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Biomedical subjects

Z Yang

Publications and source records attributed to Z Yang.

At least 793 records · Page 44Linked to original sources
PubMed1994

Structural features in heparin which modulate specific biological activities mediated by basic fibroblast growth factor.

The biological activity of basic fibroblast growth factor (bFGF) is influenced greatly by direct binding to heparin and heparan sulphate (HS). Heparin-derived oligosaccharides have been utilized to determine the structural requirements present in the polymer that account for binding to bFGF. We had previously demonstrated that fragments > 6 mer can inhibit the interaction between cell surface heparan sulphate proteoglycan (HSPG) and bFGF, and bFGF-induced proliferation of adrenocortical endothelial (ACE) cells. In contrast, oligosaccharides > 10 mer can enhance the binding of bFGF to its high-affinity receptor or support bFGF-induced mitogenesis in ACE cells (Ishihara et al., J. Biol. Chem., 268, 4675-4683, 1993). We have extended these studies to size- and structure-defined oligosaccharides from heparin, 2-O-desulphated (2-O-DS-) heparin, 6-O-desulphated (6-O-DS-) heparin, carboxy-reduced (CR-) heparin and carboxy-amidomethylsulphonated (AMS-) heparin. Oligosaccharides from these polymers were fractionated on a bFGF-affinity column and were assessed as inhibitors or enhancers of specific bFGF-derived biological activities. The results of these studies indicate that both 2-O-sulphate and the negative charge of the carboxy group [L-iduronic acid (IdoA) residues] are required for specific interactions of heparin-derived oligosaccharides with bFGF and for modulation of bFGF mitogenic activity. In addition, the charge of the carboxy groups in uronic acids can be replaced by other functional groups with a negative charge, such as the amidomethyl sulphonate moiety described here.

Animals↗
PubMed1994

Comparison of models for nucleotide substitution used in maximum-likelihood phylogenetic estimation.

Using real sequence data, we evaluate the adequacy of assumptions made in evolutionary models of nucleotide substitution and the effects that these assumptions have on estimation of evolutionary trees. Two aspects of the assumptions are evaluated. The first concerns the pattern of nucleotide substitution, including equilibrium base frequencies and the transition/transversion-rate ratio. The second concerns the variation of substitution rates over sites. The maximum-likelihood estimate of tree topology appears quite robust to both these aspects of the assumptions of the models, but evaluation of the reliability of the estimated tree by using simpler, less realistic models can be misleading. Branch lengths are underestimated when simpler models of substitution are used, but the underestimation caused by ignoring rate variation over nucleotide sites is much more serious. The goodness of fit of a model is reduced by ignoring spatial rate variation, but unrealistic assumptions about the pattern of nucleotide substitution can lead to an extraordinary reduction in the likelihood. It seems that evolutionary biologists can obtain accurate estimates of certain evolutionary parameters even with an incorrect phylogeny, while systematists cannot get the right tree with confidence even when a realistic, and more complex, model of evolution is assumed.

Computer Simulation↗
PubMed1994

A codon-based model of nucleotide substitution for protein-coding DNA sequences.

A codon-based model for the evolution of protein-coding DNA sequences is presented for use in phylogenetic estimation. A Markov process is used to describe substitutions between codons. Transition/transversion rate bias and codon usage bias are allowed in the model, and selective restraints at the protein level are accommodated using physicochemical distances between the amino acids coded for by the codons. Analyses of two data sets suggest that the new codon-based model can provide a better fit to data than can nucleotide-based models and can produce more reliable estimates of certain biologically important measures such as the transition/transversion rate ratio and the synonymous/nonsynonymous substitution rate ratio.

Animals↗
PubMed1994

Human GATA-3 trans-activation, DNA-binding, and nuclear localization activities are organized into distinct structural domains.

