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Biomedical subjects

Y Zhu

Publications and source records attributed to Y Zhu.

At least 235 records · Page 13Linked to original sources
PubMed2001

[The effects of adenosine, interleukin-1 and theophylline on the expression of A2 adenosine receptor mRNAs in peripheral blood mononuclear cells from asthmatic patients].

OBJECTIVE: To explore the roles of A2a and A2b adenosine receptors(A2aAR and A2bAR) in the pathogenesis of bronchial asthma. METHODS: Eleven asthmatics and 11 healthy subjects were included in this investigation. Peripheral blood mononuclear cells(PBMCs) were obtained after density centrifugation on Ficoll-Hypaque. The expression of A2aAR and A2bAR mRNAs in PBMCs was examined by use of the reverse transcription-polymerase chain reaction (RT-PCR) and image pattern analysis semiquantitation method. RESULTS: The expression of A2aAR mRNA in PBMCs from asthmatics was not enhanced, compared with that of healthy subjects(P > 0.05). Adenosine or IL-1 or theophylline was not observed to have effect on A2aAR mRNA (P > 0.05). A2bAR gene expression in PBMCs was more markedly in patients with asthma than in normal individuals (P < 0.05). Adenosine and IL-1 significantly increased A2bAR mRNAs in asthmatics. Theophylline inhibited A2bAR gene expressions. The expression of A2bAR mRNA in PBMCs was positively correlated to serum total immunoglobulin E (TIgE) level in asthmatics (r = 0.72, P < 0.01). The expressions of A2bAR mRNA elevated by adenosine or IL-1 were correlated positively with serum TIgE(r = 0.78 or r = 0.61; P < 0.05) and negatively with the forced expiratory volume in first second to predicted value ratio (FEV1%) (r = -0.62 or r = -0.81; P < 0.05) in asthmatics. CONCLUSION: These results indicated that the expression of A2bAR mRNAs in PBMCs was more remarkable in asthmatics than in healthy subjects; that adenosine or IL-1 potentiated the mRNA expression of A2bAR in PBMCs in asthmatic patients, which was correlated with allergy state and the degree of airway obstruction; and that theophylline might antagonize adenosine by inhibiting A2bAR mRNA.

Adenosine↗
PubMed2001

[Diagnosis and treatment of one hundred and eighty-nine patients with chronic pancreatitis].

OBJECTIVE: To summarize the experience of the diagnosis and therapy of chronic pancreatitis (CP). METHODS: 189 patients with chronic pancreatitis confirmed surgically from 1983 to Aug 1999 admitted in our hospital were retrospectively studied. RESULTS: Of all 189 patients, the average age was forty-eight years old. The ratio of male to female is 2.1:1. The proportion of confirmed diagnosis to CP is 51.3% within one year and 80.4% within the first five years. The positive rate for diagnosis was 71.9% by CT and 76.9% by ERCP respectively. The positive rate of PABA was 69.7%. While 136(72%) patients received operations, the rate of complication was low. One patient died of infection after pancreatic fistula at the seventh day after surgery, and 97.8% of patients suffered less pain. CONCLUSIONS: The early diagnosis of CP is difficult. As a delicate operation program set at appropriate time is of vital importance for modifying the course of the disease and improving patients' life quality.

Adolescent↗
PubMed2001

[A multicenter study of efficacy and safety of oseltamivir in treatment of naturally acquired influenza].

OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza in China. METHODS: A randomized, double-blinded, placebo controlled trial of oseltamivir was conducted in China. Individuals of 18 to 65 years were enrolled presenting within 36 hours of influenzal symptoms and elevated temperature of 37.8 or higher. They should have at least two of the following symptoms: nasal congestion, sore throat, cough, myalgia, fatigue, headache, chill and sweating) during an influenza outbreak in the community. Individuals were randomized either to oseltamivir group (75 mg twice daily for 5 days) or placebo group. RESULTS: A total of 478 individuals were recruited, 16(3.35%) failed to follow up or refused to continue the trial, 3 (0.6%) were excluded immediately before taking medication because they did not meet the entry criteria and 8 (1.7%) individuals were excluded in the blinding review meeting because of protocol violation. Altogether 451 individuals were analyzed for efficacy as intent-to-treat population (ITT) (216 oseltamivir, 235 placebo) and 273 individuals were identified as influenza-infected through laboratory test; they were defined as intent-to-treat infected population (ITTI) (134 oseltamivir, 139 placebo). For safety analysis, 459 individuals were included. In ITTI population, the cumulative alleviation proportion in oseltamivir group was significantly higher than that of placebo group (P = 0.046 6). The median duration of illness was 91.6 hours [95% confident interval (CI) 80.2 - 101.3 hours] in oseltamivir group and 95.0 hours (95% CI 84.5 - 105.3 hours) in placebo group. The median area under the curve (AUC) of decreased total score was significantly higher in oseltamivir group than in placebo group, being 1 382.9 and 1 236.7 score-hours respectively (P = 0.019 6). The median duration of fever and myalgia were 27.9 and 35.5 hours in oseltamivir group, being significantly shorter than that of 51.5 and 36.0 hours in placebo group (P = 0.000 1 and 0.036 1). The median AUC of decreased score for fever and nasal symptom was 337.9 and 108.5 in oseltamivir group, being significantly higher than that of 311.3 and 43.3 in placebo group (P = 0.011 8 and 0.040 3). The proportion of subjects reporting fever in oseltamivir group were significantly lower than that in placebo group at 36, 60, 72, 96, 120 and 132 hours after the initiation of treatment (P = 0.049, 0.001, 0.001, 0.007, 0.007 and 0.030). The amount of paracetamol taken, incidence of secondary complications and antibiotics usage associated with secondary complications were similar in the two groups (P = 0.085 1, 0.944, 1.000). For ITT population, similar results were seen. Adverse events reported were similar in oseltamivir and placebo group. The main adverse events were gastrointestinal symptoms, headache, vertigo, and rashes. CONCLUSION: Oseltamivir was effective and well tolerated in the treatment of early naturally acquired influenza.

Acetamides↗
PubMed2000

Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitors.

A previous report from these laboratories identified the N-3-benzylimidazoquinazolinone nucleus as a more selective PDE5 inhibitor template compared to the pyrazolopyrimidine of sildenafil. This paper describes in detail the structure-activity relationships of a set of sulfonamide analogues, several of which are both more potent and more selective PDE5 inhibitors in vitro than sildenafil. The synthesis, in vitro enzyme activity and selectivity, and in vitro functional and preclinical pharmacokinetic assessment of molecules in this series are described.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Magnetic-field-induced structural transitions in a ferrofluid emulsion.

A ferrofluid emulsion, subjected to a slowly increasing magnetic field, exhibits a complicated structural behavior: a gas of Brownian particles changes to columnar solid structures due to induced dipole interaction. Two transition (intermediate) structural regimes are observed: (i) randomly distributed chains and particles and (ii) distinct thin columns and randomly distributed chains and particles. Three structural transition magnetic fields are found, one marking each structural transition, from the initial to the final structural regime. A structural diagram of the structural transition magnetic fields, H(C), versus particle volume fractions, straight phi, is constructed experimentally. Theoretical models of scaling calculations, based upon the dominant magnetic interaction in each structural regime, give the three structural transition magnetic-field relations as H(C1) proportional to straight phi(-1/2), H(C2) proportional to straight phi(-1/4), and H(C3) proportional to (straight phi(gamma)/G2)exp(piG/straight phi((gamma/2))), where gamma=0.39 and G=0.29 for our sample. The final end shape of columns and the relative position between columns show that the end-end repulsion between chains is important in the structural formation.

