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Biomedical subjects

X Y Liu

Publications and source records attributed to X Y Liu.

At least 37 records · Page 2Linked to original sources

Phospholipase A(2)-catalyzed membrane leakage studied by immobilized liposome chromatography with online fluorescent detection.

Unilamellar liposomes composed of phosphatidylcholine with an entrapped self-quenching fluorescent dye, calcein, were immobilized in chromatographic gel beads by avidin-biotin binding. Bee venom phospholipase A(2) (PLA(2)) was applied in a small amount onto the immobilized liposome column. The release of calcein from the immobilized liposomes resulting from the catalyzed hydrolysis of the phospholipids was detected online by immobilized liposome chromatography (ILC) using a flow fluorescent detector. The PLA(2)-catalyzed membrane leakage of the immobilized liposomes as studied with ILC was found to be affected by the gel pore size used for immobilization, by liposome size, and as expected by the concentration of calcium, but was unaffected by the flow rate of ILC. The largest PLA(2)-induced calcein release from the liposome column was detected on large unilamellar liposomes immobilized on TSK G6000PW or Sephacryl S-1000 gel in the presence of 1 mM Ca(2+) in the aqueous mobile phase. Comparison with the PLA(2)-catalyzed membrane leakage in free liposome suspensions, we conclude that the fluorescent leakage from liposomes hydrolyzed by PLA(2) can be rapidly and sensitively detected by ILC runs using large amount of immobilized liposomes with entrapped fluorescent dye.

Animals↗

Effect of liposome type and membrane fluidity on drug-membrane partitioning analyzed by immobilized liposome chromatography.

Immobilized liposome chromatography (ILC) has been proven to be a useful method for the study or rapid screening of drug-membrane interactions. To obtain an adequate liposomal membrane phase for ILC, unilamellar liposomes were immobilized in gel beads by avidin-biotin binding. The retardation of 15 basic drugs on the liposome column could be converted to membrane partitioning coefficients, K(LM). The effects of small or large unilamellar liposomes and multilamellar liposomes on the drug-membrane partitioning were compared. The K(LM) values for both small and large liposomes were similar, but higher than those for the multilamellar liposomes. The basic drugs showed stronger partitioning into negatively charged liposomes than into either neutral liposomes or positively charged liposomes. The membrane fluidity of the immobilized liposomes was modulated by incorporating cholesterol into the liposomal membranes, by changing the acyl chain length and degree of unsaturation of the phospholipids, and by changing the temperature for ILC runs. Our data show that K(LM) obtained using ILC correlated well with those reported by batch studies using free liposomes. It is concluded that negatively charged or cholesterol-containing large unilamellar liposomes are suitable models for the ILC analysis of drug-membrane interactions.

Chromatography, Liquid↗

Analgesic domains of interferon-alpha.

Interferon-alpha (IFNalpha) is not only an immunoregulatory factor, but is also an analgesic molecule. We ever reported that there exist distinct domains in IFNalpha molecule that mediate immune and analgesic effects respectively and inferred that the analgesic domain locates around the 122nd Tyr residue of IFNalpha molecule in the tertiary structure. After the 36th Phe residue, which was located closely to the 122nd Tyr residue in the tertiary structure, was mutated to Ser using site-directed mutagenesis, the analgesic activity of this mutant lost completely, but the antiviral activity of IFNalpha still maintained 40.5% of wild type IFNalpha. The results suggest that the 36th Phe residue is one of the constituent for the analgesic domain of IFNalpha and inferred that the analgesic domain of IFNalpha consists of the 122nd Tyr and the residues around the 122nd in the tertiary structure, which include the 36th Phe.

Analgesics↗

Neurologic complications due to catheterization.

In our university cardiac center, the incidence of a cohort of children with acute neurologic complications resulting from cardiac catheterization performed for acyanotic or cyanotic congenital heart disease is 0.38% (14 children of a total of 3,648 catheterization procedures). Neurologic complications consisted of convulsion (n = 10), stroke (n = 6), intracranial hemorrhage (n = 2), extrapyramidal features (n = 1), paraplegia (n = 1), visual impairment (n = 1), hearing impairment (n = 1), and brachial plexus injury (n = 1). The main risk factors included prolonged duration of catheterization procedure and interventional manipulation in addition to cardiac catheterization. The possible mechanisms causing brain injury included cerebral embolism from local clots and hypoxia resulting from complications during the procedure. Other complications included intracranial hemorrhage secondary to anticoagulation and peripheral plexopathy because of prolonged fixed posture during anesthesia. The prognosis for the majority of patients with stroke is good. Neurologic sequelae, such as global developmental delay or epilepsy, occurred in those with hypoxic-ischemic encephalopathy.

