Biomedical subjects

X Xu

Publications and source records attributed to X Xu.

At least 559 records · Page 31Linked to original sources

PubMed1998

Murine protein kinase CK2 alpha': cDNA and genomic cloning and chromosomal mapping.

Protein kinase CK2 (casein kinase II) is a heterotetrameric enzyme implicated in many essential regulatory pathways in cells. We have determined the sequence of the murine CK2 alpha' cDNA that encodes a 350-amino-acid protein that would have 99 and 98% homology with the human and chicken proteins, respectively, and is also highly homologous to murine CK2 alpha. To clarify the sequence of the 5' end of the cDNA and to elucidate the structure and regulation of the gene, we obtained a bacterial artificial chromosome clone that contains the 35-kb CK2 alpha' gene. The gene consists of 12 small exons; the 5' end, including the first exon and intron, is extremely GC rich and contains a CpG island. The putative promoter contains potential binding sites for a variety of transcriptional factors but appears to lack CCAAT- or TATA-like elements. A polymorphic dinucleotide repeat in the fifth intron allowed us to map the CK2 alpha' gene to murine Chromosome 8.

Amino Acid Sequence↗

PubMed1998

Development of a method for quantitation of retinol and retinyl palmitate in human serum using high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry.

A method for the quantitative analysis of the vitamin A compounds all-trans-retinol and all-trans-retinyl palmitate was developed using high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (APCI-LC-MS). Unlike previous quantitative mass spectrometric methods for vitamin A, HPLC separations were carried out using a C30 reversed-phase column instead of GC separation. Because no sample hydrolysis or derivatization was necessary, retinyl palmitate was preserved for analysis instead of being hydrolyzed to retinol. Human serum was analyzed following simple hexane extraction without saponification or any additional purification. A comparison of APCI and electrospray ionization showed that only APCI produced a linear response over all four orders of magnitude of retinol and three orders of magnitude of retinyl palmitate concentrations. Selected ion monitoring of the fragment ion of m/z 269 was used for APCI quantitation of both retinol and retinyl palmitate, since it was the base peak and the only abundant ion in the mass spectra of both compounds and the internal standard, retinyl acetate. The ion of m/z 269 corresponded to loss of water, loss of palmitic acid, or elimination of acetic acid from the protonated molecules of retinol, retinyl palmitate and retinyl acetate, respectively. The limit of detection of APCI-LC-MS for all-trans-retinol and all-trans-retinyl palmitate was determined to be approximately 34 fmol/microliter and 36 fmol/microliter (0.670 pmol all-trans-retinol and 0.720 pmol all-trans-retinyl palmitate injected in 20 microliters on-column), respectively. The limit of quantitation was approximately 500 fmol/microliter and 250 fmol/microliter (10 pmol and 5 pmol injected in 20 microliters on-column) for retinol and retinyl palmitate, respectively.

Chromatography, High Pressure Liquid↗

PubMed1998

Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.

Amino Acid Sequence↗

PubMed1998

The role of yeast VDAC genes on the permeability of the mitochondrial outer membrane.

In addition to the POR1 gene, which encodes the well-characterized voltage dependent anion-selective channel (YVDAC1) of the mitochondrial outer membrane, the yeast Saccharomyces cerevisiae contains a second gene (POR2) encoding a protein (YVDAC2) with 50% sequence identity to YVDAC1. Mitochondria isolated from yeast cells deleted for the POR1 gene (delta por1) had a profoundly reduced outer membrane permeability as measured by the ability of an intermembrane space dehydrogenase to oxidize exogenously added NADH. Mitochondria missing either YVDAC1 or both YVDAC1 and YVDAC2 showed a 2-fold increase in the rate of NADH oxidation when the outer membrane was deliberately damaged. Mitochondria from parental cells showed only a 10% increase indicating that the outer membrane is highly permeable to NADH. In the absence of YVDAC1, we calculate that the outer membrane permeability to NADH is reduced 20-fold. The low NADH permeability in the presence of YVDAC2 was not due to the low levels of YVDAC2 expression as mitochondria from cells expressing levels of YVDAC2 comparable to those of YVDAC1 in parental cells showed no substantial increase in NADH permeability, indicating a minimal role of YVDAC2 in this permeability. The residual permeability may be due to other pathways because cells missing both genes can still grow on nonfermentable carbon sources. However, YVDAC1 is clearly the major pathway for NADH flux through the outer membrane in these mitochondria.