Journal Article↗
PubMed2000

Picometer accuracy in measuring lattice displacements across planar faults by interferometry in coherent electron diffraction

We calculate the shadow image in far field below a thin crystal when a coherent electron source is placed at micrometer distances above the specimen, and note that the presence of a planar fault results in very strong oscillatory contrast. We realize these predictions experimentally using a field-emission electron source in a microscope. With this technique, we determine displacement vectors at planar faults with an accuracy down to 1 pm in studies of the Bi2Sr2CaCu2O8 superconductor containing thin intercalated layers.

Journal Article↗
PubMed2000

Phytochrome B binds with greater apparent affinity than phytochrome A to the basic helix-loop-helix factor PIF3 in a reaction requiring the PAS domain of PIF3.

The signaling pathways by which the phytochrome (phy) family of photoreceptors transmits sensory information to light-regulated genes remain to be fully defined. Evidence for a relatively direct pathway has been provided by the binding of one member of the family, phyB, to a promoter-element-bound, basic helix-loop-helix protein, PIF3, specifically upon light-induced conversion of the photoreceptor molecule to its biologically active conformer (Pfr). Here, we show that phyA also binds selectively and reversibly to PIF3 upon photoconversion to Pfr, but that the apparent affinity of PIF3 for phyA is 10-fold lower than for phyB. This result is consistent with previous in vivo data from PIF3-deficient Arabidopsis, indicating that PIF3 has a major role in phyB signaling, but a more minor role in phyA signaling. We also show that phyB binds stoichiometrically to PIF3 at an equimolar ratio, suggesting that the resultant complex is the unit active in transcriptional regulation at target promoters. Deletion mapping suggests that a 37-aa segment present at the N terminus of phyB, but absent from phyA, contributes strongly to the high binding affinity of phyB for PIF3. Conversely, deletion mapping and point mutation analysis of PIF3 for determinants involved in recognition of phyB indicates that the PAS domain of PIF3 is a major contributor to this interaction, but that a second determinant in the C-terminal domain is also necessary.

Arabidopsis↗
PubMed2000

Facile chemoselective synthesis of dehydroalanine-containing peptides.

Useful methodology is described for the synthesis of dehydroalanine residues (II) within peptides. The unnatural amino acid (Se)-phenylselenocysteine (I) can be incorporated into growing peptide chains via standard peptide synthesis procedures. Subsequent oxidative elimination affords a dehydroalanine at the desired position. The oxidation conditions are mild and tolerate functionalities commonly found in peptides, including variously protected cysteine residues. To illustrate its utility, cyclic lanthionines have been synthesized by this method.

Alanine↗
PubMed2000

Stimulation of 5-HT(1A) receptors reduces apoptosis after transient forebrain ischemia in the rat.

It has recently been shown that 5-HT(1A) receptor stimulation reduced the infarct volume after occlusion of the middle cerebral artery in rats. Since there is increasing evidence that apoptosis is involved in neurodegenerative diseases and stroke, we investigated whether the 5-HT(1A) agonist Bay x 3702 could protect neurons against apoptotic damage in a rat model of transient forebrain cerebral ischemia. Bay x 3702 (4 microg/kg i.v.) caused a 10% reduction of neuronal damage in the hippocampal CA1 subfield. Higher doses of Bay x 3702 (40 and 12 microg/kg i.v.) did not cause any neuroprotective effect, most likely because of the strong reduction of mean arterial blood pressure during the period of Bay x 3702 infusion. Bay x 3702 (4 microg/kg i.v.) diminished DNA laddering in the hippocampus and striatum 4 days after 10 min forebrain ischemia. These results were confirmed by TUNEL-staining. The anti-apoptotic effect was abolished by additional treatment with the 5-HT(1A) receptor antagonist WAY 100635 (1 mg/kg). Taken together, the results suggest that Bay x 3702 can rescue hippocampal as well as striatal neurons from apoptotic cell death in vivo via stimulation of 5-HT(1A) receptors.

