The genetic basis for variation in radiation sensitivity in the general population.
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DNA↗
Biomedical subjects
T Xi
Publications and source records attributed to T Xi.
[Progress in the studies on the evaluation of biocompatibility of biomaterials].
Biocompatibility remains the central theme for biomaterials applications in medicine. It generally refers to the compatibility between the biomaterials and the receptor, including tissue-compatibility and blood-compatibility. The definition of the biocompatibility has been greatly changed in recent years; it is now accepted as involving two principle areas, one is the principle of 'biosafety', the second is the principle of 'biofunctionality'.
Biocompatible Materials↗
Human PON2 gene at 7q21.3: cloning, multiple mRNA forms, and missense polymorphisms in the coding sequence.
We report the cloning and characterization of human PON2, a paraoxonase-related gene-2 that is physically linked with PON1 and PON3 on 7q2l.3. PON2 is ubiquitously expressed and we identified several mRNA forms produced by alternative splicing, or by the use of a second transcription start site. We also describe two polymorphisms in the coding sequences that, in the protein deduced from the longest open reading frame, predict an alanine-to-glycine substitution at residue 147 and a serine-to-cysteine substitution at residue 310.
Amino Acid Sequence↗
A common variant in PPP1R3 associated with insulin resistance and type 2 diabetes.
Selected candidate genes have been analyzed in the Pima Indians of Arizona based on evidence that insulin resistance and type 2 diabetes have significant genetic determinants. An amino acid substitution at codon 905 of the glycogen-targeting subunit of type 1 protein phosphatase that regulates skeletal muscle glycogenesis was recently reported to be associated with changes in insulin action in Danish subjects. In addition to the variant at 905, we report here a novel substitution at codon 883 and common variant of an "ATTTA" element in the 3'-untranslated region (UTR) of the corresponding gene (PPP1R3). The 3'-UTR variant resembled the mRNA-destabilizing AT(AU)-rich elements (AREs) and resulted in a 10-fold difference in reporter mRNA half-life, was correlated with PPP1R3 transcript and protein concentrations in vivo, and was associated with insulin resistance and type 2 diabetes in the Pimas. The variant is more common in Pimas (0.56) than in Caucasians (0.40). Because of its apparent effect on expression of PPP1R3, it may, in part, contribute to the higher prevalence of type 2 diabetes in this Native American population.
Adult↗
Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human.
Different isoenzymes of pyruvate dehydrogenase kinase (PDK) inhibit the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1alpha subunit, thus contributing to the regulation of glucose metabolism. By positional cloning in the 7q21.3-q22.1 region linked with insulin resistance and non-insulin-dependent diabetes mellitus in the Pima Indians, we identified a gene encoding an additional human PDK isoform, as evidenced by its amino acid sequence identity (>65%) with other mammalian PDKs, and confirmed by biochemical analyses of the recombinant protein. We performed detailed comparative analyses of the gene, termed PDK4, in insulin-resistant and insulin-sensitive Pima Indians, and detected five DNA variants with comparable frequencies in both subject groups. Using quantitative reverse transcription polymerase chain reaction, we found that the variants identified in the promoter and 5'-untranslated region did not correlate with differences in mRNA level in skeletal muscle and adipose tissue. We conclude that alterations in PDK4 are unlikely to be the molecular basis underlying the observed linkage at 7q21.3-q22.1 in the Pima Indians. Information about the genomic organization and promoter sequences of PDK4 will be useful in studies of other members of this family of mitochondrial protein kinases that are important for the regulation of glucose metabolism.
Adipose Tissue↗
Biological activities of human tumor necrosis factor-alpha and its novel mutants.
Biological activities of human tumor necrosis factor-alpha (hTNF-alpha) and its mutants were compared. In cytotoxicity assay with L929 cells, one mutant, designated as TNF-B, showed 4.5-fold higher activity than TNF examined. And TNF-B also increased cytostatic activity and decreased protein synthesis against U937 cells. In receptor binding assay, TNF-B had almost the same affinity for TNF receports on L929 cells as hTNF-alpha. But another mutant, TNFarg, markedly decreased the all activities of hTNF-alpha and had lower affinity for receports on different types of target cell. These results indicated that the relative activity of TNFs to target cells may correlate with their affinity for receports. We also found that TNF-B retained the cytotoxicity of hTNF-alpha for HEp-2 cells. TNF-B also had two-fold higher affinity than hTNF-alpha for receptors on HEp-2 cells (only carrying hTNF-R55) and lower affinity for receptors on U937 cells (expressing mainly hTNF-R75). These results suggested that TNF-B might still interact with the human TNF-R55 receptor, but it might largely lose its ability to bind to human TNF-R75. Changes of biological activity of TNFs might be due to an altered affinity to the different types of TNF receptor on the target cells.
