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Y Zhang

Publications and source records attributed to Y Zhang.

At least 433 records · Page 24Linked to original sources
PubMed2001

Ionizing radiation-induced apoptosis in ataxia-telangiectasia fibroblasts. Roles of caspase-9 and cellular inhibitor of apoptosis protein-1.

Ionizing radiation (IR) has been shown to induce apoptosis to a greater extent in a fibroblast cell line AT5BIVA derived from an individual with ataxia-telangiectasia (AT) than in control fibroblasts. However, the signaling pathway that underlies IR-induced apoptosis in AT cells has remained unknown. The mechanism of apoptosis in response to gamma-irradiation has now been examined in three AT fibroblast lines (AT3BIVA, AT4BIVA, and AT5BIVA) derived from different individuals with AT. The apoptotic indexes of these cell lines at 72 h after irradiation were 12, 31, and 35%, respectively, compared with a value of 2.3% for control fibroblasts. Immunoblot analysis and fluorometric assays revealed that the extents of IR-induced activation of caspase-3 and caspase-9 were markedly greater in AT4BIVA and AT5BIVA cells than in AT3BIVA and control cells. Furthermore, the basal abundance of the apoptotic inhibitor, a cellular inhibitor of apoptosis proteins (c-IAP-1), was markedly reduced in AT4BIVA and AT5BIVA cells compared with that in AT3BIVA and control cells. The overexpression of either caspase-9 mutant forms or recombinant c-IAP-1 in AT5BIVA cells inhibited the IR-induced activation of caspases-3 and 9 and reduced the apoptotic index of the irradiated cells. These results indicate that the extent of IR-induced apoptosis in different AT cell lines is inversely related to the abundance of c-IAP-1 and directly related to the extent of activation of caspases-3 and 9.

Amino Acid Substitution↗
PubMed2001

The scaffolding protein CASK mediates the interaction between rabphilin3a and beta-neurexins.

CASK, a member of the membrane-associated guanylate kinase (MAGUK) superfamily, binds to the carboxyl-terminus of beta-neurexins on the intracellular side of the presynaptic membrane. The guanylate kinase-like (GUK) domains of MAGUKs lack kinase activities, but might be important for mediating specific protein-protein interaction. By a yeast two-hybrid approach, we identified an interaction between the GUK domain of CASK and the C2B domain of rabphilin3a, a presynaptic protein involved in synaptic vesicle exocytosis. The interaction was confirmed by in vitro GST pull-down and co-immunoprecipitation assays. It was proposed that presynaptic vesicles might be guided to the vicinity of points of exocytosis defined by beta-neurexins via the interaction between rabphilin3a-CASK-beta-neurexins.

Adaptor Proteins, Signal Transducing↗
PubMed2001

[Population biology of Streptococcus pneumoniae carried by healthy children in Shanghai].

OBJECTIVE: To investigate the population biology of Streptococcus pneumoniae carried by healthy children. METHODS: Drug resistant patterns and serotypes of 222 strains were determined. PFGE, BOX PCR and pbp fingerprint techniques were used to analyze the homology among strains. RESULTS: Among 222 nasopharyngeal isolates from 5 day-care centers, there were 32 penicillin intermediate Streptococcus pneumoniae (PISP, MIC 0.125 approximately 1 mg/L), and no penicillin resistant Streptococcus pneumoniae (PRSP, MIC >/= 2 mg/L) was found. The main serotypes of all strains were 23F (25.7%), 6A (13.1%), 19F (10.8%), and 6B (8.1%). The serotypes of PISP were mainly 23F (50%), 19A (15.6%) and 19F (15.6%). Among the 32 PISP strains, 8 BOX PCR clusters and 7 PFGE types were identified. The resistance patterns, serotypes, BOX PCR and pbp fingerprints of PFGE type A strains were highly consistent. In day care center (DCC) SY, the penicillin resistant rate was 31.8%, being much higher than the average level. Twenty of the 21 PISP strains isolated from this DCC belonged to PFGE type A or B. CONCLUSIONS: The penicillin resistant rate of Streptococcus pneumoniae carried by healthy children in 5 DCCs of Shanghai was still low. However in one DCC, there could be a prevalence of some resistant clones which resulted in high penicillin resistant rate.

Anti-Bacterial Agents↗
PubMed2001

Sharp spectral lines observed in gamma-ray ionized parahydrogen crystals.

