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Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 1,297 records · Page 72Linked to original sources
PubMed1999

[Deferoxamine protects against gentamicin ototoxicity].

OBJECTIVE: To study the prevention of gentamicin(GM) ototoxicity by deferoxamine(DFO) in the guinea pig. METHODS: Guinea pigs were randomly assigned to three experimental groups (GM-treated alone, DFO-treated alone, GM and DFO in combination) and one control group. Acoustic brainstem response (ABR), the surface preparation and transmission electron microscopy were utilized to evaluate the hearing thresholds and the cochlear morphology. To explore the mechanism associated with deferoxamine protection, serum levels of GM, BUN and Cr, together with concentration of MDA, SOD and iron in cochlear and renal tissues were measured. RESULTS: The GM group developed up to 40-60 dB of the threshold shifts at 8 kHz while the GM + DFO group developed only 15-25 dB of the threshold shifts (P < 0.05). Moorphological changes were consistent with functional changes. DFO did not alter serum levels of GM. Renal function of GM group was damaged obviously. However, changes of MDA, SOD and iron were not significant (P > 0.05). MDA and iron concentrations in cochlear tissue of the GM + DFO group were significantly lower than those in the GM group (P < 0.05) while SOD level was much higher than that in GM group. CONCLUSION: This study suggests that free radical and iron involve in GM ototoxicity and DFO may become a promising therapeutic agent that can be used to reduce gentamicin ototoxicity.

Animals↗
PubMed1999

HBV X protein (HBX) interacts with general transcription factor TFIIB both in vitro and in vivo.

OBJECTIVE: In order to demonstrate the binding of HBV X protein (HBX) with the general transcription factor TFIIB. METHODS: In vitro glutathion S-transferase (GST) resin Pull-Down assay and Far-Western Blotting assay, in vivo Co-immunoprecipition assay were used. RESULTS: The X199 (51-99) domain of HBX is reponsible for HBX binding to TFIIB. While the d10 domain (125-295) of TFIIB is required for TFIIB binding to HBX. When the two basic amino acids (K) at position 178 and 189 of TFIIB were substituted by neutral amino acids (L), the binding of TFIIB K178L and K189L to HBX was siginificantly reduced. When the the basic amino acids were substituted by the acidic amino acids (E), the binding of TFIIB K178E and K189E to HBX were almost lost. In vitro results of HBX binding to TFIIB were further confirmed by in vivo co-immunoprecipitation assay. Our results also indicated that the Woodchuck hepatitis virus X protein (WHX) interacts with TFIIB. CONCLUSION: These results suggested that the communication between HBX and general transcription factor TFIIB is one of the mechanisms which account for its transcriptional transactivation.

Binding Sites↗
PubMed1999

[Double resonance multiphoton spectrum of high excited state of iodine].

The F0u(+) ion-pair state of I2 was studied in detail by using optical-optical double resonance multiphoton ionization spectroscopy technique. The OODR-MPI spectra were analyzed and identified based on the molecular constants published. The progression with a spacing of 37 cm(-1) at T(e) = 52 400 cm(-1) is identified to be the highly vibrational levels of F0u(+) state, and the transition pathway of excitation and ionization by multiphoton was determined.

English Abstract↗
PubMed1999

[Determination of metals in atmospheric particulates by atomic absorption spectrometric method (AAS) with CA-CN micropore membrane filters used for sampling].

A new sampling method of atmospheric particulates using 0.22 microm pore diameter micropore membrane filters was introduced. Copper, lead, zinc cadmium, manganese, iron, nickel and chromium in atmospheric particulates were determined by atomic absorption spectrometry. This sampling method has shown several advantages: easy, complete and fast digestion; low membrane blank; increased flexibility to surrounding temperature change; high elution recovery, standard addition recovery, precision and accuracy.

Metals↗
PubMed1998

Accurate 3' end processing and adenylation of human signal recognition particle RNA and alu RNA in vitro.

