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Biomedical subjects

H Deng

Publications and source records attributed to H Deng.

At least 37 records · Page 2Linked to original sources
PubMed2002

Evidence for a major gene for bone mineral density/content in human pedigrees identified via probands with extreme bone mineral density.

Bone mineral content (BMC) and/or bone mineral density (BMD, i.e. BMC scaled by bone size) are major determinants for osteoporosis, which is a serious health problem. The major determinant of variation in BMD/BMC is genetic. The few studies now available are inconsistent in the identification and/or even in the existence of major gene(s) for BMD/BMC. In 51 human pedigrees with 941 individuals (526 measured for phenotypes) identified via probands with extreme BMD values, we performed complex segregation analyses to test the existence of a genetic locus with a major effect on BMD/BMC variation. We analyzed BMD and BMC at the spine, hip and wrist jointly by employing, as the study phenotype, factor scores (FS) of the principle component that explains approximately 75% of the total BMD/BMC variation at the three sites. The results indicate that a major gene exists with a codominant effect that is responsible for approximately 16% of the FS variation when adjusted for significant effects of sex, body weight and age. A significant genotype-x-sex-x-age interaction was found, which may explain approximately 14% of the FS variation after adjusting for body weight. Testing of various models did not provide support for shared familial environmental effects but suggested the existence of residual polygenic effects, which may explain approximately 50% of the FS variation when adjusting for sex, body weight and age. This study indicates a promising aspect of studies to identify a major gene for BMD/BMC variation in our pedigrees identified via extreme probands.

Bone Density↗
PubMed2002

A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin.

The growth and persistence of solid tumors and their metastasis are angiogenesis-dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is a potent angiogenesis inhibitor. To investigate whether intramuscular administration of vasostatin gene has the antitumor activity in mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a control vector. Production and secretion of vasostatin protein by COS cells transfected with the plasmid DNA encoding vasostatin (pSecTag2B-vaso) were confirmed by Western blot analysis and ELISA. Conditioned medium from vasostatin-transfected COS cells apparently inhibited human umbilical vein endothelial cell (HUVEC) and mouse endothelial cell (SVEC4-10) proliferation, compared with conditioned medium from the COS cells transfected with control vector or non-transfected cells. Treatment with pSecTag2B-vaso twice weekly for 4 weeks resulted in the inhibition of tumor growth and the prolongation of the survival of tumor-bearing mice. The sustained high level of vasostatin protein in serum could be identified in ELISA. Angiogenesis was apparently inhibited in tumor by immunohistochemical analysis. Angiogenesis was also inhibited in the chicken embryo CAM assay and mouse corneal micropocket assay. The increased apoptotic cells were found within the tumor tissues from the mice treated with plasmid DNA encoding vasostatin. Taken together, the data in the present study indicate that the cancer gene therapy by the intramuscular delivery of plasmid DNA encoding vasostatin, is effective in the inhibition of the systemic angiogenesis and tumor growth in murine models. The present findings also provide further evidence of the anti-tumor effects of the vasostatin, and may be of importance for the further exploration of the application of this molecule in the treatment of cancer.

Angiogenesis Inhibitors↗
PubMed2002

A novel locus (DSAP2) for disseminated superficial actinic porokeratosis maps to chromosome 15q25.1-26.1.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is a chronic cutaneous disorder characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. It develops in teenagers in sun-exposed areas of skin and usually follows an autosomal dominant inheritance pattern. The first locus for DSAP was localized to chromosome 12q23.2-24.1, but no gene responsible for porokeratosis has been identified to date. OBJECTIVES: To determine whether DSAP is a genetically heterogeneous disorder and to identify the disease gene locus in a three-generation Chinese family with DSAP. METHODS: Genetic linkage analysis was carried out in this family using 15 microsatellite markers between D12S1671 and D12S369 on chromosome 12q, followed by a genome-wide scan with 382 microsatellite markers from the autosomes. RESULTS: Genetic linkage analysis with chromosome 12q markers suggested that the locus in this family is not linked to chromosome 12q. A genome-wide scan and fine mapping finally localized the locus for DSAP in this family to a 6.4-cM region between markers D15S1023 and D15S1030 at chromosome 15q25.1-26.1. This DSAP locus was named DSAP2. CONCLUSIONS: The previous results and this study have shown that DSAP is a genetically heterogeneous disorder; a novel locus for DSAP, termed DSAP2, was mapped to a 6.4-cM region between markers D15S1023 and D15S1030.