Animals↗
PubMed2000

MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins.

p300 acetylates and activates the tumor suppressor p53 after DNA damage. Here, we show that MDM2, a negative-feedback regulator of p53, inhibited p300-mediated p53 acetylation by complexing with these two proteins. First, we purified a p300-MDM2-p53 protein complex from HeLa nuclear extracts, which was inactive in p53 acetylation, but active in histone acetylation. Also, wild-type, but not N-terminally deleted, MDM2 inhibited p53 acetylation by p300 in vitro and in vivo. This inhibition was specific for p53, because MDM2 did not affect acetylation of histones or the C terminus of p73 by p300. Consequently, wild-type, but not the mutant, MDM2 repressed the p300-stimulated sequence-specific DNA-binding and transcriptional activities of p53. These results demonstrate that an additional mechanism of p53 inactivation by MDM2 is to inhibit p53 acetylation by p300.

Acetylation↗
PubMed2000

(-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor.

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity.

Acetylcholine↗
PubMed2000

Comparison of two immobilization techniques using portal film and digitally reconstructed radiographs for pediatric patients with brain tumors.

PURPOSE: To compare the accuracy of two immobilization techniques for pediatric brain tumor patients. METHODS AND MATERIALS: We analyzed data from 128 treatments involving 22 patients. Patients were immobilized with either a relocatable head frame (12 patients) or a vacuum bag (10 patients). Orthogonal portal films were used as verification images. Errors in patient positioning were measured by comparing verification images with digitally reconstructed radiographs generated by a three-dimensional treatment-planning system. RESULTS: With the head frame, systematic errors ranged from 1.4 mm to 2.1 mm; random errors, from 1.7 mm to 2.1 mm. With the vacuum bag, systematic errors ranged from 2.1 mm to 2.5 mm; random errors, from 2.0 mm to 2.6 mm. For the head frame, the mean length of the radial displacement was 4.4 mm; 90% of the total three-dimensional deviation was less than 6.8 mm. The corresponding values for the vacuum bag were 5.0 and 6.6 mm, respectively. CONCLUSIONS: The head frame and vacuum bag techniques limit the random and systematic errors in each of the three directions to within +/- 5 mm. We have used these results to determine the margin used to create the planning target volume for conformal radiation therapy.

Brain Neoplasms↗
PubMed2000

Conformational transition of DNA in electroreduction studied by in situ UV and CD thin layer spectroelectrochemistry.

Electrochemically induced three conformational transitions of calf thymus DNA from B10.4 to Z10.2-DNA and from B10.2 to B10.4 and to C-DNA in 10 mM phosphate buffer solution (pH 7.21) at glassy carbon electrode are found and studied by in situ circular dichroism (CD) thin layer spectroelectrochemistry with singular value decomposition least square (SVDLS) analysis. It indicates that the so-called B10.2 form and the C-form of DNA may be composed of B10.4 and left-A DNA and of B10.4 and right-A DNA, respectively. The irreversible electrochemical reduction of adenine and cytosine groups in the DNA molecule is studied by UV-Vis spectroelectrochemistry. Some electrochemical parameters alpha n = 0.17, E0' = -0.70 V (vs. Ag/AgCl), and the standard heterogeneous electron transfer rate constant, k0 = 1.8 x 10(-5) cm s(-1), are obtained by double logarithmic analysis and non-linear regression.

Animals↗
PubMed2000

A facile synthesis of the tetrasaccharide repeating unit of mannoglucan from Microellobosporia grisea.

A facile synthesis of the tetrasaccharide repeating unit of mannoglucan from Microellobosporia grisea was achieved through coupling of 4,6-O-benzylidene-1,2-O-ethylidene-alpha-D-glucopyranose with per-O-benzoylated mannopyranosyl trichloroacetimidate, followed by debenzylidenation, selective 6-O-mannopyranosylation, then hydrolysis of the 1,2-O-ethylidene group, 1,2-O-acetylation and conversion to the 1-trichloroacetimidate, and subsequent condensation of the activated trisaccharide with allyl 2,3,6-tri-O-benzoyl-alpha-D-glucopyranoside.