Genes, Fungal↗

PubMed1998

In vitro and in vivo mechanisms of action of the antiproliferative and immunosuppressive agent, brequinar sodium.

Intracellular pyrimidine nucleotides (PyN) can be synthesized de novo from glutamine, CO2, and ATP, or they can be salvaged from preformed pyrimidine nucleosides. The antiproliferative and immunosuppressive activities of brequinar sodium (BQR) are thought to be due to the inhibition of the activity of dihydroorotate dehydrogenase, which results in a suppression of de novo pyrimidine synthesis. Here we describe the effects of the pyrimidine nucleoSide, uridine, on the antiproliferative and immunosuppressive activities of BQR. In vitro reduction of PyN levels in Con A-stimulated T cells and inhibition of cell proliferation by low concentrations of BQR (< or =65 microM) are reversed by uridine. However, uridine is unable to reverse the effects of high concentrations of BQR (> or =65 microM). The ability of BQR to induce anemia in BALB/c mice is prevented by the coadministration of uridine. In contrast, the immunosuppressive activity of BQR is unaffected by similar doses of uridine. PyN levels in the bone marrow, but not in the spleen, are depressed in mice treated with BQR. These observations suggest that the induction of anemia by BQR is due to depletion of intracellular PyN in hemopoietic stem cells located in the bone marrow. They also suggest that the mechanism of immunosuppression by BQR may be only marginally dependent on depletion of intracellular PyN in lymphocytes located in the periphery. We report a novel activity of BQR: inhibition of tyrosine phosphorylation, and hypothesize that the immunosuppressive activity may be due, in part, to this unsuspected ability of BQR to inhibit tyrosine phosphorylation in lymphocytes.

Animals↗

PubMed1998

Cloning and characterization of two isoforms of the zebrafish thyrotroph embryonic factor (tef alpha and tefbeta).

We have cloned and sequenced two cDNAs representing two isoforms of the zebrafish thyrotroph embryonic factor (TEF) gene products (tef alpha and beta), a member of the PAR subfamily of bZIP transcription factors. The two isoforms encode two potential proteins of 300 and 293 amino acids respectively. Sequence comparison analysis indicate that the zebrafish tefs show high homology to PAR family of transcription factors of other species in the PAR domain, DNA binding domain and leucine zipper domain. Expression analysis by Northern blot and RT-PCR indicates that tef alpha and tefbeta are expressed in adult fish and throughout the zebrafish embryonic development. In addition, the two tefs are expressed in some adult tissues, but not others.

Amino Acid Sequence↗

PubMed1998

Angiotensinogen gene and hypertension in Chinese.

The renin-angiotensin system plays a major role in regulating blood pressure and maintaining electrolyte and volume homeostasis. Previously, the angiotensinogen gene, which encodes the key substrate for renin within this system, has been reported linked to and associated with essential hypertension in White Europeans, African-Caribbeans, and Japanese. Therefore, we investigated whether the angiotensinogen gene might be similarly implicated in the pathogenesis of essential hypertension in Chinese by carrying out linkage analysis in 310 hypertensive sibling pairs. Genotypes for two diallelic DNA polymorphisms observed at amino acid residues 174 (T174M) and 235 (M235T) within the coding sequence and for two highly informative dinucleotide (GT)-repeat sequences (one in the 3' flanking region, and one at a distance of 6.1 cM from the gene) were determined. Affected sibpair analysis conducted according to three different algorithms (S.A.G.E./SIBPAL, MAPMAKER/ SIBS, and APM methods) revealed no evidence for linkage of the angiotensinogen gene to hypertension. Our data indicate that molecular variants of this gene do not appear to contribute materially to the pathogenesis of primary hypertension among Chinese (a notion supported by concomitant, direct estimates of power), and that the disease relevance of this gene may vary therefore depending on ethnicity.

