Biomedical subjects

Z Xu

Publications and source records attributed to Z Xu.

At least 109 records · Page 6Linked to original sources

PubMed2001

Regulation by the medial amygdala of copulation and medial preoptic dopamine release.

The medial preoptic area (MPOA) is a critical integrative site for male copulatory behavior in most vertebrate species. Extracellular dopamine (DA) is increased in the MPOA of male rats immediately before and during copulation. DA agonists microinjected into the MPOA of male rats facilitate and DA antagonists inhibit sexual behavior. A major source of input to the MPOA is the medial amygdala (MeA), which processes and relays olfactory information to the MPOA. We now report that microinjections of a DA agonist into the MPOA of animals with excitotoxic lesions of the amygdala restored copulatory ability that was lost after the lesions. Moreover, radio-frequency lesions of the MeA impaired copulation and blocked the increases in extracellular DA seen in animals with sham lesions during exposure to a receptive female and during copulation. Thus, both copulatory ability and the MPOA DA response, during exposure to a receptive female and during copulation, are facilitated by input from the MeA to the MPOA.

Amygdala↗

PubMed2001

cAMP inhibits inducible nitric oxide synthase expression and NF-kappaB-binding activity in cultured rat hepatocytes.

BACKGROUND: The inducible nitric oxide synthase (iNOS) is strongly expressed following inflammatory stimuli. Adenosine 3',5'-cyclic monophosphate (cAMP) increases iNOS expression and activity in a number of cell types but decreases cytokine-stimulated iNOS expression in hepatocytes. The mechanisms for this effect are unknown. METHODS: Rat hepatocytes were stimulated with cytokines to induce iNOS and cultured with cAMP agonists dibutyryl-cAMP (dbcAMP), 8-bromo-cAMP, and forskolin (FSK). Nitric oxide synthesis was assessed by supernatant nitrite levels and iNOS expression was measured by Northern and Western blot analyses. Nuclear factor kappaB binding was assessed by electromobility shift assay. RESULTS: Cyclic AMP dose dependently decreased NO synthesis in response to a combination of proinflammatory cytokines or interleukin-1beta (IL-1beta) alone. The adenylate cyclase inhibitor SQ 22,536 increased cytokine- or IL-1beta-stimulated NO synthesis. dbcAMP decreased iNOS mRNA expression and iNOS protein expression. Both dbcAMP and glucagon decreased iNOS promoter activity in rat hepatocytes transfected with the murine iNOS promoter and decreased DNA binding of the transcription factor NF-kappaB. CONCLUSION: These data suggest that cAMP is important in hepatocyte iNOS expression and agents that alter cAMP levels may profoundly alter the response of hepatocytes to inflammatory stimuli through effects onthe iNOS promoter region and NF-kappaB.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2001

Bioactivities of culture supernatants from retroviral packaging cells carrying the mouse Fas ligand gene.

The bioactivities of culture supernatants from retroviral packaging cells carrying the mouse Fas ligand (mFasL) gene was investigated. FasLcDNA was cloned into PLXIN with an internal ribosome entry site to link two cistrons through gene recombination technology, PLXIN and the recombinant vector PLFIN were separately transfected into PA317 retrovirus packing cell line by lipofectamine 2000, and the resistant clones were selected with G418 selective medium. The integration of genome DNA was assayed by genomic DNA PCR. NIH3T3 cells were transduced by the culture supernatants from PA317 carrying the mFasLcDNA gene, and were selected with G418 selective medium, so as to select the PLFIN-PA317 clone capable of producing higher titer of supernatants. The levels of mFasL protein on NIH3T3 cells membrane were assayed by flow cytometry (FCM). The biological activity of mFasL on NIH3T3 cells membrane was investigated by the inducing apoptosis of Fas+ Yac-1 cells co-cultured with NIH3T3 cells expressing Fas ligand. To explore the direct mFasL cytotoxicity of culture supernatants from retroviral packaging cells carrying the mFasL gene, the culture supernatants from PLFIN-PA317 and PLXIN-PA317 were separately co-cultured with Yac-1 cells in parallel. The recombinant PLFIN was successfully constructed. The highest titer of supernatants from twelve resistant clones was 8.5 x 10(5) colony-forming-unit (CFU)/ml. The NIH3T3 cells transfected by above supernatants had a higher level of mFasL (53.81 +/- 6.9%), and significantly induced the apoptosis of Fas+ Yac-1 cells (56.78 +/- 4.5%), as both were cocultured for 5 h at 1:1 ratio, whereas it is 7.08 +/- 3.4% in control group (P < 0.01). Supernatant from PLFIN-PA317 could also directly induce the apoptosis of Yac-1 within 5 h of incubation. Thus, the culture supernatants from PLFIN-PA317 possessed both infectivity and cytotoxicity of mFasL.

