procollagen mRNA level. CONCLUSION: GE and QU inhibited hepatic stellate cell proliferation and collagen synthesis that might have a protective role against liver fibrosis.

Cell Division↗

PubMed2001

[Antifibrotic effects of genistein and quercetin in vitro].

AIM: To study the antifibrotic effects of genistein (GE) and quercetin (QU) on rat hepatic stellate HSC-T6 cell proliferation stimulated with platelet-derived growth factor (PDGF), collagen synthesis and type I procollagen messenger RNA (mRNA) expression stimulated with transforming growth factor beta 1 (TGF beta 1). METHODS: Cell proliferation was measured by crystal violet staining assay. Collagen synthesis was determined by 3H-proline incorporation assay. Type I procollagen mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: GE (25-70 mumol.L-1) and QU (6.25-50 mumol.L-1) concentration-dependently attenuated PDGF-drive HSC-T6 cell proliferative activity. TGF beta 1-stimulated collagen synthesis was also reduced. This was associated with a decrease of type I procollagen mRNA, indicating an effect at a pretranslational level. CONCLUSION: GE and QU may have therapeutic potential against liver fibrosis by regulating PDGF and TGF beta 1 actions.

Animals↗

PubMed2000

betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system.

We report the identification of betaIV spectrin, a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512. The betaIV spectrin gene is located on human and mouse chromosomes 19q13.13 and 7b2, respectively. Alternative splicing of betaIV spectrin generates at least four distinct isoforms, numbered betaIVSigma1-betaIVSigma4 spectrin. The longest isoform (betaIVSigma1 spectrin) includes an actin-binding domain, followed by 17 spectrin repeats, a specific domain in which the amino acid sequence ERQES is repeated four times, several putative SH3-binding sites and a pleckstrin homology domain. betaIVSigma2 and betaIVSigma3 spectrin encompass the NH(2)- and COOH-terminal halves of betaIVSigma1 spectrin, respectively, while betaIVSigma4 spectrin lacks the ERQES and the pleckstrin homology domain. Northern blots revealed an abundant expression of betaIV spectrin transcripts in brain and pancreatic islets. By immunoblotting, betaIVSigma1 spectrin is recognized as a protein of 250 kD. Anti-betaIV spectrin antibodies also react with two additional isoforms of 160 and 140 kD. These isoforms differ from betaIVSigma1 spectrin in terms of their distribution on subcellular fractionation, detergent extractability, and phosphorylation. In islets, the immunoreactivity for betaIV spectrin is more prominent in alpha than in beta cells. In brain, betaIV spectrin is enriched in myelinated neurons, where it colocalizes with ankyrin(G) 480/270-kD at axon initial segments and nodes of Ranvier. Likewise, betaIV spectrin is concentrated at the nodes of Ranvier in the rat sciatic nerve. In the rat hippocampus, betaIVSigma1 spectrin is detectable from embryonic day 19, concomitantly with the appearance of immunoreactivity at the initial segments. Thus, we suggest that betaIVSigma1 spectrin interacts with ankyrin(G) 480/270-kD and participates in the clustering of voltage-gated Na(+) channels and cell-adhesion molecules at initial segments and nodes of Ranvier.

Amino Acid Sequence↗

PubMed2000

Direction-dependent corticofugal modulation of frequency-tuning curves of inferior collicular neurons in the big brown bat, Eptesicus fuscus.

This study examined if corticofugal modulation of subcortical frequency-tuning curves varied with sound direction. Both excitatory and inhibitory frequency tuning curves of inferior collicular neurons of the big brown bat, Eptesicus fuscus were plotted before and during electrical stimulation in the auditory cortex at two sound directions (contra-40 degrees and ipsi-40 degrees). Most collicular neurons had broader excitatory frequency-tuning curves at contra-40 degrees but had broader inhibitory frequency-tuning curves at ipsi-40 degrees. Cortical electrical stimulation changed the excitatory minimum thresholds of most collicular neurons at a greater degree at ipsi-40 degrees than at contra-40 degrees. However, cortical electrical stimulation produced a greater increase in the sharpness of excitatory frequency-tuning curves of most corticofugally inhibited collicular neurons at contra-40 degrees but produced a greater decrease in the sharpness of excitatory frequency-tuning curves of most corticofugally facilitated collicular neurons at ipsi-40 degrees. Cortical electrical stimulation also produced a greater change in the sharpness of inhibitory frequency-tuning curves of most corticofugally inhibited collicular neurons at contra-40 degrees than at ipsi-40 degrees. Possible mechanisms for this direction-dependent corticofugal modulation of frequency-tuning curves of collicular neurons are discussed.

Animals↗

PubMed2000

Efficient light harvesting through carotenoids.

We review the factors that control the efficiency of carotenoid-chlorophyll excitation transfer in photosynthetic light harvesting. For this we summarize first the recently developed theory that describes electronic couplings between carotenoids and chlorophylls and we outline in particular the influence of length of conjugated system and of symmetry breaking on the couplings. We focus hereby on the structurally solved lycopene-BChl system of LH 2 from Rhodospirillum molischianum and the peridinin-Chl a system of PCP from Amphidinium carterae. In addition, we review recent spectroscopic data for neurosporene, spheroidene and lycopene, three carotenoids with different lengths of conjugated systems. On the basis of the measured energies, emission lineshapes, solution and protein environment lifetimes for their 2A ( g ) (-) and 1B ( u ) (+) states as well as of the theoretically determined couplings, we conclude that the transfer efficiencies from the 2A ( g ) (-) state are controlled by the Car(2A ( g ) (-) )-BChl(Q(g)) electronic couplings and the 2A ( g ) (-) --> 1A ( g ) (-) internal conversion rates. We suggest that symmetry breaking and geometry rather than length of conjugated system dominate couplings involving the 2A ( g ) (-) state. Differences in transfer efficiencies from the 1B ( u ) (+) state in LH 2 and PCP are found to be dominated by the differences in spectral overlap. The role of the 1B ( u ) (+) state is likely to be influenced by a lower-lying (in longer polyenes), optically forbidden 1B ( u ) (-) state.

Journal Article↗