Alleles↗

PubMed1998

Benzene exposure, glutathione S-transferase theta homozygous deletion, and sister chromatid exchanges.

Recent studies have shown a strong positive correlation between chromosomal aberrations and future cancer risk. Sister chromatid exchange (SCE) has been widely applied in monitoring early biological effects to assess human genetic risk of cancer at the population level. We studied 45 Chinese workers (23 in the painting workshop of a glass factory with occupational exposure to benzene, and 22 fitters and planers in the punching and planing machine workshops of a nearby shipyard without such an exposure) to examine the association between occupational exposure to benzene and SCE frequency in peripheral blood lymphocytes. We also sought to investigate whether the glutathione S-transferase class theta gene (GSTT1) affects individual susceptibility to cytogenetic damage induced by in vivo exposure to benzene or in vitro exposure to diepoxybutane. The time-weighted average concentrations of benzene were 0.71 ppm in the exposed group and 0.03 ppm in the non-exposed group. Controlling for age, gender and educational level, cigarette smoking was significantly associated with increased SCE frequencies (P < 0.05), while GSTT1 genotype was significantly associated with DEB-induced SCEs (P < 0.01). There was no relationship between benzene exposure and baseline or DEB-induced SCEs. After stratification by smoking status, the GSTT1 deletion was a significant predictor of DEB-induced SCEs for both smokers (P < 0.05) and nonsmokers (P < 0.01). A significant benzene-GSTT1 interaction was found in nonsmokers (P < 0.05). Our study suggests that GSTT1 is an important determinant of heterogeneity in individual susceptibility to chromosomal damage associated with exposure to benzene.

Adult↗

PubMed1998

Virus-encoded receptors for cytokines and chemokines.

A number of viruses, particularly members of the poxvirus, herpesvirus and retrovirus families, have adapted to the vertebrate immune responses by capturing and modifying cellular genes which regulate the host immune system. Included among these host-derived virus genes are modified versions of receptors for cytokines or chemokines. Most of these receptor homologs, also called viroceptors, are either secreted glycoproteins or are located at the infected cell surface. Although these viroceptors can act in different ways, collectively they function by modifying the cytokine network to the advantage of the virus rather than the host.

Animals↗

PubMed1998

Generation of influenza transfectants using purified recombinant nucleocapsid protein.

Affinity-purified type A influenza virus nucleocapsid protein expressed by a recombinant baculovirus vector was used in in vitro RNA transcription reactions to create RNP complexes containing a synthetic influenza A virus NS gene. When used in transfection assays, the baculovirus-expressed NP was shown to be biologically active allowing the efficient isolation of transfectant viruses containing the artificially-introduced NS gene. The results demonstrate that NP is the only virion protein necessary in the reconstituted RNP complexes used for transfection thus eliminating the need for purified RNP complexes containing active polymerase.

Baculoviridae↗

PubMed1998

The future of genetic epidemiology.

Genetic epidemiology is a hybrid discipline whose ultimate aim is to identify and to characterize population-level factors that contribute to disease. Genetic epidemiologists often pursue this aim through the design and implementation of studies that simultaneously invoke principles in population genetics, epidemiology, molecular biology and biostatistics. However, traditional (and much contemporary) research in genetic epidemiology has barely tapped the potential that these disciplines have to work together. It is our view that future genetic epidemiology inquiry will benefit greatly from stronger integration of these disciplines and is likely to converge on themes in fields as diverse as demography, classical population and evolutionary genetics, pharmacoepidemiology, and ecology. The ultimate focus of this research will be evolution and maintenance of disease within and across populations.

Genetics, Population↗

PubMed1998

Comparison of bactericidal activity after multidose administration of clarithromycin, azithromycin, and ceruroxime axetil against Streptococcus pneumoniae.