Amino Acid Sequence↗
Biological activities of human tumor necrosis factor-alpha and its novel mutants.
Biological activities of human tumor necrosis factor-alpha (hTNF-alpha) and its mutants were compared. In cytotoxicity assay with L929 cells, one mutant, designated as TNF-B, showed 4.5-fold higher activity than TNF examined. In receptor binding assay, TNF-B had almost the same affinity for TNF receptors on L929 cells as hTNF-alpha. We also found that TNF-B retained the cytotoxicity of hTNF-alpha for HEp-2 cells. TNF-B also had two-fold higher affinity than hTNF-alpha for receptors on HEp-2 cells (only carrying hTNF-R55) and lower affinity for receptors on U937 cells (expressing mainly hTNF-R75). These results suggested that TNF-B might still interact with the human TNF-R55 receptor, but it might largely lose its ability to bind to human TNF-R75. Changes of biological activity of TNFs might be due to an altered affinity to the different types of TNF receptor on the target cells.
Amino Acid Sequence↗
Effects of menidipine on dihydropyridines binding sites in cardiac and cerebral membranes from old rats with left ventricular hypertrophy.
AIM: To study the effects of menidipine (Men) on the affinity and density of dihydropyridines (DHP) binding sites in the cell membranes of left ventricle (LV) and brain in elderly renovascular hypertensive rats (RVHR) with LV hypertrophy. METHODS: Renovascular hypertension was produced by clipping the left renal artery in 20-month-old rats. The affinity and density of DHP binding sites in the cell membranes of LV and brain were assessed by radioligand assay. RESULTS: Men (20 mg.kg-1.d-1 ig for 9 wk) decreased markedly the systolic blood pressure and the LV weight (P < 0.01). Though not affecting the density of DHP receptor (Bmax), Men markedly decreased the total number of DHP binding sites in hypertrophied LV (from 5.95 +/- 0.62 to 4.0 +/- 1.1 pmol.LV). Men also reduced Bmax of DHP binding sites in the thalamus (from 522 +/- 27 to 371 +/- 24 pmol/g protein) and hippocampus (from 498 +/- 26 to 332 +/- 32 pmol/g protein). CONCLUSION: Men reversed the LV hypertrophy from renovascular hypertension accompanied with reduced total number of DHP binding sites in the cell membranes of LV and Bmax of the cell membranes of thalamus and hippocampus from elderly LV hypertrophied rats.
Animals↗
Degradation of polyetherurethane by subcutaneous implantation into rats. II. Changes of contact angles, infrared spectra, and nuclear magnetic resonance spectra.
In vivo degradation of polyetherurethanes (PEUs) was studied using two kinds of PEUs, U-3 and U-8, coated on a base film of ethylene/vinyl alcohol copolymer (EVAL). U-3 is a nonsegmented PEU prepared from 4,4'-diisocyanatodiphenylmethane (MDI) and poly(tetramethylene oxide) (PTMO 1000). U-8 is a segmented PEU prepared from MDI, PTMO 1000, and 1,4-butanediol. Previous studies of PEUs were conducted using gel permeation chromatography and scanning electron microscopy. In this study, the explanted materials were examined with contact angle measurement, ATR-FTIR, and nuclear magnetic resonance (NMR) spectroscopies. All data obtained by these methodologies indicate that the PTMO/MDI oligomers diffused to the material surface in the early stage of implantation. Then, the low-molecular-weight fraction of the oligomers leached out from the surface to the exudate. Degradation became dominant after 2-4 weeks. In the case of PU-8, the PTMO fraction decreased approximately 35-40% from the surface at 24 weeks postimplantation. In the case of PU-3, the loss of coating material (U-3) on the base film (EVAL) was observed after 10 weeks. The PTMO fraction of the surface U-3 remained on EVAL at 6 weeks postimplantation, however, it was 64% of the initial material. The molecular weight of the U-3 remaining on EVAL also decreased. Degradation of U-3 occurred more rapidly than that of U-8. The data obtained with our materials were insufficient in determining evidence of oxidative degradation with IR or NMR spectra.
Animals↗
Human macrophage colony stimulating factor (HM-CSF) expressed in baculovirus infected insect cells is biologically active in its monomeric form.
hM-CSF was reported to have biological activity only in a dimeric form. Using oligonucleotide-directed mutagenesis of hM-CSF (1-149aa) cDNA, we have substituted Ser31 for Cys31 which forms intermolecular disulfide bond in native hM-CSF. The mutant hM-CSF cDNA was expressed in insect BmN cells using baculovirus as a vector under the control of polyhedrin promoter. Biological activity analysis and radioligand receptor assay both showed that there was little difference between the mutant hM-CSF and the native dimeric hM-CSF. These results strongly support that the biologically active human M-CSF in its monomeric form can be expressed in recombinant baculovirus infected insect cells.
