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Biomedical subjects

W Zhang

Publications and source records attributed to W Zhang.

At least 613 records · Page 34Linked to original sources

Correlation between total and EDTA/DTPA-extractable trace elements in soil and wheat.

Wheat and wheat products are more important sources of energy and nutrients in diets of people in many cultures compared to other foods. The daily consumption of wheat is about 200 g/d/person in Western Europe and North America. On the other hand, 400-450 g of wheat and wheat products are consumed daily by average Turkish people. Wheat samples collected from the Iskenderun region in 1995 and 1996 and Ankara and Istanbul regions in 1995 were analyzed for their trace element content by instrumental neutron activation analysis (INAA). In addition, 13 soil samples were collected from the Iskenderun region in 1996. Total soil samples were analyzed by INAA and atomic absorption spectrometry (AAS), EDTA-extractable elements by INAA, and DTPA-extractable elements by AAS. Correlation analysis and enrichment factor calculations were applied to the trace element results. In wheat samples, a strong correlation was found between the elements such as Sc, La, Sm, Rb, and K whose main source is soil. The concentration of Se appeared to show larger variations among different regions. No significant correlation was observed for elements such as As and Se whose main sources in the atmosphere are anthropogenic activities.

Edetic Acid↗

Opening of Rice Floret in Rapid Response to Methyl Jasmonate.

Effects of methyl jasmonate (MeJA) on rice floret opening were investigated in seven cultivars or hybrid combinations covering various variety types. Intact or excised panicles, judged to have florets just before anthesis, were soaked in 4 x 10(-5) - 4 x 10(-3)M MeJA solutions for 2 min at different temperatures. The results indicated that MeJA significantly induced opening of rice florets within about 30 min, with the most rapid induction occurring just 6 min after treatment. Numbers of induced opening florets are correlated with MeJA concentrations. Higher concentrations of MeJA induced more florets. pH values had no influence on MeJA effect, but MeJA required less time and induced more florets at 34 degrees C than at 25 degrees C. As far as we know, this is the first evidence that floret opening is induced by plant hormones. CO(2) evolution from panicles was also increased by MeJA treatment. Field experiments revealed that perfect flowering synchrony between the cytoplasmic male sterile (CMS) and restorer lines in hybrid seed production could be obtained by spraying MeJA solution on CMS line plants at the rate of 25 mg/m(2). As a result, many more hybrid seeds were harvested.

Journal Article↗

The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D1, D2, D3, 5HT2A and muscarinic receptors.

The atypical antipsychotic olanzapine was compared to other atypical as well as typical antipsychotic agents for in vivo occupancy of D1, D2, D3, 5HT2, and muscarinic receptors in rat brain. Blockade of D2 receptors was determined by measuring the levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). To assess the interaction with phosphoinositide (PI)-coupled 5HT2A and muscarinic receptors in vivo, we used a novel radiometric technique to measure in vivo PI hydrolysis. The antagonism of olanzapine and other antipsychotic agents on 5HT2A and muscarinic receptors was determined by in vivo blockade of PI hydrolysis, stimulated by the 5HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) or the muscarinic agonist pilocarpine. Olanzapine inhibited 5HT2, D2, and D3 in vivo binding with high potency (ID50=0.15, 0.6 and 1.2 mg/kg, IP, respectively), while inhibiting D1 and muscarinic in vivo binding with much less potency (ID50 > 10 mg/kg, IP). The binding of olanzapine to D2 receptors in neostriatum was well correlated with the increase of DOPAC (ED200 = 0.8 mg/kg, IP) in vivo, indicating dopamine D2 antagonism. In vivo PI hydrolysis was increased by DOI in frontal cortex and by pilocarpine in hippocampus up to 2- and 7-fold above the basal level, respectively. The agonist-induced increases in PI hydrolysis were fully blocked by the 5HT2A antagonist MDL100907 and the muscarinic antagonist scopolamine, indicating the mediation by 5HT2A receptors in frontal cortex and PI-coupled muscarinic receptors (ml, m3, and m5) in hippocampus, respectively. Olanzapine was about 8-fold more potent in vivo in blocking DOI-induced stimulation of PI hydrolysis (ID50 = 0.1 mg/kg, IP) than pilocarpine-induced stimulation of PI hydrolysis (ID50 = 0.8 mg/kg, IP). In conclusion, olanzapine is more potent in blocking the 5HT2A receptor than D1, D2, D3 and muscarinic receptors in vivo, consistent with its favorable clinical profiles. In addition, the novel in vivo PI hydrolysis assay proved to be a useful and reliable in vivo method to assess the functional efficacy of compounds that interact with the 5HT2 and muscarinic receptors.

