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Biomedical subjects

Z Yang

Publications and source records attributed to Z Yang.

951 records · Page 53Linked to original sources
PubMedDate not supplied

Strain-dependent anterior segment neovascularization following intravitreal gene transfer of basic fibroblast growth factor (bFGF).

BACKGROUND: A promising strategy for delaying death of photoreceptor cells in retinal degenerative disease is to support survival of these cells through intraocular delivery of growth/neurotrophic factors. One factor that has received great attention is basic fibroblast growth factor (bFGF; fgf-2), a known stimulator of angiogenesis. We evaluated the potential for neovascularization induced by adenovirus-mediated intravitreal delivery of bFGF. METHODS: Recombinant adenoviruses carrying the low molecular weight (18 kD) or the high molecular weight (22, 23 and 24 kD) forms of human bFGF, driven by the cytomegalovirus (CMV) promoter/enhancer, were prepared. Viruses were delivered to eyes of different strains of mice and rats through intravitreal injection. Contralateral eyes were injected with control virus carrying a reporter gene [green fluorescent protein (GFP) or lacZ]. Transgene expression was assessed by Western analysis and by immunohistochemistry. Neovascularization was evaluated in vivo and histologically at termination of the experiment. RESULTS: Adenovirus-mediated delivery of the 18 kD form of bFGF resulted in anterior segment neovascularization in a strain-dependent fashion. Generation of new blood vessels was not observed after injection of the higher molecular weight forms of bFGF or of control solutions. CONCLUSION: The low molecular weight form (18 kD) (but not the high molecular weight forms) of bFGF drives angiogenic response in the anterior segment of specific strains of mice. Genetic modifiers may contribute to and/or prevent neovascularization induced by bFGF.

Adenoviridae↗
PubMedDate not supplied

Liver disease in pregnancy and fetal fatty acid oxidation defects.

Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzymes, and low platelets (the HELLP syndrome) are serious disorders of the third trimester with high maternal and perinatal morbidity and mortality. Over the past decade, several clinical observations have demonstrated an association between these maternal syndromes and a recessively inherited fatty acid oxidation disorder, long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. Many women who carried LCHAD-deficient fetuses developed maternal liver disease. Over the past few years, we and others have made significant progress in understanding the molecular basis for this fetal-maternal interaction. Here, we review the studies in literature that led to the establishment of this causative association with particular emphasis on the molecular analysis that delineated the molecular basis of this association. The likely mechanisms for the genotype-phenotype correlations in pediatric LCHAD deficiency and the fetal-maternal interaction are discussed. Finally, the potential implications of our current knowledge for families with pediatric LCHAD deficiency and for women who develop AFLP and HELLP syndrome are discussed.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMedDate not supplied

A study of optimal configuration and control of a multi-chamber balloon for intraaortic balloon pumping.

Balloon configuration and control scheme are important for the optimization of assistance of the failing heart with an intraaortic balloon pumping device. In this work, the configuration of a multi-chamber balloon and control schemes have been investigated by using a hemodynamic model and computer simulation methods. Following the simulation study, physical testing and animal experiments were performed to demonstrate the simulation results. Results show that the optimal configuration and controlled multi-chamber balloon can provide better assistance to the failing heart. Based on the simulation and experimental results, it was found that the shape of the rear chamber of a multi-chamber balloon is critical. The optimal control scheme was to inflate the rear chamber first and deflate it last.

Animals↗
PubMedDate not supplied

Orientation, structure, wet-spinning, and molecular basis for supercontraction of spider dragline silk.

This manuscript reviews work from our laboratory that addresses the orientation, secondary structure, wet-spinning, and molecular basis for supercontraction of spider silk. It identifies the poly(alanine) runs as the crystalline regions, establishes the degree of orientation of these regions, and identifies the secondary structural elements of the conserved L-G-X-Q (X = G, S, or N) regions. It also describes methods for spinning very small amounts of protein polymers and it sets forth several molecular-level hypotheses concerning supercontraction.

Amino Acid Sequence↗
PubMedDate not supplied

Overexpression of sense or antisense human gastrin mRNA does not affect proliferation of normal rat kidney fibroblasts.