The objective of this study was to compare the duration of serum bactericidal activity (SBA) for clarithromycin, azithromycin, and cefuroxime axetil in 12 young healthy volunteers after 5 days of therapy (dosed to steady-state) against two strains each of penicillin (PCN)-susceptible, -intermediate, and -resistant Streptococcus pneumoniae. This was a randomized, 3-way crossover study. All isolates were susceptible to clarithromycin (MICs 0.125 mg/l) and azithromycin (MICs 0.25-0.5 mg/l), while cefuroxime axetil susceptibilities correlated with PCN. Results showed that SBA was maintained for 100% of the dosing interval for clarithromycin and 50-100% for azithromycin regardless of PCN susceptibility when standard doses were employed. Cefuroxime axetil was active only against the PCN-susceptible isolate for 50% of the dosing interval, indicating that it should only be used for PCN-susceptible S. pneumoniae.

Anti-Bacterial Agents↗

PubMed1998

Blood pressure at age 3-24 years in a rural community in Anhui, China.

PURPOSE: This community-based study in Anhui, China examined the sex-specific pattern of blood pressure (BP) and its major determinants between age 3 and 24 years. METHODS: BP, height, weight, and related covariates were obtained from all eligible subjects by consistent methods. A generalized additive model was used to explore independent relations between BP and covariates. The sample for analyses included a total of 14,277 subjects (7244 males and 7033 females). RESULTS: Systolic blood pressure (SBP) increased linearly with age to an apparent plateau around the age of 15 years in girls and 20 years in boys. Diastolic blood pressure (DBP) essentially paralleled SBP. Until the age of 10, both SBP and DBP were similar in boys and girls; thereafter, values for boys surpassed those for girls with an average difference of 9 mmHg and 4 mmHg for SBP and DBP, respectively, at 20 years of age. This sex difference appeared to persist into early adulthood. The independent relation between BP and each of the three major determinants (age, height, and weight) was nonlinear over the age range studied. Sex-specific regression models with linear terms for age, height and weight were developed for each of four age groups (3-9, 10-14, 15-19, 20-24 years). The 5th, 10th, 90th, and 95th percentiles based on the percentage of predicted values can serve as the cutoffs for low, normal-low, normal-high, and high BP. The predicted values were derived from the above regression models that take into account an individual's sex, age, height, and weight. CONCLUSIONS: This analysis provided important basis for classification of hypertension status and subsequent investigation of environmental risk factors in this population.

Adolescent↗

PubMed1998

Comparison of the amnestic effects of NMDA receptor antagonist MK-801 and nitric oxide synthase inhibitors: L-NAME and L-NOARG in goldfish.

Investigations indicate that the induction of long-term potentiation (LTP) may be mediated by postsynaptic N-methyl-D-aspartate (NMDA) receptors and that the maintenance of LTP may be initiated by nitric oxide (NO), a retrograde messenger carrying signals backward from the postsynaptic to the presynaptic neuron. The present study compared amnestic effects of dizocilpine maleate (MK-801), an NMDA receptor antagonist, and nitro-L-arginine-methyl-ester (L-NAME) and N-nitro-L-arginine (L-NOARG), nitric oxide (NO) inhibitors, in goldfish, using active-avoidance conditioning as the learning paradigm. The results showed that MK-801 and NO inhibitors produced anterograde amnesia at doses that did not impair performance processes necessary for learning to occur. Furthermore, MK-801 did not produce retrograde amnesia, whereas L-NAME did, suggesting that MK-801 impaired learning whereas NO inhibitors impaired memory consolidation and possibly also learning.

Amnesia↗

PubMed1998

Neutral endopeptidase and angiotensin-converting enzyme inhibitors increase nitric oxide production in isolated canine coronary microvessels by a kinin-dependent mechanism.

