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Biomedical subjects

Z Sun

Publications and source records attributed to Z Sun.

At least 217 records · Page 12Linked to original sources
PubMed1997

[Studies on mutagenicity of polycyclic aromatic hydrocarbon-DNA adduct].

Mutagenic effect of polycyclic aromatic hydrocarbon (PAH)-DNA adduct was studied to explore mechanism of carcinogenecity of PAH. Adduct was formed by chemical group protection and nucleophilic displacement methods with modification of deoxyadenosine by PAH-dihydrodiol epoxide. Partial analogous sequence of human protooncogene ras (H-ras) containing mutagenic hotspot 61 codon (CAG) was synthesized by a DNA assembler and DNA was duplicated with a template of partial analogous sequence containing adduct protooncogene. Results showed that PAH-DNA adduct could obviously affect the process of DNA duplication, cause interruption of duplication of DNA or translesional bypass, lower fidelity of duplication, and induce misincorporation of bases in corresponding locus of the adduct, with point mutation of transversion (from A-T to T-A).

DNA Adducts↗
PubMed1996

cAMP-response element modulator tau is a positive regulator of testis angiotensin converting enzyme transcription.

Testis angiotensin-converting enzyme (ACE) is a unique form of ACE, only produced by male germ cells, and results from a testis-specific promoter found within the ACE gene. We have investigated the role of cAMP-response element modulator (CREM)tau in testis ACE transcription. In gel shift experiments, testes nuclear proteins retard an oligonucleotide containing the cAMP-response element (CRE) found at position -55 in the testis ACE promoter. Anti-CREM antibody supershifts this complex. Competitive gel shift shows that recombinant CREM tau protein and testis nuclear proteins have a similar specificity of binding to the tests ACE CRE. Functional analysis using in vitro transcription and transfection studies also demonstrate that CREM tau protein is a transcriptional activator of the testis ACE promoter. Western blot analysis identifies CREM tau protein in the protein-DNA complex formed between nuclear proteins and the testis ACE CRE motif. This analysis also identified other CREM isoforms in the gel-shifted complex, which are thought to be CREM tau 1/2, CREM alpha/beta, and S-CREM. These data indicate that CREM tau isoforms play an important role as a positive regulator in the tissue-specific expression of testis ACE.

Animals↗
PubMed1996

Cloning and functional analysis of the beta-carotene hydroxylase of Arabidopsis thaliana.

An Arabidopsis thaliana cDNA encoding the enzyme beta-carotene hydroxylase was identified by functional complementation in Escherichia coli. The product of this cDNA adds hydroxyl groups to both beta rings of the symmetrical beta-carotene (beta,beta-carotene) to form zeaxanthin (beta,beta-carotene-3,3'-diol) and converts the monocyclic beta-zeacarotene (7',8'-dihydro-beta,psi-carotene) to hydroxy-beta-zeacarotene (7',8'-dihydro-beta,psi-carotene-3-ol). The epsilon rings of delta-carotene (epsilon,psi-carotene) and alpha-zeacarotene (7',8'-dihydro-epsilon,psi-carotene) are poor substrates for the enzyme. The predicted amino acid sequence of the A. thaliana enzyme resembles the four known bacterial beta-carotene hydroxylase enzymes (31-37% identity) but is much longer, with an N-terminal extension of more than 130 amino acids. Truncation of the cDNA to produce a polypeptide lacking the first 69 amino acids does not impair enzyme activity in E. coli. Truncation to yield a polypeptide of a length comparable with the bacterial enzymes (lacking 129 N-terminal amino acids) resulted in the accumulation of the monohydroxy intermediate beta-cryptoxanthin (beta,beta-carotene-3-ol), predominantly, when beta-carotene was provided as the substrate. It is suggested that amino acid residues 70-129 of the A. thaliana enzyme may play a role in formation of a functional homodimer.

Amino Acid Sequence↗
PubMed1996

Identification and analysis of the human and murine putative chromatin structure regulator SUPT6H and Supt6h.