Adolescent↗
PubMed2002

Production of duck-chicken chimeras by transferring early blastodermal cells.

Duck blastodermal cells isolated from Stage X embryos of Maya ducks were injected into subgerminal cavity of recipient Stage X chicken embryos treated with gamma-irradiation or untreated. Eleven somatic chimeras were obtained based on plumage color and were raised to sexual maturity. To test for germline chimerism, progeny tests were performed by mating the chimeras with Maya ducks. A total of 622 eggs was collected and incubated. Fertility rate and hatchability were 2.9% (18/622) and 1.0% (6/622), respectively. The six duck hatchlings were from Chimera 9801 and were considered to be derived from the germ cells developed from the donor Maya blastodermal cells, indicating that Chimera 9801 is a germline chimera.

Animals↗
PubMed2002

Anaerobic digestion of olive oil mill effluents together with swine manure in UASB reactors.

Combined anaerobic digestion of olive oil mill effluent (OME) with swine manure, was investigated. In batch experiments was shown that for anaerobic degradation of OME alone nitrogen addition was needed. A COD:N ratio in the range of 65:1 to 126:1 was necessary for the optimal degradation process. Furthermore, it was found that methane productions rates during digestion of either swine manure alone or OME alone were much lower than the rates achieved when OME and manure were digested together. Admixing OME with manure at a concentration of 5 to 10% OME resulted in the highest methane production rates. Using upflow anaerobic sludge blanket (UASB) reactors, it was shown that codigestion of OME with swine manure (up to 50% OME) was successful with a COD reduction up to 75%. The process was adapted for degradation of OME with stepwise increase of the OME load to the UASB reactor. The results showed that the high content of ammonia in swine manure, together with content of other nutrients, make it possible to degrade OME without addition of external alkalinity and without addition of external nitrogen source. Anaerobic treatment of OME in UASB reactors resulted in reduction of simple phenolic compounds such as mequinol, phenyl ethyl alcohol and ethyl methyl phenol. After anaerobic treatment the concentration of these compounds was reduced between 75 and 100%. However, the concentration of some degradation products such as methyl phenol and ethyl phenol were detected in significantly higher concentrations after treatment, indicating that the process has to be further optimised to achieve satisfactory removal of all xenobiotic compounds.

Agriculture↗
PubMed2001

Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions.

The Sir2 enzyme family is responsible for a newly classified chemical reaction, NAD(+)-dependent protein deacetylation. New peptide substrates, the reaction mechanism, and the products of the acetyl transfer to NAD(+) are described for SIR2. The final products of SIR2 reactions are the deacetylated peptide and the 2' and 3' regioisomers of O-acetyl ADP ribose (AADPR), formed through an alpha-1'-acetyl ADP ribose intermediate and intramolecular transesterification reactions (2' --> 3'). The regioisomers, their anomeric forms, the interconversion rates, and the reaction equilibria were characterized by NMR, HPLC, 18O exchange, and MS methods. The mechanism of acetyl transfer to NAD(+) includes (1) ADP ribosylation of the peptide acyl oxygen to form a high-energy O-alkyl amidate intermediate, (2) attack of the 2'-OH group on the amidate to form a 1',2'-acyloxonium species, (3) hydrolysis to 2'-AADPR by the attack of water on the carbonyl carbon, and (4) an SIR2-independent transesterification equilibrating the 2'- and 3'-AADPRs. This mechanism is unprecedented in ADP-ribosyl transferase enzymology. The 2'- and 3'-AADPR products are candidate molecules for SIR2-initiated signaling pathways.