Progastrin-derived peptides have been reported to stimulate mitogenesis in Swiss 3T3 fibroblasts [P. Singh, A. Owlia, R. Espeijo, B. Dai, Novel gastrin receptors mediate mitogenic effects of gastrin and processing intermediates of gastrin on Swiss 3T3 fibroblasts: Absence of detectable cholecystokinin (CCK)-A and CCK-B receptors. J. Biol. Chem. 270 (1995) 8429-8438]. The aim of the present study was to determine the generality of these findings, by investigating the effect of endogenous and exogenous progastrin-derived peptides on the proliferation of the normal rat kidney fibroblast cell line NRK. Levels of endogenous progastrin-derived peptides were modified by stable transfection of NRK cells with tetracycline-repressible plasmids containing sequences encoding human gastrin in either the sense or antisense orientation. Expression of sense and antisense gastrin mRNA was demonstrated by reverse transcriptase PCR and by radioimmunoassay, and cell proliferation rates were determined by the colorimetric MTT assay. Sense clones produced full length human progastrin, but significant quantities of glycine-extended or amidated gastrin17 were not detected. Concentrations of endogenous rat progastrin in antisense clones were significantly lower than concentrations in clones transfected with vector only. However no difference in proliferation rate was observed between sense, antisense and vector-transfected clones. No stimulation of proliferation was observed in synchronised untransfected NRK cells after supplementation of media with gastrin17 or gastrin17gly in the concentration range 0.3 to 100 nM. Our results do not provide evidence in support of the hypothesis that endogenous or exogenous progastrin-derived peptides act as growth factors in NRK fibroblasts.

Animals↗
PubMedDate not supplied

An improved method for disruption of microbial cells with pressurized carbon dioxide.

Disruption of microbial cells by pressurized carbon dioxide at both subcritical and supercritical temperatures has been previously investigated. This method differs in principle from other disruption techniques and was found to have potential applications for rupture of a variety of microorganisms. However, it is not as effective for some of the microbial cells, including yeast, of which the cell walls are extremely robust and rigid. This work suggests an alternative operation to improve the disruption rates of cells by repeatedly releasing the applied fluid pressure within the cells in the midst of a disruption process. The improvement is substantial at all the experimental conditions studied.

Carbon Dioxide↗
PubMedDate not supplied

Expression in Escherichia coli of the flavin-containing monooxygenase D (form II) from adult human liver: determination of a distinct tertiary amine substrate specificity.

The cDNA for a major component of the family of flavin-containing monooxygenases (FMOs) present in adult human liver (i.e., HLFMO-D) has been cloned and expressed in a prokaryotic system. Escherichia coli strain NM522 was transformed with pTrcHLFMO-D, and the HLFMO-D cDNA was expressed under the control of the Trc promoter. A variety of tertiary amine substrates [i.e., chlorpromazine and 10-[(N,N-dimethylamino)alkyl]- 2-(trifluoromethyl)phenothiazines] were efficiently oxygenated by HLFMO-D cDNA expressed in E. coli or by adult human liver microsomes. Approximate dimensions of the substrate binding channel for both adult human liver microsomal FMO and cDNA-expressed HLFMO-D were apparent from an examination of the N-oxygenation of a series of 10-[(N,N-dimethylamino)alkyl]-2-(trifluoromethyl)phenothiazines. The substrate regioselectivity studies suggest that adult human liver FMO form D possesses a distinct substrate specificity compared with form A FMO from animal hepatic sources. It is likely that the substrate specificity observed for cDNA-expressed adult human liver FMO-D may have consequences for the metabolism and distribution of tertiary amines and phosphorus- and sulfur-containing drugs in humans and may provide insight into the physiologic substrate(s) for adult human liver FMO.

Animals↗
PubMedDate not supplied

Regio- and stereoselective oxygenations by adult human liver flavin-containing monooxygenase 3. Comparison with forms 1 and 2.

The cDNA for the adult human liver flavin-containing monooxygenase (form 3) (FMO3) was cloned, sequenced, and expressed in Escherichia coli. The cDNA-expressed FMO3 was used to investigate the regio- and stereoselective N- and S-oxygenation of a number of tertiary amines and sulfides, respectively. For comparison, the N- and S-oxygenation of the same chemicals and drugs were examined with adult human liver microsomes from a normal healthy female donor and FMO1 from pig liver and FMO2 from rabbit lung. Both cDNA-expressed FMO3 and adult human liver microsomes N-oxygenated trifluoperazine or 10-(N,N-dimethylaminoalkyl)-phenothiazines with similar substrate specificities. The substrate specificity for FMO3 differed, however, from that of pig liver FMO1. Nucleophilic sulfur-containing compounds [i.e., thiobenzamide, (4-bromophenyl)-1,3-oxathiolane, and 2-methyl-1,3-benzodithiole] were efficiently S-oxygenated by cDNA-expressed FMO3 and adult human liver microsomes. Stereoselective S-oxygenation of (+)- and (-)-(4-bromophenyl)-1,3-oxathiolane and 2-methyl-1,3-benzodithiole was therefore investigated. In general, the stereoselectivity observed for S-oxygenation in the presence of FMO3 was similar to that observed in the presence of adult human liver microsomes. In most cases examined, however, the stereoselectivity for S-oxygenation was quite distinct from that observed for pig liver FMO1. We conclude that FMO3 is the major form of FMO active in adult human liver. Because the stereoselectivity for X-oxygenation and the substrate specificity for tertiary amine N-oxygenation by cDNA-expressed FMO3 are distinct from those of pig liver FMO1, we conclude that the binding channel for each isoform is quite different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

The incidence of insulin-dependent diabetes mellitus in urban districts of Shanghai (1989-1993).