GATA-3 is a zinc finger transcription factor which is expressed in a highly restricted and strongly conserved tissue distribution pattern in vertebrate organisms, specifically, in a subset of hematopoietic cells, in cells within the central and peripheral nervous systems, in the kidney, and in placental trophoblasts. Tissue-specific cellular genes regulated by GATA-3 have been identified in T lymphocytes and the placenta, while GATA-3-regulated genes in the nervous system and kidney have not yet been defined. We prepared monoclonal antibodies with which we could dissect the biochemical and functional properties of human GATA-3. The results of these experiments show some anticipated phenotypes, for example, the definition of discrete domains required for specific DNA-binding site recognition (amino acids 303 to 348) and trans activation (amino acids 30 to 74). The signaling sequence for nuclear localization of human GATA-3 is a property conferred by sequences within and surrounding the amino finger (amino acids 249 to 311) of the protein, thereby assigning a function to this domain and thus explaining the curious observation that this zinc finger is dispensable for DNA binding by the GATA family of transcription factors.

Antibodies, Monoclonal↗
PubMed1994

Thrombin-induced endothelium-dependent inhibition and direct activation of platelet-vessel wall interaction. Role of prostacyclin, nitric oxide, and thromboxane A2.

BACKGROUND: Platelet-vessel wall interaction plays an important role in acute cardiovascular disorders. Thrombin is a potent platelet activator but also has profound effects on the endothelium. Endothelial cells possess antithrombotic activity by releasing nitric oxide and prostacyclin, both potent vasodilators and platelet inhibitors. We studied the role of thrombin as a regulator of platelet-vessel wall interaction in isolated human arteries suspended in organ chambers for isometric tension recording. METHODS AND RESULTS: In arteries with endothelium, thrombin (0.01 to 1 U/mL) induced endothelium-dependent relaxations, which were reduced by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/L) and/or indomethacin (10(-5) mol/L). Human platelets (75,000/microL) evoked only marginal contractions in arteries with endothelium (3 +/- 3% of the contraction to KCl 100 mmol/L; NS), which were markedly enhanced by endothelial removal (22 +/- 4%; P < .05). Thrombin (1 U/mL) did not affect the response to platelets in arteries with (6 +/- 5%; NS) but induced a huge contraction in rings without endothelium (53 +/- 6%; P < .01 versus control without endothelium). The potent contraction to thrombin-activated platelets (1000 to 75,000/microL) in arteries without endothelium was markedly inhibited by the thromboxane A2 synthetase/receptor antagonist ridogrel (10(-5) mol/L; P < .005 versus control) and the single-acting thromboxane receptor blocker SQ-30741 (10(-7) mol/L; P < .01 versus control). CONCLUSIONS: Thus, thrombin directly stimulates platelets to release thromboxane A2, inducing potent vasoconstriction, which is prevented by the simultaneous thrombin-induced release of prostacyclin and nitric oxide from endothelial cells. In arteries devoid of functional endothelial cells, as occurs in patients with coronary artery disease, a combined inhibition of thromboxane production and action provides a potent therapeutic tool to interfere with the thrombin-induced activation of platelet-vessel wall interaction.

Coronary Vessels↗
PubMed1994

Human tissue kallikrein induces hypotension in transgenic mice.

We investigated the role of the kallikrein-kinin system in blood pressure control by developing transgenic mice overexpressing human tissue kallikrein. Two lines of transgenic mice carrying the human tissue kallikrein gene under the control of the mouse metallothionein metal-responsive promoter were established. Human tissue kallikrein was identified in pancreas, salivary gland, kidney, liver, and spleen of the transgenic mice by a specific radioimmunoassay for human tissue kallikrein. The immunoreactive human tissue kallikrein reached high levels in the circulation. The linear displacement curves for the transgenic product were parallel with the human tissue kallikrein standard curve, indicating their immunologic identity. The expression of human tissue kallikrein transcript in the transgenic mice was further confirmed by Northern blot analysis and by reverse transcription-polymerase chain reaction followed by Southern blot. Both lines of transgenic mice had significantly lowered blood pressure (86.4 +/- 13.5 mm Hg [mean +/- SD], n = 8 and 78.9 +/- 12.4 mm Hg, n = 8) compared with control mice (100.9 +/- 5.0 mm Hg, n = 8). Induction with zinc did not lower the blood pressure further despite elevated expression of the transgene. Administration of aprotinin, a potent tissue kallikrein inhibitor, restored the blood pressure of the transgenic mice but had no significant effect on control littermates. Our findings raise the possibility of tissue kallikrein being a powerful modulator of blood pressure and provide a new animal model for the study of blood pressure regulation.

