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Biomedical subjects

Z Yang

Publications and source records attributed to Z Yang.

At least 253 records · Page 14Linked to original sources
PubMed2000

Active micromixer for microfluidic systems using lead-zirconate-titanate (PZT)-generated ultrasonic vibration.

A micromixer using direct ultrasonic vibration is first reported in this paper. The ultrasonic vibration was induced by a bulk lead-zirconate-titanate (PZT; 5 x 4 x 0.2 mm), which was excited by a 48 kHz square wave at 150 V (peak-to-peak). Liquids were mixed in a chamber (6 x 6 x 0.06 mm) with an oscillating diaphragm driven by the PZT. The oscillating diaphragm was in the size of 6 x 6 x 0.15 mm. Ethanol and water were used to test the mixing effectiveness. The laminar flows of ethanol (115 microL/min) and water (100 microL/min) were mixed effectively when the PZT was excited. The entire process was recorded using a video camera.

Animals↗
PubMed2000

Preliminary studies on the application of retinal thickness analyzer in the diagnosis of glaucoma.

The patients with glaucoma underwent the examination of retinal thickness analyzer (RTA) to explore the diagnostic value of RTA in glaucoma. The retina of 6 mm x 6 mm size (approximately 20 degrees, centered on the macula) at the posterior pole was scanned by using RTA to obtain the images in 35 eyes of 22 patients with glaucoma. The images were processed by using SAS software package. The retinal thickness in the patients with glaucoma showed diffuse or local thinning. Twenty-seven eyes was definitely diagnosed as having glaucoma. There was a very significant difference in retinal thickness measurements by RTA between normal group and glaucomatous group (P = 0.0012). Except the measurements at the detected point 6 having no difference, the measurements at the detected point 3 showed a significant difference and the remaining 7 detected points presented a very significant difference between the two groups. Of the detected 9 points, the changes at the points 4, 8, and 9 were the most obvious. The discrete analysis was performed on the glaucomatous patients by a discriminant function established through the data at the detected points 4, 8 and 9 and the accurate estimate rate for the diagnosis of glaucoma was up to 80.77%. The measurements of RTA examination was consistent with the results of the vision field test. It was suggested that diffuse or local thinning of retinal thickness exists in the patients with glaucoma. The temporal inferior arcuate fibers and the papillomacular bundle between the macular and optic nerve heads showed a serious damage. The sensitivity of RTA examination was higher than visual field test.

Adolescent↗
PubMed2000

Terminal warm blood cardioplegia improves the recovery of myocardial electrical activity. A retrospective and comparative study.

OBJECTIVE: The effect of terminal warm blood cardioplegia was analyzed in 191 patients undergoing either coronary artery bypass grafting (CABG) or prosthetic heart valve replacement between Jan. 1990 and Dec. 1995. METHODS: Patients were subdivided into 3 historical cohorts based on the method of myocardial protection: Group A (n = 106), multidose cold crystalloid glucose-potassium cardioplegia, alone; Group B (n = 37), cold crystalloid glucose-potassium cardioplegia plus terminal warm blood cardioplegia, Group C (n = 48), cardioplegia induction with cold crystalloid glucose-potassium cardioplegia, maintenance with multidose cold blood cardioplegia, and terminal warm blood cardioplegia. RESULTS: Of patients undergoing CABG, 5.6% of group A, 70.4% of group B, and 86.7% of group C spontaneously resumed sinus rhythm after aortic declamping, as did 9.1% of group A, 60.0% of group B, and 55.6% of group C of patients undergoing prosthetic heart valve replacement. The incidence of spontaneous recovery was significantly better in groups B and C than in group A (p < 0.05). Over 90% of patients without terminal warm blood cardioplegia developed ventricular fibrillation or tachycardia requiring electrical cardioversion (p < 0.05). Postoperatively, patients without terminal warm blood cardioplegia required temporary epicardial pacing more frequently than those with terminal warm blood cardioplegia (p < 0.05). In patients undergoing prosthetic heart valve replacement, groups B and C, the incidence of postoperative atrial fibrillation was significantly lower than in group A. CONCLUSION: Terminal warm blood cardioplegia thus promoted better postoperative electrophysiological cardiac recovery.

Arrhythmias, Cardiac↗
PubMed2000

The Myxococcus xanthus wbgB gene encodes a glycosyltransferase homologue required for lipopolysaccharide O-antigen biosynthesis.