3,4-Dihydroxyphenylacetic Acid↗

Origin of stroma cells in long-term bone marrow cultures from patients with acute myeloid leukemia.

Bone marrow stroma cells from patients with acute myeloid leukemia (AML) display a variety of functional abnormalities. In order to determine whether this is related to an imbalance in the proportion of different stroma cell types or to integration of leukemic progeny into the regulatory cell network, stroma layers were established in mycophenolic acid-treated long-term marrow cultures from 16 patients with AML and 42 controls and analyzed by means of simultaneous membrane immunofluorescence and interphase cytogenetics. Macrophages were identified by CD14 expression, fibroblasts by staining with the AS02 antibody, and malignant cells by leukemia-specific numerical chromosome aberrations, including monosomy 7 and trisomy 8. Compared with normal controls, there was a slight decrease in the proportion of stroma fibroblasts (52+/-27% versus 77+/-5%) in 10-week-old cultures from patients with AML. Two of five AML patients with trisomy 8 and both patients with monosomy 7 had evidence of leukemic stroma cells. Most malignant cells were CD14+ macrophages (3.8-98.1% of all CD14+ cells), but some were AS02+ (2.8-5.2%). AML stroma layers showed a reduced capacity to support the growth of normal hematopoietic cells in standard two-stage long-term cultures, but this was unrelated to the presence or absence of leukemic stroma elements. In conclusion, AML populations vary with respect to their ability to produce a malignant microenvironment. Functional defects in the hematopoietic microenvironment, however, are not limited to AML patients with cytogenetically abnormal stroma cells, but extend to cases without evidence of malignant stroma cells.

Acute Disease↗

Modulation of glycinergic synaptic current kinetics by octanol in mouse hypoglossal motoneurons.

Octanol-induced changes in the kinetics of glycinergic inhibitory postsynaptic currents (IPSCs) were investigated by whole-cell recording from hypoglossal motoneurons in mouse brainstem slices. Octanol (1 mM) prolonged the decay time constants (tau(decay)) of stimulus-evoked IPSCs (e-IPSCs) by 202+/-67% (SE). The depression of e-IPSC amplitudes was dose-dependent with an EC50 of 475 microM. Octanol also reduced the amplitude and prolonged the decay time constant of glycinergic currents evoked by local pressure ejection of glycine (I(gly)). Replacement of extracellular Na+ by choline and application of the specific glycine transporter GLYT1 inhibitor, sarcosine, lengthened tau(decay) of I(gly), but did not change the decay time constants of e-IPSCs. Intracellular acidification by the weak organic acid salt sodium propionate (30 mM) reduced the e-IPSC amplitude by 22+/-9% and prolonged tau by 18+/-6%. Sodium propionate also prolonged the decay time constants of I(gly) by 28+/-11%. The observed effects on decay kinetics were much smaller than those caused by octanol. The data show that octanol prolongs the decay time course of glycinergic synaptic currents by mechanisms independent of glycine uptake or intracellular acidification. We conclude that the effects were most probably due to direct action on postsynaptic glycine receptors.

Amino Acid Transport Systems, Neutral↗

Transitional change in interaction between HIF-1 and HNF-4 in response to hypoxia.

The roles of the erythropoietin (Epo) 3' enhancer in the activation of gene expression in response to hypoxia were investigated. The enhancer contains hypoxia-inducible enhancer binding site 1 (HIF-1 element) and two direct repeats of hexanucleotide consensus nuclear receptor half site (HNF-4 element). HIF-1, which is a heterodimeric complex of HIF-1 alpha and aryl hydrocarbon receptor nuclear translecator (ARNT), binds to HIF-1 element. HNF-4 binds to HNF-4 element as a homodimeric complex. Studies on mutant reporter plasmids demonstrated that both HIF-1 alpha and HNF-4 elements were necessary for augmentation of the enhancer activity, since mutation of either the HIF-1 or the HNF-4 element caused loss of inducibility under hypoxic conditions. Mammalian two-hybrid experiments in vivo revealed that transitional change took place from the interaction of HNF-4 with ARNT to that with HIF-1 alpha in response to hypoxia. Such interactive domains were identified in amino acids 369-465 containing the C-terminal of HNF-4 and amino acids 1-458 containing basic helix-loop-helix (bHLH) and Per-ARNT-AHR-Sim (PAS) domains of ARNT in normoxia. Also, an extended sequence containing ligand and dimerization domains, and the C-terminal of HNF-4 (amino acids 135-465), and the PAS domain (amino acids 106-526) of HIF-1 alpha were used for the interaction between the two transcription factors in hypoxia. From these data, the functional significance of the transitional change in the augmentation of gene expression by the Epo enhancer in hypoxia is discussed.