Human signal recognition particle (SRP) RNA is transcribed by RNA polymerase III and terminates with -GUCUCUUUUOH on its 3' end. Our previous studies showed that the three terminal uridylic acid residues of human SRP RNA are post-transcriptionally removed and a single adenylic acid residue is added, resulting in a 3' end sequence of -GUCUCUAOH (Sinha, K. M., Gu, J., Chen, Y., and Reddy, R. (1998) J. Biol. Chem. 273, 6853-6859). In this study we show that the Alu RNA, corresponding to the 5' and 3' ends of SRP RNA, is also accurately processed and adenylated in vitro. Alu RNAs containing 7 or 11 additional nucleotides on the 3' end were accurately processed and then adenylated. Deletion analysis showed that an 87-nucleotide-long motif comprising of the 5' and 3' ends, including stem IV of the Alu RNA, is sufficient and necessary for the 3' end processing and adenylation. A 73-nucleotide-long construct with deletion of stem IV, required for the binding of SRP 9/14-kDa proteins, was neither processed nor adenylated. The adenylated Alu RNA as well as adenylated SRP RNA were bound to the SRP 9/14-kDa heterodimer and were immunoprecipitated by specific antibodies. A significant fraction of SRP RNA in the nucleoli was found to be processed and adenylated. These data are consistent with nascent SRP and/or Alu RNAs first binding to SRP 9/14-kDa protein heterodimer, followed by the removal of extra sequence on the 3' end and then the addition of one adenylic acid residue in the nucleus, before transport into the cytoplasm.

Adenosine Monophosphate↗
PubMed1998

Regionalized metabolic activity establishes boundaries of retinoic acid signalling.

The competence of a cell to respond to the signalling molecule retinoic acid (RA) is thought to depend largely on its repertoire of cognate zinc finger nuclear receptors. XCYP26 is an RA hydroxylase that is expressed differentially during early Xenopus development. In Xenopus embryos, XCYP26 can rescue developmental defects induced by application of exogenous RA, suggesting that the enzymatic modifications introduced inhibit RA signalling activities in vivo. Alterations in the expression pattern of a number of different molecular markers for neural development induced upon ectopic expression of XCYP26 reflect a primary function of RA signalling in hindbrain development. Progressive inactivation of RA signalling results in a stepwise anteriorization of the molecular identity of individual rhombomeres. The expression pattern of XCYP26 during gastrulation appears to define areas within the prospective neural plate that develop in response to different concentrations of RA. Taken together, these observations appear to reflect an important regulatory function of XCYP26 for RA signalling; XCYP26-mediated modification of RA modulates its signalling activity and helps to establish boundaries of differentially responsive and non-responsive territories.

Amino Acid Sequence↗
PubMed1998

Shaping limbs by apoptosis.

Programmed cell death has long been recognized as an important mechanism of normal embryonic development. In the developing limb, massive programmed cell death apparently plays a critical role in controlling the amount of mesodermal tissue, sculpting overall limb shape, and defining the digits. Cell death in the limb bud has been shown to be regulated by a number of factors, including environmental conditions and epithelial-mesenchymal interactions. Removing the ectoderm overlying the interdigital region results in inhibition of cell death and ectopic cartilage formation in the subjacent mesenchyme. Recently, several signaling factors and genes have been implicated in the control of cell death in the limb bud. FGFs may acts as trophic factors that interfere with cell death. There is evidence that BMPs and Msx genes participate in regulating cell death. BMPs may in some cases trigger the cell death cascade, while Msx gene products regulate Bmp expression. A correlation between FGF, BMP and Msx in interdigital cell death is discussed.

Animals↗
PubMed1998

IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells.

Although autoreactive T cells recognizing self myelin Ags are present in most individuals, autoimmune disease of the central nervous system is a relatively rare medical condition. Development of autoimmune disease may require not only the presence of autoreactive T cells but also that autoreactive T cells become activated. Activation of T cells may require a minimum of two signals: an Ag-specific signal delivered by MHC-peptide complex and a second signal delivered by costimulatory molecules or cytokines. Although in vitro studies have suggested that cytokines, especially proinflammatory cytokines such as IL-1, IL-6, and TNF are involved in T cell activation, their precise roles in vivo are not clear. To determine the roles of proinflammatory cytokines in T cell activation in vivo and in the development of autoimmune disease, we have studied experimental autoimmune encephalomyelitis (EAE) in mice deficient in IL-6. We found that IL-6-deficient mice were completely resistant to EAE induced by myelin oligodendrocyte glycoprotein (MOG), whereas IL-6-competent control mice developed EAE characterized by focal inflammation and demyelination in the central nervous system and deficiency in neurologic functions. Furthermore, we established that the resistance to EAE in IL-6-deficient mice was associated with a deficiency of MOG-specific T cells to differentiate into either Th1 or Th2 type effector cells in vivo. These results strongly suggest that IL-6 plays a crucial role in the activation and differentiation of autoreactive T cells in vivo and that blocking IL-6 function can be an effective means to prevent EAE.

Animals↗
PubMed1998

Termination of Ca2+ release by a local inactivation of ryanodine receptors in cardiac myocytes.