Adenosine Diphosphate Ribose↗
PubMed2001

Vibrational structure of dihydrofolate bound to R67 dihydrofolate reductase.

R67 is a Type II dihydrofolate reductase (DHFR) that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate by facilitating the addition of a proton to N5 of DHF and the transfer of a hydride ion from NADPH to C6. Because this enzyme is a plasmid-encoded DHFR from trimethoprim-resistant bacteria, extensive studies on R67 with various methods have been performed to elucidate its reaction mechanism. Here, Raman difference measurements, conducted on the ternary complex of R67.NADP(+).DHF believed to be an accurate mimic of the productive DHFR.NADPH.DHF complex, show that the pK(a) of N5 in the complex is less than 4. This is in clear contrast to the behavior observed in Escherichia coli DHFR, a substantially more efficient enzyme, where the pK(a) of bound DHF at N5 is increased to 6.5 compared with its solution value of 2.6. A comparison of the ternary complexes in R67 and E. coli DHFRs suggests that enzymic raising of the pK(a) at N5 can significantly increase the catalytic efficiency of the hydride transfer step. However, R67 shows that even without such a strategy an effective DHFR can still be designed.

Folic Acid↗
PubMed2001

Aryllead(IV) reagents in synthesis: formation of the C11 quaternary center of N-methylwelwitindolinone C isothiocyanate.

The reaction of lead(IV) 4-indolyl triacetate with substituted methyl 2-oxo-1-cyclohexanecarboxylates has been investigated as a route to the natural product N-methylwelsitindolinone C isothiocyanate. Reaction of lead(IV) reagent 18 with beta-ketoester 20 affords the desired coupled material in excellent yield and diastereoselectivity. Reaction: see text.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

[Gly40Ser mutation of glucagon receptor gene and NIDDM in Han nationality].

OBJECTIVE: To ascertain whether Gly40Ser mutation in exon 2 of glucagon receptor (GCG-R) gene is associated with late-onset non-insulin-dependent diabetes millitus (NIDDM) in Chinese. METHODS: We selected 82 NIDDM patients and 136 controls of Han nationality in Hunan province, and detected Gly40Ser mutation using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: None of Gly40Ser mutation was found in all subjects. CONCLUSIONS: The mutation doesn't associate with NIDDM in Chinese, even though the mutation was reported to be associated with NIDDM in certain French and Caucasians, genetic heterogeneity of NIDDM among ethnic groups should be considered.

Adolescent↗
PubMed2001

Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis.

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of TG-rich lipoproteins. To elucidate the physiological roles of LPL in lipid and lipoprotein metabolism, we generated transgenic rabbits expressing human LPL. In postheparinized plasma of transgenic rabbits, the human LPL protein levels were about 650 ng/ml, and LPL enzymatic activity was found at levels up to 4-fold greater than that in nontransgenic littermates. Increased LPL activity in transgenic rabbits was associated with as much as an 80% decrease in plasma triglycerides and a 59% decrease in high density lipoprotein-cholesterol. Analysis of the lipoprotein density fractions revealed that increased expression of the LPL transgene resulted in a remarkable reduction in the level of very low density lipoproteins as well as in the level of intermediate density lipoproteins. In addition, LDL cholesterol levels in transgenic rabbits were significantly increased. When transgenic rabbits were fed a cholesterol-rich diet, the development of hypercholesterolemia and aortic atherosclerosis was dramatically suppressed in transgenic rabbits. These results demonstrate that systemically increased LPL activity functions in the metabolism of all classes of lipoproteins, thereby playing a crucial role in plasma triglyceride hydrolysis and lipoprotein conversion, and that overexpression of LPL protects against diet-induced hypercholesterolemia and atherosclerosis.

Animals↗
PubMed2001

Affected sibling pair linkage analysis of qualitative and quantitative traits for schizophrenia on chromosome 22 in a Chinese population.

