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Biomedical subjects

L Deng

Publications and source records attributed to L Deng.

At least 91 records · Page 5Linked to original sources

[Detection of numerical chromosome aberrations in sperm of workers exposed to benzene series by two-color fluorescence in situ hybridization].

OBJECTIVE: To study the numerical aberrations of sex chromosomes in sperm of workers exposed to benzene series. METHODS: The interphase sperm from workers of exposed and control groups were hybridized using two color fluorescence in situ hybridization with X and Y(alpha)-satellite chromosome specific DNA probes, and the aneuploidy frequencies of X and Y chromosome in X and Y sperms were detected simultaneously. RESULTS: Geometric mean concentration of benzene in workplace air was 83.95 mg/m(3), one fold higher than national maximum allowable concentration. A total of 74,517 sperm nuclei in 13 benzene-exposed workers and 89,662 sperm nuclei in 13 control workers were counted. Frequencies of disomic sperm for X, Y and XY were (0.15 +/- 0.05)%, (0.13 +/- 0.05)% and (0.20 +/- 0.11)% in workers exposed to benzene series, and (0.10 +/- 0.04)%, (0.10 +/- 0.04)% and (0.13 +/- 0.06)% in control workers. There was statistical difference in disomic frequency of X sperm and overall disomic frequency between the benzene series-exposed workers (0.15% and 0.48%, respectively) and the control workers (0.10% and 0.33%, respectively). CONCLUSION: Exposed to benzene at higher concentration may induce increase in aneuploidy frequency of sperm sex chromosome in exposed workers.

Adult↗

[Expression and clinical significance of p53 protein and p21(WAF1) in non-small-cell lung carcinoma].

OBJECTIVE: To investigate the relationships between expression of tumor suppressor gene p53 protein, p21(WAF1), clinicopathology and prognosis in human non-small-cell lung carcinoma (NSCLC). METHODS: SP immunohistochemistry performed in all cases. RESULTS: One hundred forty-seven resected NSCLC were examined. There were 63 squamous cell carcinomas, 66 adenocarcinomas, 14 adenosquamous carcinomas and 4 large cell carcinomas. Overall 90 (61.2%) of the 147 cases had positive p53 staining. The positive ratios of p53 overexpression of squamous cell carcinomas, adenocarcinomas, adenosquamous carcinomas and large cell carcinomas were 63.5% (40/63), 57.6% (38/66), 71.4% (10/14) and 50% (2/4) respectively. The average positive ratio of p21(WAF1) expression was 40.1% (59/147) in lung carcinoma. The positive ratios of p21(WAF1) expression of squamous cell carcinomas, adenocarcinomas, adenosquamous carcinomas and large cell carcinomas were 41.3% (26/63), 42.4% (28/66), 28.6% (4/14) and 25% (1/4) respectively. Over expression of p53 protein was associated with prognosis of the patients with adenocarcinomas. The positive ratio of p53 expression in over 3 year survival patients was 75% (21/28) and in less than 3 year survival, 44.7% (17/38) (P < 0.025). The positive expression of p21(WAF1) was related to prognosis of NSCLC. The ratio of 3-year survival (64.4%) in p21(WAF1) positive NSCLC was much higher than in p21(WAF1) negative patients (46.6%) (P < 0.05). Prognosis of patients with p53 positive but p21(WAF1) negative expression was poorer than those with p53 negative and p21(WAF1) positive NSCLC (P < 0.01). CONCLUSION: These findings suggest that over expression of p53 in adenocarcinomas could be used as a prognostic factor for patients. p21(WAF1) is of protein has a definite value in judging the prognosis in NSCLC. Combined expression of p53 and p21(WAF1) can be used as the prognostic markers in NSCLC and are of significance in estimating the prognosis of patients.

Adenocarcinoma↗

[Ca II triplet equivalent widths of spiral galaxy M31 and elliptical galaxy M32].

The Calcium II triplet (Ca II T) lines in the near infrared spectral region is very important feature for late type stars, which serves as an important metallicity indicator for such stars. This is also true for stellar systems composed mainly of late type stars, such as old stellar clusters and galaxies. In this work, we made observations of the very famous spiral galaxy M31 and its dwarf elliptical companion M32, using the OMR spectrograph attached to the 2.16-meter telescope in Beijing Astronomical Observatory. Near-infrared spectra of the nuclear and disk regions on M31, as well as two slices along the major and the minor axis of M32, are derived. Equivalent widths of the Ca II triplet lines are measured using normal astrophysical spectrum analyzing techniques. The results are fundamental data for these two galaxies, which can be applied to researches for stellar population analysis of these galaxies.