We have isolated and sequenced SUPT6H and Supt6h, the human and murine homologues of the Saccharomyces cerevisiae and Caenorhabditis elegans genes SPT6 (P using 1603 aa = 6.7 e-95) and emb-5 (P using 1603 aa = 7.0 e-288), respectively. The human and murine SPT6 homologues are virtually identical, as they share >98% identity and >99% similarity at the protein level. The derived amino acid sequences of these two genes predict a 1603-aa protein (human) and a 1726-bp protein (mouse), respectively. There were several known features, including a highly acidic 5'-region, a degenerate SH2 domain, and a leucine zipper. These features are consistent with a nuclear protein that regulates transcription, whose extreme conservation underscores the likely importance of this gene in mammalian development. Expression of human and murine SPT6 homologues was analyzed by Northern blotting, which revealed a 7. 0-kb transcript that was expressed constitutively. The SPT6 homologue was mapped to chromosome 17q11.2 in human by somatic cell hybrid analysis and in situ hybridization. These data indicate that SUPT6H and Supt6h are functionally analogous to SPT6 and emb-5 and may therefore regulate transcription through establishment or maintenance of chromatin structure.

Amino Acid Sequence↗
PubMed1996

Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways.

SPK1/RAD53/MEC2/SAD1 of Saccharomyces cerevisiae encodes an essential protein kinase that is required for activation of replication-sensitive and DNA damage-sensitive checkpoint arrest. We have investigated the regulation of phosphorylation and kinase activity of Spk1p during the cell cycle and by conditions that activate checkpoint pathways. Phosphorylation of Spk1p is induced by treatment of cells with agents that damage DNA or interfere with DNA synthesis. Although only S- and G2-phase cdc mutants arrest with hyperphosphorylated Spk1p, damage-induced phosphorylation of Spk1p can occur in G1 and M as well. Hydroxyurea (HU) induces phosphorylation of kinase-defective forms of Spk1p, demonstrating that this regulated phosphorylation of Spk1p occurs in trans. HU-induced phosphorylation is associated with increased catalytic activity of Spk1p. Furthermore, overexpression of wild-type SPK1, but not checkpoint-defective alleles, delays progression through the G1/S boundary. Damage-dependent phosphorylation of Spk1p requires both MEC1 and MEC3, whereas MEC1 but not MEC3, is required for replication block-induced phosphorylation. These data support the model that Spk1p is an essential intermediate component in a signal transduction pathway coupling damage and checkpoint functions to cell cycle arrest. This regulation is mediated through a protein kinase cascade that potentially includes Mec1p and Tel1p as the upstream kinases.

Alkaline Phosphatase↗
PubMed1996

Interleukin-5 receptor alpha subunit gene regulation in human eosinophil development: identification of a unique cis-element that acts lie an enhancer in regulating activity of the IL-5R alpha promoter.

Further functional and biochemical characterization of the nuclear factor(s) which interacts with the EOS1 enhancer-like element in the IL-5R alpha promoter is currently in progress. Since different transcription factors recognize and interact with DNA in distinct fashions and with distinct structural motifs, we have modeled potential binding of the EOS1 factor to its cis-element based upon its methylation interference pattern (Fig. 2), using a cylindrical DNA helical projection (Fig. 6). Over a length of two helical turns, all nuclear protein contacts indicated by methylation interference map to one side of the DNA helix, suggesting that EOS1 binds in the major groove, across the minor groove, and on only one side of the helix. Further review of the model also reveals a potential diad symmetry for the binding site, suggestive of binding by a homodimer and consistent with the formation of the two DNA-protein complexes in our electrophoretic mobility shift experiments that could represent interactions with monomer versus dimer. Comparison of the EOS1 binding motif to similar models for the binding of other transcription factor families for which structural crystallographic and/or binding data is available suggests a similarity of the EOS1 complex to that of the bacterial helix-turn-helix phage lambda and 434 repressor-operator complexes, and the Cys4 zinc finger glucocorticoid response element (GRE) DNA-binding motifs, all of which show similar diad symmetry and binding in the major groove on one side of the DNA. The possibility that EOS1 functions as a GRE is being investigated, especially since there is a consensus AP-1 site at bp -440 to -432 of the IL-5R alpha promoter, immediately adjacent to the EOS1 binding site (see Fig. 5 in reference [36]) and AP-1/GRE interactions have been identified for composite response elements in the regulation of a number of different genes. The identification or cloning of EOS1, a potentially novel and eosinophil lineage-active transcription factor, should enhance our understanding of the processes involved in eosinophil development in particular and myeloid lineage commitment and differentiation in general.