We performed nonparametric linkage analysis on 136 families with two or more siblings with schizophrenia from Sichuan, southwestern China. In addition to categorical diagnosis, we used quantitative trait information from the Positive and Negative Symptom Scale and the modified Overt Aggression Scale. Categorical analysis using the diagnosis of schizophrenia and a maximum likelihood identity-by-descent method produced scores of close to 0 throughout the whole region tested. Multipoint analysis allowed exclusion of most markers with a relative risk of > 2, but did not exclude the possibility of a relative risk of < 1.5 for four of the markers. Our results provide no significant evidence for a locus for schizophrenia on chromosome 22. Quantitative linkage analysis using the PANSS-G scale score produced a maximum LOD score of approximately 1.2 with the marker D22S310, using either the Haseman-Elston method or maximum likelihood variance estimation with or without dominance. PANSS-N produced a maximum LOD score of 1.2 at the D22S283 locus. LOD score of about 1 are easily produced by chance. Thus, we conclude that under quantitative trait we also find no evidence of linkage between schizophrenia and markers on chromosome 22 in our Chinese sibling pair sample.

Adolescent↗
PubMed2001

Identification of the 6-sulfate binding site unique to alpha-subunit-containing isozymes of human beta-hexosaminidase.

In humans, beta-hexosaminidase A (alphabeta) is required to hydrolyze GM2 ganglioside. A deficiency of either the alpha- or beta-subunit leads to a severe neurological disease, Tay-Sachs or Sandhoff disease, respectively. In mammals beta-hexosaminidase B (betabeta) and S (alphaalpha) are other major and minor isozymes. The primary structures of the alpha- and beta-subunits are 60% identical, but only the alpha-containing isozymes can efficiently hydrolyze beta-linked GlcNAc-6-SO(4) from natural or artificial substrates. Hexosaminidase has been grouped with glycosidases in family 20. A molecular model of the active site of the human hexosaminidase has been generated from the crystal structure of a family 20 bacterial chitobiase. We now use the chitobiase structure to identify residues close to the carbon-6 oxygen of NAG-A, the nonreducing beta-GlcNAc residue of its bound substrate. The chitobiase side chains in the best interactive positions align with alpha-Asn(423)Arg(424) and beta-Asp(453)Leu(454). The change in charge from positive in alpha to negative in beta is consistent with the lower K(m) of hexosaminidase S, and the much higher K(m) and lower pH optimum of hexosaminidase B, toward sulfated versus unsulfated substrates. In vitro mutagenesis, CHO cell expression, and kinetic analyses of an alphaArg(424)Lys hexosaminidase S detected little change in V(max) but a 2-fold increase in K(m) for the sulfated substrate. Its K(m) for the nonsulfated substrate was unaffected. When alphaAsn(423) was converted to Asp, again only the K(m) for the sulfated substrate was changed, increasing by 6-fold. Neutralization of the charge on alphaArg(424) by substituting Gln produced a hexosaminidase S with a K(m) decrease of 3-fold and a V(max) increased by 6-fold for the unsulfated substrate, parameters nearly identical to those of hexosaminidase B at pH 4.2. As well, for the sulfated substrate at pH 4.2 its K(m) was increased 9-fold and its V(max) decreased 1.5-fold, values very similar to those of hexosaminidase B obtained at pH 3.0, where its betaAsp(453) becomes protonated.

Amino Acid Sequence↗
PubMed2001

Vibrational structure of GDP and GTP bound to RAS: an isotope-edited FTIR study.

A complete vibrational description of the bonding of a ligand to a protein requires the assignment of both symmetric and antisymmetric vibrational modes. The symmetric modes of isotopically enriched enzyme-bound ligands can be obtained by Raman difference spectroscopy, but until now, the antisymmetric modes, which require IR difference spectroscopy, have not been generally accessible. We have developed the methodology needed to perform IR difference spectroscopy, assign the antisymmetric modes, and accurately describe bonding. The method is used to assess the bonding changes that occur as Mg.GDP and Mg.GTP move from solution into the active site of RAS. Binding to RAS opens the nonbridging, O--P--O angle of the gamma-phosphate of GTP by 2.7 degrees, yet the angular freedom (dispersion of the O--P--O angle) of the gamma-phosphate is comparable to that in solution. In contrast, the motion of the beta-phosphate of GDP is highly restricted, suggesting that it positions the gamma-phosphate for nucleophilic attack. The beta,gamma-bridging O-P bond of bound GTP is slightly weakened, being lengthened by 0.005 A in the active site, corresponding to a bond order decrease of 0.012 valence unit (vu). The observed binding changes are consistent with a RAS-mediated hydrolysis mechanism that parallels that for solution hydrolysis.