Acute Disease↗

Active immunization against gonadotrophin-releasing hormone in Chinese male pigs.

We have investigated, under the normal conditions of local Chinese pig farming, castration of young male pigs by vaccination with a newly developed vaccine against gonadotrophin releasing hormone (GnRH). Because of the very early onset of puberty, long fattening period and relatively harsh circumstances in Chinese pig production, an investigation of the endocrine response of Chinese breeds to this type of vaccination was of particular interest. Fifteen crossbred boars (Yorkshire x Yanan) from three different litters were randomly assigned to three groups of five animals each. The first group was immunized at 13 weeks of age with a GnRH tandem dimer OVA-conjugate in Specol and received a booster immunization 8 weeks later. The second group was injected with Specol alone and served as untreated controls. The remaining group was surgically castrated at the time of weaning (at 6 weeks of age). Pigs were fed ad libitum from weaning onwards. All animals were slaughtered at 31 weeks of age. Immunized boars had undetectable or low serum testosterone (0.09 +/- 0.12 ng/ml), low fat androstenone (0.05 +/- 0.01 microg/g) levels and very low testes weights (19.1 +/- 4.3 g). Intact controls had much higher serum levels of testosterone (9.76 +/- 4.81 ng/ml), fat androstenone levels (2.26 +/- 0.87 microg/g) and testes weights (114.3 +/- 29.41 g) at slaughter. Both the immunized and castrated group grew significantly faster than intact boars (p < 0.01). Average daily gains in immunized, castrated and intact animals were 0.69 +/- 0.08, 0.63 +/- 0.05 and 0.42 +/- 0.07 kg (mean +/- SD), respectively. The present data demonstrate for the first time that the newly developed anti-GnRH vaccine works very well under practical Chinese pig farming conditions, and can be an attractive alternative to surgical castration.

Age Factors↗

A new sesquiterpene lactone from Tsoongiodendron odorum Chun.

A new sesquiterpene lactone (1) was obtained from the cytotoxic fraction of 95% ethanol extract of root barks of Tsoongiodendron odorum Chun together with two known sesquiterpene lactones, costunolide (2) and parthenolide (3). The structure of 1 was elucidated as 5alpha, 6alpha, 7beta, 10beta- 11alpha, 13-dihydro-4(15)-eudesmene-12, 6-olide on the basis of chemical and spectral evidence including X-ray diffraction analysis. Costunolide showed cytotoxic activity against human leukemia (HL-60) cell line. Parthenolide showed promising cytotoxic activities in vitro against HCT-8, Bel-7402, SKOV3, KB, HELA and EJ cell lines. Also, the cytotoxic ethyl acetate fraction of ethanol extract of the root barks from which three chemical components were isolated showed promising cytotoxic activities in vitro against KB, BGC-823, Bel-7402, HCT-8, HL-60 cell lines.

Antineoplastic Agents, Phytogenic↗

Single nucleotide polymorphisms in the human reduced folate carrier: characterization of a high-frequency G/A variant at position 80 and transport properties of the His(27) and Arg(27) carriers.

The presence of sequence variants in the human reduced folate carrier (hRFC) was assessed in leukemia blasts from children with acute lymphoblastic leukemia (ALL) and in normal peripheral blood specimens. A CATG frame shift insertion at position 191 was detected in 10-60% of hRFC transcripts from 10 of 16 ALL specimens, by RFLP analysis and direct sequencing of hRFC cDNAs. In genomic DNAs prepared from 105 leukemia (n = 54) and non-leukemia (n = 51) specimens, PCR amplifications and direct sequencing of exon 3 identified a high-frequency G to A single nucleotide polymorphism at position 80 that resulted in a change of arginine-27 to histidine-27. The allelic frequencies of G/A80 were nearly identical for the non-leukemia (42.2% CGC and 57.8% CAC) and leukemia (40.7% CGC and 59.3% CAC) genomic DNAs. In cDNAs prepared from 10 of these ALL patients, identical allelic frequencies (40 and 60%, respectively) were recorded. In up to 62 genomic DNAs, hRFC-coding exons 4-7 were PCR-amplified and sequenced. A high-abundance C/T696 polymorphism was detected with nearly identical frequencies for both alleles, and a heterozygous C/A1242 sequence variant was identified in two ALL specimens. Both C/T696 and C/A1242 were phenotypically silent. In transport assays with [(3)H]methotrexate and [(3)H]5-formyl tetrahydrofolate, nearly identical uptake rates were measured for the arginine-27- and histidine-27-hRFC proteins expressed in transport-impaired K562 cells. Although there were no significant differences between the kinetic parameters for methotrexate transport for the hRFC forms, minor (approximately 2-fold) differences were measured in the K(i)s for other substrates including Tomudex, 5,10-dideazatetrahydrofolate, GW1843U89, and 10-ethyl-10-deazaaminopterin and for 5-formyl tetrahydrofolate.

