Biomedical subjects

Y Xia

Publications and source records attributed to Y Xia.

At least 181 records · Page 10Linked to original sources

PubMed1998

Recent advances in the discovery and development of flavonoids and their analogues as antitumor and anti-HIV agents.

Antitumor and anti-HIV flavonoids and their analogues will be reviewed with emphasis on those discovered in our laboratory. The active antitumor compounds include the antileukemic tricin (1) and kaempferol-3-O-beta-D-glucopyranoside (2) from Wikstroemia indica, the cytotoxic hinokiflavone (3) from Rhus succedanea, the cytotoxic isoflavone (8) from Amorpha fruticosa, two dihydroxypentamethoxyflavones (9, 10) from Polanisia dodencandra. The development of synthetic 2-phenyl-4-quinolones as potent cytotoxic antimitotic flavonoid analogues and 2-phenylthiochromen-4-ones as potent antitumor flavonoid analogues will be presented. Selected results from other laboratories and antitumor-related biological studies also will be discussed. Flavonoids have also been investigated as potential anti-HIV agents. In our laboratory, acacetin-7-O-beta-D-galactopyranoside (131) from Chrysanthemum morifolium and chrysin (102), as well as apigenin-7-O-beta-D-glucopyranoside (130), from Kummerowia striata, have been found to exhibit anti-HIV activity. In other studies, some flavonoids and related compounds have been investigated as inhibitors of HIV-1 reverse transcriptase, protease, and integrase. The isolation and structural modification of such plant-derived active principles provide a continuing source of potential antitumor and anti-HIV agents.

Animals↗

PubMed1998

Interspecies comparative genome hybridization and interspecies representational difference analysis reveal gross DNA differences between humans and great apes.

Comparative chromosome G-/R-banding, comparative gene mapping and chromosome painting techniques have demonstrated that only few chromosomal rearrangements occurred during great ape and human evolution. Interspecies comparative genome hybridization (CGH), used here in this study, between human, gorilla and pygmy chimpanzee revealed species-specific regions in all three species. In contrast to the human, a far more complex distribution of species-specific blocks was detected with CGH in gorilla and pygmy chimpanzee. Most of these blocks coincide with already described heterochromatic regions on gorilla and chimpanzee chromosomes. Representational difference analysis (RDA) was used to subtract the complex genome of gorilla against human in order to enrich gorilla-specific DNA sequences. Gorilla-specific clones isolated with this technique revealed a 32-bp repeat unit. These clones were mapped by fluorescence in situ hybridization (FISH) to the telomeric regions of gorilla chromosomes that had been shown by interspecies CGH to contain species-specific sequences.

Animals↗

PubMed1998

A mixed population of immature and mature leucocytes in umbilical cord blood results in a reduced expression and function of CR3 (CD11b/CD18).

Neonatal neutrophils express less membrane and cytoplasmic CR3 (iC3b-receptor, Mac-1, alphaM beta2-integrin) than do adult neutrophils, and it has been suggested that this renders neonatal neutrophils deficient in diapedesis and bactericidal activity. The reason(s) for this deficiency are unknown. In this study, CR3 expression and the CR3-dependent respiratory burst activity of individual neonatal neutrophils are quantified in comparison with adult leucocytes using flow cytometry. Monocytes and neutrophils are defined as CD14highCD15low and CD14lowCD15high, respectively. Although neonatal neutrophils bore less CR3 on average than did adult neutrophils, neonatal neutrophils were more heterogeneous and many neonatal neutrophils expressed adult levels of CR3. Because of higher neutrophil concentrations in cord versus adult blood, the calculated number of neutrophils in cord blood expressing high amounts of CR3 was equivalent to that of adult blood. Similar findings were made with monocytes. The size of the CR3-dependent respiratory burst stimulated by particulate beta-glucan correlated directly with the expression of CR3 by individual neutrophils. With neonatal and adult neutrophils having comparable CR3 densities, the respiratory burst activities were equivalent. Wright-Giemsa differential staining of the subset of neonatal neutrophils with low CR3 levels isolated by fluorescence-activated cell sorting showed a higher proportion of immature cells than the sorted population expressing high CR3 levels. Therefore, higher proportions of immature cells in cord blood probably explain previous reports of deficient CR3 expression and function. The typical neutrophilia of cord blood may compensate for this apparent deficiency by providing adult concentrations of mature neutrophils.