We have observed sharp infrared spectral lines ( Deltanu approximately 60 MHz FWHM) in gamma-ray ionized para- H2 crystals. The lines are assigned to the Q1(0) transition of H2 near H+3 and H-, which becomes optically active and Stark shifted by the Coulomb fields of the ions. A simple model calculation gives a spectrum which agrees approximately with the observation. The spectrum stays the same over many days, demonstrating the stability of the ionized system. The remarkable sharpness and reproducibility of the line positions indicate uniformity of the local structure surrounding the charges.

Journal Article↗
PubMed2001

5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells.

The 5-HT(2A/2C) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) stimulates hypothalamic neurons to increase the secretion of several hormones. This study addressed two questions: 1) are the neuroendocrine effects of DOI mediated via activation of 5-HT(2A) receptors; and 2) which neurons are activated by 5-HT(2A) receptors. The 5-HT(2A) antagonist (+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (MDL 100,907; 0.001, 0.01, or 0.1 mg/kg, s.c.) was administered before rats were challenged with DOI (2.5 mg/kg, i.p.). MDL 100,907 produced a dose-dependent inhibition (ED(50) congruent with 0.001 mg/kg) of the effect of DOI on plasma levels of ACTH, corticosterone, oxytocin, prolactin, and renin without altering basal hormone levels. Complete blockade of the effect of DOI was achieved for all hormones at MDL 100,907 doses of 0.01-0.1 mg/kg. In a parallel experiment, DOI was injected 2 hr before killing to determine its effects on the expression of Fos, the product of the immediate early gene c-fos. DOI induced an increase in Fos immunoreactivity in corticotropin-releasing factor (CRF) and in oxytocin-expressing neurons but not in vasopressin-containing neurons in the hypothalamic paraventricular nucleus or CRF cells in the amygdala. Pretreatment with MDL 100,907 (0.1 mg/kg, s.c.) blocked the DOI-induced increase in Fos expression in all regions including the hypothalamus, amygdala (central and corticomedial), bed nucleus of the stria terminalis, and prefrontal cortical regions. The combined neuroanatomical and pharmacological observations suggest that the neuroendocrine responses to DOI are mediated by activation of neurons in the hypothalamic paraventricular nucleus and associated circuitry. Furthermore, selective activation of 5-HT(2A) receptors mediates the hormonal and Fos-inducing effects of DOI.

Adrenocorticotropic Hormone↗
PubMed2001

Different processes are involved in human brain for shape and face comparisons.

Fifteen subjects participated in a matching task of visual stimuli. Two sequentially presented stimuli in a pair were the same shape (shape match), different shapes (shape mismatch), same human face (face match) or different faces (face mismatch). All four kinds of stimulus pairs were of equal probability. The shape mismatch pairs elicited a negative event-related potential component N270 (Peak latency: 262.1+/-16.5 ms, P4) after the second stimulus onset, while the face mismatch evoked N270 with longer peak latency (301.2+/-19.8 ms, P4) and N450. There exists a specific system for mismatch processing of a complex stimulus (face) in the human brain.

Cerebral Cortex↗
PubMed2001

Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways.

Emerging evidence indicates that reactive oxygen species are important regulators of vascular function. Although NAD(P)H oxidases have been implicated as major sources of superoxide in the vessel wall, the molecular identity of these proteins remains unclear. We recently cloned nox1 (formerly mox-1), a member of a new family of gp91(phox) homologues, and showed that it is expressed in proliferating vascular smooth muscle cells (VSMCs). In this study, we examined the expression of three nox family members, nox1, nox4, and gp91(phox), in VSMCs, their regulation by angiotensin II (Ang II), and their role in redox-sensitive signaling. We found that both nox1 and nox4 are expressed to a much higher degree than gp91(phox) in VSMCS: Although serum, platelet-derived growth factor (PDGF), and Ang II downregulated nox4, they markedly upregulated nox1, suggesting that this enzyme may account for the delayed phase of superoxide production in these cells. Furthermore, an adenovirus expressing antisense nox1 mRNA completely inhibited the early phase of superoxide production induced by Ang II or PDGF and significantly decreased activation of the redox-sensitive signaling molecules p38 mitogen-activated protein kinase and Akt by Ang II. In contrast, redox-independent pathways induced by PDGF or Ang II were unaffected. These data support a role for nox1 in redox signaling in VSMCs and provide insight into the molecular identity of the VSMC NAD(P)H oxidase and its potentially critical role in vascular disease.