Amino Acid Substitution↗

[A study on steam generator in solid amine CO2 purification system].

Objective. To solve the key problems of power matching between process of CO2 steam desorption and process of steam generation, as well as water/vapor separation. Method. Solid amine desorption process was studied by thermodynamic analysis and experiments. The distribution rule of desorption energy was found out and then the power consumption of steam generator was decided. Ceramic insert was designed to separate water and vapor making use of surface tension. Finally, the steam generator was designed on system requirements. Result. Experiments proved that the steam generator can satisfy the demand of the system as well as successfully separate water and vapor, in addition, the selected power is suitable. Conclusion. The design on steam generator was right and practicable.

Air Conditioning↗

[Principle demonstration of nutrient delivery system in a space vegetable planting prototype facility].

Objective. To develop a nutrient delivery system for space vegetable planting prototype facility to be used in future space station, and to preliminarily testify its feasibility through ground-based demonstration experiments. Method. A nutrient delivery system in a space vegetable planting prototype facility was designed and fabricated, and ground based demonstration experiments of plant cultivation were conducted. Result. Nutrient could be steadily delivered to plant cultivation matrixes through capillary action, water content of planting matrixes could be controlled automatically and maintained constant, and the planted material lettuce showed basically normal morphology and color. Conclusion. The nutrient delivery system in a space vegetable planting prototype facility could basically meet the requirements for plant nutrient delivery under space microgravity environmental condition.

Capillary Action↗

[A study of the relation between interval of the injury and the reaction of neurons, glial cells after experimental brain contusion].

OBJECTIVE: To observe the change of c-fos protein(Fos) and nerve growth factor receptor (NGFR) staining in the brain of rat after experimental brain contusion. METHODS: Immunohistochemistry of c-fos and NGFR were applied to investigate the brain contusion. RESULTS: (1) The expression of Fos protein could be observed at 0.5 h after injury and then increased with the prolonging of time. By 3 h after injury, the positive staining cells could be detected massively not only in and round the wound site but also in other areas of the whole ipsilateral cortex. The stains decreased 6-12 h later and could hardly be detected 1 d after the brain contusion. The control-experiment is negative. (2) NGFR positive staining cells could be found round the wound area 1 d postlesion. At 3 d following injury, a peak of massive positively stained cells appeared both in number and in intensity, showing significant differences compare with that of 1 d after damage (P < 0.01). 5 d later the positive express declined slowly. The express in the control-rat is negative. CONCLUSION: There is a rule that the expression of Fos and NGFR positive staining changes with time going after brain contusion, which will be of great value in estimation of brain injury time. Detection of Fos can be used for time deduction in earlier period after injury, while NGFR in later period. They are also very important for distinguishing between antemortem or postmortem injury.

Animals↗

[Clinical and experimental study on multiple sclerosis with bushen gusui tablet].

OBJECTIVE: To observe the therapeutic effect of Bushen Gusui tablet (BSGS) in treating multiple sclerosis (MS) and its effects on experimental allergic encephalomyelitis (EAE) in guinea pigs. METHODS: Forty-three MS patients were treated with BSGS and their clinical symptoms, signs of nerve function, recurrent frequency, evoked potential and changes in magnetic resonance imaging (MRI) were observed. The EAE model of guinea pigs was induced by homogenate of rabbit spinal cord and complete Freund's adjuvant (CFA), the animals were treated with BSGS and compared with prednisone acetate, which was served as control. The mortality and pathomorphology of EAE animals were observed. The contents of serum interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor (TNF) as well as myelin basic protein (MBP) were determined. RESULTS: BSGS could improve symptoms and signs of MS patients and reduce recurrent frequency. The total effective rate was 88.37%. High dose BSGS could obviously reduce incidence of EAE, inhibit inflammatory reaction of brain and spinal cord as well as demyelination, and simultaneously inhibit the activity of serum IL-2, IL-6, TNF and MBP, in comparing with model group (P < 0.01). There were insignificant difference as compared with prednisone acetate group (P > 0.05). CONCLUSION: BSGS had certain effect on both MS patients and EAE model animals, which indicated that it was worth further studying and clinical application.

