Biomedical subjects

Y Qian

Publications and source records attributed to Y Qian.

At least 91 records · Page 5Linked to original sources

PubMed2000

beta-amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment.

Treatment of rat pheochromocytoma cells (PC 12) cells with beta-amyloid peptide-(1-42) for 24 h induced a concentration-dependent decrease in cellular redox activity in the dose range of 1 to 20 microM. These effects were markedly attenuated by pretreatment with 2 mM LiCl for 7 days, whereas 1-day pretreatment was ineffective. Measurements of live and dead cells by double-staining with fluorescein diacetate and propidium iodide, respectively revealed that protracted lithium pretreatment attenuated PC 12 cell death induced by beta-amyloid-(1-42) and cerebellar granule cell death induced by beta-amyloid-(25-35). Preceding PC 12 cell death, beta-amyloid peptide elicited a slight decrease in protein levels of Bcl-2. Conversely, 7-day pretreatment with lithium resulted in an approximate doubling of Bcl-2 protein levels in cells treated with or without beta-amyloid peptide-(1-42). Lithium-induced Bcl-2 upregulation was temporally associated with the cytoprotective effects of this drug. Thus, lithium protection against beta-amyloid peptide neurotoxicity might involve Bcl-2 overexpression, and lithium treatment for Alzheimer's disease should be reexamined.

Amyloid beta-Peptides↗

PubMed2000

Lead targets GRP78, a molecular chaperone, in C6 rat glioma cells.

Exposure to potentially neurotoxic levels of lead (Pb) occurs in about 9% of American children under 6 years of age. Astroglia in the brain serve as a Pb depot, sequestering Pb and preventing its contact with the more sensitive neurons. Astroglia have the capacity to adapt to Pb exposure, and as such are able to tolerate relatively high intracellular Pb accumulation. This tolerance mechanism has yet to be defined in biochemical terms. In the present study, we present evidence that glucose-regulated protein (GRP78), a molecular chaperone in the ER, participates directly or indirectly in the tolerance mechanism. Exposure of cultured C6 rat glioma cells, an astroglia-like cell line, to 1 microM Pb acetate for 1 week raised the intracellular levels of two proteins, one of which was identified by sequence analysis as GRP78. GRP78 accumulation started within 1 day and progressed with time of exposure. Studies in vitro showed that GRP78 bound tightly to affinity columns with Pb(2+) as the affinity ligand and bound weakly when either Zn(2+) or Ni(2+) replaced the Pb(2+). The reduced form of GSH and BSA did not compete with GRP78 to chelate Pb(2+). However, the heavy metal binding domain (HMB) of Menkes protein competed with GRP78 for chelating Pb(2+). The data provide evidence that GRP78 may be a component of the Pb tolerance mechanism through its direct interaction with Pb(2+). Its increased synthesis could be part of the adaptive response to Pb exposure.

Amino Acid Sequence↗

PubMed2000

The carboxy terminus of AFAP-110 modulates direct interactions with actin filaments and regulates its ability to alter actin filament integrity and induce lamellipodia formation.

The actin filament-associated protein AFAP-110 is an SH2/SH3 binding partner for Src. AFAP-110 contains several protein-binding motifs in its amino terminus and has been hypothesized to function as an adaptor molecule that could link signaling proteins to actin filaments. Recent studies using deletional mutagenesis demonstrated that AFAP-110 can alter actin filament integrity in SV40 transformed Cos-1 cells. Thus, AFAP-110 may be positioned to modulate the effects of Src upon actin filaments. In this report, we sought to determine whether (a) AFAP-110 could interact with actin filaments directly and (b) deletion mutants could affect actin filament integrity and cell shape in untransformed fibroblast cells. The data demonstrate that the carboxy terminus of AFAP-110 is both necessary and sufficient for actin filament association, in vivo and in vitro. Analysis of the carboxy terminus revealed a mean 40% similarity with other known actin-binding motifs, indicating a mechanism for binding to actin filaments. AFAP-110 can also induce lamellipodia formation. Contiguous with the alpha-helical, actin-binding motif is an alpha-helical, leucine zipper motif. Deletion of the leucine zipper motif (AFAP(Deltalzip)) followed by cellular expression enabled AFAP(Deltalzip) to alter actin filament integrity and cell shape in untransformed cells as evidenced by the induction of lamellipodia formation. We hypothesize that AFAP-110 may be an important signaling protein that can directly modulate changes in actin filament integrity and induce lamellipodia formation.

