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Biomedical subjects

Lin Xu

Publications and source records attributed to Lin Xu.

At least 91 records · Page 5Linked to original sources
PubMed2005

Covalent assembly of shortened multiwall carbon nanotubes on polyelectrolyte films and relevant electrochemistry study.

A significant and versatile approach was developed for perpendicularly aligning multiwall carbon nanotubes on diverse substrates suitable for layer-by-layer self-assembly. The multiwall carbon nanotubes (s-MWNTs) used were shortened with oxidation under ultrasonic and functionalized with acyl chloride in thionyl chloride (SOCl2). The monolayer of s-MWNTs perpendicularly grafted to the substrate was obtained by dipping the polyelectrolyte modifying substrate into a tetrahydrofuran suspension of the functionalized s-MWNTs. The interaction proved to be stable and not liable to be affected by the ambience. Transmission electron microscopy and atomic force microscopy were used to examine the morphology of the MWNTs and s-MWNTs grafted on the substrates. Raman spectroscopy was applied to verify the existence of s-MWNTs for assembly, and Fourier transform infrared absorption spectra were used to investigate the interaction pattern between s-MWNTs and polyelectrolyte. The electrochemistry properties of the monolayer of s-MWNTs when the substrate was indium-tin oxide were studied.

Journal Article↗
PubMed2005

[The effect of cell killing and apoptosis by human herpes simplex virus- thymidine kinase/ganciclovir system combined with allitride in BIU87 cells].

OBJECTIVE: To study the killing effect of human herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) system combined with allitride and the possible apoptosis mechanism in BIU87 cells. METHODS: The cytotoxicity after combination were estimated by theamine blue tetrazolium bromide (MTT). The morphological changes were observed with inverted microscope and in-situ cell apoptosis detection kit. Changes of apoptosis rate and cell cycle were assessed by flow cytometry. B-cell lymphoma-2 (bcl-2), bax, caspase-3 (cysteine aspartate specific proteinase) mRNA changes were detected by reverse transcriptase polymerase chain reaction, and caspase-3 activity was estimated with colorimetry. RESULTS: For combination group, the cell killing rate was raised to 72.50% to compare with 35.00% of GCV and 37.00% of allitride separately and there was a synergistic effect between these two drugs. The cell apoptosis was induced in all three groups and for the combination group the time of S-phase and G(2)-phase arrest were earlier than other two groups. Both drugs could inhibit the expression of bcl-2 and promote the expression and activity of caspase-3. CONCLUSIONS: The combination of HSV-TK/GCV system with allitride can inhibit the proliferation of BIU87 cells congenerously through apoptosis, which may be correlated with S- and G(2)-phase arrest, down-regulation of bcl-2 and increased caspase-3 expression and its activity.

Apoptosis↗
PubMed2005

Electrophysiological properties of human hypothalamic hamartomas.

The hypothalamic hamartoma (HH) is a rare developmental malformation often characterized by gelastic seizures, which are usually refractory to medical therapy. The mechanisms of epileptogenesis operative in this subcortical lesion are unknown. In this study, we used standard patch-clamp electrophysiological techniques combined with histochemical approaches to study individual cells from human HH tissue immediately after surgical resection. More than 90% of dissociated HH cells were small (6-9 microm soma) and exhibited immunoreactivity to the neuronal marker NeuN, and to glutamic acid decarboxylase, but not to glial fibrillary acidic protein. Under current-clamp, whole-cell recordings in single dissociated cells or in intact HH slices demonstrated typical neuronal responses to depolarizing and hyperpolarizing current injection. In some cases, HH cells exhibited a "sag-like" membrane potential change during membrane hyperpolarization. Interestingly, most HH cells exhibited robust, spontaneous "pacemaker-like" action potential firing. Under voltage-clamp, dissociated HH cells exhibited functional tetrodotoxin (TTX)-sensitive Na(+) and tetraethylammonium-sensitive K(+) currents. Both GABA and glutamate evoked whole-cell currents, with GABA exhibiting a peak current amplitude 10-fold greater than glutamate. These findings suggest that human HH tissues, associated with gelastic seizures, contained predominantly small GABAergic inhibitory neurons that exhibited intrinsic "pacemaker-like" behavior.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2005

Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo.