Electron Spin Resonance Spectroscopy↗
PubMed2001

Dynamics of protein ligand binding on multiple time scales: NADH binding to lactate dehydrogenase.

Although the importance of atomic motion to how proteins function has been conjectured for several decades, the characterization of protein dynamics on multiple time scales is scant. This is because of severe experimental and theoretical difficulties, particularly characterizing the nanosecond to millisecond time scales. Here, we apply advanced laser-induced temperature-jump relaxation spectroscopic techniques to examine the kinetics of NADH binding to lactate dehydrogenase over this time scale. The bimolecular rate process, at about 290 micros, is easily observed as are multiple faster events (with relaxation times of 200 ns, 3.5 micros, and 24 micros), revealing a rich dynamical nature of the binding step. The results show that there are multiple structures of bound enzyme-ligand complexes, some of which are likely to be far from the catalytically productive structure. The results have important implications for interpretations of the binding thermodynamics of ligands to LDH and, by extension, to other proteins. The observed processes likely play a role in the dynamics of the chemistry that is catalyzed by lactate dehydrogenase.

Animals↗
PubMed2001

Entanglement, interference, and measurement in a degenerate parametric oscillator.

Quantum dynamical equations of motion for homodyne detection of the degenerate optical parametric oscillator are solved exactly. Nonclassical photon statistics are shown to be a consequence of interference of probability amplitudes, entanglement of photon pairs from such an oscillator, and the role of measurement in quantum evolution.

Journal Article↗
PubMed2001

Precise measurement of the positive muon anomalous magnetic moment.

A precise measurement of the anomalous g value, a(mu) = (g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron. The result a(mu+) = 11 659 202(14) (6) x 10(-10) (1.3 ppm) is in good agreement with previous measurements and has an error one third that of the combined previous data. The current theoretical value from the standard model is a(mu)(SM) = 11 659 159.6(6.7) x 10(-10) (0.57 ppm) and a(mu)(exp) - a(mu)(SM) = 43(16) x 10(-10) in which a(mu)(exp) is the world average experimental value.

Journal Article↗
PubMed2001

Toward high-throughput genotyping: dynamic and automatic software for manipulating large-scale genotype data using fluorescently labeled dinucleotide markers.

To efficiently manipulate large amounts of genotype data generated with fluorescently labeled dinucleotide markers, we developed a Microsoft database management system, named. offers several advantages. First, it accommodates the dynamic nature of the accumulations of genotype data during the genotyping process; some data need to be confirmed or replaced by repeat lab procedures. By using, the raw genotype data can be imported easily and continuously and incorporated into the database during the genotyping process that may continue over an extended period of time in large projects. Second, almost all of the procedures are automatic, including autocomparison of the raw data read by different technicians from the same gel, autoadjustment among the allele fragment-size data from cross-runs or cross-platforms, autobinning of alleles, and autocompilation of genotype data for suitable programs to perform inheritance check in pedigrees. Third, provides functions to track electrophoresis gel files to locate gel or sample sources for any resultant genotype data, which is extremely helpful for double-checking consistency of raw and final data and for directing repeat experiments. In addition, the user-friendly graphic interface of renders processing of large amounts of data much less labor-intensive. Furthermore, has built-in mechanisms to detect some genotyping errors and to assess the quality of genotype data that then are summarized in the statistic reports automatically generated by. The can easily handle >500,000 genotype data entries, a number more than sufficient for typical whole-genome linkage studies. The modules and programs we developed for the can be extended to other database platforms, such as Microsoft SQL server, if the capability to handle still greater quantities of genotype data simultaneously is desired.

Alleles↗