Base Sequence↗

Linker for activation of T cells (LAT), a novel immunohistochemical marker for T cells, NK cells, mast cells, and megakaryocytes: evaluation in normal and pathological conditions.

LAT (linker for activation of T cells) is an integral membrane protein of 36-38 kd that plays an important role in T cell activation. Using a rabbit polyclonal antibody generated against the cytosolic portion of LAT, we investigated the immunohistochemical expression of LAT in normal and pathological hematolymphoid tissues. LAT reacts with human T cells in paraffin sections, including decalcified bone marrow trephines. LAT appears early in T cells at the thymocyte stage and before TdT expression in embryos, and is expressed in peripheral lymphoid tissues, without restriction to any T cell subpopulations. In addition to T cells, natural killer (NK) cells (evaluated with flow cytometry), megakaryocytes and mast cells are also LAT-positive, whereas B cells and other myeloid and monocytic derived cells are negative. Tested on a total of 264 paraffin-embedded tissue biopsies, LAT reacted with the great majority (96.8%) of T/NK-cell neoplasms, covering the full range of T cell maturation. Although antibodies to both LAT and CD3 had a similarly high sensitivity in the staining of T/NK-cell lymphomas, when used in conjunction, they successfully identified a higher number of cases (98.4%). Atypical megakaryocytes from different hematological disorders, as well as mast cells in mastocytosis were also LAT-positive, but all neoplasms of B cell origin, Hodgkin's lymphomas, and several nonlymphoid malignancies were negative. These data indicate that the anti-LAT antibody may be of value to diagnostic histopathologists for the identification of T cell neoplasms.

Adaptor Proteins, Signal Transducing↗

Loss of retinoic acid receptor-beta expression is an early event during esophageal carcinogenesis.

We recently observed that growth inhibition of esophageal cancer cells by retinoic acid (RA) was associated with both constitutive expression and RA-induced up-regulation of RA receptor beta (RAR-beta). Cell lines that did not express RAR-beta were also resistant to RA. To explore the expression of RAR-beta mRNA in vivo, we analyzed esophageal tissue specimens from 16 normal mucosae, 30 dysplastic lesions, and 157 esophageal tumors by in situ hybridization. RAR-beta was detected in 88% (14/16) of normal esophageal tissues and in 96% (96/100) of distant normal esophageal mucosa from cancer specimens. In contrast, RAR-beta was expressed in only 57% (17/30) of dysplastic lesions and in 54% (84/157) of carcinomas. Among esophageal carcinomas RAR-beta mRNA was expressed in 62% (26/42) of well-differentiated, 54% (27/50) of moderately differentiated, and only 29% (4/14) of poorly differentiated SCCs. Our data suggest that the loss of RAR-beta expression is an early event associated with esophageal carcinogenesis and the status of squamous differentiation.

Aged↗

The importance of coulombic end effects: experimental characterization of the effects of oligonucleotide flanking charges on the strength and salt dependence of oligocation (L8+) binding to single-stranded DNA oligomers.

Binding constants Kobs, expressed per site and evaluated in the limit of zero binding density, are quantified as functions of salt (sodium acetate) concentration for the interactions of the oligopeptide ligand KWK6NH2 (designated L8+, with ZL = 8 charges) with three single-stranded DNA oligomers (ss dT-mers, with |ZD| = 15, 39, and 69 charges). These results provide the first systematic experimental information about the effect of changing |ZD| on the strength and salt dependence of oligocation-oligonucleotide binding interactions. In a comparative study of L8+ binding to poly dT and to a short dT oligomer (|ZD| = 10),. Proc. Natl. Acad. Sci. USA. 93:2511-2516) demonstrated the profound thermodynamic effects of phosphate charges that flank isolated nonspecific L8+ binding sites on DNA. Here we find that both Kobs and the magnitude of its power dependence on salt activity (|SaKobs|) increase monotonically with increasing |ZD|. The dependences of Kobs and SaKobs on |ZD| are interpreted by introducing a simple two-state thermodynamic model for Coulombic end effects, which accounts for our finding that when L8+ binds to sufficiently long dT-mers, both DeltaGobso = -RT ln Kobs and SaKobs approach the values characteristic of binding to poly-dT as linear functions of the reciprocal of the number of potential oligocation binding sites on the DNA lattice. Analysis of our L8+-dT-mer binding data in terms of this model indicates that the axial range of the Coulombic end effect for ss DNA extends over approximately 10 phosphate charges. We conclude that Coulombic interactions cause an oligocation (with ZL < |ZD|) to bind preferentially to interior rather than terminal binding sites on oligoanionic or polyanionic DNA, and we quantify the strong increase of this preference with decreasing salt concentration. Coulombic end effects must be considered when oligonucleotides are used as models for polyanionic DNA in thermodynamic studies of the binding of charged ligands, including proteins.