Myxococcus xanthus is a gram-negative soil bacterium that initiates a complex developmental program in response to starvation. A transposon insertion (Tn5-lac omega109) mutant with developmental deficiencies was isolated and characterized in this study. A strain containing this insertion mutation in an otherwise wild-type background showed delayed developmental aggregation for about 12 h and sporulated at 1-2% of the wild-type level. Tn5-lac omega109 was found to have disrupted the M. xanthus wbgB gene, which is located 2.1 kb downstream of the M. xanthus lipopolysacharide (LPS) O-antigen biosynthesis genes wzm wzt wbgA. The deduced polypeptide sequence of WbgB shares significant similarity with bacterial glycosyltransferases including M. xanthus WbgA. The wbgB::Tn5-lac omega109 mutant was found to be defective in LPS O-antigen synthesis by immunochemical analysis. Further mutational analysis indicated that the defects of the wbgB::Tn5-lac omega109 mutant were not the result of polar effects on downstream genes. Various motility assays demonstrated that the Tn5-lac omega109 mutation affected both social (S) and adventurous (A) gliding motility of M. xanthus cells. The pleiotrophic effects of wbgB mutations indicate the importance of LPS O-antigen biosynthesis for various cellular functions in M. xanthus.

Amino Acid Sequence↗
PubMed2000

Maximum likelihood estimation on large phylogenies and analysis of adaptive evolution in human influenza virus A.

Algorithmic details to obtain maximum likelihood estimates of parameters on a large phylogeny are discussed. On a large tree, an efficient approach is to optimize branch lengths one at a time while updating parameters in the substitution model simultaneously. Codon substitution models that allow for variable nonsynonymous/synonymous rate ratios (omega = d(N)/d(S)) among sites are used to analyze a data set of human influenza virus type A hemagglutinin (HA) genes. The data set has 349 sequences. Methods for obtaining approximate estimates of branch lengths for codon models are explored, and the estimates are used to test for positive selection and to identify sites under selection. Compared with results obtained from the exact method estimating all parameters by maximum likelihood, the approximate methods produced reliable results. The analysis identified a number of sites in the viral gene under diversifying Darwinian selection and demonstrated the importance of including many sequences in the data in detecting positive selection at individual sites.

Algorithms↗
PubMed2000

Decreased cisplatin/DNA adduct formation is associated with cisplatin resistance in human head and neck cancer cell lines.

PURPOSE: To evaluate the correlation between cisplatin sensitivity, intracellular glutathione, and platinum/DNA adduct formation (measured by atomic absorption spectroscopy) in a series of seven head and neck cancer cell lines, and to evaluate the effect of biochemical modulation of glutathione on platinum/DNA adduct formation and repair. METHODS: Cisplatin/DNA adducts were measured by atomic absorption spectroscopy. Glutathione content was measured by enzymatic assay and was modulated with buthionine sulfoximine. Apoptosis was measured by double-labeled flow cytometry. RESULTS: Intracellular glutathione concentration was strongly correlated with cisplatin resistance (P = 0.002, R2 = 0.7). There was also a statistically significant inverse correlation between cisplatin/DNA adduct formation and the IC50 for cisplatin in these cell lines. (P = 0.0004, R2 = 0.67). In addition, resistant cells were able to repair approximately 70% of cisplatin/DNA adducts at 24 h, while sensitive cells repaired less than 28% of adducts in the same period. However, despite the positive correlation between cellular glutathione and cisplatin resistance, there was no direct correlation between intracellular glutathione concentration and platinum/DNA adduct formation. Further, depletion of intracellular glutathione by buthionine sulfoximine did not dramatically alter formation of cisplatin/DNA adducts even though it resulted in marked increase in cisplatin cytotoxicity and was associated with increased apoptosis. CONCLUSIONS: These results suggest that glutathione has multiple effects not directly related to formation of cisplatin/DNA adducts, but may also be an important determinant of the cell's ability to repair cisplatin-induced DNA damage and resist apoptosis.

Antineoplastic Agents↗
PubMed2000

Extracellular magnesium deficiency induces contraction of arterial muscle: role of PI3-kinases and MAPK signaling pathways.

The present study investigated the actions of extracellular Mg2+ ([Mg2+]o) deficiency on isolated rat aortae and rat aortic smooth muscle cells (RASMC). Exposure of isolated, intact rat aortic rings to Mg(2+)-free or Mg(2+)-deficient medium (0.15-0.6 mM) produced endothelium-independent, concentration-dependent contractions: the lower the [Mg2+]o, the stronger the contraction. Pre- or post-incubation of the vessels with low concentrations of U0126, SB-203580, PD-98059, wortmannin, LY-294002, or a SH2 domain inhibitor peptide suppressed [Mg2+]o deficiency-induced contractions significantly. The concentrations of these antagonists required for half-maximal inhibition (IC50) were not very different from the inhibitory constants (Ki) for these drugs. A variety of specific pharmacological antagonists of several known endogenously-formed vasoconstrictors did not inhibit or attenuate the contractions induced by low [Mg2+]o. Mg(2+)-free medium induced a 6- to 7-fold increase in intracellular Ca2+ ([Ca2+]i) in RASMC. Pre- or post-treatment of the cells with U0126, SB-203580, PD-98059, wortmannin, LY-294002, or a SH2 domain inhibitor peptide markedly inhibited the increments in ([Ca2+]i) in RASMC induced by exposure to Mg(2+)-free medium. The present findings suggest that Mg(2+)-deficiency-induced contractions of rat aortae are associated with activation of several cellular signal pathways, such as mitogen-activated protein kinase, phosphatidylinositol-3 (PI3) kinases, and SH2 domain-containing proteins.