3T3 Cells↗

PubMed2001

A centromeric satellite sequence in the Pacific oyster (Crassostrea gigas Thunberg) identified by fluorescence in situ hybridization.

A highly repetitive satellite sequence was previously identified in the Pacific oyster Crassostrea gigas Thunberg. The sequence has 168 bp per unit, present in tandem repeats, and accounts for 1% to 4% of the genome. We studied the chromosomal location of this satellite sequence by fluorescence in situ hybridization (FISH). A probe was made by polymerase chain reaction and incorporation of digoxigenin-11-dUTP. Hybridization was detected with fluorescein-labeled antidigoxigenin antibodies. FISH signals were located at centromeric regions of 7 pairs of the Pacific oyster chromosomes. No interstitial site was found. Signals were strong and consistent on chromosomes 1, 2, 4, and 7, but weak or variable on chromosomes 5, 8, and 10. No signal was observed on chromosomes 3, 6, and 9. Our results showed that this sequence is clearly a centromeric satellite, disputing its previous assignment to the telomeric and submetacentric regions of 2 chromosomes. No signal was detected in the American oyster (Crassostrea virginica Gmelin).

Journal Article↗

PubMed2001

Morphine-induced spinal cholinergic activation: in vivo imaging with positron emission tomography.

Positron emission tomography (PET) imaging of spinal cord in monkeys with a cholinergic tracer demonstrates increased spinal cholinergic activity in response to an analgesic dose of morphine, and this PET result correlates with measurement of acetylcholine spillover into spinal cord extracellular space induced by morphine, as measured by microdialysis. Previous studies in rats, mice, and sheep demonstrate activation of spinal cholinergic neurons by systemic opioid administration, and participation of this cholinergic activity in opioid-induced analgesia. Testing the relevance of this observation in humans has been limited to measurement of acetylcholine spillover into lumbar cerebrospinal fluid. The purpose of this study was to apply a recently developed method to image spinal cholinergic terminals non-invasively via PET and to test the hypothesis that the tracer utilized would reflect changes in local cholinergic activity. Following Animal Care and Use Committee approval, seven adult male rhesus monkeys were anesthetized on three separate occasions. On two of the occasions PET scans were performed using [(18)F] (+)-4-fluorobenzyltrozamicol ([(18)F]FBT), which selectively binds to the vesicular acetylcholine (ACh) transporter in the presynaptic cholinergic terminals. PET scans were preceded by injection of either saline or an analgesic dose of IV morphine (10 mg/kg). On the third occasion, microdialysis catheters were inserted in the spinal cord dorsal horn and acetylcholine concentrations in dialysates determined before and after IV morphine injection. Morphine increased cholinergic activity in the spinal cord, as determined by blood flow corrected distribution volume of [(18)F]FBT in the cervical cord compared to the cerebellum. Morphine also increased acetylcholine concentrations in microdialysates from the cervical cord dorsal horn. The one animal which did not show increased spinal cholinergic activity by PET from this dose of morphine also did not show increased acetylcholine from this morphine dose in the microdialysis experiment. These data confirm the ability to use PET to image spinal cholinergic terminals in the monkey spinal cord and suggest that acute changes in cholinergic activity can be imaged with this non-invasive technique. Following preclinical screening, PET scanning with [(18)F]FBT may be useful to investigate mechanisms of analgesic action in normal humans and in those with pain.

Acetylcholine↗

PubMed2001

Temporal and spatial variations in slow axonal transport velocity along peripheral motoneuron axons.

