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Biomedical subjects

J Du

Publications and source records attributed to J Du.

At least 73 records · Page 4Linked to original sources
PubMed2001

Regulation of apolipoprotein secretion by long-chain polyunsaturated fatty acids in newborn swine enterocytes.

Long-chain polyunsaturated fatty acids (LC-PUFA) are important in the development of the immature nervous system, and adding these fatty acids to infant formula has been proposed. To determine the effect of n-3 LC-PUFA on apolipoprotein secretion and lipid synthesis in newborn swine enterocytes, differentiated IPEC-1 cells were incubated for 24 h with docosahexaenoic acid (DHA; 22:6) or eicosapentaenoic acid (EPA; 20:5) complexed with albumin at a fatty acid concentration of 0.8 mM or albumin alone (control) added to the apical medium. Oleic acid (OA; 18:1) was used a control for lipid-labeling studies. Both DHA and EPA reduced apolipoprotein (apo) B secretion by one-half, whereas EPA increased apo A-I secretion. The increased apo A-I secretion occurred primarily in the high-density lipoprotein fraction. These changes in apoprotein secretion were not accompanied by significant changes in synthesis. Modest decreases in apo B mRNA levels were observed for DHA and EPA, whereas there were no changes in apo A-I mRNA abundance. EPA reduced cellular triacylglycerol labeling by one-half, and DHA and EPA decreased cellular phospholipid labeling compared with OA. Labeled triacylglycerol secretion was decreased 75% by EPA, and DHA doubled labeled phospholipid secretion. If present in vivo, these effects should be considered before supplementing infant formula with these fatty acids.

Animals↗
PubMed2001

Developmental expression of neurokinin A and functional neurokinin-2 receptors in lung.

Peribronchial smooth muscle constriction causes airway stretch, an important mechanical force in developing lung. Little is known about factors influencing these spontaneously active muscle elements. We measured contractile activity of neurokinin (NK) receptors on fetal intrapulmonary smooth muscle by tracheal perfusion assay (n = 11). Injecting either capsaicin or the NK(2) receptor agonist [NLE(10)]NKA resulted in significant (P < 0.05) bronchoconstriction. A specific NK(2) receptor antagonist inhibited constriction caused by endogenous tachykinins released by capsaicin. We then examined NK(2) receptor (n = 44) and NKA (n = 23) ontogeny in human lung. NKA immunostaining was identified in peribronchial nerves in samples with gestational age >12 wk. NK(2) receptor protein was identified in peribronchial and perivascular smooth muscle. These results indicate that endogenous tachykinins released by the developing lung act via NK(2) receptors to cause smooth muscle constriction. We speculate that tachykinins could modulate lung development.

Adult↗
PubMed2001

Biodistribution, blood half-life, and receptor binding of a somatostatin-dextran conjugate.

Derivatives of somatostatin (sms) are attracting increasing interest as part of the treatment of several cancer diseases expressing sms receptors (srs). Radiolabeled sms analogs can additionally be used for systemic radiotherapy and for diagnostic investigations. Glycosylated sms-14 (sms-dextran70) was characterized regarding in vitro srs binding, biodistribution, and blood half-life in mice. Rat brain cortex membranes (expressing srs 2) were used for the srs binding study. Tyr3-Octreotide was used as positive control. The binding data were analyzed by competition curve analysis. In the biodistribution study, the Bolton-Hunter reagent was used for the radioiodination of sms-dextran70. Organs and blood were collected at different time-points and the percentage of the injected dose per gram of tissue (%ID/g) was calculated. The conjugate was administered subcutaneously (sc). The sms-dextran70 showed high srs binding affinity (i.e., in the same nanomolar range as the reference ligand Tyr3-octreotide (IC50 approximately 2.5 nM). The blood half-life was approx 27 h after reaching maximum blood concentration 24 h postinjection. Because of the molecular weight of the conjugate (i.e., approx 75,000) being above the kidney threshold for dextran (i.e., 50,000), the digestion and excretion is assumed to be mainly through the hepatobiliary system. Increased uptake was seen in the adrenals, which are receptor-positive organs. Some accumulation was seen in the stomach, indicating certain deiodination of the conjugate label. The sms-dextran70 showed promising properties and its clinical relevance is currently being evaluated in clinical phase I-II studies.