Adult↗

PubMed1998

Oligomeric interaction of the PapB transcriptional regulator with the upstream activating region of pili adhesin gene promoters in Escherichia coli.

Transcriptional regulation of the pap genes, which encode fimbrial adhesins in uropathogenic Escherichia coli, depends on an upstream activating region. This region contains binding sites for a transcription factor, PapB, which is a member of a growing family of putative regulatory proteins found in several virulence-associated fimbrial gene systems. To assess the nature of the PapB binding sites, we studied different naturally occurring variants and a number of in vitro constructed mutant binding sites. DNase I footprinting analysis and visualization of the PapB-DNA complex by atomic force microscopy showed that the protein occupied a DNA region of more than 50 bp. Purified PapB protein was shown to recognize a motif including a 9 bp repeat sequence containing T/A triplets at a conserved position. PapB binding was affected by distamycin, and the results were consistent with the possibility that the binding to DNA occurred through minor groove interaction. From these analyses and estimation of the relative number of PapB proteins per binding site, we suggest that PapB binds the DNA in an oligomeric fashion and may function as an architectural factor in the transcriptional control of adhesin expression.

Adhesins, Bacterial↗

PubMed1998

Expression pattern of synucleins (non-Abeta component of Alzheimer's disease amyloid precursor protein/alpha-synuclein) during murine brain development.

The non-Abeta component of Alzheimer's disease amyloid precursor protein (NACP) is predominantly a neuron-specific presynaptic protein that may play a central role in neurodegeneration because NACP fragments are found in Alzheimer's disease amyloid and a mutation in the NACP gene is associated with familial Parkinson's disease. In addition, NACP may play an important role during synaptogenesis and CNS development. To understand better the patterns of NACP expression during development, we analyzed the levels of this protein as well as the levels of another synaptic protein (synaptophysin) by ribonuclease protection assay, western blotting, and immunocytochemistry in fetal, juvenile, and adult mouse brain. From embryonic day 12 to 15, there was a slight increase, which was then followed by a more dramatic increase at later time points. Immunocytochemical staining for NACP increases throughout these stages as well. Although NACP appeared early in CNS development, synaptophysin levels started to rise at a later stage. These findings support the contention that NACP might be important for CNS development. Furthermore, the cytosolic component of NACP precedes the particulate component in development, indicating that a redistribution of the protein to the membrane fraction may be important for events later in neuronal development and in synaptogenesis.

Alzheimer Disease↗

PubMed1998

Association of CYP2D microsatellite polymorphism with Lewy body variant of Alzheimer's disease.

OBJECTIVE: To examine the genetic association of CYP2D6 locus with Lewy body variant (LBV) and Parkinson's disease (PD). METHODS: Allelic association was studied in patients with pure AD, LBV, and PD by using the CYP2D microsatellite, the (dG-dT)n dinucleotide repeat (n=16 to 27) located between CYP2D8P and CYP2D7 genes, and the CYP2D6 B and D mutations. RESULTS: We found overrepresentation of the alleles longer than 21 repeat (the long-type alleles) in LBV (allele frequency, 0.313) (odds ratio=1.99, p=0.019 by chi2 test) and in PD (0.298) (odds ratio=1.86, p=0.037), but not in pure AD (0.196), compared with the age-matched control (0.186). Strong association was noted of the long-type alleles with the CYP2D6 B mutation (odds ratio=88.50, p < 0.001 by Fisher's exact test), but not with the D mutation or the deletion of CYP2D6 gene. CONCLUSIONS: The CYP2D locus is closely associated with LBV and PD. The CYP2D6 B mutation may be involved in pathogenesis of LBV and PD in a dominant-negative manner, or in the linkage disequilibrium of the CYP2D microsatellite to another pathogenic gene locus.