English Abstract↗

Phase-coherent amplification of matter waves

Phase-coherent matter-wave amplification was demonstrated using Bose- Einstein-condensed rubidium-87 atoms. A small seed matter wave was created with coherent optical Bragg diffraction. Amplification of this seed matter wave was achieved by using the initial condensate as a gain medium through the superradiance effect. The coherence properties of the amplified matter wave, studied with a matter-wave interferometer, were shown to be locked to those of the initial seed wave. The active matter-wave device demonstrated here has great potential in the fields of atom optics, atom lithography, and precision measurements.

Journal Article↗

Substituted isoquinolines and quinazolines as potential antiinflammatory agents. Synthesis and biological evaluation of inhibitors of tumor necrosis factor alpha.

A series of isoquinolin-1-ones and quinazolin-4-ones and related derivatives were prepared and evaluated for their ability to inhibit tumor necrosis factor alpha (TNFalpha) production in human peripheral blood monocytes stimulated with bacterial lipopolysaccharide (LPS). In an effort to optimize the TNFalpha inhibitory activity, a homologous series of N-alkanoic acid esters was prepared. Several electrophilic and nucleophilic substitutions were also carried out. Alkanoic acid esters of four carbons were found to be optimum for activity in both the isoquinoline and quinazoline series. Ring substituents such as fluoro, bromo, nitro, acetyl, and aminomethyl on the isoquinoline ring resulted in a significant loss of activity. Likewise, similar groups on the quinazoline ring also reduced inhibitory activity. However, the 6- and 7-aminoquinazoline derivatives, 75 and 76, were potent inhibitors, with IC(50) values in the TNFalpha in vitro assay of approximately 5 microM for each. An in vivo mouse model of pulmonary inflammation was then used to evaluate promising candidate compounds identified in the primary in vitro assay. Compound 75 was selected for further study in this inhalation model, and was found to reduce the level of TNFalpha in brochoalveolar lavage fluid of LPS-treated mice by about 50% that of control mice. Thus, compounds such as 75, which can effectively inhibit proinflammatory cytokines such as TNFalpha in clinically relevant animal models of inflammation and fibrosis, may have potential as new antiinflammatory agents. Finally, a quinazoline derivative suitable to serve as a photoaffinity radiolabeled compound was prepared to help identify the putative cellular target(s) for these TNFalpha inhibitors.

Animals↗

Mitotic recombination produces the majority of recessive fibroblast variants in heterozygous mice.

Mice heterozygous at Aprt (adenine phosphoribosyltransferase) were used as a model to study in vivo loss of heterozygosity (LOH) in normal fibroblasts. Somatic cell variants that exhibited functional loss of the wild-type Aprt in vivo were recovered as APRT-deficient cell colonies after culturing in selection medium containing 2, 6-diaminopurine (DAP), an adenine analog that is toxic only to cells with APRT enzyme activity. DAP-resistant (DAP(r)) fibroblast variants were recovered at a median frequency of 12 x 10(-5) from individual ears from progeny of crosses between mouse strains 129/Sv and C3H/HeJ. The frequency of DAP(r) variants varied greatly among individual ears, suggesting that they preexisted in vivo and arose at various times during development. Polymorphic molecular markers and a cytological marker on the centromere of chromosome 8 made it possible to discriminate between each of six possible mechanistic pathways of LOH. The majority (about 80%) of the DAP(r) variants were a consequence of mitotic recombination. The prevalence of mitotic recombination in regions proximal to Aprt did not correlate with meiotic map distances. In particular, there was a higher than expected frequency of crossovers within the interval 59 cM to 67 cM. The high spontaneous frequency of Aprt LOH, mediated primarily by mitotic recombination, is fully consistent with our previous results with human peripheral T cells from individuals known to be heterozygous at APRT. Thus, this Aprt heterozygote mouse is a valid model for studying somatic mutagenesis and mitotic recombination in vivo.

Adenine Phosphoribosyltransferase↗

Potent, elective human beta3 adrenergic receptor agonists containing a substituted indoline-5-sulfonamide pharmacophore.