3T3 Cells↗

PubMed2000

Kv4.2 phosphorylation by cyclic AMP-dependent protein kinase.

Recent evidence suggests that K(+) channels composed of Kv4.2 alpha-subunits underlie a transient current in hippocampal CA1 neurons and ventricular myocytes, and activation of the cAMP second messenger cascade has been shown to modulate this transient current. We determined if Kv4.2 alpha-subunits were directly phosphorylated by cAMP-dependent protein kinase (PKA). The intracellular domains of the amino and carboxyl termini of Kv4.2 were expressed as glutathione S-transferase fusion protein constructs; we observed that both of these fusion proteins were substrates for PKA in vitro. By using phosphopeptide mapping and amino acid sequencing, we identified PKA phosphorylation sites on the amino- and carboxyl-terminal fusion proteins corresponding to Thr(38) and Ser(552), respectively, within the Kv4.2 sequence. Kinetic characterization of the PKA sites demonstrated phosphorylation kinetics comparable to Kemptide. To evaluate PKA site phosphorylation in situ, phospho-selective antisera for each of the sites were generated. By using COS-7 cells expressing an EGFP-Kv4.2 fusion protein, we observed that stimulation of the endogenous PKA cascade resulted in an increase in phosphorylation of Thr(38) and Ser(552) within Kv4.2 in the intact cell. We also observed modulation of PKA phosphorylation at these sites within Kv4.2 in hippocampal area CA1. These results provide insight into likely sites of regulation of Kv4.2 by PKA.

Amino Acid Sequence↗

PubMed2000

Association analysis between mood disorder and monoamine oxidase gene.

To ascertain whether mood disorders, including bipolar and unipolar, are genetically associated with the monoamine oxidase A (MAOA) or monoamine oxidase B (MAOB) gene in the Chinese population, 132 cases of mood disorder and 88 normal controls were genotyped for the MAOA(CA)n, MAOB(GT)n, and MAOB(TG)n loci by the method of amplification fragment length polymorphism. Among 132 cases with mood disorder, eight alleles (size: 112-126 bp) of locus MAOA(CA)n, 12 alleles (size: 168-198 bp) of locus MAOB(GT)n, and nine alleles (size: 195-213 bp) of locus MAOB(TG)n were observed. Comparison of the allele frequency of the three loci showed no difference between mood disorder cases and normal controls on average. When each group was stratified into several subgroups, significant differences were found. On the MAOA(CA)n locus, the frequency of 116 bp allele was higher in the female bipolar disorder cases (0.2581) compared with that in the female unipolar disorder patients (0.1154) (Z=2.15, p<0. 05). On the MAOB(GT)n locus, the frequency of 180 bp allele was higher in bipolar disorder patients (0.1579) than that in normal controls (0.0678) (Z=2.05, p<0.05). The frequency of this allele was even higher in female bipolar disorder patients (0.1719) than that in female normal controls (0.0541). On the MAOB(TG)n locus, the frequency of 205 bp allele was higher in female bipolar disorder patients (0.6406) than that in female normal controls (0.4375) (Z=2. 17, p<0.05). For the unipolar disorder patients, the frequency of this allele was higher in female cases (0.5222) than that in male cases (0.1818) (Z=3.49, p<0.05). As for association studies, significant association between bipolar disorder and MAOB gene was detected. For the 180 bp allele of MAOB(GT)n, the relative risk (RR) of biploar versus normal control was 2.58 (p<0.05), and the RR of female bipolar disorder versus female normal control was 3.63 (p<0. 05). For the 205 bp allele of MAOB(TG)n, the RR of female bipolar disorder versus female normal control was 2.29 (p<0.05). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:12-14, 2000.

Alleles↗

PubMed2000

Prompt Iron Enrichment, Two r-Process Components, and Abundances in Very Metal-Poor Stars.

We present a model to explain the wide range of abundances for heavy r-process elements (mass number A>130) at low [Fe/H]. This model requires rapid star formation and/or an initial population of supermassive stars in the earliest condensed clots of matter in order to provide a prompt or initial Fe inventory. Subsequent Fe and r-process enrichment was provided by two types of supernovae: one producing heavy r-elements with no Fe on a rather short timescale and the other producing light r-elements (A</=130) with Fe on a much longer timescale.

Journal Article↗

PubMed2000

Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing.

Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, the mRNA is broadly distributed among neurons. When expressed in AtT-20 cells, proSAAS is secreted via the regulated pathway and is also processed at paired-basic cleavage sites into smaller peptides. Overexpression of proSAAS in the AtT-20 cells substantially reduces the rate of processing of the endogenous prohormone proopiomelanocortin. Purified proSAAS inhibits prohormone convertase 1 activity with an IC(50) of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.

Adrenal Glands↗

PubMed2000

Topical soluble tumor necrosis factor receptor type I suppresses ocular chemokine gene expression and rejection of allogeneic corneal transplants.

OBJECTIVE: To determine the effect of topical soluble tumor necrosis factor receptor type I (sTNFR-I) on survival of murine orthotopic corneal transplants and on ocular chemokine gene expression after corneal transplantation. METHODS: BALB/c mice (N = 50) were used as recipients of multiple minor H-disparate corneal transplants from B10.D2 donors. After orthotopic corneal transplantation, mice were randomized in a masked fashion to receive either topical sTNFR-I or vehicle 3 times daily, and all grafts were evaluated for signs of rejection and neovascularization by slitlamp biomicroscopy for 8 weeks. Ocular chemokine gene expression in sTNFR-I- and vehicle only-treated groups was determined using a multiprobe ribonuclease protection assay. RESULTS: Hosts treated with topical sTNFR-I experienced significantly enhanced corneal allograft survival compared with animals treated with vehicle alone (P =.01). Moreover, postoperative messenger RNA levels of RANTES and macrophage inflammatory protein-1beta in sTNFR-I-treated eyes were substantially suppressed compared with vehicle-treated eyes. Vehicle-treated eyes bearing rejected allografts expressed higher levels of messenger RNA for both chemokines than control eyes bearing accepted allografts. CONCLUSIONS: Topical treatment with sTNFR-I promotes the acceptance of allogeneic corneal transplants and inhibits gene expression of 2 chemokines (RANTES and macrophage inflammatory protein-1beta) associated with corneal graft rejection. CLINICAL RELEVANCE: Our findings support the feasibility of a topical anticytokine strategy as a means of reducing corneal allograft rejection without resorting to the use of potentially toxic immunosuppressive drugs.

Administration, Topical↗

PubMed2000

Seroprevalence against Norwalk-like human caliciviruses in beijing, China.

Serum specimens from 1,109 individuals at different ages in Beijing, China, were collected between April 1996 and March 1997 and tested for IgG antibodies against human caliciviruses using enzyme immune assays (EIAs). Baculovirus-expressed recombinant Norwalk virus (rNV) and Mexican virus (rMxV) capsid proteins were used as antigens. The seroprevalence was 89% for rNV and 91% for rMxV. Similar seroprevalence between the two antigens was observed in individual age groups and both genders. Infants had a high seroprevalence (99% for NV and 94% for MxV) at birth. The lowest seroprevalence (41% for rNV and 36% for rMxV) was at 7-11 months of age. A sharp increase in seroprevalence occurred in early childhood, with 65% and 70% at one, 85% and 90% at three, and 100% and 98% at 8-9 years of age for rNV and rMxV, respectively. Forty-three individuals had antibody against rNV but not rMxV and 63 individuals had antibody against rMxV but not rNV, indicating different levels of exposure to the two strains in these individuals. This is the first report of surveillance of antibodies against NV-like viruses in China. The observed high prevalence and early age antibody acquisition suggest that infection by these two human calicivirus strains is common in this population.

Adolescent↗

PubMed2000

Multiple origins of Tibetan Y chromosomes.

The genetic origin of Tibetans was investigated using Y chromosome markers. A total of three populations were studied, two from central Tibet speaking central Tibetan and one from Yunnan speaking Kham. Two dominant paternal lineages (>80%) were identified in all three populations with one possibly from central Asia (YAP+) and the other from east Asia (M122C). We conclude that Tibetan Y chromosomes may have been derived from two different gene pools, given the virtual absence of M122C in central Asia and YAP+ in east Asia, with drift an unlikely mechanism accounting for these observations.

Alu Elements↗

PubMed2000

Characterization and expression of an EB1 protein in Ictalurus punctatus neutrophils.