Animals↗
PubMed1994

Catheter-mediated pulmonary vascular gene transfer and expression.

The study and treatment of pulmonary diseases may be greatly facilitated by in vivo expression of specific recombinant genes in the pulmonary vasculature and lung parenchyma. To evaluate the feasibility of gene transfer to the pulmonary vasculature, cationic liposomes and adenoviral vectors encoding a human placental alkaline phosphatase (hpAP) gene were delivered into a pulmonary artery of 24 pigs by percutaneous right heart catheterization. Pulmonary tissue was harvested within 20 minutes or 5, 14, or 28 days later and was analyzed for gene transfer and expression. Five days after exposure to liposomes or adenoviral vectors, transfer of DNA and expression of mRNA were demonstrated in transfected lung tissue. Recombinant alkaline phosphatase protein was observed in both the vasculature and in alveolar septa but not in the bronchi. Expression of hpAP protein was observed at 5 days, was diminished at 14 days, and was absent 28 days after gene transfer with both liposome and adenoviral vectors. No major adverse effects of gene expression were detected by histological examination of the transfected lung segments compared with control segments. Gene transfer to the lung by either vector was not associated with significant biochemical abnormalities or histological changes 5, 14, or 28 days later in other organs, including carotid artery, heart, liver, spleen, kidney, skeletal muscle, ovary, and testes. These studies demonstrate that after intravascular gene delivery to the lung, recombinant genes are expressed in the vasculature and alveoli. This approach may provide a useful model for the experimental study of pulmonary vascular diseases, including pulmonary fibrosis and pulmonary thrombosis disorders.

Adenoviridae↗
PubMed1994

Tissue factor expression in bovine endothelial cells induced by Pasteurella haemolytica lipopolysaccharide and interleukin-1.

Pasteurella haemolytica in cattle produces fibrino-hemorrhagic pleuropneumonia characterized by extensive pulmonary microvascular thrombosis and parenchymal necrosis. The purpose of this in vitro study was to determine if P. haemolytica lipopolysaccharide (LPS) promotes vascular thrombosis by inducing a procoagulant state in vascular endothelial cells. After treatment of confluent monolayers of bovine pulmonary artery endothelial cells with various concentrations of either P. haemolytica LPS or Escherichia coli LPS, the procoagulant activity of the endothelial cells was determined using a chromogenic assay dependent on cellular tissue factor expression. The LPS treatment induced significant increases in cellular tissue factor expression in a LPS concentration- and time-dependent manner. Highest levels of tissue factor were present at 22 hours after treatment, although high LPS concentrations induced moderate tissue factor levels at 5 hours after treatment. Interleukin-1 also induced tissue factor expression in endothelial cells and enhanced the LPS-induced effects. This interleukin-1 effect could be diminished by concurrent use of an interleukin-1 receptor antagonist. These results demonstrate that LPS and cytokine promotion of a procoagulant state in endothelial cells occurs in vitro. Similar mechanisms may play a role in P. haemolytica-mediated pulmonary vascular thrombosis.

Animals↗
PubMed1994

ANF(1-28) is a potent suppressor of pro-opiomelanocortin (POMC) mRNA but a weak inhibitor of beta EP-LI release from AtT-20 cells.