A series of compounds possessing an N-substituted indoline-5-sulfonamide pharmacophore was prepared and evaluated for their human beta3 adrenergic receptor agonist activity. The SAR of a wide range of urea and heterocyclic substituents is discussed. 4-Octyl thiazole compound 8c was the most potent and selective compound in the series, with 2800-fold selectivity over beta1 binding and 1400-fold selectivity over beta2 binding.

Adrenergic Agonists↗

L-770,644: a potent and selective human beta3 adrenergic receptor agonist with improved oral bioavailability.

L-770,644 (9c) is a potent and selective agonist of the human beta3 adrenergic receptor (EC50 = 13 nM). It shows good oral bioavailability in both dogs and rats (%F = 27), and is a full agonist for glycerolemia in the rhesus monkey (ED50 = 0.21 mg/kg). Based on its desirable in vitro and in vivo properties, L-770,644 was chosen for further preclinical evaluation.

Administration, Oral↗

[Using the method of two-color fluorescence in situ hybridization to detect aneuploidy of human sperms]

OBJECTIVE: To develope the method of two-color fluorescence in situ hybridization (FISH) assay and use it for detecting the aneuploidy frequency of human sperm chromosome. METHODS: Sperm sample was washed three times and the slides were prepared. The sperm heads were decondensed with dithiothreitol (DTT) and lithium diiodosalicylate (LIS). Then, the sperm nuclei were hybridized with biotin labeled alpha satellite X chromosome DNA probe (DXZ1) and digoxigenin labeled alpha satellite Y chromosome DNA probe (DYZ3). The hybridization signals were detected with CY3-Streptavidin, goat antistrepavidin for biotin labeled probe and with mouse antidigoxigenin, rabbit antimouse-FITC for digoxigenin labeled probe. RESULTS: Under the Nikon fluorescence microscope, the hybridization signals in the sperm heads were clearly visible. The sperm with one red hybridization signal was X chromosome sperm (X sperm), and the sperm with one green hybridization signal in the sperm head was Y chromosome sperm (Y sperm). In the case of two hybridization signals in one sperm head, the sperm should be a numerical abnormal one. By using two color FISH with one euchromosome probe and one sex chromosome probe, the sperm with same color of two hybridization signals in one sperm head could be identified as aneuploidy sperm or diploid sperm. CONCLUSION: The two color FISH assay may be used to detect the aneuploidy frequency of human sperms that were exposed to mutagents and environmental potential aneuoploidogenic agents.

Journal Article↗

A well-collimated quasi-continuous atom laser

Extraction of sodium atoms from a trapped Bose-Einstein condensate (BEC) by a coherent, stimulated Raman process is demonstrated. Optical Raman pulses drive transitions between trapped and untrapped magnetic sublevels, giving the output-coupled BEC fraction a well-defined momentum. The pulsed output coupling can be run at such a rate that the extracted atomic wave packets strongly overlap, forming a highly directional, quasi-continuous matter wave.

Journal Article↗

Human beta3 adrenergic receptor agonists containing cyclic ureidobenzenesulfonamides.

Human beta3 adrenergic receptor agonists containing 5-membered ring ureas were shown to be potent partial agonists with excellent selectivity over beta1 and beta2 binding. L-760,087 (4a) and L-764,646 (5a) (beta3 EC50 = 18 and 14 nM, respectively) stimulate lipolysis in rhesus monkeys (ED50 = 0.2 and 0.1 mg/kg, respectively) with minimal effects on heart rate. Oral absorption in dogs is improved over other urea analogs.

Administration, Oral↗

A polyadenylylation-specific RNA-contact site on the surface of the bifunctional vaccinia virus RNA modifying protein VP39 that is distinct from the mRNA 5' end-binding "cleft".