Animals↗
PubMed2001

[Effects of yinchenhao decoction on normal animals and animal models of diabetes mellitus].

OBJECT: To study the effects of yinchenhao Decoction on the blood glucose level in a variety of animal models and its mechanism. METHODS: Normal mice, rats model of ailoxan (ALX)-induced diabetes mellitus (DM), mice model of ALX-DM and rats model of dexamethasone (DX)-induced insulin resistance (IR) were used. RESULTS: yinchenhao Decoction was able to inhibit the hyperglycemia by ALX-induced mice(P < 0.01), significantly reduce level of FBG in normal mice, ALX-DM mice and rats (P < 0.05-0.01), improve IGT and lower 2hBG (P < 0.01) after OGTT in DX-induced insulin-resistant rats. CONCLUSIONS: The results suggest that yinchenhao Decoction possesses similar hypoglycemic action to meftormin and gliclazied.

Animals↗
PubMed2001

Alleviation of hypoxic pulmonary vascular structural remodeling by L-arginine.

OBJECTIVE: To explore the effect of L-arginine on hypoxic pulmonary vascular structural remodeling and its possible mechanisms. METHODS: Eighteen Wistar rats were randomly divided into three groups: the hypoxia group, the hypoxia with L-arginine group and the control group. Pulmonary artery mean pressure was evaluated with right cardiac catheterization. Pulmonary vascular structural changes were also observed. Plasma concentration of nitric oxide (NO) was measured via spectrophotometry, and endothelin-1 (ET-1) mRNA expression in pulmonary artery endothelial cells was detected using in situ hybridization. RESULTS: The pulmonary artery mean pressure was significantly high in hypoxic rats than in normal controls (20.33 +/- 2.18 mm Hg vs 15.38 +/- 1.05 mm Hg, P < 0.05). Microstructural and ultrastructural analysis revealed the development of hypoxic pulmonary vascular structural remodeling in the hypoxic rats. Meanwhile, the plasma NO concentration was markedly lower in the hypoxic rats than in controls (P < 0.05). The expression signals of ET-1 mRNA by pulmonary artery endothelial cells of hypoxic rats strengthened obviously. L-arginine ameliorated pulmonary hypertension (16.73 +/- 1.35 mm Hg vs 20.33 +/- 2.18 mm Hg, P < 0.05) as well as pulmonary vascular structural remodeling in the hypoxic rats in association with an increase in plasma NO concentration (P < 0.05) and inhibited ET-1 mRNA expression by the endothelial cells of pulmonary arteries. CONCLUSION: L-arginine might play an important role in the regulation of hypoxic pulmonary vascular structural remodeling and hypoxic pulmonary hypertension. The mechanism is probably related to promoting NO production and, as a result, inhibiting ET-1 mRNA expression by pulmonary artery endothelial cells in hypoxic rats.

Animals↗
PubMed2001

[A study of heart rate variability in asthma].

OBJECTIVE: To study the changes of autonomic nervous function in the young adult with asthma through the heart rate variability(HRV). METHODS: Two groups of young adults, 23 healthy volunteers and 69 asthmatic young adults were divided into three groups according to the severity of asthma. Twenty-four hours Holter monitored and heart rate variability analysed. RESULTS: The HF and pNN50 that showed the vagal tone in asthma subjects increased as compared with the normal group, while the LF and SDANN that mainly showed the sympathetic tone decreased(P < 0.01). These values were remarkable in the severe asthma group (P < 0.01). CONCLUSION: Even in mormal condition when patients are free of asthmatic attack, autonomic nervous function of asthmatics differ from that of normal young adults.

Adult↗
PubMed2001

[The effect of salvia miltiorrhiza and shengmai on inflammatory mediator and renal function of post-operative patients with obstructive jaundice].