Controversies remain whether atrial natriuretic factor (ANF) may play a role in modulating the release of POMC derived peptides from pituitary corticotrophs. Employing AtT-20 mouse pituitary tumour cells, we report here the effects of rat ANF(1-28) and sodium nitroprusside (SNP), both of which augment cellular levels of cGMP through activating particulate and soluble guanylyl cyclases respectively, on the expression of POMC mRNA abundance. Furthermore, the cellular contents and secretion of (beta endorphin-like immunoreactivity) beta EP-LI from these cultures were also examined. Whereas the abundance of POMC mRNA was found to be markedly suppressed following 4h of incubation with rANP(1-28) (0.01 to 1 microM), SNP (0.1 to 10 microM) and dibutyryl-cGMP (1 to 100 microM) in a dose related manner, only a modest reduction in the release and cell contents of beta EP-LI was found in some of these cultures. It is also of interest to note that in all the cases examined, the inhibitory effect was associated with a significant suppression of cAMP levels in the cultures. Taken together, our present findings suggest that ANF may play a more important role in suppressing the production than the release of POMC related peptides from AtT-20 cells. Thus, it raises the possibility that hypothalamic ANF may likewise modulate the function of the pituitary-adrenal axis through exerting a greater effect on inhibiting the production than the secretion of pituitary ACTH.

Animals↗
PubMed1994

Identification of the major components of the high molecular weight crystallins from old human lenses.

High molecular weight aggregates from the water soluble portion of four lenses from older donors were examined by mass spectrometric techniques that permitted unambiguous identification of the principal components as alpha A-, alpha B- and gamma s-crystallins. Post-translational modifications that were located and identified included deamidations in alpha A and gamma s and an intramolecular disulfide bond in alpha A-crystallin. The C-terminus of alpha A was not found, supporting previous suggestions that this portion of the protein may be important in preventing aggregation.

Aged↗
PubMed1994

Use of avian cytokines in mammalian embryonic stem cell culture.

Mouse blastocyst-derived embryonic stem (ES) cells are multipotent cells that can be used in vitro as models of differentiation and in vivo can contribute to all embryonic tissues including the germ line. The culture of ES cells requires a source of leukemia inhibitory factor (LIF), often provided by culture with a mouse fibroblast (STO) feeder layer, buffalo rat liver cell-conditioned media (BRL-CM), or the addition of recombinant LIF. To date, all of the ES cell culture systems use mammalian sources of LIF. We found that mouse ES cells can be maintained for over 10 passages in an undifferentiated state with media conditioned by a chicken liver cell line (LMH-CM) or on a feeder layer made with primary chicken embryonic fibroblasts (CEF). These ES cells can undergo both spontaneous and induced differentiation, which is associated with the disappearance or reduction of the expression of alkaline phosphatase and SSEA-1, similar to that observed for ES cells cultured with BRL-CM or STO feeder layers. The ES cells cultured in LMH-CM did not express cytokeratin Endo-A antigen recognized by TROMA-1, but their differentiated progeny did express this antigen. In contrast to LMH-CM, Endo-A was expressed in ES cells cultured on CEF feeder layers and in differentiated progeny. These results indicate that avian cells can produce a LIF-like cytokine that is active in inhibiting the differentiation of mouse ES cells. This could provide a biological end point for the isolation and characterization of avian LIF.

Alkaline Phosphatase↗
PubMed1994

[Endothelial cell injury and changes in anti-coagulation properties induced by burn serum in vitro].

The purpose of this study is to clarify the effect of burn rabbit serum on the function and structure of endothelial cells in vitro. Morphological study (inverted microscopy, scanning electron microscopy), and determinations of LDH, 6-keto-PGF1 alpha and tissue-type plasminogen activator in the culture medium, changes in the ability of anti-adhesion of platelet to endothelial cells and anti-aggregation property of platelet, etc. were performed. The main results and conclusions were as follows: (1) Rabbit serum obtained in the early stage exerted obvious toxic effects on endothelial cells, functional changes appeared earlier than structural, and in the later changes in intercellular junction and cellular surface appeared earlier; (2) Burn rabbit serum significantly reduced the ability of anti-adhesion of platelet to endothelial cell and anti-aggregation property of platelet, and it might be the primary cause of local micro-thrombosis; (3) Because of the destruction of endothelial surface, the ability of fibrinolysis of endothelial cells was reduced. The activity of tPA might be inhibited b PAI-1, although the content of tPA in the culture medium seemed to be increased after endothelial cell injury.