VP39 is a bifunctional mRNA-modifying protein that acts as both an mRNA cap-specific 2'-O-methyltransferase and a processivity factor for VP55, the vaccinia poly(A) polymerase catalytic subunit. Although regions of the protein surface required for methyltransferase function are well defined, it has been unclear whether the protein polyadenylylation function requires direct RNA contact and, if so, where the contact site(s) might be located on the protein surface. Here, we show that the VP55-VP39 heterodimer forms a stable complex with a 50mer oligonucleotide bearing a U2-N25-U motif, as opposed to the U2-N15-U motif that is optimal for stable complex formation with VP55 alone. An oligonucleotide bearing a U2-N25-U motif in which the downstream U residue is replaced with 4thioU can be efficiently photocrosslinked to VP39, but only in the context of the VP55-VP39 heterodimer. By partial proteolysis of end-labeled VP39, the site of oligonucleotide photocrosslinking was localized to the region of VP39 between residues Lys90 and Arg122. Peptide microsequencing and confirmatory mutagenesis identified the side-chain of Arg107 as the photocrosslinking site. Substitution of this residue with lysine abolished photocrosslinking entirely, consistent with the established RNA binding role of arginine in other RNA-binding proteins. This study provides clear evidence for a polyadenylylation-specific RNA-contact site on the surface of VP39, which is distinct from the RNA-binding methyltransferase "cleft" characterized in recent crystallographic and biochemical studies.

Base Sequence↗

Cloning and expression of a gene encoding a Campoletis sonorensis polydnavirus structural protein.

Polydnaviruses are the only known group of mutualistic viruses. They are required for successful parasitization in many braconid and ichneumonid parasitoids. The intimacy of this mutualistic association is indicated by the integration and vertical transmission of polydnaviruses in wasp genomes and by their asymptomatic, developmentally regulated replication. The evolution of this mutualism raises several interesting issues that require a better understanding of the viral genome and viral replication. To develop probes for virus replication and morphogenesis, we have begun to characterize several viral structural proteins. A 699 bp cDNA encoding the p12 viral structural protein was cloned and sequenced. The p12 gene localizes to viral segment Y and encodes a predicted protein of 92 amino acids that does not encode a signal peptide and is unrelated to known peptide or nucleic acid sequences. The p12 mRNA is detected at the onset of virus replication. mRNA titers increase with increasing rates of virus replication. Polyclonal antisera raised against histidine-tagged p12 protein expressed in bacteria reacted specifically with the p12 polypeptide in Western blots of CsPDV virions. The p12 polypeptide was not detected in non-replicative wasp or lepidopteran tissues by Western blot analyses but was readily detected in protein extracts of wasp ovaries. The data indicate that the p12 gene is a viral gene encoding a virion protein and provides a specific probe for virus replication that will be useful for studying the evolution of this group of mutualistic viruses.

Amino Acid Sequence↗

Staphylococcus aureus cap5P encodes a UDP-N-acetylglucosamine 2-epimerase with functional redundancy.

The serotype 5 capsule gene cluster of Staphylococcus aureus comprises 16 genes (cap5A through cap5P), but little is known about how the putative gene products function in capsule biosynthesis. We propose that the N-acetylmannosaminuronic acid (ManNAcA) component of the S. aureus serotype 5 capsular polysaccharide (CP5) is synthesized from a UDP-N-acetylglucosamine (UDP-GlcNAc) precursor that is epimerized to UDP-N-acetylmannosamine (UDP-ManNAc) and then oxidized to UDP-ManNAcA. We report the purification and biochemical characterization of a recombinant UDP-GlcNAc 2-epimerase encoded by S. aureus cap5P. Purified Cap5P converted approximately 10% of UDP-GlcNAc to UDP-ManNAc as detected by gas chromatography-mass spectrometry. The epimerization of UDP-GlcNAc to UDP-ManNAc occurred over a wide pH range and was unaffected by divalent cations. Surprisingly, CP5 expression in S. aureus was unaffected by insertional inactivation of cap5P. Sequence homology searches of the public S. aureus genomic databases revealed the presence of another putative UDP-GlcNAc 2-epimerase on the S. aureus chromosome that showed 61% identity to Cap5P. Redundancy of UDP-GlcNAc 2-epimerase function in S. aureus was demonstrated by cloning the cap5P homologue from strain Newman and complementing an Escherichia coli rffE mutant defective in UDP-GlcNAc 2-epimerase activity. Our results confirm the putative function of the S. aureus cap5P gene product and demonstrate the presence of a second gene on the staphylococcal chromosome with a similar function.

Bacterial Proteins↗

[Using the method of two-color fluorescence in situ hybridization to detect aneuploidy of human sperms].