OBJECTIVE: To investigate the effect of salvia miltiorrhiza and shengmai (SS) on inflammatory mediator and renal function in patients with obstructive jaundice (OJ). METHODS: This study included three groups: the OJ patients receiving SS for 6 days after operation (the SS group, n = 15); the OJ patients not receiving SS (the OJ group, n = 15); the patients with other hepato-biliary disorders (the Non-OJ group, n = 15). The levels of ET, LPs, TNF-alpha, IL-6, IL-8 and urine RBP, TFR, ALB were measured one day before operation and 1, 4, 7 days after operation. RESULTS: The SS group's LPs, TNF-alpha, IL-6, IL-8, ET, RBP, TFR and ALB levels were obviously lower on Day 7 after operation as compared with those on Day 1 after operation (P < 0.05). The urine RBP and ALB levels were significantly lower in the SS group than in the OJ group (P < 0.05). CONCLUSION: The post-operative use of salvia miltiorrhiza and shengmai for patients with obstructive jaundice may effectively decrease the postoperative levels of plasma LPs, ET, TNF-alpha, IL-6 and IL-8. At the same time, salvia miltiorrhiza and shengmai may protect renal function by inhibiting inflammatory mediator and improving blood dynamics.

Adult↗
PubMed2001

[Purification and properties of endoglucanases from Aspergillus aculeatus SM-L22].

The five endoglucanases(CMCase) components from Aspergillus aculeatus SM-L22 were separated and purified by exclusion chromatography and ion-exchange chromatography. Five components(EG II-1, EG II-2, EG III-1, EG III-2 and EG IV) had molecular weights of 38.7, 34.4, 31.4, 36.9 and 23.7 kD by SDS-PAGE, respectively, and IEF showed their pI were pH < 3.5, < 3.5, 4.9, 4.4 and 5.0, respectively. All of them have maximum reactive activities at pH 3.5-4.0; and the optimum temperatures were 55 degrees C, 60 degrees C, 60 degrees C-70 degrees C, 60 degrees C-70 degrees C and 60 degrees C, respectively. EG II-1 and EG II-2 can only act such morphological substrates as CMC or phosphated cellulose, but EG III-1, EG III-2 and EG IV can active xylan also. The activities of all components were stimulated by Fe2+ except EG IV, EG III-2 was activited mostly by Fe2+. The kinetics' showed that there were no relativies between the affectivity of cellulases and its Km.

Aspergillus↗
PubMed2001

[Detection of DNA of Toxoplasma gondii in rat by using polymerase chain reaction].

OBJECTIVE: To study the significance of DNA of Toxoplasma gondii in peripheral blood. METHODS: DNA of T. gondii in peripheral blood of 50 infected rats was detected by polymerase chain reaction. A pair of primers was designed, according to the sequence P30 gene specific to T. gondii, to amplify DNA from T. gondii by PCR. RESULTS: The primers amplified DNA specifically from T. gondii and could not amplify DNA from humans, uninfected rat and mouse and from Trichomonas vaginalis and Entamoeba histolytica. DNA of two Toxoplasma parasites was detected by 35 cycles of amplification, indicating a fair sensitivity of the PCR system. CONCLUSION: PCR may have a value for early diagnosis of T. gondii infection in rat.

Animals↗
PubMed2001

[K. pneumoniea endotoxin induced mice beta-defensin-4 mRNA expression and its signaling transduction].