Aged↗

PubMed1998

Association of apolipoprotein E polymorphism and concentration with serum lipids and apolipoprotein level in the Chinese from Shanghai.

The influence of apolipoprotein E polymorphism and apoE level on serum lipids and apolipoproteins was investigated in 71 healthy people and 43 patients with coronary artery disease from Shanghai. The frequency of apoE alleles was 0.06 for epsilon2, 0.86 for epsilon3, and 0.07 for epsilon4 in the healthy group, and 0.14 for epsilon2, 0.77 for epsilon3, and 0.09 for epsilon4 in the coronary artery disease group. There was no significant difference in the frequency of apoE alleles between these two groups. Serum levels of triglyceride and apo AI did not differ according to apoE genotypes, whereas serum level of apoB was significantly different according to apoE genotypes (p<0.05) both in healthy and coronary artery disease groups. However, in the healthy group, apo epsilon2 allele carriers had significantly higher level of apoE than apo epsilon3 and epsilon4 allele carriers (p<0.001) and apo epsilon4 allele carriers had significantly higher level of total cholesterol than apo epsilon3 and epsilon2 allele carriers. These were not observed in the coronary artery disease group. ApoE concentration was positively correlated with cholesterol, apoAI, and apoB levels in the control subjects and no significant correlation was observed with triglyceride level. In contrast, apoE level was positively related only to triglyceride level in the coronary artery disease group. In the control group, apoE genotypes and apoE level explained together 19.3% and 26.6% of the variability of apoB and cholesterol level, respectively, apoE polymorphism explained 23% of the variability of apoE level and apoE level explained 13.2% of the variability of apoAI level. In the coronary artery disease group, only apoE level explained 41.7% of triglyceride variability. Finally we compared our results with those previously obtained in a French healthy population, the Stanislas cohort. Results suggested that there were some difference between the Chinese control and the French subjects.

Adult↗

PubMed1998

[A study of photographic standardization in rhinoplasty].

OBJECTIVE: A method of photographic standardization for rhinoplasty is presented. METHOD: To delineate the nose objectively before and after rhinoplasty, we designed a method to standardize picturing by using the points and lines in the face and camera in nasal photography. RESULT: With the help of anatomic points in the face and lines in the camera, we can maintain the camera at a constant position to the face. In this way, the nasal picture is more comparable and instructive. CONCLUSION: This method has been proved to be helpful in rhinoplasty.

Female↗

PubMed1998

[Study on a deletion polymorphism of the angiotensin converting enzyme gene in pregnancy induced hypertension].

OBJECTIVE: To study a polymorphism and allele frequency of the angiotensin converting enzyme (ACE) gene in pregnancy induced hypertension (PIH). METHODS: Polymerase chain reaction (PCR) for detection of ACE gene polymorphism was performed to show the deletion/insertion (D/I) polymorphism in intron 16 of ACE gene. A 490 bp(I) and 190 bp(D) PCR products were identified, corresponding to the PCR amplification of the the allele with or without the insertion. RESULTS: Derived allele frequencies for insertion and deletion were the different between 35 PIH and 25 control subjects. Compared the frequency of D allele gene (0.76) and the percentage of the ACE DD genotype (65.7%) in the PIH patients with the frequency (0.28) and the percentage (8.0%) in the control population, they were significant higher in individuals with PIH (P < 0.001). CONCLUSIONS: There was an excess of DD genotype and the frequency of D allele gene in PIH, confirming the genetic variation in the ACE locus could be involved in the risk of PIH and suggesting the ACE gene may contribute to the pathogenesis of PIH.

Adult↗

PubMed1998

[Effect of dietary selenium on the activities of glutathione peroxidase and deiodinase in rat liver].