Actinomycetales↗
PubMed2000

Improgan, a cimetidine analog, induces morphine-like antinociception in opioid receptor-knockout mice.

Improgan is an analog of the H(2) antagonist cimetidine that does not act on known histamine receptors, but induces highly effective analgesia in rodents following intracerebroventricular (icv) administration. Since the mechanism of action of this compound remains unknown, improgan analgesia was characterized presently with the tail immersion nociceptive test in mutant mice lacking either the mu (exon 1 of MOR-1), delta (exon 2 of DOR-1) or kappa (exon 3 of KOR-1) opioid receptor. Improgan (30 microg, icv) induced reversible, maximal analgesia in both sexes of all three genotypes (+/+, +/- and -/-) of MOR-1 mutant mice 10 and 20 min after administration, whereas morphine analgesia was reduced (+/-) or abolished (-/-) in these subjects. In DOR-1 mutant mice, improgan was equally effective in all three genotypes, despite the reduction (+/-) or complete loss (-/-) of delta opioid receptor (3H-[D-Pen(2), D-Pen(5)]enkephalin, DPDPE) binding. Similarly, improgan analgesia was equivalent in all three genotypes of KOR-1 mutant mice, whereas kappa-mediated analgesia (U50,488) and kappa opioid (3H-U69,593) binding were abolished in the homozygous (-/-) mice. These studies demonstrate that improgan analgesia does not require intact MOR-1, DOR-1, or KOR-1 genes, and support the hypothesis that improgan-like analgesics act in the CNS by non-opioid mechanisms.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

Safety and immunogenicity of adjuvanted and unadjuvanted subunit influenza vaccines administered intranasally to healthy adults.

Antigen-specific mucosal immunity is thought to be important for protection against influenza virus infection. Currently licensed parenteral influenza vaccines stimulate the production of serum antibodies, but are poor inducers of mucosal immunity. The adjuvant MF59 has been shown to enhance the humoral immune response to parenteral influenza vaccine in humans and the mucosal immune response to intranasally-administered influenza vaccine in mice. We conducted an open-label safety study followed by an observer-blind, randomized trial comparing the immune response to intranasally-administered subunit influenza vaccine adjuvanted with MF59, unadjuvanted subunit influenza vaccine, and placebo. Adverse reactions did not occur significantly more frequently in vaccinees than placebo recipients. Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza vaccine, 19 (61%), 8 (26%), and 11 (35%) developed a mucosal IgA response to influenza A/H1N1, A/H3N2, and B, respectively. The percentage of subjects with a serum antibody response was slightly lower. The immune responses to adjuvanted vaccine were not significantly different from those to unadjuvanted vaccine. Both vaccines gave more frequent responses than seen in placebo recipients, indicating the potential of intranasal inactivated vaccines to stimulate local IgA responses.

Adjuvants, Immunologic↗
PubMed2000

Templated Synthesis of CdS/PAN Composite Nanowires under Ambient Conditions.

CdS/PAN (polyacrylonitrile) composite nanowires were prepared by templated synthesis under ambient conditions, using a 4 : 1 (v/v) distilled water-isopropyl alcohol solvent mixture and Na(2)S(2)O(3) as sulfur source. Transmission electron microscopy images showed typical CdS/PAN nanowires with diameters less than 6 nm and lengths from 200 nm to 1 µm. CdS/PAN nanowires were also characterized by FT-infrared spectra (FTIR), X-ray powder diffraction (XRD) patterns, and UV-vis spectra. It is found that the feed mole ratio of CdCl(2) to AN exerts a significant influence on the formation and morphology of CdS/PAN nanowires. In addition, possible mechanism of the reactive process was presented. Copyright 2000 Academic Press.

Journal Article↗