Neuronal axons are cellular extensions that can reach more than a meter in length. To maintain such a structure, macromolecules synthesized in cell bodies must be transported to the distal axons. Proteins associated with membranous organelles are generally transported in several fast transported groups, while cytoplasmic proteins, mostly composed of cytoskeletal proteins, are transported in slowly transported groups. Neurofilaments are a main component in the slowly transported group. Composed of three polypeptide subunits (NF-H, NF-M and NF-L), they are the most abundant cytoskeletal element in large myelinated axons. In various neurological or neurotoxic disorders, selective accumulation of neurofilaments was observed in different compartments of a neuron (cell bodies, proximal or distal axons). The underlying mechanism for this regional selectivity has been unclear. Using the classical pulse labeling method, we examined the changes in neurofilament transport velocity in transgenic mice that overexpress different neurofilament subunits. We present evidence that at least three velocities of neurofilament transport exist along peripheral motor axons. Each of these velocities was altered differently depending on which neurofilament subunit was overexpressed. We suggest that neurofilament transport in motor axons consists of multiple successive stages and that each of these stages is carried out by different transport mechanisms. These differences provide a basis for the regional deficiencies in axonal transport associated with several neurological disorders.

Animals↗

PubMed2001

Biocompatibility and performance of the Wallstent and several covered stents in a sheep iliac artery model.

PURPOSE: To compare the biocompatibility and performance of various stent-grafts to those of a bare stent in an ovine model with a subchronic (3 months) endpoint. MATERIALS AND METHODS: Three different types of stent-grafts (ePTFE/nitinol, n = 8; polyester/nitinol, n = 8; and polycarbonate urethane/cobalt-alloy, n = 8) and a bare stent as a control (Ni-Co-Ti-steel-alloy, n = 8) were implanted in the iliac arteries in eight female sheep. One type of each stent-graft was implanted per animal, two implants at each side. The implantation sites for each type varied from animal to animal. Angiographic control and intravascular ultrasound (IVUS) imaging were performed before and after implantation, after 2 months, and before explantation at 3 months and were used to characterize patency and to assess intimal hyperplasia. After 3 months, the implants were retrieved and subjected to histologic evaluation (after methacrylate embedding, cutting, and histologic staining) to characterize the biologic response. RESULTS: Implantation was technically successful in all procedures. At 2 and 3 months after implantation, all segments in which stents had been implanted were patent. Marked neointima formation was found in the polyester-covered stent-graft that showed significant luminal narrowing of 50%, compared to the ePTFE-covered (24%) and polycarbonate urethane-covered endoprostheses (22%), as well as the bare stent (Wallstent; 9%; P < .001). A minimal inflammatory vessel wall reaction was demonstrated for the polyester-covered and ePTFE-covered endoprostheses; the polycarbonate urethane-covered stent-graft's response was demonstrable but not significantly different from that of the Wallstent. At 3 months, the ePTFE-covered stent-graft showed incomplete (>90%) endothelial coverage; in the other endoprostheses, complete but partially immature endothelialization was found. CONCLUSION: All stent-grafts induced an inflammatory vessel wall reaction with neointimal hyperplasia. The polyester-covered endoprosthesis caused a marked reaction with 50% luminal stenosis. Endothelialization was retarded with the ePTFE-covered stent-graft. The bare stent performed best in regard to neointimal formation and caused the least inflammatory response.

Alloys↗

PubMed2001

Reactions of electron-deficient alkynes and allenes under phosphine catalysis.

The development of some new synthetic reactions derived from nucleophilic addition of phosphines to electron-deficient carbon-carbon triple bonds is described. These reactions show that the phosphine plays the role of a nucleophile as well as an excellent leaving group. The central problem is to generate a 1,3-dipole from alkynoates or allenoates (2,3-butadienoates) by interaction with various phosphines. This study illuminates the unusual phenomena and shows how this understanding allows control of the reaction.

Journal Article↗

PubMed2001

Antioxidant activity of tocopherols, tocotrienols, and gamma-oryzanol components from rice bran against cholesterol oxidation accelerated by 2,2'-azobis(2-methylpropionamidine) dihydrochloride.