Repeated vivid recalls or flashbacks of traumatic memories and memory deficits are the cardinal features of post-traumatic stress disorder (PTSD). The underlying mechanisms are not fully understood yet. Here, we examined the effects of very strong fear conditioning (20 pairings of a light with a 1.5-mA, 0.5-s foot shock) and subsequent reexposure to the conditioning context (chamber A), a similar context (chamber B), and/or to the fear conditioned stimulus (CS) (a light) on synaptic plasticity in the hippocampal CA1 area in anesthetized Sprague-Dawley rats. The conditioning procedure resulted in very strong conditioned fear, as reflected by high levels of persistent freezing, to both the contexts and to the CS, 24 h after fear conditioning. The induction of long-term potentiation (LTP) was blocked immediately after fear conditioning. It was still markedly impaired 24 h after fear conditioning; reexposure to the conditioning chamber A (CA) or to a similar chamber B (CB) did not affect the impairment. However, presentation of the CS in the CA exacerbated the impairment of LTP, whereas the CS presentation in a CB ameliorated the impairment so that LTP induction did not differ from that of control groups. The induction of long-term depression (LTD) was facilitated immediately, but not 24 h, after fear conditioning. Only reexposure to the CS in the CA, but not reexposure to either chamber A or B alone, or the CS in chamber B, 24 h after conditioning, reinstated the facilitation of LTD induction. These data demonstrate that unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm can have profound effects on hippocampal synaptic plasticity, which may aid to understand the mechanisms underlying impairments of hippocampus-dependent memory by stress or in PTSD.

Animals↗
PubMed2005

Long-term depression in rat CA1-subicular synapses depends on the G-protein coupled mACh receptors.

The subiculum, which is the primary target of CA1 pyramidal neurons and sending efferent fibres to many brain regions, serves as a hippocampal interface in the neural information processes between hippocampal formation and neocortex. Long-term depression (LTD) is extensively studied in the hippocampus, but not at the CA1-subicular synaptic transmission. Using whole-cell EPSC recordings in the brain slices of young rats, we demonstrated that the pairing protocols of low frequency stimulation (LFS) at 3 Hz and postsynaptic depolarization of -50 mV elicited a reliable LTD in the subiculum. The LTD did not cause the changes of the paired-pulse ratio of EPSC. Furthermore, it did not depend on either NMDA receptors or voltage-gated calcium channels (VGCCs). Bath application of the G-protein coupled muscarinic acetylcholine receptors (mAChRs) antagonists, atropine or scopolamine, blocked the LTD, suggesting that mAChRs are involved in the LTD. It was also completely blocked by either the Ca2+ chelator BAPTA or the G-protein inhibitor GDP-beta-S in the intracellular solution. This type of LTD in the subiculum may play a particular role in the neural information processing between the hippocampus and neocortex.

2-Amino-5-phosphonovalerate↗
PubMed2005

An optimized murine model of ferric chloride-induced arterial thrombosis for thrombosis research.

INTRODUCTION/OBJECTIVES: Animal models are important tools in thrombosis research and preclinical drug development. Ferric chloride has been widely used to induce arterial thrombosis in a variety of species. However, almost all previous reports applied a very high concentration of ferric chloride (10-60%) to induce thrombus formation leading to difficulties in evaluating the efficacy of antithrombotic agents. Thus, the purpose of this study was to refine the ferric-chloride-induced thrombosis model to be better suited for thrombosis research. METHODS AND RESULTS: Dose-dependent study was used to identify a threshold concentration of ferric chloride sufficient for consistent occlusion (as reflected by the Doppler blood flow) of the carotid artery in C57BL/6 mice. Ferric chloride concentration at or about a threshold of 2.5% was found to be sensitive to anticoagulant (e.g., heparin) and antiplatelet (e.g., clopidogrel) agents. In contrast, the vessel rapidly occluded at or above 5% ferric chloride concentration despite pretreatment with the antithrombotic agents, even at doses that exerted maximal prolongation of tail bleeding time. CONCLUSIONS: Our study provides a simple, sensitive and highly controlled method for limiting vessel injury in mice to better detect the efficacy of antithrombotic drugs and/or evaluate therapeutic targets.

Animals↗
PubMed2005

The role of p38 in the regulation of Na+-Ca2+ exchanger expression in adult cardiomyocytes.

The Na(+)-Ca(2+) exchanger is crucial in the regulation of [Ca(2+)](i) in the cardiac myocyte. The exchanger is upregulated in cardiac hypertrophy and failure. This upregulation can have an effect on calcium transients and possibly contribute to diastolic dysfunction and an increased risk of arrhythmias. Here we use adenovirus mediated gene expression to examine the role of p38 MAP kinase in upregulation of the exchanger in adult cardiac myocytes. We demonstrate that p38 mediates a part of the alpha-adrenergic stimulated upregulation of the Na(+)-Ca(2+) exchanger gene. Overexpression of dominant-negative p38 isoforms and activated MKK3 and MKK6 in isolated adult cardiac myocytes demonstrates that p38 activation is sufficient for NCX1 promoter upregulation and that this is mediated primarily by the p38alpha isoform. Lastly, this work demonstrates that the p38alpha stimulated upregulation of the NCX1 promoter is mediated via the -80 CArG box element. This is the first time that a specific role for p38alpha in gene regulation has been demonstrated in isolated adult cardiomyocytes and provides an important clue to our understanding some of the factors regulating exchanger gene expression in the hypertrophic and failing heart.