OBJECTIVE: To investigate the in vivo effects of Klebsiella pneumoniae endotoxin(LPS) on beta-defensin expression and the relevant signaling transduction pathway. METHODS: A LPS tolerant mouse C3H/HeJ with a point mutation at Toll-like receptor-4 (TLR4) gene and its wild type strain C3H/HeN were used in this study. C3H/HeJ and C3H/HeN were injected with 4 mg/kg of LPS intraperitoneally. The tracheas, lungs and kidneys of the C3H/HeJ and C3H/HeN were collected respectively at different LPS-treated time points, and the total RNA of each sample was extracted. The expression of mice beta-defensin-3 and/or beta-defensin-4 mRNA in these tissues was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The sequence of cDNA amplified from the lung of C3H/HeN treated by LPS for 24 h was analyzed. By using western blot, p-I kappa B alpha (phosphorylated I kappa B alpha) and I kappa B alpha of in the lungs of C3H/HeJ and C3H/HeN were detected at different time points after treatment with LPS or without LPS. RESULTS: 1. beta-defensin-4 mRNA was detected in the lungs of C3H/HeN after 24 h treatment with LPS. In contrast, no signal was determined in C3H/HeJ mice with LPS treatment and the C3H/HeN mice without LPS treatment. 2. Compared with the control, increas of the p-I kappa B alpha was observed in the lungs of C3H/HeN at 4 h after treatment with LPS, while both the p-I kappa B alpha and I kappa B alpha contents showed a tendency to go down at 8 h after treatment and dramatically decreased at 24 h. But there were no changes in the of p-I kappa B alpha and I kappa B alpha content the lungs of C3H/HeJ under the same conditions. CONCLUSION: K. pneumoniea endotoxin could induce the expression of beta-defensin-4 mRNA in the lung of C3H/HeN, and TLR4-mediated NF-kappa B activation signaling pathway may be responsible for this event.

Amino Acid Sequence↗
PubMed2001

Bioactivity of bioresorbable osteosynthetic devices made of hydroxyapatite/poly-DL-lactide composites: an experimental study.

AIM: To investigate the bioactivity of the self-designed biodegradable osteosynthetic devices made of resorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) composites. METHOD: Forty-three rabbits with a transverse transcondylar osteotomy of the distal femur were fixed intramedullary by a HA/PDLLA rod, the duration of follow-up were 3, 6, 12, 24 and 36 weeks. Histological, scanning electron microscopic (SEM), energy dispersive X-ray (EDX) and biomechanical analyses were done. RESULTS: Active new bone formation and direct bone-bonding were seen at the bone-implant interface. Generous apatite crystals deposited and grew on the surface of the composites at 3 approximately 6 weeks postoperation. The interfacial shear strength increased significantly. CONCLUSION: Through the incorporating of resorbable HA microparticles, specific bone-bonding and active osteogenic capacity is introduced. This kind of bioactivity, together with other properties such as sufficient mechanical strength, enhanced biocompatibility and radiopacity, which are intrinsically unobtainable in totally resorbable polymer/polymer systems, make the HA/PDLLA composites become a desirable material for the internal fixation of cancellous bone.

Absorbable Implants↗
PubMed2000

Determination of the enaminone DM5, an anti-epileptic agent, in mouse plasma and brain tissue by high-performance liquid chromatography with ultraviolet detection.

Enaminone derivatives of the 4-carbomethoxy-5-methylcyclohexane-1,3-dione series represent a new and potentially active series of compounds for the treatment of Epilepsy. Enaminone esters have been previously evaluated as compounds with potent oral anticonvulsant activity similar to class 1 anticonvulsants phenytoin, carbamazepine, and lamotrigine. DM5, a member of this class with -Cl in the para-substituted position, has been assessed to have the most potent pharmacological activity (ED50) in both the mouse and rat. A selective and specific high-performance liquid chromatography method was developed to quantitate DM5 in plasma and brain tissue in mice. Reverse phase chromatography with ultraviolet (lambda = 307 nm) detection was utilized to quantitate eluate. A C18 analytical column was used and the mobile phase consisted of acetonitrile and 0.05 M NaH2PO4 buffer (60:40; v/v). Liquid-liquid extraction with ether was used to extract the DM5 from plasma or brain homogenates. DM5 and carbamazepine (internal standard) eluted at approximately 6.0 and 9.0 min without any interfering peaks. The calibration curves were found to be linear (r > or = 0.9999) in the range of 0.1-5.0 microg/ml or microg/g. Intra-run precision's were in all in the range of 90%. The absolute recovery of the analyte in brain and plasma samples was < or = 90%. The valid method accurately quantified DM5 in plasma and brain tissue samples collected from a pharmacokinetic study consisting of an intravenous bolus in the tail vein of wild type and genetically altered mice.

Aniline Compounds↗
PubMed2000

Engagement of the CrkL adapter in interleukin-5 signaling in eosinophils.