Anions↗

The effect of a neuropeptide Y antagonist, BIBP 3226, on short-term arterial pressure control in conscious unrestrained rats with congestive heart failure.

The effects of a neuropeptide Y (NPY) Y1-receptor antagonist (BIBP 3226) on mean arterial pressure (MAP) and heart rate were investigated in conscious unrestrained rats with chronic congestive heart failure. The rats were randomly assigned to 2 groups, and received either BIBP 3226 or its inactive enantiomer (BIBP 3435) as an intravenous infusion (6 mg/kg/h for 1.5 h, respectively). Before, during and after the infusion, rats were stressed with a jet of air and received a bolus injection of NPY (2 nmol/kg iv.). There was no difference between the 2 groups in resting MAP and heart rate before, during or after infusion (BIBP 3226 vs. BIBP 3435). The effects of exogenous NPY on MAP were significantly attenuated in BIBP 3226 group during and 1 h after the infusion (p<0.05). The tissue NPY levels in heart, adrenal gland and kidney in heart failure rats were not different from those in sham-operated rats. The results suggest that Y1-receptor mechanisms are of minor importance in the short-term control of basal MAP and heart rate in conscious unrestrained rats with congestive heart failure.

Animals↗

Immortalized hippocampal cells contain functional luteinizing hormone/human chorionic gonadotropin receptors.

We used immortalized HN33p cells as surrogates for hippocampal neurons to investigate the functional importance of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors. The use of various detection techniques demonstrated that HN33p cells contain LH/hCG receptor transcripts and receptor protein that can bind 125I-hCG. Culturing them with highly purified hCG resulted in a significant, although modest, dose-and time-dependent and hormone specific increase in steady state 5-lipoxygenase (5-LO) mRNA and protein levels. The studies on signaling revealed that treatment of HN33p cells with hCG resulted in a robust dose- and a time-dependent significant increase in media cyclic AMP levels. In addition, treatment with a protein kinase (PK)A inhibitor, isoquinolinesulfonamide (H-89), but not with a PKC inhibitor, bisindolylmaleimide (Bis), prevented hCG from increasing the 5-LO protein levels. Pretreatment of HN33p cells for 48 hrs with 2 microM antisense, but not sense, phosphorothioate oligodeoxy-nucleotides (ODN) synthesized from mouse LH/hCG receptor sequence resulted in a dramatic decrease in LH/hCG receptor protein levels. In the antisense, but not in sense, ODN-treated cells, hCG was unable to increase cyclic AMP and 5-LO protein levels, suggesting that receptors are required for hCG to work in HN33p cells.

Animals↗

Three-dimensional computer-simulated prostate models: lateral prostate biopsies increase the detection rate of prostate cancer.

OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D) computer-assisted prostate biopsy simulator based on whole-mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. METHODS: We obtained digital images of 201 step-sectioned whole-mounted radical prostatectomy specimens. 3D computer simulation software was developed to accurately depict the anatomy of the prostate and all individual tumor foci. Additional peripheral devices were incorporated into the system to perform interactive prostate biopsies. We obtained 18 biopsies of each prostate model to determine the detection rates of various biopsy protocols. RESULTS: The 10- and 12-pattern biopsy protocols had a 99.0% detection rate; the traditional sextant biopsy protocol rate was only 72.6%. The 5-region biopsy protocol had a 90.5% detection rate and the 14-pattern, which includes all the biopsies used in the patterns above, only added 1 additional positive case (99.5%). Transitional zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. Only one positive model was obtained when the transitional zone biopsies were added. The lateral sextant pattern had a detection rate of 95.5%, and the 4-pattern lateral biopsy protocol had a 93.5% detection rate. CONCLUSIONS: Our results suggest that all the biopsy protocols that use laterally placed biopsies based on the 5-region anatomic model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.

Biopsy, Needle↗

Endothelin-1 stimulates c-fos mRNA expression in C6 glioma cells via MAP kinase pathway.