Adenoviridae↗
PubMed2005

Nanopantography: a new method for massively parallel nanopatterning over large areas.

We report a radically different approach to the versatile fabrication of nanometer-scale preselected patterns over large areas. Standard lithography, thin film deposition, and etching are used to fabricate arrays of ion-focusing microlenses (e.g., small round holes through a metal/insulator structure) on a substrate such as a silicon wafer. The substrate is then placed in a vacuum chamber, a broad-area collimated beam of ions is directed at the substrate, and electric potentials are applied to the lens arrays such that the ions focus at the bottoms of the holes (e.g., on the wafer surface). When the wafer is tilted off normal (with respect to the ion beam axis), the focal points in each hole are laterally displaced, allowing the focused beamlets to be rastered across the hole bottoms. In this "nanopantography" process, the desired pattern is replicated simultaneously in many closely spaced holes over an area limited only by the size of the broad-area ion beam. With the proper choice of ions and downstream gaseous ambient, the method can be used to deposit or etch materials. Data show that simultaneous impingement of an Ar(+) beam and a Cl(2) effusive beam on an array of 950-nm-diam lenses can be used to etch 10-nm-diam features into a Si substrate, a reduction of 95x. Simulations indicate that the focused "beamlet" diameters scale directly with lens diameter, thus a minimum feature size of approximately 1 nm should be possible with 90-nm-diam lenses that are at the limit of current photolithography. We expect nanopantography to become a viable method for overcoming one of the main obstacles in practical nanoscale fabrication: rapid, large-scale fabrication of virtually any shape and material nanostructure. Unlike all other focused ion or electron beam writing techniques, this self-aligned method is virtually unaffected by vibrations, thermal expansion, and other alignment problems that usually plague standard nanofabrication methods. This is because the ion focusing optics are built on the wafer.

Crystallization↗
PubMed2005

A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking.

X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base-excision repair pathway. Functional Polymorphisms in the XRCC1 gene may lead to decreased DNA repair capacity and thus confer inherited predisposition to cancer risk. In this case-control study of 710 patients with incident lung cancer and 710 cancer-free controls who were frequency matched on age, sex and residential area, we genotyped a novel T>C transition at the promoter region (-77T>C) of XRCC1 and other two common non-synonymous polymorphisms (Arg194Trp and Arg399Gln) to determine their associations with risk of lung cancer. We found that compared with the -77TT wild-type homozygote, the variant genotypes were associated with significantly increased risk of lung cancer [adjusted odds ratio (OR)=1.51; 95% confidence interval (CI)=1.17-1.94 for -77TC; OR=2.98; 95% CI=0.93-9.59 for -77CC; and OR=1.55; 95% CI=1.21-1.98 for -77TC/CC]. By contrast, no significant associations were observed between the other two exonic variants (Arg194Trp and Arg399Gln) and lung cancer risk. Furthermore, we observed a 9.82-fold increased risk (95% CI=5.66-17.02) for heavy smokers carrying the -77C variant (-77TC/CC) and a 4.07-fold increased risk (95% CI=2.85-5.81) for heavy smokers not carrying the variant. However, the interaction between the -77T>C variant and cumulative smoking was not statistically significant (P=0.1560). These findings indicate that the new XRCC1 -77T>C polymorphism may contribute to the aetiology of lung cancer. Further functional studies are warranted to elucidate the underlying molecular mechanisms of the association.

Adenocarcinoma↗
PubMed2005

Factors characterizing Staphylococcus epidermidis invasiveness determined by comparative genomics.

Virulence mechanisms of the leading nosocomial pathogen Staphylococcus epidermidis are poorly understood. We used microarray-based genome-wide comparison of clinical and commensal S. epidermidis strains to identify putative virulence determinants. Our study revealed high genetic variability of the S. epidermidis genome, new markers for invasiveness of S. epidermidis, and potential targets for drug development against S. epidermidis infections.

Bacterial Proteins↗
PubMed2005

Conversion of Staphylococcus epidermidis strains from commensal to invasive by expression of the ica locus encoding production of biofilm exopolysaccharide.