In order to investigate the effect of dietary selenium on the activities of glutathione peroxidase and deiodinase and the least selenium requirement for their optimal activities, fifty four male weanling Wistar rats of 50-60g body weight were randomly divided into 9 groups and were fed with semisynthetic diets of different selenium level for 20 weeks. The selenium in the diets were 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.1, 0.2 and 5 mg/kg diet respectively. The body weight of ratsin the ninth group was different significantly from the seventh and eighth group, but those in the other eight groups were not significantly different. The activities of liver glutathione peroxidase in 0.1, 0.2 and 5 mg/kg groups were the highest among the nine groups. So at least 0.1 mg/kg diet is required for its normal activity. The activities of the liver type I deiodinase of nine groups were high from 0.05 to 0.2 mg/kg diet groups and at least Se 0.05 mg/kg diet is required for its normal activity.

Animals↗

PubMed1998

[The relation between human fetal growth and the blood levels of insulin-like growth factor-I].

OBJECTIVE: To determine the relation between human fetal growth and the levels of insulin growth factor-I (IGF-I) in both the maternal and fetal compartments. METHODS: Serum samples were obtained from pregnant woman(n = 171) and their neonate cord blood(n = 164) between 32-42 weeks of gestation. The woman and the neonate were divided into three groups by the birth weight of newborn. In large for gestational age (LGA) group, the 77 cases were from pregnant woman and the 64 cases were from their neonate; in average for gestational age (AGA) group, the 59 cases were from pregnant woman, the 59 cases were from their neonate; and in small for gestational age (SGA) group, the 35 cases were from pregnant woman and 43 cases were from their neonate. The serum samples were analyzed by radioimmunoassay for the levels of IGF-I. RESULTS: The levels of IGF-I in the neonatal serum were lower than those in maternal blood (P < 0.01). The levels of IGF-I in SGA group were lower than those in the other groups (P < 0.05). There was significant correlation between gestational ages and the levels of IGF-I (r = 0.91-0.98), but not in SGA group (r = 0.21-0.81). There was a direct correlation between the levels of IGF-I in the cord blood and the neonatal weight (P < 0.05). CONCLUSIONS: These data demonstrate that the level of expression and regulation of IGF-I in maternal and fetal compartments were independent of each other. The IGF-I level in cord blood is shown to be adjunctively and directly associated with fetal size in pregnancies and the IGF-I plays the precise role in deviant fetal growth.

Adult↗

PubMed1998

[A research on chemical dynamic changes and drug efficacy of SMS compound prescription: chemical researches on shenmaisan prescription (I)].

To clarify the material base of the distinct curative effect of Shengmaisan (SMS) compound prescription, a study was made on the dynamics of chemical constituents in the decoction prepared according to the compound prescription. From the decoction a new compound was isolated and identified by UV, IR, MS and NMR as 5-hydroxymethy-2-furaldehyde (5-HMF). The study suggests that the distinct curative effect of SMS compound prescription hinges on a material base which is different chemically from that in the other three single drugs used separately, thus presenting scientific criteria for rational compatibility and quality check in making preparations on compound prescriptions.

Drug Combinations↗

PubMed1998

The liver isoform of carnitine palmitoyltransferase I is activated in neonatal rat cardiac myocytes by hypoxia.