We have identified an EB1 gene (CfEB1) and protein in channel catfish neutrophils. The complete cDNA sequence is 1725 bp and the putative protein is composed of 258 amino acids. Western blot analysis of channel catfish neutrophil cell membrane with a monoclonal antibody (14I) yielded a 28 kD protein band with the protein preparation. Aside from neutrophils only a small percentage of other cells tested expressed detectable amounts of EB1 as determined by flow cytometry. Furthermore, EB1 expression increased after phorbol dibutyrate stimulation of neutrophils or incubation of catfish neutrophils with Edwardsiella ictaluri. Nonpermeabilized, fixed catfish neutrophils demonstrated immunofluorescent staining with 14I indicating that EB1 is apparently externally oriented in catfish neutrophils. This is the first report of the external orientation of the EB1 molecule. Because of its increase after stimulation and detection on cell membranes, EB1 may participate in catfish neutrophil cell regulation, signal transduction, or cell membrane changes necessary for phagocytosis.

Amino Acid Sequence↗

PubMed2000

Nanofabrication of self-assembled monolayers using scanning probe lithography.

This Account focuses on our recent and systematic effort in the development of generic scanning probe lithography (SPL)-based methodologies to produce nanopatterns of self-assembled monolayers (SAMs). The key to achieving high spatial precision is to keep the tip-surface interactions strong and local. The approaches used include two AFM-based methods, nanoshaving and nanografting, which rely on the local force, and two STM-based techniques, electron-induced diffusion and desorption, which use tunneling electrons for fabrication. In this Account we discuss the principle of these procedures and the critical steps in controlling local tip-surface interactions. The advantages of SPL will be illustrated through various examples of production and modification of SAM nanopatterns and their potential applications.

Chemistry↗

PubMed2000

Computational fluid dynamics analysis of hydrodynamic bearings of the VentrAssist rotary blood pump.

The computational fluid dynamics (CFD) package CFX-TASCflow was applied to simulate the flows through the blood pump hydrodynamic bearings. The three-dimensional flow patterns through the bearings were predicted and the hydraulic performance analyzed. The computations were carried out at 3 axial positions of the pump impeller. Net lift force away from the nearer part of the housing increased when the impeller moved closer to this part. Radial force and drag force were also found. Separated flows were observed at the leading and trailing edge of the bearing gap. To test the CFD package, a series of two-dimensional computations were also carried out for various bearing geometries. The results were compared with published experimental data.

Equipment Design↗

PubMed2000

Twenty-five-year panorama of corneal immunology: emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection.

PURPOSE: To describe the most recent advances in our understanding of the cellular and molecular mechanisms involved in the immunopathogenesis of corneal immunoinflammatory disorders including microbial keratitis, peripheral ulcerative keratitis. and allograft rejection. METHODS: Review of the published peer-reviewed literature that has contributed significantly to our modern understanding of corneal immunology. In addition, the authors have summarized the information in conceptual diagrams that highlight the critical cellular and molecular pathways that lead to corneal immune responses in the two most thoroughly studied corneal immune disorders, herpes simplex keratitis (HSK) and transplant rejection. RESULTS: In spite of the wide array of molecular and cellular factors that mediate corneal immunity, critical mechanistic facets are shared by the various corneal immunoinflammatory disorders. These include activation and migration of local antigen-presenting cells (APCs), including Langerhans cells (LCs), upregulation in pleiotropic proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alfa (TNF-alpha) that can mediate a wide array of immune functions in addition to up-regulating protease expression. and chemokines that play a critical role on the one hand in attracting nonantigen-specific inflammatory cells such as neutrophils and on the other in attracting CD4+ T helper type 1 (Th1) cells that mediate most of the destruction in the cornea. CONCLUSIONS: In the last 25 years, we have seen our field develop from a descriptive stage into a new phase where the fundamental processes that mediate and effect corneal immunity are being accurately deciphered. It is anticipated that this new knowledge will allow development of specific molecular and genetic therapeutic strategies that could target critical steps in the immunopathogenesis of disease without the untoward side-effects of nonspecific generalized immune suppression that still remains the standard of care today.

Animals↗

PubMed2000

Two mixed-metal carboxylate-base adducts

The crystal structures of hexa-&mgr;-propionato-1:2kappa(6)O:O';1:3kappa(6)O:O'-diquinoline-2ka ppaN,3kappaN-calcium(II)dizinc(II), [CaZn(2)(C(3)H(5)O(2))(6)(C(9)H(7)N)(2)], and hexa-&mgr;-pivalato-1:2kappa(6)O:O';1:3kappa(6)O:O'-diquinoline-2kapp aN,3kappaN-calcium(II)dicobalt(II), [CaCo(2)(C(5)H(9)O(2))(6)(C(9)H(7)N)(2)], are described. Both contain a linear array of one Ca(II) ion and two M(II) (M = Zn, Co) ions connected by two sets of three carboxylate ligands in syn-syn bridging modes. The distorted tetrahedral geometry around the M(II) ion is completed by a quinoline N atom. The central Ca(II) ion occupies a crystallographic inversion centre and is octahedrally coordinated by six carboxyl O atoms in each structure. The Zn(II). Ca(II) and Co(II).Ca(II) distances are 3.8504 (9) and 3.7929 (5) A, respectively.