OBJECTIVE: To develop the method of two-color fluorescence in situ hybridization (FISH) assay and use it for detecting the aneuploidy frequency of human sperm chromosome. METHODS: Sperm sample was washed three times and the slides were prepared. The sperm heads were decondensed with dithiothreitol (DTT) and lithium diiodosalicylate (LIS). Then, the sperm nuclei were hybridized with biotin labeled alpha satellite X chromosome DNA probe (DXZ1) and digoxigenin labeled alpha satellite Y chromosome DNA probe (DYZ3). The hybridization signals were detected with CY3-Streptavidin, goat antistrepavidin for biotin labeled probe and with mouse antidigoxigenin, rabbit antimouse-FITC for digoxigenin labeled probe. RESULTS: Under the Nikon fluorescence microscope, the hybridization signals in the sperm heads were clearly visible. The sperm with one red hybridization signal was X chromosome sperm (X sperm), and the sperm with one green hybridization signal in the sperm head was Y chromosome sperm (Y sperm). In the case of two hybridization signals in one sperm head, the sperm should be a numerical abnormal one. By using two color FISH with one euchromosome probe and one sex chromosome probe, the sperm with same color of two hybridization signals in one sperm head could be identified as aneuploidy sperm or diploid sperm. CONCLUSION: The two color FISH assay may be used to detect the aneuploidy frequency of human sperms that were exposed to mutagents and environmental potential aneuoploidogenic agents.

Aneuploidy↗

Potent and selective human beta(3)-adrenergic receptor antagonists.

Although the functional presence of beta(3)-adrenergic receptors (beta(3)-AR) in rodents is well established, its significance in human adipose tissue has been controversial. One of the issues confounding the experimental data has been the lack of potent and selective human beta(3)-AR ligands analogous to the rodent-specific agonist BRL37344. Recently, we described a new class of aryloxypropanolamine beta(3)-AR agonists that potently and selectively activate lipolysis in rhesus isolated adipocytes and stimulate the metabolic rate in rhesus monkeys in vivo. In this article, we describe novel and selective beta(3)-AR antagonists with high affinity for the human receptor. L-748,328 and L-748,337 bind the human cloned beta(3)-AR expressed in Chinese hamster ovary (CHO) cells with an affinity of 3.7 +/- 1.4 and 4.0 +/- 0.4 nM, respectively. They display an affinity of 467 +/- 89 and 390 +/- 154 nM for the human beta(1)-AR. Their selectivity for human beta(3)-AR versus beta(2)-AR is greater than 20-fold (99 +/- 43 nM) and 45-fold (204 +/- 75 nM), respectively. These compounds are competitive antagonists capable of inhibiting the functional activation of agonists in a dose-dependent manner in cells expressing human cloned beta(3)-AR. Moreover, both L-748,328 and L-748,337 inhibit the lipolytic response elicited by the beta(3)-AR agonist L-742,791 in isolated nonhuman primate adipocytes. The aryloxypropanolamine benzenesulfonamide ligands illustrated here and elsewhere demonstrate high-affinity human beta(3)-AR binding. In addition, we describe specific 3'-phenoxy substitutions that transform these compounds from potent agonists into selective antagonists.

Adipocytes↗

cDNA representational difference analysis of differentially expressed cDNA sequences in human nasopharyngeal carcinoma.

OBJECTIVE: To search differentially expressed sequences correlated with pathogenesis of human nasopharyngeal carcinoma (NPC), including the candidates of tumor suppressor genes. METHODS: Representational difference analysis (RDA) was performed to isolate differentially expressed sequences between cDNA from normal human primary cultures of nasopharyngeal epithelial cells and cDNA from NPC cell line HNE1. The source of differentially expressed products were proved by Southern blot, Northern blot and in situ hybridization. The fragments were cloned with pGEM-T easy kit and sequenced by the chain termination reaction. RESULTS: Four differentially expressed cDNA fragments were isolated in the fourth subtractive hybridization using cDNA from normal human nasopharyngeal epithelial cells as tester amplicon and cDNA from NPC cell line HNE1 as driver amplicon by cDNA RDA. These differential cDNA fragments revealed that they really came from the tester amplicon and were not expressed or down-regulated in the NPC HNE1 cells. Some of the genes were expressed only in human nasopharyngeal epithelial cells but deleted or down-regulated in the biopsies of NPC. Of these obtained clones, some were the sequences of the human known genes including house-keeping genes, the others represented novel gene sequences. CONCLUSION: The differentially expressed products including the candidates of tumor-suppressor genes may be associated with the initiation of the NPC.

DNA, Complementary↗