Fatty acids are the preferred substrate of ischemic, reperfused myocardium and may account for the decreased cardiac efficiency during aerobic recovery. Neonatal cardiac myocytes in culture respond to hypoxia/serum- and glucose-free medium by a slow decline in ATP which reverses upon oxygenation. This model was employed to examine whether carnitine palmitoyltransferase I (CPT-I) modulates high rates of beta-oxidation following oxygen deprivation. After 5 h of hypoxia, ATP levels decline to 30% control values and CPT-I activity is significantly stimulated in hypoxic myocytes with no alteration in cellular carnitine content or in the release of the mitochondrial matrix marker, citrate synthase. This stimulation was attributed to an increase in the affinity of hypoxic CPT-I for carnitine, suggesting that the liver CPT-I isoform is more dominant following hypoxia. However, there was no alteration in hypoxic CPT-I inhibition by malonyl-CoA. DNP-etomoxiryl-CoA, a specific inhibitor of the liver CPT-I isoform, uncovered identical Michaelis kinetics of the muscle isoform in control and hypoxic myocytes with activation of the liver isoform. Northern blotting did not reveal any change in the relative abundance of mRNA for the liver vs. the muscle CPT-I isoforms. The tyrosine phosphatase inhibitor, pervanadate, reversed the hypoxia-induced activation of CPT-I and returned the affinity of cardiac CPT-I for carnitine to control. Reoxygenation was also associated with a return of CPT-I activity to control levels. The data demonstrate that CPT-I is activated upon ATP depletion. Lower enzyme activities are present in control and reoxygenated cells where ATP is abundant or when phosphatases are inhibited. This is the first suggestion that phosphorylation may modulate the activity of the liver CPT-I isoform in heart.

Adenosine Triphosphate↗

PubMed1998

Hyperbaric oxygen as a signal transducer: upregulation of platelet derived growth factor-beta receptor in the presence of HBO2 and PDGF.

The purpose of this study was to test the hypothesis that hyperbaric oxygen (HBO2) may function by modifying the signal transduction pathway of growth factors or their receptors, or both. Studies were conducted with platelet derived growth factor (PDGF) and HBO2 using an established rabbit ear wound model. PDGF, a dimeric compound composed of A chain and B chain components, is found as PDGF-A, AB, and BB. It exerts its effects on cells by binding to one of two membrane-bound receptors, the alpha receptor or the beta receptor. Acutely ischemic wounds in rabbit ears were treated with saline or PDGF-BB and then animals were treated with hyperbaric air or oxygen at 2 atm abs (202.6 kPa). Hyperbaric air was without significant effect compared with control rabbits who breathed air at ambient pressure. Combined treatment with HBO2 plus PDGF-BB was synergistic in upregulating mRNA for PDGF-beta receptor. No treatments, whether alone or in combination, altered mRNA levels for PDGF-alpha receptor or for PGDF-A.

Animals↗

PubMed1997

Synthesis and evaluation of polycyclic pyrazolo[3,4-d]pyrimidines as PDE1 and PDE5 cGMP phosphodiesterase inhibitors.

Polycyclic pyrazolo[3,4-d]pyrimidines (represented by 3 and 4) were synthesized as analogues of the recently reported polycyclic guanine phosphodiesterase (PDE) inhibitors. From the structure-activity relationship (SAR) development of a series of compounds, it was discovered that C-3 benzyl and N-2 methyl disubstitution on the pyrazole ring gave the best combination of potency and selectivity for PDE1 and PDE5 cGMP PDEs as represented by compound 4c: PDE1, IC50 = 60 nM; PDE3, IC50 = 55,000 nM; PDE5, IC50 = 75 nM. These compounds were also evaluated in vivo and found to be good orally active antihypertensives in laboratory animal models. Finally, comparisons were made of the in vitro and in vivo profiles of the pyrazolo-[3,4-d]pyrimidine compound 4c with those of two representative guanine compounds.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1997

Direct measurement of nitric oxide generation from nitric oxide synthase.