Animals↗
PubMed1994

[Biodistribution of monoclonal antibody and Fab fragment and antitumor effect of their conjugates on hepatoma xenografts].

McAb 3A5, a rat monoclonal antibody directed against human hepatoma cells, and its Fab fragment were compared on their biodistribution and the therapeutic effects of their conjugates linked to C1027, a highly potent antitumor antibiotic, on the growth of human hepatoma xenografts in nude mice. Biodistribution study with 125I-labeled McAb 3A5 and its Fab fragment in hepatoma-bearing nude mice revealed that ID%/g values of McAb 3A5 were higher than those of the Fab fragment in tumor, liver, spleen and kidney; however, the T/NT ratios of Fab were higher than those of McAb 3A5. Imaging study with 131I-3A5 and 131I Fab showed that clear images of the tumor emerged 12h after injection of Fab and 40 h after that of McAb 3A5. IC50 values for McAb-C1027 and Fab-C1027 were 4.2 x 10(-14) mol/L, 8.6 x 10(-16) mol/L, respectively. Fab-C1027 conjugate was 49-fold more potent than McAb-C1027. Therapeutic effect of the conjugates was evaluated with hepatoma xenograft in nude mice. When treatment started 3 days after sc transplantation of the tumor with equivalent dose of C1027, 0.15 mg/kg, i.v., x3, tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 68% and 66%, respectively. When the treatment started on day 10 after transplantation with 0.10 mg/kg, i.v., x6, tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 24% and 54%, respectively. The results showed that compared with the intact McAb, Fab fragment displays higher specificity in biodistribution and exerts stronger inhibitory effect on the growth of established tumor xenografts.

Aminoglycosides↗
PubMed1994

[Study on size distribution of 8 polycylic aromatic hydrocarbons in airborne suspended particulates indoor and outdoor].

During Jan. 20-27, 1992, the size distribution of 8 polycyclic aromatic hydrocarbons (PAHs) in airborne suspended particulates in Tokyo, Japan was studied. The results showed that PAHs, 79.0%-94.5% in indoor air and 65.4%-90.4% in outdoor air, were associated with aerodynamic diameter less than 2.5 microns particles. The contents of these PAHs in indoor air were: pyrene (Py) 1.98, benzo (a) anthracene (BaA) 0.92, benzo (k) fluoranthene (BkF) 0.91, benzo (a) pyrene (BaP) 2.13, dibenzo (a,h) anthracene (dBahA) 0.30, benzo (b) chrysene (BbC) 0.15, benzo (g,h,i) perylene (BghiP) 2.56, dibenzo (a,e) pyrene (dBaeP) 0.23 ng/m3 and in outdoor air 3.93, 2.01, 1.41, 2.91, 0.40, 0.19, 3.65 and 0.30 ng/m3 respectively. The indoor/outdoor ratios for these PAHs ranged from 0.46 to 0.79. These PAHs contents were significantly correlative with one another and so were between the PAHs contents and the concentrations of airborne particulates both indoor and outdoor (the correlation coefficients ranged from 0.774 to 0.999). The PAHs contents (excluding Py) and the concentrations of airborne particulates between outdoor and indoor samples also correlated well with each other (correlation coefficients ranged from 0.821 to 0.944).

Air Pollutants↗
PubMed1994

[The compensatory changes of unstriped muscles of portal vein and superior mesenteric artery in rabbits infected with schistosomiasis].

We observed the changes of unstriped muscle of portal vein and superior mesenteric artery in rabbits infected with schistosomiasis in different stages with Masson trichrome stain. The results showed compensatory hypertrophy and hyperplasia of unstriped muscle of internal and medial layer of portal vein and superior mesenteric artery. It is concluded that the portal system is volume vessel as well as resistance vessel, which can counteract the intrahepatic resistance, maintaining the liver blood flow supply. The hyperdynamic circulation of viscera contributes to elevation of constrict power of the superior mesenteric artery, resulting in compensatory hypertrophy and hyperplasia of the unstriped muscle.

Animals↗