To test if biofilm formation in Staphylococcus epidermidis is dependent on the polysaccharide intercellular adhesin, whose biosynthesis is driven by the ica locus, a plasmid containing the ica locus was transferred to three ica-negative strains. Using in vitro biofilm assays and a rat central venous catheter infection model, we confirmed the importance of the ica locus for biofilm production and pathogenesis of S. epidermidis.

Animals↗
PubMed2005

[Evaluation of the mycobacterial interspersed repetitive units typing as a practical approach in molecular epidemiology of Mycobacterium tuberculosis].

OBJECTIVE: To introduce a new genotyping method, mycobacterial interspersed repetitive units (MIRU) typing, for Mycobacterium tuberculosis and to evaluate its feasibility. METHODS: Mycobacterium tuberculosis strains stored at Shanghai Municipal Center for Disease Control and Prevention during 2000 to 2002, were randomly selected by simple digital table and genotyped by MIRU and Spoligotyping. RESULTS: By Spoligotyping method, 91 strains were typed to 20 genotypes, of which 89% (81/91) strains belonged to Beijing genotype, while by MIRU method, these strains were divided into 46 genotypes. The MIRU typing showed high discriminatory power, especially for the Beijing genotype strains. The 81 Beijing genotype strains could be subdivided into 39 different MIRU genotypes. In this sample collection, 12 MIRU loci showed different discriminative according to their allelic diversity. Locus 26 showed highly discriminative, while locus 16, 31, and 40 showed moderately discriminative. CONCLUSIONS: MIRU genotyping is a simple and fast method. Its numerical result facilitates the comparison among strains of Mycobacterium tuberculosis from different labs.

Bacterial Typing Techniques↗
PubMed2005

[Observation of IR spectra from doped SO(2)4- / ZrO2 nanosolid superacid].

In this paper, ZrO(OH)2 was prepared with sol-gel method, then a series of metal-ions-doped SO(2)4- /ZrO2 nanosolid superacids were prepared by impregnated ZrO(OH)2 using diluted H2SO4 and Ni2+ , Al3+, Sn4+, Ag+ , Sn2+ etc. salt solutions. The samples were characterized by IR, XRD, TEM and chemical analysis method. The result shows that the IR spectra of samples are the characteristic spectra of the solid superacids. The stretching frequencies of Zr--O and S==O in Ni2+ and Sn4+ doped samples are obviously increased, the v(Zr-o) values of Zr--O increase from 485 cm(-1) for SO(2)4- /ZrO2 to 500 cm(-1) for both Ni2+ and Sn4+ doped samples, the v(as) values of S==O increase from 1 390 cm(-1) for So(2)4- /ZrO2 to 1405 and 1400 cm(-1) for Ni2+ and Sn4+ doped samples respectively, but that in Sn2+ doped sample increases a little. It is indicated that the samples doped by Ni2+ and Sn4+ show higher super acidity than SO(2)4- /ZrO2 . The IR spectra of samples were determined at different calcination temperatures. It was found that the stretching frequencies of Zr--O and S==O in Ni2+ and Al3+ doped samples are obviously increased with the increase in calcination temperature, but that in Ag+ doped sample is not.

Aluminum↗
PubMed2005

[Genetic polymorphism of 6 short-tandem repeat loci in Miao minority group of Rongshui county in Guangxi province].

OBJECTIVE: To investigate the distributions of six short-tandem repeat (STR) loci, namely D7S820, D13S317, D16S539, HUMCSF1PO, HUMTPOX and HUMTH01, in Miao minority group at Rongshui county in Guangxi province and construct the relevant genetic database. METHODS: Sodium-citrated blood specimens were collected from 208 healthy unrelated Miao individuals in Rongshui county. The DNAs from the specimens were extracted with phenol-chloroform method; AmplFSTR Identifier PCR Amplification Kit was used to amplify the extracted DNAs, and 3100 Genetic Analyzer was used to analyze and screen the amplified products. RESULTS: In this study, 7, 8, 6, 7, 5, 7 alleles were observed at the 6 STR loci respectively. The expected distribution of genotype accorded with Hardy-Weinbery equilibrium. The total discrimination power, cumulative paternity exclusion power and total polymorphism information were 0.999995, 0.9959 and 0.9987 respectively. CONCLUSION: The results demonstrate that these 6 STR loci are of high polymorphism and hereditary stability and are in accord with Mendel's law. The data obtained are valuable in population genetics research, forensic application, and individual identifications.

Adolescent↗
PubMed2004

Acute functional effects of cyclosporine-A and methylprednisolone treatment in adult rats exposed to transient ischemic stroke.