Animals↗
PubMed2001

[Mycophenolate mofetil in the treatment of primary nephrotic syndrome].

OBJECTIVE: To investigate the efficacy and safety of mycophenolate mofetil (MMF) on treating refractory primary nephrotic syndrome. METHODS: Forty-one patients with refractory nephrotic syndrome confirmed by renal biopsy, 19 with minor lesion (minimal lesion nephropathy and mesangial proliferative glomerulonephritis), 18 with membranous nephropathy (MN), 3 with focal segmental glomerulosclerosis (FSGS), and one with mesangioproliferative glomerulonephritis (MPGN), were treated by MMF combined with prednisone. The initial dosage of MMF was 1.0 - 2.0 g/d for three months and then the dosage was tapered gradually. The duration of MMF treatment was at least six months. Prednisone at the dose of 20 - 60 g/d was used at the beginning of the combined treatment and then the dosage was tapered gradually. Follow-up interview was conducted regularly. Four patients were rebiopsyed by the end of observation. RESULTS: The combined treatment of MMF/prednisone decreased the urine protein and elevated the serum albumin significantly among patients with minor lesion and MN (P < 0.001). All patients with minor lesion achieved clinical remission. Eleven of the nineteen cases responded within four weeks, and twelve of them obtained complete clinical remission. The dosage of prednisone could be tapered smoothly among the steroid dependent patients. Thirteen of the eighteen patients with MN achieved remission, however only six responded within four weeks and only three of them achieved complete clinical remission. During the treatment, four patients experienced transient increase of urine protein due to infection and recovered spontaneously without alteration of treatment. Side effects were tolerable except one case was withdrawn due to the decrease of hemoglobin. Renal function remained stable during the treatment. No obvious alteration could be found in renal biopsy by the end of treatment among four patients. CONCLUSION: MMF is an effective and safe immunosuppressive agent for refractory nephrotic syndrome.

Adolescent↗
PubMed2001

Association of a polymorphism of the dopamine transporter gene with externalizing behavior problems and associated temperament traits: a longitudinal study from infancy to the mid-teens.

There have been reports that a variable number of tandem repeats (VNTR) polymorphism situated in the 3' untranslated region of the dopamine transporter gene is associated with attention-deficit hyperactivity disorder. On the basis of these findings, we predicted an association of this polymorphism with hyperactivity, other externalizing behavior problems, and related temperament traits in a general population sample. The association was investigated using children participating in a longitudinal study of childhood temperament and development. DNA was taken from 660 children who had been assessed for temperament from 4-8 months to 15-16 years, and for behavior problems from 3-4 to 15-16 years. No significant associations were found at any age. There are a number of methodological differences from earlier studies that might explain the lack of associations with hyperactivity. It is also possible that the earlier findings are not replicable.

Adolescent↗
PubMed2001

Sp1 and ETS family transcription factors regulate the mouse Mta2 gene expression.

Dynamic changes in chromatin structure through nucleosome remodelling and core histone tail acetylation play important roles in transcriptional regulation. The purification and functional characterization of a nucleosome remodelling and histone deacetylase complex, NuRD, has suggested that nucleosome remodelling and core histone tail modification are potentially linked processes. MTA2, a component of the NuRD complex, plays an important role in regulating histone deacetylase activity of the NuRD complex. Similar to the candidate metastasis associated protein MTA1, an elevated level of MTA2 correlates with cellular proliferation. To understand the regulation of Mta2 transcription, we characterized the mouse Mta2 gene and its transcriptional regulatory elements. We found that MTA2 is encoded by 18 exons that span 10 kb. Primer extension analysis identified a major transcriptional start site locates 259 base pairs upstream of the ATG translational start codon. Transient transfection studies localized its promoter, lacking a canonical TATA box, to within 60 base pairs upstream of the transcriptional start site. Gel-mobility-shift and mutagenesis studies revealed that Sp1 and ETS elements play important roles in regulating Mta2 transcription. Information concerning the regulation of the Mta2 gene expression will be useful in understanding the regulation of NuRD histone deacetylase activity, which in turn will help in our general understanding of the transcriptional repression mechanism.

3T3 Cells↗
PubMed2001

Characterization of HIV-specific proliferative T cell responses in HIV-infected persons.