Adolescent↗

[Antitumor effect of lidamycin-containing monoclonal antibody immunoconjugate with downsized-molecule].

OBJECTIVE: To develop a novel monoclonal antibody (mAb) immunoconjugate with downsized-molecule and highly potent antitumor effects. METHODS: The mAb conjugate was prepared by linking lidamycin (LDM), an antitumor antibiotic with extremely potent cytotoxicity, to mAb Fab' fragment. The molecular weight of Fab'-LDM was determined by non-reduced SDS-PAGE. The immunoreactivity of Fab'-LDM conjugate with cancer cells was detected by ELISA. The antitumor activity of the conjugate was determined by MTT assay, clonogenic assay, and animal model of transplantable colon carcinoma 26' (C26) in mice. RESULTS: The relative molecular mass of Fab'-LDM conjugate was approximately 65,000, suggesting a molar ratio of 1:1 between Fab' fragment and LDM in the conjugate. Fab'-LDM was reactive with hepatoma BEL-7402 and colon carcinoma 26 cells, but not reactive with KB cells. The cytotoxicity of Fab'-LDM conjugate to BEL-7402 cells, the antigen relevant cancer cells, was 13-fold more potent than that of free LDM, while the cytotoxicity of Fab'-LDM conjugate against C26 cells was 5.5-fold more potent than that of free LDM. However, the cytotoxicity of Fab'-LDM conjugate to KB cells, the antigen irrelevant cells, was similar to that of free LDM. Given by 3 intravenous injections, on day 1, 4 and 7, Fab'-LDM conjugate at doses of 0.05 mg/kg, 0.1 mg/kg and 0.2 mg/kg markedly suppressed the growth of colon carcinoma 26 in mice by 80%, 92% and 94%, respectively, whereas free LDM at 0.1 mg/kg suppressed the growth by 77%. The survival time of tumor-bearing mice was also increased by Fab'-LDM conjugate treatment. Fab'-LDM conjugate was more effective than equivalent unconjugated LDM (P < 0.01). CONCLUSIONS: The immunoconjugate composed of LDM and Fab' fragment that is characterized by downsized-molecule shows remarkable effectiveness against tumor growth.

Aminoglycosides↗

[Effect of mm-LDL on NF-kB activation in endothelial cell].

OBJECTIVE: To investigate the signal transduction pathway of NF-kB activated by minimally modified low density lipoprotein (mm-LDL) in endothelial cells and the effect of NF-kB on platelet derived growth factor b (PDGFb) mRNA expression. METHODS: mm-LDL was prepared through iron oxidation by dialyzing the native LDL against FeSO4 in PBS. Endothelial cells were incubated in a medium containing mm-LDL, TNF, and IL-1 respectively and electrophoretic mobility shift assay (EMSA) was displayed to check on the activation of NF-kB. Luciferase reporter gene was analysed to investigate the effect of nuclear factor inducing kinase (NIK), inhibitor of NF-kB kinase alpha (IKK alpha) and inhibitor of NF-kB kinase beta (IKK beta) on NF-kB activation. In addition, endothelial cells were transfected using PDGFb promoter-luciferase for reporter gene analysis or transfected with mut-NIK for slot blot analysis to study the effect of NF-kB on PDGFb mRNA expression. RESULTS: mm-LDL was able to activate NF-kB in endothelial cells. mut-NIK and mut-IKK beta inhibited luciferase activity induced by mm-LDL. mm-LDL could also enhance luciferase activity controlled by upstream sequence of PDGFb promoter which contains element interacting with NF-kB. Result of slot blot showed inhibition of PDGFb mRNA expression by mut-NIK in the endothelial cells stimulated by mm-LDL. CONCLUSION: mm-LDL may activate NF-kB through NIK-IKK beta pathway and promote PDGFb mRNA expression in endothelial cells.

Cells, Cultured↗

[Computer-assisted acquisition and analysis of high-resolution spectrum].