Interleukin-5 (IL-5) drives the terminal differentiation of myeloid progenitors to the eosinophil lineage; blocks eosinophil apoptosis; and primes eosinophils for enhanced functional activities in allergic, parasitic, and other eosinophil-associated diseases. Here we describe a novel signaling pathway activated by the IL-5 receptor in eosinophils involving the CrkL adapter protein. We determined whether IL-5 induces activation of CrkL and STAT5 in eosinophils using both the human eosinophil-differentiated AML14.3D10 cell line and purified peripheral blood eosinophils from normal donors. Stimulation of AML14.3D10 cells or blood eosinophils with IL-5 induced rapid tyrosine phosphorylation of the CrkL adapter and STAT5 and the association of CrkL and STAT5 in vivo as evidenced by the detection of STAT5 in anti-CrkL immunoprecipitates. The resulting CrkL.STAT5 complexes translocated to the nucleus and bound STAT5 consensus DNA-binding sites present in the promoters of IL-5-regulated genes, as shown in gel mobility and antibody supershift assays. IL-5 also induced marked activity of an 8X-GAS (interferon gamma-activated site)-luciferase reporter construct in transient transfections of AML14.3D10 eosinophils, demonstrating that these complexes play a functional role in IL-5 signaling. CrkL was also found to interact, via its N-terminal SH3 domain, with C3G, a guanine exchange factor for the small G-protein Rap1, which was also rapidly activated in an IL-5-dependent manner in these cells, establishing that CrkL mediates downstream activation of at least two signaling cascades in IL-5-stimulated eosinophils. Thus, the CrkL adapter plays an important role in IL-5 signaling in the eosinophil, acting as a nuclear adapter for STAT5 and as an upstream regulator of the C3G-Rap1 signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Synthesis and antiviral activity of oxaselenolane nucleosides.

As dioxolane and oxathiolane nucleosides have exhibited promising antiviral and anticancer activities, it was of interest to synthesize isoelectronically substituted oxaselenolane nucleosides, in which the 3'-CH(2) is replaced by a selenium atom. To study structure-activity relationships, various pyrimidine and purine oxaselenolane nucleosides were synthesized from the key intermediate, (+/-)-2-benzoyloxymethyl-1,2-oxaselenolane 5-acetate (6). Among the synthesized racemic nucleosides, cytosine and 5-fluorocytosine analogues exhibited potent anti-HIV and anti-HBV activities. It was of interest to obtain the enantiomerically pure isomers to determine if they have differential antiviral activities. However, due to the difficult and time-consuming nature of enantiomeric synthesis, a chiral HPLC separation was performed to obtain optical isomers from the corresponding racemic mixtures. Each pair of enantiomers of Se-ddC and Se-FddC was separated by an amylose chiral column using a mobile phase of 100% 2-propanol. The results indicate that most of the anti-HIV activity of both cytosine and fluorocytosine nucleosides resides with the (-)-isomers.

Anti-HIV Agents↗
PubMed2000

Arsenite induces apoptosis of murine T lymphocytes through membrane raft-linked signaling for activation of c-Jun amino-terminal kinase.

Because of its dual roles in acute toxicity and in therapeutic application in cancer treatment, arsenic has recently attracted a renewed attention. In this study, we report NaAsO(2)-induced signal cascades from the cell surface to the nucleus of murine thymic T lymphocytes that involve membrane rafts as an initial signal transducer. NaAsO(2) induced apoptosis through fragmentation of DNA, activation of caspase, and reciprocal regulation of Bcl-2/Bax with the concomitant reduction of membrane potential. We demonstrated that NaAsO(2)-induced caspase activation is dependent on curcumin-sensitive c-Jun amino-terminal kinase and barely dependent on SB203580-sensitive p38 kinase or PD98059-sensitive extracellular signal-regulated kinase. Additionally, staurosporine, which severely inhibited the activation of mitogen-activated protein (MAP) family kinases and c-Jun, partially blocked the NaAsO(2)-mediated signal for poly(ADP-ribose) polymerase (PARP) degradation. Potentially as the initial cell surface event for intracellular signaling, NaAsO(2) induced aggregation of GPI-anchored protein Thy-1 and superoxide production. This Thy-1 aggregation and subsequent activation of MAP family kinase and c-Jun and the degradation of PARP induced by NaAsO(2) were all inhibited by DTT, suggesting the requirement of interaction between arsenic and protein sulfhydryl groups for those effects. beta cyclodextrin, which sequestrates cholesterol from the membrane rafts, inhibited NaAsO(2)-induced activation of protein tyrosine kinases and MAP family kinases, degradation of PARP, and production of superoxide. In addition, beta cyclodextrin dispersed NaAsO(2)-induced Thy-1 clustering. These results suggest that a membrane raft integrity-dependent cell surface event is a prerequisite for NaAsO(2)-induced protein tyrosine kinase/c-Jun amino-terminal kinase activation, superoxide production, and downstream caspase activation.