In heart, a robust regulatory mechanism is required to counteract the regenerative Ca2+-induced Ca2+ release from the sarcoplasmic reticulum. Several mechanisms, including inactivation, adaptation, and stochastic closing of ryanodine receptors (RyRs) have been proposed, but no conclusive evidence has yet been provided. We probed the termination process of Ca2+ release by using a technique of imaging local Ca2+ release, or "Ca2+ spikes", at subcellular sites; and we tracked the kinetics of Ca2+ release triggered by L-type Ca2+ channels. At 0 mV, Ca2+ release occurred and terminated within 40 ms after the onset of clamp pulses (0 mV). Increasing the open-duration and promoting the reopenings of Ca2+ channels with the Ca2+ channel agonist, FPL64176, did not prolong or trigger secondary Ca2+ spikes, even though two-thirds of the sarcoplasmic reticulum Ca2+ remained available for release. Latency of Ca2+ spikes coincided with the first openings but not with the reopenings of L-type Ca2+ channels. After an initial maximal release, even a multi-fold increase in unitary Ca2+ current induced by a hyperpolarization to -120 mV failed to trigger additional release, indicating absolute refractoriness of RyRs. When the release was submaximal (e.g., at +30 mV), tail currents did activate additional Ca2+ spikes; confocal images revealed that they originated from RyRs unfired during depolarization. These results indicate that Ca2+ release is terminated primarily by a highly localized, use-dependent inactivation of RyRs but not by the stochastic closing or adaptation of RyRs in intact ventricular myocytes.

Animals↗
PubMed1998

Shigella-induced apoptosis is dependent on caspase-1 which binds to IpaB.

We report here that the Shigella invasion plasmid antigen (Ipa)B, which is sufficient to induce apoptosis in macrophages, binds to caspase (Casp)-1, but not to Casp-2 or Casp-3. Casp-1 is activated and its specific substrate interleukin-1beta is cleaved shortly after Shigella infection. Macrophages isolated from Casp-1 knock-out mice are not susceptible to Shigella-induced apoptosis, although they respond normally to other apoptotic stimuli. Shigella kills macrophages from casp-3, casp-11, and p53 knock-out mice as well as macrophages overexpressing Bcl-2. We propose that Shigella induces apoptosis by directly activating Casp-1 through IpaB, bypassing signal transduction events and caspases upstream of Casp-1. Taken together these data indicate that Shigella-induced apoptosis is distinct from other forms of apoptosis and seems uniquely dependent on Casp-1.

Animals↗
PubMed1998

Insulin-like growth factor binding proteins localize to discrete cell culture compartments in periosteal and osteoblast cultures from fetal rat bone.

Insulin-like growth factor (IGF)-I and IGF-II are expressed at biologically effective levels by bone cells. Their stability and activity are modulated by coexpression of IGF binding proteins (IGFBPs). Secreted IGFBPs may partition to soluble, cell-associated, and matrix-bound compartments. Extracellular localization may sequester, store, or present IGFs to appropriate receptors. Of the six IGFBPs known, rat osteoblasts synthesize all but IGFBP-1. Of these, IGFBP-3, -4, and -5 mRNAs are induced by an increase in cAMP. Little is known about extracellular IGFBP localization in bone and nothing about IGFBP expression by nonosteoblastic periosteal bone cells. We compared basal IGFBP expression in periosteal and osteoblast bone cell cultures and assessed the effects of changes in cAMP-dependent protein kinase A or protein kinase C. Basal IGFBP gene expression differed principally in that more IGFBP-2 and -5 occurred in osteoblast cultures, and more IGFBP-3 and -6 occurred in periosteal cultures. An increase in cAMP enhanced IGFBP-3, -4, and -5 mRNAand accordingly increased soluble IGFBP-3, -4, and -5 and matrix-bound IGFBP-3 and -5 in both bone cell populations. In contrast, protein kinase C activators suppressed IGFBP-5 mRNA, and its basal protein levels remained very low. We also detected low Mr bands reactive with antisera to IGFBP-2, -3, and -5, suggesting proteolytic processing or degradation. Our studies reveal that various bone cell populations secrete and bind IGFBPs in selective ways. Importantly, inhibitory IGFBP-4 does not significantly accumulate in cell-associated compartments, even though its secretion is enhanced by cAMP. Because IGFBPs bind IGFs less tightly in cell-bound compartments, they may prolong anabolic effects by agents that increase bone cell cAMP.

Animals↗
PubMed1998

[Assessment for effect of low level lead-exposure on neurobehavior in workers of printing house].