Animals↗
[Effects of m-nifedipine on dihydropyridine binding sites in the cell membranes of kidney and lung from left ventricular hypertrophied elderly rats].
Effects of m-nifedipine (m-Nif) on the affinity and density of dihydropyridine (DHP) binding sites in the cell membranes of kidney and lung were investigated using the LVH (left ventricular hypertrophy) induced by Goldblatt (2k-1c) renovascular hypertension in elderly rats. m-Nif markedly reduced blood pressure, left ventricular weight, and decreased the density (Bmax) of DHP binding sites in the cell membranes of kidney and lung from 699 +/- 112, 759 +/- 35 fmol.mg-1 protein to 482 +/- 29, 381 +/- 33 fmol.mg-1 protein. No difference was observed between groups in dissociation constant (KD) values of DHP binding sites. The results suggest that m-Nif could markedly decrease DHP binding sites in the membranes of kidney and lung from cardiac hypertrophied elderly rats.
Animals↗
[Effects of m-nifedipine on left ventricular diastolic function and Ca2+ content of myocardial and cerebral mitochondria and artery tissues in left ventricular hypertrophied rats].
Left ventricular hypertrophy (LVH) was induced by renal hypertension in rats. m-Nifedipine (m-Nif, ig 20 mg.kg-1.d-1 for 9 wk) decreased LV weight in the renovascular hypertensive rats (P < 0.01). The LV compliance in LVH group was significantly decreased compared with that in sham- operated group. The LV stiffness constant, Ca2+ content in left ventricular myocardial and cerebral mitochondria, aorta, and tail artery were markedly raised. m-Nif could markedly reduce the LV stiffness constant, improve the LV compliance, and decrease the Ca2+ content of left ventricular myocardial mitochondria and tissues of artery from LVH rats. These effects of m-Nif were similar to those of nifedipine at the same dosage.
Animals↗
Interaction of silkworm larvae expressed monomeric hM-CSF with its receptor on murine bone marrow derived macrophage.
Human macrophage colony-stimulating factor (hM-CSF) expressed in the silkworm larvae was monomeric. The nature of the interaction of iodinated monomeric M-CSF with murine bone marrow derived macrophage (BMM) was studied. On incubation with 2 nM [125I]M-CSF at 4 degrees C, approximately 90% of the maximal binding occurred within 15 min with a plateau around 1hr which then gradually declined. Scatchard plot analysis showed that the Kd for the monomeric M-CSF is 5.3 x 10(-10) M and the number of binding sites per cell is 4 x 10(4). Competition experiment indicated that cellular binding of the iodinated monomeric rhM-CSF was almost as effective as the native M-CSF. The results show that the interchain disulfide bond of M-CSF is not essential for the natural folding of active M-CSF.
Animals↗
Degradation of polyetherurethane by subcutaneous implantation into rats. I. Molecular weight change and surface morphology.
Two kinds of polyetherurethane (PEU), U-3 and U-8, were coated in thin layers on an ethylene-vinylalcohol copolymer (EVAL) film 0.1 mm thick. U-3 is a nonsegmented PEU prepared from 4,4'-diisocyanatodiphenylmethane (MDI) and poly(tetramethylene oxide) of Mn = 1,000 (PTMO 1000), and U-8 is a segmented PEU prepared from MDI, PTMO 1000, and 1,4-butanediol. The coating thicknesses were 0.0068 and 0.022 mm for U-3 and U-8, respectively. These coated films were implanted subcutaneously into rats and retrieved after various weeks. The coatings on the retrieved samples were dissolved in tetrahydrofuran (THF), and the average molecular weight (MW) was determined by injecting the THF solution into a gel permeation chromatograph. In the case of U-3, MW increased after 2 weeks, then decreased over the implantation period. After 10 weeks, U-3 almost disappeared from the base film. In the case of U-8, MW reached the maximum at 4 weeks postimplantation then decreased gradually over the implantation period. The rate and degree of MW change were greater in U-3 than in U-8. Here, we argue that, in the early stage, low molecular weight PTMO/MDI oligomers leached out from the PEUs to the inflammatory exudate to increase MW, and in the later stage macrophage attachment/activation had a role in the degradation of PEUs. The surface morphologic changes observed by scanning electron microscopy are also discussed.