Animals↗
PubMed1996

Patterns and conformations of commonly occurring supersecondary structures (basic motifs) in protein data bank.

Short peptides connecting alpha-helices and beta-strands have been analyzed in 240 proteins refined at resolutions of 0.25 nm or better. Connecting peptides of lengths between one and five residues have been classified as part of supersecondary motifs of four types: alpha alpha, alpha beta, beta alpha, and beta beta. Careful consideration has been given to the definition of secondary structures on the basis of hydrogen bonds and main-chain conformational angles. Using five classes of residue conformation-a, b, e, l, t-in the nonregular structure regions of phi, psi space, 34 classes of supersecondary motifs occurring at least five times have been identified. Among these 34 classes, 11 classes that occur more than 25 times are commonly occurring supersecondary structure motifs. The patterns and conformations of the 11 commonly occurring supersecondary structure motifs have been characterized, demonstrating that patterns and conformations adopted by supersecondary structure motifs are limited. The results have relevance to structure prediction, comparative modeling, and protein folding.

Amino Acids↗
PubMed1996

Molecular dissection of a cosmid from a gene-rich region in 17q21 and characterization of a candidate gene for alpha-N-acetylglucosaminidase with two cDNA isoforms.

A cosmid mapped to human Chromosome (Chr) 17q21, c140c10, was found to contain a CpG island. We completed the sequence analysis of c140c10 because of two considerations: the cosmid contained an STS from the 17-beta-hydroxysteroid dehydrogenase gene (17-HSD), which was believed to be a neighbor of the breast cancer susceptibility gene, BRCA1; CpG islands are usually associated downstream and/or upstream of human genes. Computer-based exon trapping of the cosmid sequence revealed putative additional exons. With two of those exons used as a probe to screen human placental cDNA libraries, two cDNA isoforms for a novel gene, designated as ufHSD, were isolated. The amino acid sequence of the open reading frames of the cDNA showed no significant homology to any protein in the data base. However, it is possible that our cDNAs are from the gene for alpha-acetylglucosaminidase, which has recently been localized to the same region. Northern analyses show that the major isoform is expressed in all tissues tested, with the highest expression in blood leukocytes and lowest in brain. Finally, our study has shown that the 46.7-kb cosmid c140c10 encompasses loci for five genes and pseudo-genes: PsiPTP4A, ufHSD, 17-HSDI, 17-HSDII, and 22A1.

Acetylglucosaminidase↗
PubMed1996

Long-term results of operation for paravalvular abscess.