Virus-specific helper T cell responses are thought to be an important host defense in HIV infection. The proliferative responses to HIV p24, p55, and gp120 were tested in a cohort of 27 HIV-infected subjects. Vigorous proliferative responses directed at the Gag protein with stimulation indices in excess of 6 were detected in 10 of the individuals tested but an Env-specific response was present in only 1 subject. Viral load and proliferative activity to Gag were inversely correlated in untreated individuals. Proliferation was also observed in some individuals treated in the chronic phase of infection, and responses were maintained over time in the absence of detectable viremia. Positive proliferative responses could also occasionally be detected in treated persons with CD4(+) cell counts below 200/microl. Thus, vigorous Gag-specific proliferative responses are present in a minority of HIV-infected individuals and can be detected in individuals receiving highly active antiretroviral therapy at advanced disease stages. Proliferative responses are maintained for an extended time period in the presence of antiviral therapy.

Adult↗
PubMed2001

A new focal adhesion protein that interacts with integrin-linked kinase and regulates cell adhesion and spreading.

Integrin-linked kinase (ILK) is a multidomain focal adhesion (FA) protein that functions as an important regulator of integrin-mediated processes. We report here the identification and characterization of a new calponin homology (CH) domain-containing ILK-binding protein (CH-ILKBP). CH-ILKBP is widely expressed and highly conserved among different organisms from nematodes to human. CH-ILKBP interacts with ILK in vitro and in vivo, and the ILK COOH-terminal domain and the CH-ILKBP CH2 domain mediate the interaction. CH-ILKBP, ILK, and PINCH, a FA protein that binds the NH(2)-terminal domain of ILK, form a complex in cells. Using multiple approaches (epitope-tagged CH-ILKBP, monoclonal anti-CH-ILKBP antibodies, and green fluorescent protein-CH-ILKBP), we demonstrate that CH-ILKBP localizes to FAs and associates with the cytoskeleton. Deletion of the ILK-binding CH2 domain abolished the ability of CH-ILKBP to localize to FAs. Furthermore, the CH2 domain alone is sufficient for FA targeting, and a point mutation that inhibits the ILK-binding impaired the FA localization of CH-ILKBP. Thus, the CH2 domain, through its interaction with ILK, mediates the FA localization of CH-ILKBP. Finally, we show that overexpression of the ILK-binding CH2 fragment or the ILK-binding defective point mutant inhibited cell adhesion and spreading. These findings reveal a novel CH-ILKBP-ILK-PINCH complex and provide important evidence for a crucial role of this complex in the regulation of cell adhesion and cytoskeleton organization.

Actinin↗
PubMed2001

[Effects of percutaneous transluminal coronary angioplasty and stenting on QT dispersion in patients with coronary heart disease].

OBJECTIVE: The aim of this study was to approach the effects of percutaneous transluminal coronary angioplasty (PTCA) and stenting on QT dispersion (QTd) in patients with coronary heart disease. METHODS: PTCA and stenting were performed successfully on 42 patients with coronary heart disease. QTd and corrected QTd (QTcd) were obtained with a standard 12-lead ECG before and after PTCA + Stent. RESULTS: QTd and QTcd after PTCA + Stent were reduced significantly compared to those before PTCA + Stent (P < 0.01). There were no significant difference in QTd and QTcd before PTCA + Stent between single vessel lesion and multi-vessel lesion, but after PTCA + Stent, QTd and QTcd in single vessel lesion were decreased significantly compared to those in multi-vessel lesion. The ventricular arrhythmia in 9 patients was over after PTCA + Stent. CONCLUSIONS: QTd and QTcd were decreased significantly after PTCA + Stent because of the improvement of myocardial ischemia and heterogeneous repolarization in patients with coronary heart disease. The degree in decreasing QTd and QTcd was associated with compensatory circulation in coronary artery.

Adolescent↗
PubMed2001

Effects of dopaminergic agents on carrageenan hyperalgesia after intrathecal administration to rats.

The present study explored the role of dopaminergic transmission in spinal cord in a model of carrageenan-induced inflammatory pain by examining the effects of selective agonists and antagonists of dopamine receptors. The results were as follows: (1) trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g] quinoline hydrochloride (LY171555), a dopamine D(2) receptor agonist, produced anti-hyperalgesia (150 and 300 nmol) or hypoalgesia (300 nmol) in the inflamed hindpaws and non-inflamed hindpaws, respectively; spiperone hydrochloride (8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one hydrochloride), a dopamine D(2) receptor antagonist, decreased the pain threshold of non-inflamed hindpaws (300 nmol). (2) (+/-)-SKF38393 hydrochloride ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride), a dopamine D(1) receptor agonist, had no effect on either hindpaw, even at a higher dose (300 nmol); R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (R(+)-SCH23390 hydrochloride), a dopamine D(1) receptor antagonist, induced anti-hyperalgesia in the inflamed hindpaws (300 nmol). The present results suggest that the dopaminergic system in the spinal cord is involved in the central modulation of inflammatory hyperalgesia, and that the different effects are probably induced by different receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

Growth hormone (GH)-induced dimerization inhibits phorbol ester-stimulated GH receptor proteolysis.