Animals↗
PubMed2000

Monte Carlo implementation of supercoiled double-stranded DNA.

Metropolis Monte Carlo simulation is used to investigate the elasticity of torsionally stressed double-stranded DNA, in which twist and supercoiling are incorporated as a natural result of base-stacking interaction and backbone bending constrained by hydrogen bonds formed between DNA complementary nucleotide bases. Three evident regimes are found in extension versus torsion and force versus extension plots: a low-force regime in which over- and underwound molecules behave similarly under stretching; an intermediate-force regime in which chirality appears for negatively and positively supercoiled DNA and extension of underwound molecule is insensitive to the supercoiling degree of the polymer; and a large-force regime in which plectonemic DNA is fully converted to extended DNA and supercoiled DNA behaves quite like a torsionless molecule. The striking coincidence between theoretic calculations and recent experimental measurement of torsionally stretched DNA (Strick et al., Science. 271:1835, 1996; Biophys. J. 74:2016, 1998) strongly suggests that the interplay between base-stacking interaction and permanent hydrogen-bond constraint takes an important role in understanding the novel properties of elasticity of supercoiled DNA polymer.

Biophysical Phenomena↗
PubMed2000

The human and mouse MHC class III region: a parade of 21 genes at the centromeric segment.

The human major histocompatibility complex (MHC) class III region contains 57-60 structural genes spanning 654-759 kb of genomic DNA. Analysis of the sequence identities of the human and mouse genomic regions between NOTCH4 and complement C2 yields important information on the locations of the coding and regulatory sequences. It also provides insights into the relationship between protein function and level of sequence conservation, and on the clustering of genes with related functions.

Animals↗
PubMed2000

Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I.

We analyzed the mechanism of axonal transport of the amyloid precursor protein (APP), which plays a major role in the development of Alzheimer's disease. Coimmunoprecipitation, sucrose gradient, and direct in vitro binding demonstrated that APP forms a complex with the microtubule motor, conventional kinesin (kinesin-I), by binding directly to the TPR domain of the kinesin light chain (KLC) subunit. The estimated apparent Kd for binding is 15-20 nM, with a binding stoichiometry of two APP per KLC. In addition, association of APP with microtubules and axonal transport of APP is greatly decreased in a gene-targeted mouse mutant of the neuronally enriched KLC1 gene. We propose that one of the normal functions of APP may be as a membrane cargo receptor for kinesin-I and that KLC is important for kinesin-I-driven transport of APP into axons.

Alzheimer Disease↗
PubMed2000

Thrombospondin 2, a matricellular protein with diverse functions.

Thrombospondin (TSP) 2 is a close relative of TSP1 but differs in its temporal and spatial distribution in the mouse. This difference in expression undoubtedly reflects the marked disparity in the DNA sequences of the promoters in the genes encoding the two proteins. The synthesis of TSP2 occurs primarily in connective tissues of the developing and growing mouse. In the adult animal the protein is again produced in response to tissue injury and in association with the growth of tumors. Despite the abnormalities in collagen fibrillogenesis, fragility of skin, and laxity of tendons and ligaments observed in the TSP2-null mouse, TSP2 does not appear to contribute directly to the structural integrity of connective tissue elements. Instead, emerging evidence supports a mode of action of TSP2 'at a distance', i.e. by modulating the activity and bioavailability of proteases and growth factors in the pericellular environment and, very likely, by interaction with cell-surface receptors. Thus, TSP2 qualifies as a matricellular protein, as defined in the introduction to this minireview series. The phenotype of TSP2-null mice has been very helpful in providing clues to the functions of TSP2. In addition to histological and functional abnormalities in connective tissues, these mice display an increased vascularity of the dermis and subdermal tissues, increased endosteal bone growth, a bleeding defect, and a marked adhesive defect of dermal fibroblasts. Our laboratory has established that TSP2 binds matrix metalloproteinase 2 (MMP2) and that the adhesive defect in TSP2-null fibroblasts results from increased MMP2 activity. The investigation of the basis for the other defects in the TSP2-null mouse is likely to yield equally interesting results.