BACKGROUND: Operation for infective endocarditis with paravalvular abscess is reportedly associated with high mortality and morbidity rates. In an attempt to improve surgical outcome, an approach of radical resection of the abscess and inflamed tissues and reconstruction of the heart with either fresh or glutaraldehyde-fixed bovine pericardium was adopted by two surgeons at our institution. METHODS: From 1979 to 1995, 70 consecutive patients with active infective endocarditis and paravalvular abscess underwent operation. Their mean age was 49 years (range, 16 to 75 years), and 50 patients (71%) were men. Thirty-four patients had native and 36 had prosthetic valve endocarditis (8 had had composite replacement of the aortic valve and ascending aorta). Most patients (78%) were in New York Heart Association functional class IV. The principal indication for operation was cardiogenic or septic shock in 11 patients, or one or more of the following: persistent sepsis despite adequate antibiotic therapy in 36, congestive heart failure in 31, and recurrent emboli in 16. Staphylococci were responsible for the infection in 37 patients (53%). The abscess was in the mitral annulus in 11 patients, in the aortic root in 44, and in the aortic root and at least one other annulus in 15. After wide resection of the abscess, we reconstructed the heart and annuli with autologous or bovine pericardium. Mechanical heart valves were implanted in 36 patients, bioprostheses in 30, and aortic homografts in 2; valve repair was possible in 2. Sixteen patients required composite replacement of the ascending aorta and aortic valve. RESULTS: There were 9 operative deaths (13%). Infections caused by staphylococci and infections in multiple annuli were associated with increased operative mortality rates. Only 1 patient had persistent infection and required reoperation. The mean follow-up was 56 +/- 40 months. There were 12 late deaths, mostly cardiac. The actuarial survival including operative deaths was 64% +/- 8% at 8 years. In 8 patients, recurrent infective endocarditis developed 10 to 102 months after operation. The freedom from recurrent endocarditis was 76% +/- 10% at 8 years. CONCLUSIONS: This experience indicates that radical resection of the abscess and reconstruction of the heart with pericardium yield an excellent chance of eradicating the infection in patients with infective endocarditis and paravalvular abscess. The type of valve implanted may not be as important as radical resection of the abscess. These patients appear to have a greater than average risk of recurrent endocarditis.

Abscess↗
PubMed1996

Geometric mismatch of the aortic and pulmonary roots causes aortic insufficiency after the Ross procedure.

BACKGROUND: Geometric mismatch between the two semilunar valves can cause aortic insufficiency after the Ross procedure. Thus, whenever the aortic root is larger than the pulmonary root, surgical reduction of the aortic anulus or of the sinotubular junction (or both) to match the diameters of the pulmonary root is necessary to prevent late malfunction of the pulmonary autograft. METHODS: The Ross procedure was performed in 81 patients during the past 5 years. The diameters of the aortic and pulmonary roots were measured in 77 patients. Reduction of the aortic anulus and of the sinotubular junction was necessary in 27 patients, reduction of the aortic anulus alone in 12, and reduction of the sinotubular junction alone in 10. The pulmonary autograft was implanted in the subcoronary position in the aortic root in two patients, as a complete root replacement in 58, and as an inclusion root in 21. RESULTS: There was one operative death, caused by myocardial infarction. Aortic insufficiency developed in one patient who did not have measurement and reduction of the aortic anulus, and aortic root replacement was necessary 2 weeks later. Patients have been followed up from 2 to 64 months (mean 15 months). Two patients have required late reoperations: one because of pulmonary artery stenosis and the other because of a false aneurysm between the autograft and the mitral valve. The most recent Doppler echocardiographic study shows that 90% of the patients have only trace or no aortic insufficiency, and 10% have mild aortic insufficiency. CONCLUSION: This experience suggests that adjustment of the diameter of the aortic anulus or of the sinotubular junction of the aorta may be important to prevent aortic insufficiency after the Ross procedure.

Adolescent↗
PubMed1996

Comparison of changes in blood pressure and dipsogenic responsiveness to angiotensin II in male and female rats chronically exposed to cold.

In most forms of experimentally induced hypertension in rats, females develop a less severe form of the disease than males. The objective of the present study was to compare the two genders with respect to the development of cold-induced hypertension. The results of the study indicate that both males and females develop comparable elevations of blood pressure and at approximately the same rate. Thus, the blood pressures of both groups increased significantly within 2 weeks of exposure to cold and reached similar maximal levels by the seventh week. The dipsogenic responsiveness of both groups of cold-exposed rats to acute administration of the peptide hormone, angiotensin II (AngII), was increased to approximately the same extent above that of warm-adapted counterparts, suggesting an increase in the responsiveness to AngII in the brain. To assess this possibility, the induction of the oncogene, cFos, was studied in brain following IV infusion of AngII (333 ng/kg/min). Fos-like immunoreactivity (FLI) was greater (p < 0.01) in subfornical organ, supraoptic and paraventricular hypothalamic nuclei of both cold-exposed groups compared to warm-adapted controls. Thus, both male and female rats have similar elevations of blood pressure as well as increased dipsogenic and FLI responsiveness to administration of AngII during chronic exposure to cold.