A retrospective study on the incidence of insulin-dependent diabetes mellitus (IDDM) among children aged 0-14 years was carried out from 1989-1993 in urban Shanghai, China. The average annual population at risk (0-14 yr) consisted of 1,401,664 children. All the cases were collected from the hospitals (primary source) and from primary and middle schools and kindergartens (second source) with independent validation of case ascertainment. There were 53 IDDM cases from the primary source, 23 from the secondary source, with a total of 58. The ascertainment corrected total number of IDDM cases was 67 by the capture-recapture method. The average crude annual incidence rate was 0.83 [95% confidence interval (CI) 0.61-1.04] and ascertainment corrected incidence rate 0.96 (95% CI 0.80-1.12) per 100,000. Peak incidence fell in 1992 and in the 9 year-old group. The incidence of childhood IDDM in the urban districts of Shanghai was reconfirmed to be the lowest in the world but by comparing the results of former investigations a trend was found of increasing incidence of IDDM.

Adolescent↗
PubMedDate not supplied

Vascular endothelial growth factors and liver diseases.

Vascular endothelial growth factor plays an important role in neovascularization both in normal tissues and most tumors. It has been extensively investigated recently in various hepatic diseases such as primary and secondary hepatocellular carcinoma, liver cirrhosis, hepatitis and even benign tumors in liver. Vascular endothelial growth factor has been verified to be closely involved in the development and metastases of hepatocellular carcinoma and correlated to the high risk of hepatic metastases and a poor prognosis in gastrointestinal cancer. Using antibodies to vascular endothelial growth factor or other drugs to suppress its expression has also been successfully tried to restrain hepatocellular carcinoma cells and metastases in vitro and in animal models. The protein of vascular endothelial growth factor has an inclination to increase in acute and chronic hepatitis and tends to decrease in cirrhosis both in tissue expression and circulating levels. This circulating level is closely related to the Child-Pugh classification in cirrhotic liver. However, there are indeed some disagreements concerning vascular endothelial growth factor and liver disease, for example, opinions on the positive rates of vascular endothelial growth factor in protein and mRNA level are far from reaching a general consensus. Further study should be performed in the future in antitumor research and its significance in the process of liver cirrhosis.

Acute Disease↗
PubMedDate not supplied

Stereo- and regioselective N- and S-oxidation of tertiary amines and sulfides in the presence of adult human liver microsomes.

Adult human liver microsomes supplemented with NADPH catalyzed the regioselective N-oxygenation of the aliphatic tertiary amine and S-oxidation of the phenothiazine sulfur atom of several 10-(N,N-dimethylaminoalkyl)phenothiazines. In addition, (+)- and (-)-4-bromophenyl-1,3-oxathiolane were converted to the corresponding S-oxides in the presence of NADPH and adult human liver microsomes. The (+) and (-) enantiomers of 4-bromophenyl-1,3-oxathiolane were converted to the S-oxides with low and high stereoselectivity, respectively. Studies on the biochemical mechanism for N-oxygenation of 10-(N,N-dimethylaminoalkyl)phenothiazines suggested that this reaction was catalyzed by the flavin-containing monooxygenase (form II), although cytochrome P-450 2D6 may also have contributed to N-oxide formation. S-Oxidation of chlorpromazine was catalyzed mainly by cytochrome P-450 3A. S-Oxidation of 10-(N,N-dimethylaminoalkyl)phenothiazines was catalyzed by a number of cytochromes P-450, including cytochromes P-450 2A6, 2C8, and 2D6. S-Oxygenation of (+)-4-bromophenyl-1,3-oxathiolane produced a mixture of the cis- and trans diastereomers in a process probably dependent on both hepatic monooxygenase systems. (-)-4-Bromophenyl-1,3-oxathiolane was converted almost exclusively to the trans-S-oxide in a process likely dependent on the adult human liver flavin-containing monooxygenase (form II). Development of regio- and stereochemical probes of adult human liver flavin-containing monooxygenase (form II) and cytochromes P-450 activity may be useful for eventual in vitro-in vivo correlations, but may require approaches quite distinct from that currently used for animal monooxygenases.

Adolescent↗