Animals↗
PubMed2000

The Rrop GTPase switch turns on polar growth in pollen.

Pollen-tube growth not only represents an essential stage of plant reproduction but also provides an attractive model for studying cell polarity and morphogenesis. For many years, pollen-tube growth has been known to require a tip-focused Ca2+ gradient and dynamic F actin, but the way that these are controlled remained a mystery until recently. Rop appears to be activated at growth sites by a tip-localized growth cue, acting as a central switch that controls the polar growth of pollen tubes, probably having its effect through phosphoinositides and Ca2+. These findings have begun to shed light on the molecular basis of pollen-tube growth and cell morphogenesis in plants.

Actins↗
PubMed2000

The Rop GTPase: an emerging signaling switch in plants.

G proteins are ubiquitous molecular switches in eukaryotic signal transduction, but their roles in plant signal transduction had not been clearly established until recent studies of the plant-specific Rop subfamily of RHO GTPases. Rop participates in signaling to an array of physiological processes including cell polarity establishment, cell growth, morphogenesis, actin dynamics, H2O2 generation, hormone responses, and probably many other cellular processes in plants. Evidence suggests that plants have developed unique molecular mechanisms to control this universal molecular switch through novel GTPase-activating proteins and potentially through a predominant class of plant receptor-like serine/threonine kinases. Furthermore, the mechanism by which Rop regulates specific processes may also be distinct from that for other GTPases. These advances have raised the exciting possibility that the elucidation of Rop GTPase signaling may lead to the establishment of a new paradigm for G protein-dependent signal transduction in plants.

Amino Acid Sequence↗
PubMed2000

Structure of a closed form of human malic enzyme and implications for catalytic mechanism.

Malic enzymes are widely distributed in nature and have many biological functions. The crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme in a quaternary complex with NAD+, Mn++ and oxalate has been determined at 2.2 A resolution. The structures of the quaternary complex with NAD+, Mg++, tartronate or ketomalonate have been determined at 2.6 A resolution. The structures show the enzyme in a closed form in these complexes and reveal the binding modes of the cation and the inhibitors. The divalent cation is coordinated in an octahedral fashion by six ligating oxygens, two from the substrate/inhibitor, three from Glu 255, Asp 256 and Asp 279 of the enzyme, and one from a water molecule. The structural information has significant implications for the catalytic mechanism of malic enzymes and identifies Tyr 112 and Lys 183 as possible catalytic residues. Changes in tetramer organization of the enzyme are also observed in these complexes, which might be relevant for its cooperative behavior and allosteric control.

Allosteric Regulation↗
PubMed2000

Sampling SNPs.

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Alleles↗
PubMed2000

Adeno-associated virus vector mediated gene transfer to pancreatic beta cells.

Insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes is an autoimmune disease that results in destruction of the insulin-producing pancreatic islet beta cells. Several factors induce the invasion of immune cells into islets and trigger inflammation. Gene therapy approaches targeting the islet cells could be an effective treatment to prevent the onset or reverse type 1 diabetes. Allogeneic islet transplantation provides short-term treatment. However, genetically modified islets, which resist the host immune response, could provide long-term solutions. Adeno-associated virus (AAV) is emerging as a prominent vector system for delivering therapeutic genes for human gene therapy. AAV vector can transduce nondividing cells and provide long-term gene expression by integrating into host chromosome. Therefore, it is an appropriate vector system for islet cell gene therapy. To test the efficacy of AAV vector to transduce pancreatic endocrine cells, we constructed AAV vectors using plasmid pSub201. Wild-type AAV DNA analogue from plasmid psub201 was subcloned into a cloning plasmid pSP72 and AAV vectors were constructed by inserting the transgenes with heterologous promoter in place of AAV open reading frames (rep and cap). In this report we demonstrate the transduction of pancreatic islet cells with AAV vectors encoding bacterial -galactosidase enzyme or enhanced green fluorescent protein (EGFP) as reporter gene. Dispersed porcine and rat islet cells can be transduced by AAV vector, with an efficiency of 47% and 38%, respectively. In particular porcine islet insulin producing beta cells were transduced with an efficiency of 39%. Intact rat islet cells were transduced with an efficiency of 26% as estimated by FACS analysis following transduction with an AAV vector encoding EGFP. Transduction of intact rat islets with an AAV vector did not alter glucose-induced insulin secretion. AAV vector transduction was higher in transformed islet cell lines INS-1 and RIN m5F with an efficiency of 65% and 57%, respectively. These new results suggest that AAV vectors will provide an improved method of gene delivery to pancreatic islets and isolated pancreatic beta cells.

Animals↗