Although nitric oxide synthase (NOS) is widely considered as the major source of NO in biological cells and tissues, direct evidence demonstrating NO formation from the purified enzyme has been lacking. It was recently reported that NOS does not synthesize NO, but rather generates nitroxyl anion (NO-) that is subsequently converted to NO by superoxide dismutase (SOD). To determine if NOS synthesizes NO, electron paramagnetic resonance (EPR) spectroscopy was applied to directly measure NO formation from purified neuronal NOS. In the presence of the NO trap Fe2+-N-methyl-D-glucamine dithiocarbamate, NO gives rise to characteristic EPR signals with g = 2.04 and aN = 12.7 G, whereas NO- is undetectable. In the presence of L-arginine (L-Arg) and cofactors, NOS generated prominent NO signals. This NO generation did not require SOD, and it was blocked by the specific NOS inhibitor N-nitro-L-arginine methyl ester. Isotope-labeling experiments with L-[15N]Arg further demonstrated that NOS-catalyzed NO arose from the guanidino nitrogen of L-Arg. Measurement of the time course of NO formation demonstrated that it paralleled that of L-citrulline. The conditions used in the prior study were shown to result in potent superoxide generation, and this may explain the failure to measure NO formation in the absence of SOD. These experiments provide unequivocal evidence that NOS does directly synthesize NO from L-Arg.

Cell Line↗

PubMed1997

Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation.

Electrical stimulation of neonatal cardiac myocytes produces hypertrophy and cellular maturation with increased mitochondrial content and activity. To investigate the patterns of gene expression associated with these processes, cardiac myocytes were stimulated for varying times up to 72 hr in serum-free culture. The mRNA contents for genes associated with transcriptional activation [c-fos, c-jun, JunB, nuclear respiratory factor 1 (NRF-1)], mitochondrial proliferation [cytochrome c (Cyt c), cytochrome oxidase], and mitochondrial differentiation [carnitine palmitoyltransferase I (CPT-I) isoforms] were measured. The results establish a temporal pattern of mRNA induction beginning with c-fos (0.25-3 hr) and followed sequentially by c-jun (0.5-3 hr), JunB (0.5-6 hr), NRF-1 (1-12 hr), Cyt c (12-72 hr), and muscle-specific CPT-I (48-72 hr). Induction of the latter was accompanied by a marked decrease in the liver-specific CPT-I mRNA, thus supporting the developmental fidelity of this pattern of gene regulation. Consistent with a transcriptional mechanism, electrical stimulation increased c-fos, beta-myosin heavy chain, and Cyt c promoter activities. These increases coincided with a rise in their respective endogenous gene transcripts. NRF-1, cAMP response element, and Sp-1 site mutations within the Cyt c promoter reduced luciferase expression in both stimulated and nonstimulated myocytes. Mutations in the NRF-1 and CRE sites inhibited the induction by electrical stimulation (5-fold and 2-fold, respectively) whereas mutation of the Sp-1 site maintained or increased the fold induction. This finding is consistent with the appearance of NRF-1 and fos/jun mRNAs prior to that of Cyt c and suggests that induction of these transcription factors is a prerequisite for the transcriptional activation of Cyt c expression. These results support a regulatory role for NRF-1 and possibly AP-1 in the initiation of mitochondrial proliferation.

Animals↗

PubMed1997

A model for p53-induced apoptosis.

The inactivation of the p53 gene in a large proportion of human cancers has inspired an intense search for the encoded protein's physiological and biological properties. Expression of p53 induces either a stable growth arrest or programmed cell death (apoptosis). In human colorectal cancers, the growth arrest is dependent on the transcriptional induction of the protein p21WAF1/CIP1 , but the mechanisms underlying the development of p53-dependent apoptosis are largely unknown. As the most well documented biochemical property of p53 is its ability to activate transcription of genes, we examined in detail the transcripts induced by p53 expression before the onset of apoptosis. Of 7,202 transcripts identified, only 14 (0.19%) were found to be markedly increased in p53-expressing cells compared with control cells. Strikingly, many of these genes were predicted to encode proteins that could generate or respond to oxidative stress, including one that is implicated in apoptosis in plant meristems. These observations stimulated additional biochemical and pharmacological experiments suggesting that p53 results in apoptosis through a three-step process: (1) the transcriptional induction of redox-related genes; (2) the formation of reactive oxygen species; and (3) the oxidative degradation of mitochondrial components, culminating in cell death.

Amino Acid Sequence↗