Angiotensin II↗
PubMed1996

In vitro models of biocompatibility: a review.

The objectives of this paper were to define in vitro biocompatibility of materials, to discuss some of the issues concerning why conclusions from tissue culture are sometimes different from in vivo biocompatibility, to give highlights of the sequence of the development of these in vitro assays from the early 1950s to their present state of development, and to discuss possible future trends for in vitro testing. In vitro biocompatibility tests were developed to simulate and predict biological reactions to materials when placed into or on tissues in the body. Traditional assays have measured cytotoxicity by means of either an end-stage event, (i.e., permeability of cytoplasmic membranes of dead and dying cells, or some metabolic parameter such as cell division or an enzymatic reaction). In vitro assays for initiation of inflammatory and immune reactions to materials have also begun to appear in the literature. More recently, the concept of dentin barrier tests has been introduced for dental restorative materials. Four models which measure both permeability and biological effects of materials are compared and discussed. Future efforts may be directed toward development of materials which will allow or promote function and differentiation of tissues associated with materials. New analytical procedures and understanding of optimal characteristics of materials should improve our ability to develop more biocompatible materials. Both molecular biology techniques, and altered design of material surfaces may make the materials either more or less reactive to the biological milieu. These trends suggest a greater future role of the biological sciences in the development of biomaterials.

Animals↗
PubMed1996

In vitro IL-1 beta and TNF-alpha release from THP-1 monocytes in response to metal ions.

OBJECTIVES: Previous studies have shown that biomaterials can activate macrophages to produce cytokines and promote an inflammatory response. Although the toxicity of many metal ions has been extensively investigated, little is known about the ability of these ions to alter cytokine release from macrophages. Yet the release of these ions from biomaterials has been well documented. Previous studies indicated that alterations in cytokine release might be expected because metal ions alter protein production in macrophages at sub-toxic concentrations. Thus, the hypothesis of this study was that metal ions can alter the secretion of cytokines from macrophages at sub-toxic concentrations. METHODS: The release of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) from macrophages was investigated when the macrophages were exposed to metal ions, with or without lipopolysaccharide (LPS), a component of dental plaque. Human THP-1 macrophages were exposed to ions of Ag, Au, Cu, Hg, and Ni for 24 h. In half of the cultures, LPS was added for the last 4 h. The release of IL-1 beta and TNF-alpha into the medium was measured using enzyme-linked immunosorbent assays. ANOVA and Tukey multiple comparison intervals were used to compare the various experimental conditions. RESULTS: None of the metal ions elevated the IL-1 beta or TNF-alpha levels after 24 h, but Ni ions significantly elevated the IL-1 beta and TNF-alpha levels after 72 h. With LPS added, Ag, Cu, and Ni significantly amplified the LPS-induced production of IL-1 beta but only Ni amplified the TNF-alpha response. These alterations in cytokine response occurred with metal ion concentrations which have been previously shown to be released from dental alloys in vitro and in vivo. SIGNIFICANCE: It appeared plausible that macrophage-cytokine mediated inflammatory responses may be altered by the presence of some metal ions in tissues, particularly Ni.

Analysis of Variance↗
PubMed1996

Functional analysis of the beta and epsilon lycopene cyclase enzymes of Arabidopsis reveals a mechanism for control of cyclic carotenoid formation.