Based on the unique characteristic of spectral line center in the whole spectrum and noise threshold, a computer approach and program for the determination of spectral line position and relative intensity automatically are presented in this paper. Exploring this approach and computer program, we pre-analyzed the partially overlapped 16 line TuFIR experiment spectra of CHF3. The results of line positions and intensities for these TuFIR spectra are in excellent agreement with the results by least-square fit with heavily manual inference. The accuracy and efficiency of this method and program will ensure their wide application in complex high-resolution molecular spectrum.

Algorithms↗

Distinct domains of IFNalpha mediate immune and analgesic effects respectively.

Interferon-alpha (IFNalpha) is not only an immunoregulatory factor, but is also an analgesic molecule. The analgesic effect of IFNalpha was mediated by mu opioid receptor. After the 129th Tyr residue of human IFNalpha was mutated to Ser, the antiviral activity almost disappeared, but there still remained a strong analgesic activity that could be blocked by naloxone. These results indicate that there exist distinct domains in the IFNalpha molecule, which mediate immune and analgesic effects respectively, and suggest that there are different receptor mechanisms inducing immune and analgesic effects of IFNalpha. However, although the antiviral activity of IFNalpha decreased to 34.1% of wild type IFNalpha after the 122nd Tyr residue was changed to Ser, the analgesic activity of this mutant was lost completely. There were significant cross reactivities between INFalpha and anti-opioid sera. These studies show strong structural and functional similarities between INFalpha and opioid peptides, and inferred that the analgesic domain locates around the 122nd Tyr residue of IFNalpha molecule in tertiary structure.

Amino Acid Substitution↗

Peptide-directed suppression of a pro-inflammatory cytokine response.

Signal-dependent nuclear translocation of transcription factor nuclear factor kappaB (NF-kappaB) is required for the activation of downstream target genes encoding the mediators of immune and inflammatory responses. To inhibit this inducible signaling to the nucleus, we designed a cyclic peptide (cSN50) containing a cell-permeable motif and a cyclized form of the nuclear localization sequence for the p50-NF-kappaB1 subunit of NF-kappaB. When delivered into cultured macrophages treated with the pro-inflammatory agonist lipopolysaccharide, cSN50 was a more efficient inhibitor of NF-kappaB nuclear import than its linear analog. When delivered into mice challenged with lipopolysaccharide, cSN50 potently blocked the production of proinflammatory cytokines (tumor necrosis factor alpha and interferon gamma) and significantly reduced the lethality associated with ensuing endotoxic shock. Based on specificity studies conducted with a mutated form of cSN50, a functional nuclear localization motif is required for this protective effect. Taken together, our findings demonstrate effective targeting of a cell-permeable peptide that attenuates cytokine signaling in vivo. This new class of biological response modifiers may be applicable to the control of systemic inflammatory reactions.

Amino Acid Sequence↗

Expression of IL-2 receptor in dorsal root ganglion neurons and peripheral antinociception.

Interleukin-2 (IL-2), a T-cell growth factor, could exert an antinociceptive effect. Intraplantar injection of human recombinant IL-2 (rIL-2) at a dose of 10000/20 microl significantly enhanced pain threshold as measured by paw withdrawal latency (PWL) to noxious radiant heat in the rat. Reverse transcription modification of polymerase chain reaction (RT-PCR) analysis showed that IL-2R alpha and beta chains were constitutively expressed in rat dorsal root ganglion (DRG) neurons. Immunohistochemistry further demonstrated that IL-2R was mainly localized to small and medium-sized neurons, which are predominantly responsible for nociceptive transmission. These observations suggest that IL-2/IL-2R system may affect neural activities including nociceptive processing in DRG.

Animals↗

Leu-enkephalin induced by IL-2 administration mediates analgesic effect of IL-2.

Interleukin-2 (IL-2) was found to have an analgesic effect in both central and peripheral nervous systems. This effect is related to opioid receptors and mediated mainly by IL-2 directly binding to opioid receptors. Using radioimmunoassay, the content of Leu-enkephalin (LEK) in some nuclei were measured at intervals after the injection of IL-2 into the lateral ventricle of rats. Levels of LEK increased in both paraventricular hypothalamic nucleus (PVN) and locus ceruleus (LOC) after IL-2 administration, suggesting that the analgesic effect of IL-2 is also related to the change of LEK in PVN and LOC induced by IL-2 administration.

Analgesics↗