Bradykinin is a substrate for both neutral endopeptidase 24.11 (NEP) and angiotensin-converting enzyme (ACE). Our previous studies showed that ACE inhibitors can stimulate nitric oxide production in coronary microvessels, which is mediated by local kinins. Whether inhibition of NEP also can affect local vascular NO production has not been established. To determine the role of NEP in the control of NO production, coronary microvessels were isolated from seven mongrel dogs. Two NEP inhibitors, phosphoramidon and thiorphan, and an ACE inhibitor, ramiprilat, were used. Nitrite, the metabolite of NO in aqueous solution, was measured by using the Griess reaction. Phosphoramidon and thiorphan (10(-6) M) increased nitrite production from 80 +/- 6 to 136 +/- 6 and 144 +/- 7 pmol/mg, respectively. Ramiprilat (10(-8) M) increased nitrite production from 78 +/- 6 to 155 +/- 7 pmol/mg wet weight. The effect of these agents on nitrite release was blocked by L-NAME, which inhibits NO synthase, HOE-140, which blocks bradykinin B2-receptor, and dichloroisocoumarin, which blocks kinin-forming enzymes. These results clearly indicate that inhibition of kinin metabolism by using neutral endopeptidase inhibitors increases NO production from coronary microvessels. Thus neutral endopeptidase plays an important role in local kinin-modulated NO production in the coronary microcirculation and NEP inhibitors may be useful clinical tools in treatment of cardiovascular disease.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Exercise reduces epicardial coronary artery wall stiffness: roles of cGMP and cAMP.

OBJECTIVE: Exercise enhances the dilation of the epicardial coronary arteries by vasodilator drugs and blood flow. Our goal was to determine whether coronary artery elastic properties were affected by brief exercise training. METHODS: Arterial pressure and left circumflex coronary artery diameter were measured in dogs. Venous bolus injections of acetylcholine 5 microg x kg(-1) (ACH) and nitroglycerin 25 microg x kg(-1) (NTG) or infusions of adenosine 0.5 microM/kg/min (ADO) were given. Fifteen-second coronary artery occlusions were performed. Dogs exercised 2 h x d(-1) for 7 d at 10.9 km x h(-1). Experiments were repeated. Pressure and coronary radius data were used to calculate vessel wall stress and incremental wall modulus, Einc. RESULTS: Baseline Einc and radius were not changed by exercise. Before exercise Einc increased similarly from baseline for all vasodilators. After exercise, the increase in Einc with ADO was unchanged. However, the increase was attenuated during ACH, abolished with occlusion, and reversed with NTG despite enhanced dilation. CONCLUSION: Data suggest that functional remodeling of epicardial arteries begins soon after starting exercise training, before changes in resting vessel diameter, is mediated by cGMP, and contributes to increased vascular dilation. Brief exercise training enhances the vasodilating capability and elastic properties of large coronary arteries.

Acetylcholine↗

PubMed1998

Reproductive hormone profile among pesticide factory workers.

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood sample was collected at the end of a work shift, when each subject also donated a semen sample. Three first-voided urine samples were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79; 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38; 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13; 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude that organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage.

Adult↗

PubMed1998

The role of gibberellin, abscisic acid, and sucrose in the regulation of potato tuber formation in vitro

The effects of plant hormones and sucrose (Suc) on potato (Solanum tuberosum L.) tuberization were studied using in vitro cultured single-node cuttings. Tuber-inducing (high Suc) and -noninducing (low Suc or high Suc plus gibberellin [GA]) media were tested. Tuberization frequencies, tuber widths, and stolon lengths were measured during successive stages of development. Endogenous GAs and abscisic acid (ABA) were identified and quantified by high-performance liquid chromatography and gas chromatography-mass spectrometry. Exogenous GA4/7 promoted stolon elongation and inhibited tuber formation, whereas exogenous ABA stimulated tuberization and reduced stolon length. Indoleacetic acid-containing media severely inhibited elongation of stolons and smaller sessile tubers were formed. Exogenous cytokinins did not affect stolon elongation and tuber formation. Endogenous GA1 level was high during stolon elongation and decreased when stolon tips started to swell under inducing conditions, whereas it remained high under noninducing conditions. GA1 levels were negatively correlated with Suc concentration in the medium. We conclude that GA1 is likely to be the active GA during tuber formation. Endogenous ABA levels decreased during stolon and tuber development, and ABA levels were similar under inducing and noninducing conditions. Our results indicate that GA is a dominant regulator in tuber formation: ABA stimulates tuberization by counteracting GA, and Suc regulates tuber formation by influencing GA levels.

Journal Article↗