Animals↗
PubMed2000

MGSA/GRO-mediated melanocyte transformation involves induction of Ras expression.

The MGSA/GRO protein is endogenously expressed in almost 70% of the melanoma cell lines and tumors, but not in normal melanocytes. We have previously demonstrated that over-expression of human MGSA/GROalpha, beta or gamma in immortalized murine melanocytes (melan-a cells) enables these cells to form tumors in SCID and nude mice. To examine the possibility that the MGSA/GRO effect on melanocyte transformation requires expression of other genes, differential display was performed. One of the mRNA's identified in the screen as overexpressed in MGSA/GRO transformed melan-a clones was the newly described M-Ras or R-Ras3 gene, a member of the Ras gene superfamily. Over-expression of MGSA/GRO upregulates M-Ras expression at both the mRNA and protein levels, and this induction requires an intact glutamine-leucine-arginine (ELR)-motif in the MGSA/GRO protein. Western blot examination of Ras expression revealed that K- and N-Ras proteins are also elevated in MGSA/GRO-expressing melan-a clones, leading to an overall increase in the amount of activated Ras. MGSA/GRO-expressing melan-a clones exhibited enhanced AP-1 activity. The effects of MGSA/GRO on AP-1 activation could be mimicked by over-expression of wild-type M-Ras or a constitutively activated M-Ras mutant in control melan-a cells as monitored by an AP-1-luciferase reporter, while expression of a dominant negative M-Ras blocked AP-1-luciferase activity in MGSA/GRO-transformed melan-a clones. In the in vitro transformation assay, over-expression of M-Ras mimicked the effects of MGSA/GRO by inducing cellular transformation in control melan-a cells, while over-expression of dominant negative M-Ras in MGSA/GROalpha-expressing melan-a-6 cells blocked transformation. These data suggest that MGSA/GRO-mediated transformation requires Ras activation in melanocytes.

Animals↗
PubMed2000

Activity- and Ca(2+)-dependent modulation of surface expression of brain-derived neurotrophic factor receptors in hippocampal neurons.

Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal survival and synaptic plasticity in the central nervous system (CNS) in an activity-dependent manner, but the underlying mechanisms remain unclear. Here we report that the number of BDNF receptor TrkB on the surface of hippocampal neurons can be enhanced by high frequency neuronal activity and synaptic transmission, and this effect is mediated by Ca(2+) influx. Using membrane protein biotinylation as well as receptor binding assays, we show that field electric stimulation increased the number of TrkB on the surface of cultured hippocampal neurons. Immunofluorescence staining suggests that the electric stimulation facilitated the movement of TrkB from intracellular pool to the cell surface, particularly on neuronal processes. The number of surface TrkB was regulated only by high frequency tetanic stimulation, but not by low frequency stimulation. The activity dependent modulation appears to require Ca(2+) influx, since treatment of the neurons with blockers of voltage-gated Ca(2+) channels or NMDA receptors, or removal of extracellular Ca(2+), severely attenuated the effect of electric stimulation. Moreover, inhibition of Ca(2+)/calmodulin-dependent kinase II (CaMKII) significantly reduced the effectiveness of the tetanic stimulation. These findings may help us to understand the role of neuronal activity in neurotrophin function and the mechanism for receptor tyrosine kinase signaling.

6-Cyano-7-nitroquinoxaline-2,3-dione↗