Journal Article↗

PubMed2000

Intranasal administration of 2/6-rotavirus-like particles with mutant Escherichia coli heat-labile toxin (LT-R192G) induces antibody-secreting cell responses but not protective immunity in gnotobiotic pigs.

We investigated the immunogenicity of recombinant double-layered rotavirus-like particle (2/6-VLPs) vaccines derived from simian SA11 or human (VP6) Wa and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were administered to gnotobiotic pigs intranasally (i.n.) with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT), as mucosal adjuvant. Pigs were challenged with virulent Wa (P1A[8],G1) human rotavirus at postinoculation day (PID) 21 (two-dose VLP regimen) or 28 (three-dose VLP regimen). In vivo antigen-activated antibody-secreting cells (ASC) (effector B cells) and in vitro antigen-reactivated ASC (derived from memory B cells) from intestinal and systemic lymphoid tissues (duodenum, ileum, mesenteric lymph nodes [MLN], spleen, peripheral blood lymphocytes [PBL], and bone marrow lymphocytes) collected at selected times were quantitated by enzyme-linked immunospot assays. Rotavirus-specific immunoglobulin M (IgM), IgA, and IgG ASC and memory B-cell responses were detected by PID 21 or 28 in intestinal and systemic lymphoid tissues after i.n. inoculation with two or three doses of 2/6-VLPs with or without mLT. Greater mean numbers of virus-specific ASC and memory B cells in all tissues prechallenge were induced in pigs inoculated with two doses of SA11 2/6-VLPs plus mLT compared to SA11 2/6-VLPs without mLT. After challenge, anamnestic IgA and IgG ASC and memory B-cell responses were detected in intestinal lymphoid tissues of all VLP-inoculated groups, but serum virus-neutralizing antibody titers were not significantly enhanced compared to the challenged controls. Pigs inoculated with Wa-RF 2/6-VLPs (with or without mLT) developed higher anamnestic IgA and IgG ASC responses in ileum after challenge compared to pigs inoculated with SA11 2/6-VLPs (with or without mLT). Three doses of SA 11 2/6-VLP plus mLT induced the highest mean numbers of IgG memory B cells in MLN, spleen, and PBL among all groups postchallenge. However, no significant protection against diarrhea or virus shedding was evident in any of the 2/6-VLP (with or without mLT)-inoculated pigs after challenge with virulent Wa human rotavirus. These results indicate that 2/6-VLP vaccines are immunogenic in gnotobiotic pigs when inoculated i.n. and that the adjuvant mLT enhanced their immunogenicity. However, i.n. inoculation of gnotobiotic pigs with 2/6-VLPs did not confer protection against human rotavirus challenge.

Animals↗

PubMed2000

[Cytocompatible evaluation for skin reproducing membrane of medical fibroin].

This study was intended to evaluate the cytocompatibility of skin reproducing membrane of medical fibroin. Cell growth rate test and hemolysis test were conducted to investigate the cytotoxicity and hemolysis reaction for skin reproducing membrane. The results showed there was no obvious cytotoxicity for this kind of membrance. The hemolysis rate was 1.15%. In conclusion, skin reproducing membrane is a material of good cytocompatibility.

Animals↗

PubMed2000

[Different flow augmentations in coronary, carotid and renal arteries with ECP in experimental canines].

Different flow augmentations were found in canine's coronary, carotid and renal arteries with ECP because of their different anatomical locations in aorta. We used the Electromagnetic Blood Flowmeters to measure the blood flow pre-ECP and during ECP. The results showed ECP increased the diastolic flow of coronary, carotid and renal arteries by 24.48% +/- 1.29%, 27.18% +/- 0.94% and 20.68% +/- 0.80% respectively, decreased their systolic flow by 4.77% +/- 0.48%, 6.45% +/- 0.99% and 9.60% +/- 0.70%, but augmented their mean flow by 18.24% +/- 2.01%, 19.38% +/- 1.47% and 8.42% +/- 0.94% respectively in experimental dogs. These data demonstrate that ECP can greatly increase the mean flow of coronary and carotid arteries but at the same time patently decrease the systolic flow of renal artery.

Animals↗