Carotenoids with cyclic end groups are essential components of the photosynthetic membranes in all plants, algae, and cyanobacteria. These lipid-soluble compounds protect against photooxidation, harvest light for photosynthesis, and dissipate excess light energy absorbed by the antenna pigments. The cyclization of lycopene (psi, psi-carotene) is a key branch point in the pathway of carotenoid biosynthesis. Two types of cyclic end groups are found in higher plant carotenoids: the beta and epsilon rings. Carotenoids with two beta rings are ubiquitous, and those with one beta and one epsilon ring are common; however, carotenoids with two epsilon rings are rare. We have identified and sequenced cDNAs that encode the enzymes catalyzing the formation of these two rings in Arabidopsis. These beta and epsilon cyclases are encoded by related, single-copy genes, and both enzymes use the linear, symmetrical lycopene as a substrate. However, the epsilon cyclase adds only one ring, forming the monocyclic delta-carotene (epsilon, psi-carotene), whereas the beta cyclase introduces a ring at both ends of lycopene to form the bicyclic beta-carotene (beta, beta-carotene). When combined, the beta and epsilon cyclases convert lycopene to alpha-carotene (beta, epsilon-carotene), a carotenoid with one beta and one epsilon ring. The inability of the epsilon cyclase to catalyze the introduction of a second epsilon ring reveals the mechanism by which production and proportions of beta,beta- and beta, epsilon-carotenoids may be controlled and adjusted in plants and algae, while avoiding the formation of the inappropriate epsilon,epsilon-carotenoids.

Amino Acid Sequence↗
PubMed1996

Properties of human prolactin (PRL) and H27A-PRL, a mutant that does not bind Zn++.

The ability of protein hormones to self-associate is likely to play an important role in concentrating hormones into secretory granules; therefore, the aggregation properties of human PRL and H27A mutant were investigated. Human PRL bound (65)Zn++; the Scatchard analysis was convex up, and limited by the solubility of PRL, but at least 0.7 mole Zn++ bound per mole of PRL. Binding of (65)Zn++ to H27A-PRL was greatly reduced. The biological activity in an Nb2 cell assay and the circular dichroism spectrum of wild type and H27A-PRL were similar, indicating the H27A mutant folded correctly, and the binding of Zn++ to the high affinity site is not essential for biological activity. Dynamic light scattering measurements indicated 10 and 20 mu M Zn++ caused some aggregation of both wild type and H27A-PRL. Sedimentation equilibrium analysis indicated that PRL is primarily a monomer in the absence of Zn++ and that there is increasing self-association in the presence of 5 and 10 mu M Zn++. The mutant H27A exhibited a greater tendency to aggregate without changing detectably the mode of association. Although human PRL binds Zn++ as human GH does, it differs in that the ability to bind Zn++ and to self-associate were decoupled in PRL. Human PRL must have two types of interactions with Zn++; one is binding to a site involving histidine 27, and the other is weaker interactions that induce self-association of PRL.

Animals↗
PubMed1996

Replacement of chordae tendineae with Gore-Tex sutures: a ten-year experience.

BACKGROUND AND AIMS OF THE STUDY: Expanded polytetrafluoroethylene sutures have been used for the replacement of chordae tendineae of the mitral valve since 1985 at The Toronto Hospital. This study examines the long term results of mitral valve repair with chordal replacement with this material. MATERIALS AND METHODS: From July 1985 to December 1993, 134 consecutive patients with mitral regurgitation due to degenerative disease of the mitral valve underwent mitral valve repair with replacement of elongated or ruptured chordae tendineae with one to six (mean of 2.8) Gore-Tex sutures. The patients' mean age was 61 years, range 22-86. In addition to mitral valve repair, 14 patients underwent aortic valve surgery, three underwent replacement of the ascending aorta, six underwent tricuspid valve repair, nine underwent the maze procedure for atrial fibrillation, and 13 underwent coronary artery bypass. The patients were followed for between 20 and 116 months, mean 51 months. No patient has been lost to follow up. RESULTS: There were one operative and eight late deaths. The actuarial survival at eight years was 88% +/- 6%. Four patients required reoperation, one for persistent hemolysis and three for recurrent mitral regurgitation. The Gore-Tex chordae were not responsible for the reoperation in any patient. The freedom from reoperation at eight years was 96% +/- 2%. CONCLUSIONS: Expanded polytetrafluoroethylene sutures are excellent for chordal replacement during mitral valve repair and do not fail during the first decade following surgery. This material has allowed us to increase the probability of successful mitral valve repair in patients with degenerative disease of the mitral valve and prolapse of both leaflets.

Adult↗