Exposure of C6 glioma cells to endothelin-1 (ET-1) caused dose-dependent (10(-11) M to 10(-7) M) increments in intracellular calcium concentration ([Ca2+]i) and c-fos mRNA expression (4.5-fold) that were abolished by the endothelinA receptor antagonist, BQ610, and by inhibition of phospholipase C with U73122. ET-1 stimulated c-fos mRNA expression was also inhibited by protein kinase C inhibition (chelerythrine) and by the MAP kinase kinase inhibitor PD98059, but not by inhibitors of tyrosine kinases, protein kinase A type I or II, calmodulin kinase II, or calcium channel blockade. C6 cells treated with ET-1 demonstrated a significant increase in MAP kinase activity as evidenced by Western blotting. These results indicate a mechanism of long-term signaling by ET-1 involving an ET(A) receptor-mediated, phospholipase C(beta)-linked pathway that is dependent on protein kinase C and MAP kinase activation.

Alkaloids↗

Bacteria targeted by human natural antibodies using alpha-Gal conjugated receptor-specific glycopolymers.

Synthesis of polymerizable beta-lactosyl, Galalpha1-->3Gal and alpha-mannosyl acrylamide derivatives with either a hydrophobic aromatic spacer or a hydrophilic biocompatible oligoethoxyl spacer was accomplished. Radical terpolymerizations of beta-lactosyl monomer. alpha-mannosyl monomer, and acrylamide were conducted in aqueous media with ammonium persulfate and N,N,N',N'-tetramethylethylenediamine as initiators. The resulting water soluble glycopolymers were further transformed efficiently by a recombinant alpha1-->3 galactosyltransferase to afford mediators bearing Galalpha1-->3Gal termini as xenoactive antigens and alpha-mannosyl termini as specific ligands for bacterial cells. The binding of the resulting multivalent glycopolymer to bacteria was tested by its ability to inhibit agglutination of yeast to E. coli. The binding of human natural anti-Gal antibodies to the alpha-Gal containing glycopolymers and a monovalent alpha-Gal-Man glycoconjugate was demonstrated by an ELISA inhibition assay.

Antibodies↗

Essential role of LAT in T cell development.

The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement. Phosphorylated LAT binds many critical signaling molecules. The central role of this molecule in TCR-mediated signaling has been demonstrated by experiments in a LAT-deficient cell line. To probe the role of LAT in T cell development, the LAT gene was disrupted by targeting. LAT-deficient mice appeared healthy. Flow cytometric analysis revealed normal B cell populations but the absence of any mature peripheral T cells. Intrathymic development was blocked within the CD4- CD8- stage. No gross abnormality of NK or platelet function was observed. LAT is thus critical to both T cell activation and development.

Adaptor Proteins, Signal Transducing↗

Economic reforms and fertility behaviour in rural China: an anthropological and demographic inquiry.

How have Chinese economic reforms that started in the late 1970s affected individual fertility behavior in rural China? This research attempts to explain how the deliberate policies of institutional reforms affect fertility outcomes through processes which are both filtered by, as well as reshape, existing social institutions. It is based on fieldwork in a Hebei village from July 1992 to November 1993. It finds that after the reforms, rural Chinese marry at earlier ages. However, declining age at marriage does not increase fertility. Rural couples prefer to have fewer children, and their motivation of having girls becomes stronger.

Asia↗

Pivot residue: an analysis of domain motion in proteins.

In this study, we present an approach to identify some residues that represent the pivot points to experience conformational changes between open (unligand) and closed (ligand) forms of a protein. First, an angle, theta, formed by 4 consecutive Ca atoms in polypeptide backbones was introduced. The difference of this angle, deltatheta, from the equivalent residues between the open and the closed form was used to represent the local torsion changes in the protein structure, and the residue with the maximum among deltatheta was identified to be a pivot residue. We demonstrate the ability of our method by identifying the pivot residues from five proteins, Lysozyme mutates, Lactoferrin, Lay/Arg/Orn-binding protein, Calmodulin and Catabolit gene activator protein. These pivot residues are located at the hinges in the proteins, they are hinge points for the domain motion. These examples also show that the pivot residues are useful to distinguish the mechanism between shear motion and hinge motion in a protein.

Amino Acid Sequence↗

Sequence pattern for the occurrence of N-glycosylation in proteins.

To further understand the occurrence of N-glycosylation, 21 nonhomologous proteins with Asn-x-Ser/Thr sequence were investigated. The results showed that some oligopeptides with Gly residues (G-x-y or y-x-G) are adjacent to the N-glycosylated sequences. These oligopeptides are not only essential for the structure and function of the proteins, but they are also found to be often proteolytic processing sites. These properties suggest that these oligopeptides may be a "sequence pattern" for the occurrence of N-glycosylation. The implications of the findings for protein structure and function are discussed.

Amino Acid Sequence↗