WHO Neurobehavioral Core Test Battery (NCTB) was conducted among 28 lead-exposed workers (mean age 24.84, SD2.85) in printing house and 46 controls (mean age 22.78, SD1.45), in order to assess whether low level lead exposure may be related to neurobehavioral dysfunction. The items of test were: 1. Profile of mood state(POMS), (2) Simple reaction time, (3) Digit span, (4) Santa Anna manual dexterity, (5) Digit simbol, (6) Benton visual retention; and Prusuit aiming test. In all the NCTB test values, there was no significant difference between two groups. Multiple stepwise regression analysis shows that exposure duration is related to neurobehavior scores. Mild lead exposure may affect neurobehavior in some degree but not significant.

Adult↗
PubMed1998

Experimental autoimmune encephalomyelitis in intercellular adhesion molecule-1-deficient mice.

Intercellular adhesion molecule (ICAM)-1, or CD54, is a member of the immunoglobulin superfamily that binds to lymphocyte function-associated antigen-1 and macrophage-1 antigen. ICAM-1:LFA-1/Mac-1 interaction may be involved in both activation and extravasation of leukocytes. To determine the roles of ICAM-1 in the development of autoimmune disease, we studied experimental autoimmune encephalomyelitis (EAE) in mice deficient in ICAM-1. We found that T cell proliferation and TH1-type cytokine production in response to myelin antigen were significantly reduced in ICAM-1-deficient mice, whereas TH2-type cytokine IL-10 was increased. Unexpectedly, EAE induced by either myelin oligodendrocyte glycoprotein or myelin basic protein was significantly enhanced in mice deficient in ICAM-1. The enhancement was evidenced primarily by the increase in disease severity, mortality, and the degree of central nervous system inflammation. The cellular composition of the inflammatory infiltrates in the central nervous system is similar in control and ICAM-1-deficient mice. These results suggest that (1) ICAM-1 is involved in the activation of autoreactive TH-1, but not TH2 cells, and (2) ICAM-1 plays an important role in down-regulating autoimmune inflammation in the central nervous system.

Animals↗
PubMed1998

Randomised placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second-degree burns.

BACKGROUND: Wound healing is a dynamic process that could be accelerated by growth factors. We investigated the effect of recombinant bovine basic fibroblast growth factor (rbFGF) on burn healing in a randomised placebo-controlled trial. METHODS: We recruited 600 patients with superficial or deep second-degree burns. Patients received 150 AU/cm2 daily topical rbFGF (n=300) or placebo (n=300) plus vehicle. We assessed healing by photography, punch-biopsy, and clinical examination. FINDINGS: All patients treated with rbFGF had faster granulation tissue formation and epidermal regeneration than those in the placebo group. Superficial and deep second-degree burns treated with rbFGF healed in a mean of 9.9 (SD 2.5) days and 17.0 (4.6) days, respectively, compared with 12.4 (2.7) and 21.2 (4.9) days (p=0.0008 and p=0.0003, respectively). No adverse effects were seen locally or systemically with rbFGF. INTERPRETATION: rbFGF effectively decreased healing time and improved healing quality. Clinical benefits would be shorter hospital stays and the patient's skin quickly becoming available for harvesting and grafting.

Administration, Cutaneous↗
PubMed1998

Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase.

Recent studies have shown that the p70(s6k)/p85(s6k) signaling pathway plays a critical role in cell growth by modulating the translation of a family of mRNAs termed 5'TOPs, which encode components of the protein synthetic apparatus. Here we demonstrate that homozygous disruption of the p70(s6k)/p85(s6k) gene does not affect viability or fertility of mice, but that it has a significant effect on animal growth, especially during embryogenesis. Surprisingly, S6 phosphorylation in liver or in fibroblasts from p70(s6k)/p85(s6k)-deficient mice proceeds normally in response to mitogen stimulation. Furthermore, serum-induced S6 phosphorylation and translational up-regulation of 5'TOP mRNAs were equally sensitive to the inhibitory effects of rapamycin in mouse embryo fibroblasts derived from p70(s6k)/p85(s6k)-deficient and wild-type mice. A search of public databases identified a novel p70(s6k)/p85(s6k) homolog which contains the same regulatory motifs and phosphorylation sites known to control kinase activity. This newly identified gene product, termed S6K2, is ubiquitously expressed and displays both mitogen-dependent and rapamycin-sensitive S6 kinase activity. More striking, in p70(s6k)/p85(s6k)-deficient mice, the S6K2 gene is up-regulated in all tissues examined, especially in thymus, a main target of rapamycin action. The finding of a new S6 kinase gene, which can partly compensate for p70(s6k)/p85(s6k) function, underscores the importance of S6K function in cell growth.

Amino Acid Sequence↗