The antioxidant activities of vitamin E (alpha-tocopherol, alpha-tocotrienol, gamma-tocopherol, and gamma-tocotrienol) and gamma-oryzanol components (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, and campesteryl ferulate) purified from rice bran were investigated in a cholesterol oxidation system accelerated by 2,2'-azobis(2-methylpropionamidine) dihydrochloride. All components exhibited significant antioxidant activity in the inhibition of cholesterol oxidation. The highest antioxidant activity was found for 24-methylenecycloartanyl ferulate, and all three gamma-oryzanol components had activities higher than that of any of the four vitamin E components. Because the quantity of gamma-oryzanol is up to 10 times higher than that of vitamin E in rice bran, gamma-oryzanol may be a more important antioxidant of rice bran in the reduction of cholesterol oxidation than vitamin E, which has been considered to be the major antioxidant in rice bran. The antioxidant function of these components against cholesterol oxidation may contribute to the potential hypocholesterolemic property of rice bran.

Amidines↗

PubMed2001

Cytotoxic pheophorbide-related compounds from Clerodendrum calamitosum and C. cyrtophyllum.

Three pheophorbide-related compounds (1-3) were isolated from the leaves and stems of Clerodendrum calamitosum. The methyl ester of 3 (6) and the known (10S)-hydroxypheophytin a (7) also were isolated from leaves of the related plant Clerodendrum cyrtophyllum. Compounds 1 and 6 were isolated for the first time as naturally occurring products from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 1 and 2 exhibited strong cytotoxicity against human lung carcinoma (A549), ileocecal carcinoma (HCT-8), kidney carcinoma (CAKI-1), breast adenocarcinoma (MCF-7), malignant melanoma (SK-MEL-2), ovarian carcinoma (1A9), and epidermoid carcinoma of the nasopharynx (KB), and its etoposide- (KB-7d), vincristine- (KB-VCR), and camptothecin-resistant (KB-CPT) subclones. Compound 3 was less cytotoxic than 1 and 2. Compounds 4-6, the methyl esters of 1-3, showed strongly increased cytotoxicity compared with the parent acids. Interestingly, 6 was the most active derivative among these compounds. Compound 7 was inactive.

Adenocarcinoma↗

PubMed2001

Expression of DeltaF508 CFTR in normal mouse lung after site-specific modification of CFTR sequences by SFHR.

The development of gene targeting strategies for specific modification of genomic DNA in human somatic cells has provided a potential gene therapy for the treatment of inherited diseases. One approach, small fragment homologous replacement (SFHR), directly targets and modifies specific genomic sequences with small fragments of exogenous DNA (400-800 bp) that are homologous to genomic sequences except for the desired modification. This approach has been effective for the in vitro modification of exon 10 in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in human airway epithelial cells. As another step in the development of SFHR for gene therapy, studies were carried out to target and modify specific genomic sequences in exon 10 of the mouse CFTR (mCFTR) in vivo. Small DNA fragments (783 bp), homologous to mCFTR except for a 3-bp deletion (DeltaF508) and a silent mutation which introduces a unique restriction site (KpnI), were instilled into the lungs of normal mice using four different DNA vehicles (AVE, LipofectAMINE, DDAB, SuperFect). Successful modification was determined by PCR amplification of DNA or mRNA-derived cDNA followed by KpnI digestion. The results of these studies showed that SFHR can be used as a gene therapy to introduce specific modifications into the cells of clinically affected organs and that the cells will express the new sequence.

Animals↗

PubMed2001

Globalization of tertiary nursing education in post-Mao China: a preliminary qualitative assessment.

This article examines China's collaborative initiatives with Western countries to assess the impact of globalization on Chinese nursing education, especially at the post-secondary level, in the post-Mao era. Through the theoretical framework of mutuality, it evaluates the outcomes of globalization in two broad domains: pedagogy and system-institution-program building. In addition, case studies on two collaborative projects between Chinese nursing programs and Western institutions were conducted to further illustrate the principles of mutuality. This qualitative assessment is primarily based on a systematic review of published studies on the multifaceted dimensions of globalization in Chinese post-secondary nursing education in both English and Chinese nursing literature since 1990. It is supplemented by unpublished documents and data obtained from a research trip to China in 2000. The study concludes that globalization has been, and will remain, one of the major forces underpinning Chinese nursing education (and the nursing profession in general), which is moving towards integration into the global nursing community. However, there is a significant imbalance in the knowledge transfer equation both in the national and international context. Great efforts need to be made to synthesize nursing knowledge in the East and West to achieve an integrative nursing science.