Animals↗
[Effects of m-nifedipine on activities of Na+,K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase in myocardium and brain of elderly renovascular hypertensive rats].
Clipping the left renal artery induced marked hypertension and hypertrophy of the left ventricle in elderly (24-month-old) rats. m-Nifedipine (m-Nif, ig 20 mg.kg-1, qd x 9 wk) significantly decreased the systolic blood pressure and the weight of the left ventricle in the renovascular hypertensive rats (RVHR). In RVHR, the activities of Na+, K(+)-ATPase and Ca(2+)-ATPase in microsomes of the myocardium and brain were reduced significantly compared with those in sham-operated rats. m-Nif was found to increase the activities of these enzymes of the myocardium and brain in elderly RVHR (P > 0.01). m-Nif 10-1000 mumol.L-1 in vitro elevated the activities of Na+, K(+)-ATPase and Ca(2+)-ATPase in the myocardium and brain of RHVR. On the contrary, the myocardial and cerebral Mg(2+)-ATPase activities were higher in RVHR than in sham-operated rats. m-Nif was shown to depress markedly this enzyme both in vivo and in vitro. These results indicate that m-Nif can improve the activities on Na+, K(+)-ATPase and Ca(2+)-ATPase in the myocardium and brain in elderly RVHR.
Animals↗
[Effects of m-nifedipine and nifedipine on hemodynamics in renovascular hypertensive rats].
In the renovascular hypertensive myocardial hypertrophic rats of prevention and regressive groups, the blood pressure was lowered by m-nifedipine (m-Nif) or nifedipine (Nif) of 20 mg.kg-1.d-1, i.g., for 9 wk vs control (LVH) group (P < 0.01). From the isolated working hearts of prevention and regressive groups, it was found that AP, LVSP, +dp/dtmax, -dp/dtmax, CF, and CI values of m-Nif and Nif groups increased higher than that of LVH group, but LVEDP and T was lower in m-Nif and Nif groups. It was concluded that m-Nif exhibits the similar effects like Nif in prevention and reversion of renovascular hypertensive LVH and improvement of hemodynamics.
Animals↗
Effects of m-nifedipine on dihydropyridine binding sites in cardiac and cerebral cortex cell membranes from left ventricular hypertrophied rats.
m-Nifedipine (m-Nif 20 mg.kg-1.d-1 ig for 9 wk) decreased left ventricular weight in the renovascular hypertensive rats (P < 0.01). Though not significantly affecting the density of dihydropyridines (DHP) receptor (Bmax), m-Nif administered whether for prevention (6 wk postclipping) or for regression (9 wk postclipping), markedly decreased the total number of DHP binding sites in hypertrophied left ventricle (LV). m-Nif also reduced the dissociation constant (Kd) of DHP binding sites in the membranes of LV and cerebral cortex from cardiac hypertrophied rats (P < 0.01). These effects of m-Nif were similar to those of nifedipine (Nif) in the same dosage. The results suggest that m-Nif can prevent and regress the LV hypertrophy resulted from renovascular hypertension and reduce the total number of DHP binding sites in the membranes of LV from cardiac hypertrophied rats.
Animals↗
Prevention of tissue calcification on bioprosthetic heart valve by using epoxy compounds: a study of calcification tests in vitro and in vivo.
Calcification is the principal cause of the clinical failures of the bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. In this paper, we compared the calcification on various types of bovine pericardiums pretreated with two hydrophilic epoxy compounds adding GA post-treatment (EP 1 and EP 2), glutaraldehyde (GA)- and nontreated pericardium (Fresh), respectively, by in vitro and in vivo tests. Significant decrease of calcification was found by pretreatment with both epoxy compounds rather than with glutaraldehyde: 0.250 +/- 0.001 (Fresh), 0.276 +/- 0.058 (EP 1), 0.302 +/- 0.071 (EP 2), and 0.478 +/- 0.172 (GA) micrograms (Ca)/mg (dried tissue), respectively, after 20 days dipping in a simulating serum solution in vitro; 115.13 +/- 60.11 (Fresh), 129.84 +/- 51.08 (EP 1), 167.39 +/- 20.81 (EP 2), and 205.19 +/- 16.86 (GA) micrograms/mg, respectively, after 3 months subcutaneous implantation in rabbits. The in vitro method for evaluating calcification designed by us gave the similar order among four samples with that obtained by in vivo test. Because the bovine pericardium pretreated with the epoxy compounds adding GA post-treatment possesses the greater tenacity than that pretreated only with epoxy compounds or GA, meanwhile the calcification is also significantly decreased with this pretreatment, it may be expected that the bovine pericardium with this pretreatment will have the greater anticalcification and durability in dynamic stress.
Animals↗