Growth hormone (GH) initiates its cellular action by properly dimerizing GH receptor (GHR). A substantial fraction of circulating GH is complexed with a high-affinity GH-binding protein (GHBP) that in many species can be generated by GHR proteolysis and shedding of the receptor's ligand-binding extracellular domain. We previously showed that this proteolysis 1) can be acutely promoted by the phorbol ester phorbol 12-myristate 13-acetate (PMA), 2) requires a metalloprotease activity, 3) generates both shed GHBP and a membrane-associated GHR transmembrane/cytoplasmic domain remnant, and 4) results in down-regulation of GHR abundance and GH signaling. Using cell culture model systems, we now explore the effects of GH treatment on inducible GHR proteolysis and GHBP shedding. In human IM-9 lymphocytes, which endogenously express GHRs, and in Chinese hamster ovary cells heterologously expressing wild-type or cytoplasmic domain internal deletion mutant rabbit GHRs, brief exposure to GH inhibited PMA-induced GHR proteolysis (receptor loss and remnant accumulation) by 60-93%. PMA-induced shedding of GHBP from Chinese hamster ovary transfectants was also inhibited by 70% in the presence of GH. The capacity of GH to inhibit inducible GHR cleavage did not rely on JAK2-dependent GH signaling, as evidenced by its continued protection in JAK2-deficient gamma2A rabbit GHR cells. The GH concentration dependence for inhibition of PMA-induced GHR proteolysis paralleled that for its promotion of receptor dimerization (as monitored by formation of GHR disulfide linkage). Unlike GH, the GH antagonist, G120K, which binds to but fails to properly dimerize GHRs, alone did not protect against PMA-induced GHR proteolysis; G120K did, however, antagonize the protective effect of GH. Our data suggest that GH inhibits PMA-induced GHR proteolysis and GHBP shedding by inducing GHR dimerization and that this effect does not appear to be related to GH site 1 binding, GHR internalization, or GHR signaling. The implications of these findings with regard to GH signaling and GHR down-regulation are discussed.

Animals↗
PubMed2001

[Expression of apoptosis-related proteins in Hashimoto's thyroiditis and its pathological significance].

OBJECTIVE: To explore the role and significance of apoptosis-related proteins in the pathogenesis and pathological changes in Hashimoto's thyroiditis (HT). METHODS: Apoptotic level in thyroid tissue specimens from 17 patients with HT and 17 patients with nontoxic goiter (NTG) was evaluated by TUNEL method. Expression and distribution of Fas, FasL, Bcl-2 and Bax proteins in the specimens were investigated with immunohistochemical methods. RESULTS: A high percentage of apoptosis (32.5% +/- 12.3%) was observed by TUNEL method in thyroid follicles from HT specimens in comparison with that from NTG specimens (1.3% +/- 0.7%, P < 0.01). Positive rates of Fas, FasL, Bcl-2 and Bax in thyroid cells of NTG (35% approximately 47%) were significantly lower than those in thyroid cells of HT (88% approximately 94%, P < 0.01). The intensity of positive immunostaining for Fas, FasL, Bcl-2 and Bax in thyroid cells of HT was significantly higher than that of the controls (P < 0.01). Apoptosis and strongly positive immunostained thyroid cells with HT for Fas, FasL and Bax were mainly distributed in follicles adjacent to lymphocytic infiltrates, whereas strongly positive stained thyroid cells for Bcl-2 were mainly located in the area remote from the infiltrating lymphocytes. Staining of infiltrating lymphocytes for Fas, FasL, Bcl-2 and Bax was weak. CONCLUSION: Thyroid follicles in HT specimens exhibited high apoptotic levels. The high expression of apoptosis-related proteins Fas, FasL, Bcl-2 and Bax in thyrocytes of HT and weak expression in infiltrating lymphocytes accounted for thyroid follicle destruction and diffuse lymphocytic infiltration in HT.

Adult↗