Canada↗

PubMed2001

Baccalaureate nursing education curricula in the People's Republic of China: status, issues and reforms.

This article examines baccalaureate nursing education curricula in the People's Republic of China. Three 5-year curricula and one 4-year curriculum were content analyzed and contrasted. Findings of this study suggested that: (i) the biomedical model dominated the three 5-year traditional curricula; (ii) political-ideological content permeated all four curricula; and (iii) the reformed curriculum at Peking Union Medical College was a genuine effort toward building a new nursing curriculum model that intended to differentiate nursing education from medical education. In addition, major themes of recent curriculum reforms were highlighted. Recommendations were suggested to improve the outcomes of future curriculum endeavors. Explicit as well as implicit comparisons with an ideal-typical American generic baccalaureate nursing curriculum were made when appropriate.

China↗

PubMed2001

beta-Amyloid-induced neuronal apoptosis requires c-Jun N-terminal kinase activation.

beta-Amyloid (A beta) has been strongly implicated in the pathophysiology of Alzheimer's disease (AD), but the means by which the aggregated form of this molecule induces neuronal death have not been fully defined. Here, we examine the role of the c-Jun N-terminal kinases (JNKs) and of their substrate, c-Jun, in the death of cultured neuronal PC12 cells and sympathetic neurons evoked by exposure to aggregated A beta. The activities of JNK family members increased in neuronal PC12 cells within 2 h of A beta treatment and reached 3--4-fold elevation by 6 h. To test the role of these changes in death caused by A beta, we examined the effects of CEP-1347 (KT7515), an indolocarbazole that selectively blocks JNK activation. Inclusion of CEP-1347 (100--300 nM) in the culture medium effectively blocked the increases in cellular JNK activity caused by A beta and, at similar concentrations, protected both PC12 cells and sympathetic neurons from A beta-evoked-death. Effective protection required addition of CEP-1347 within 2 h of A beta treatment, indicating that the JNK pathway acts relatively proximally and as a trigger in the death mechanism. A dominant-negative c-Jun construct also conferred protection from A beta-evoked death, supporting a model in which JNK activation contributes to death via activation of c-Jun. Finally, CEP-1347 blocked A beta-stimulated activation of caspase-2 and -3, placing these downstream of JNK activation. These observations implicate the JNK pathway as a required element in death evoked by A beta and hence identify it as a potential therapeutic target in AD.

Alzheimer Disease↗

PubMed2001

Inhibition of K+ currents by homocysteine in rat ventricular myocytes.

INTRODUCTION: Clinical evidence suggests that increased blood levels of homocysteine may be an independent risk factor for the development of cardiovascular disease, but the functional effects of this sulfhydryl amino acid on the myocardium are poorly understood. The present study was conducted to determine the direct effects of homocysteine on the electrophysiologic properties of the heart. METHODS AND RESULTS: Whole-cell voltage-clamp recordings were made in ventricular myocytes isolated from normal rat hearts to analyze the Ca2+-independent, transient outward K+ current (I(to)), a major repolarizing current in these cells. Maximum I(to) density (measured at +60 mV) was decreased approximately 47% from baseline in the presence of 500 microM homocysteine (P < 0.05), but the amount of block varied in a frequency- and voltage-dependent manner. Decreased I(to) density was not accompanied by significant changes in voltage- or time-dependent properties of the current, nor was it affected by pretreating myocytes with the protein kinase inhibitor staurosporine. Because a portion of total extracellular homocysteine is oxidized, we examined the response to homocystine, the oxidized form of homocysteine. In myocytes superfused with 500 microM homocystine, maximum I(to) density was decreased by approximately 40% from baseline (P < 0.05). In contrast, the thiolactone form of homocysteine did not alter I(to) amplitude. CONCLUSION: These data suggest that homocysteine and its oxidized form homocystine acutely inhibit I(to) channels in ventricular myocytes by mechanisms involving the free thiol or disulfide moieties of these compounds. High homocysteine or homocystine levels may contribute to abnormal repolarization and arrhythmogenic conditions in the intact heart.

Algorithms↗

PubMed2001

Konjac-Mannan and American ginsing: emerging alternative therapies for type 2 diabetes mellitus.

Despite significant achievements in treatment modalities and preventive measures, the prevalence of diabetes has risen exponentially in the last decade. Because of these limitations there is a continued need for new and more effective therapies. An increasing number of people are using dietary and herbal supplements, even though there is a general lack of evidence for their safety and efficacy. Consequently, science based medical and government regulators are calling for more randomized clinical studies to provide evidence of efficacy and safety. Our research group has selected two such promising and functionally complementary therapies for further investigation as potentially emerging alternative therapies for type 2 diabetes: Konjac-mannan (KJM) and American ginseng (AG). We have generated a mounting body of evidence to support the claim that rheologically-selected, highly-viscous KJM, and AG with a specific composition may be useful in improving diabetes control, reducing associated risk factors such as hyperlipidemia and hypertension, and ameliorating insulin resistance. KJM has a demonstrated ability to modulate the rate of absorption of nutrients from the small bowel, whereas AG has post-absorptive effects. Consequently, it appears that KJM and AG are acting through different, yet complementary, mechanisms: KJM by increasing insulin sensitivity and AG likely by enhancing insulin secretion. Before the therapeutic potential of KJM and AG as novel prandial agents for treatment of diabetes can be fully realized, further controlled trials with larger sample sizes and of longer duration are required. A determination of the active ingredients in AG, and the rheology-biology relationship of KJM are also warranted.

Animals↗

PubMed2001

Expression of anti-neuroexcitation peptide (ANEP) of scorpion Buthus martensii Karsch in Escherichia coli.

According to the cDNA sequence of anti-neuroexcitation peptide of scorpion Buthus martensii Karsch, the putative mature anti-neuroexcitation peptide (ANEP) encoding DNA fragment was obtained by a PCR method, then was cloned into expression plasmid pET28a, fused with His tag at its 3' end. When expressed in E. coli BL21 (DE3), the expression of recombinant ANEP was 15% of total cellular proteins, while most recombinant ANEP products existed in the form of insoluble inclusion bodies. Coexpression of molecular chaperones or protein disulfide isomerase could not improve its solubility. The recombinant ANEP in the cell lysate was purified to homogeneity by metal chelating affinity chromatography and Superdex 30 chromatography. In bioassay with convulsive mice model induced by thiosemicarbazide, recombinant ANEP could apparently delay the convulsion seizure of model animals by 18% and showed anti-neuroexcitatory activity.

Animals↗

PubMed2001

American ginseng (Panax quinquefolius L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals.

BACKGROUND: We previously showed that 3 g American ginseng administered 40 min before an oral glucose challenge significantly reduces postprandial glycemia in subjects without diabetes. Whether this effect can be replicated with doses <3 g and administration times closer to the oral glucose challenge is unclear. OBJECTIVE: Our objective was to study the dosing and timing effects of American ginseng on postprandial glycemia. DESIGN: In a random crossover design, 12 healthy individuals [X +/- SEM age: 42 +/- 7 y; body mass index (BMI; in kg/m2): 24.1 +/- 1.1] received 16 treatments: 0 (placebo), 1, 2, or 3 g American ginseng at 40, 20, 10, or 0 min before a 25-g oral glucose challenge. Capillary blood was collected before administration and at 0, 15, 30, 45, 60, and 90 min after the start of the glucose challenge. RESULTS: Two-way analysis of variance showed that the main effects of treatment and administration time were significant (P < 0.05). Glycemia was lower over the last 45 min of the test after doses of 1, 2, or 3 g ginseng than after placebo (P < 0.05); there were no significant differences between doses. The reductions in the areas under the curve for these 3 doses were 14.4 +/- 6.5%, 10.6 +/- 4.0%, and 9.1 +/- 6%, respectively. Glycemia in the last hour of the test and area under the curve were significantly lower when ginseng was administered 40 min before the challenge than when it was administered 20, 10, or 0 min before the challenge (P < 0.05). CONCLUSIONS: American ginseng reduced postprandial glycemia in subjects without diabetes. These reductions were time dependent but not dose dependent: an effect was seen only when the ginseng was administered 40 min before the challenge. Doses within the range of 1-3 g were equally effective.

Adult↗