The present study examined the neuroprotective effects of immunosuppressant cyclosporine-A (CsA) and anti-inflammatory methylprednisolone (MP) in a stroke model. Adult Sprague-Dawley rats were initially subjected to transient middle cerebral artery occlusion (MCAo) then randomly assigned to one of the following treatment conditions: low dose CsA, MP, low dose CsA plus MP, high dose CsA, or vehicle. Ischemic animals that received low dose CsA, MP or vehicle exhibited significant cognitive impairments, as revealed by passive avoidance and Morris water maze tasks, at days 1-3 after stroke. In contrast, ischemic animals that received high dose CsA exhibited near normal cognitive performance throughout the test period. Ischemic animals that received low dose CsA plus MP also showed significantly less cognitive deficits but such attenuation of stroke-induced behavioral impairments was only consistently reflected in the passive avoidance task, while performance in the Morris water maze task deteriorated over time. Histological analysis at 3 days post-stroke revealed that only those ischemic animals treated with high dose CsA had significantly reduced cerebral infarcts. These observations suggest that despite overt cerebral damage, alterations in simple, but not complex, cognitive tasks produced by MCAo could be ameliorated by low dose CsA when combined with MP.

Animals↗
PubMed2004

Activation of the discoidin domain receptor 2 induces expression of matrix metalloproteinase 13 associated with osteoarthritis in mice.

Human genetic studies indicate that mutations in type IX and XI collagens result in early-onset osteoarthritis (OA) with a wide spectrum of osteochondrodysplasia. However, a convincing causal chain of events underlying the role of these collagen mutations in the pathogenesis of OA has not been elucidated. Here we show that the expression of a cell surface collagen receptor, discoidin domain receptor 2 (DDR2), is increased in chondrocytes of the articular cartilage of knee joints in mice that develop OA as a result of a heterozygous mutation in type XI collagen. At the same time point, 6 months, we also found increased expression and activity of matrix metalloproteinase 13 (MMP-13) in the mutant mouse knee cartilage. The expression of both DDR2 and MMP-13 was increased in chondrocytes cultured on plates coated with native type II collagen but not on gelatin, and overexpression of DDR2, but not of a truncated form, was found to induce the expression of MMP-13 when chondrocytes were cultured on type II collagen but not on plastic. The DDR2-induced expression of MMP-13 appears to be specific, since we did not observe induction of MMP-1, MMP-3, MMP-8, ADAMTS-4, ADAMTS-5, and IL-1 transcripts in human chondrocytes or Mmp-3, Mmp-8, Adamts-4, Adamts-5, and Il-1 in mouse chondrocytes. Our data suggest that the defect in the cartilage matrix of mice that are heterozygous for a type XI collagen mutation (cho/+) permits activation and up-regulation of DDR2 in chondrocytes. This could be due to increased exposure of chondrocytes to type II collagen as a result of the decreased amount of type XI collagen in the mutant cartilage. The specific induction of MMP-13 by DDR2 in response to its cartilage-specific ligand, type II collagen, may contribute to cartilage damage in hereditary OA.

Animals↗
PubMed2004

Conformational analysis of chirally deuterated tunicamycin as an active site probe of UDP-N-acetylhexosamine:polyprenol-P N-acetylhexosamine-1-P translocases.

Tunicamycins are potent inhibitors of UDP-N-acetyl-D-hexosamine:polyprenol-phosphate N-acetylhexosamine-1-phosphate translocases (D-HexNAc-1-P translocases), a family of enzymes involved in bacterial cell wall synthesis and eukaryotic protein N-glycosylation. Structurally, tunicamycins consist of an 11-carbon dialdose core sugar called tunicamine that is N-linked at C-1' to uracil and O-linked at C-11' to N-acetylglucosamine (GlcNAc). The C-11' O-glycosidic linkage is highly unusual because it forms an alpha/beta anomeric-to-anomeric linkage to the 1-position of the GlcNAc residue. We have assigned the (1)H and (13)C NMR spectra of tunicamycin and have undertaken a conformational analysis from rotating angle nuclear Overhauser effect (ROESY) data. In addition, chirally deuterated tunicamycins produced by fermentation of Streptomyces chartreusis on chemically synthesized, monodeuterated (S-6)-[(2)H(1)]glucose have been used to assign the geminal H-6'a, H-6'b methylene bridge of the 11-carbon dialdose sugar, tunicamine. The tunicamine residue is shown to assume pseudo-D-ribofuranose and (4)C(1) pseudo-D-galactopyranosaminyl ring conformers. Conformation about the C-6' methylene bridge determines the relative orientation of these rings. The model predicts that tunicamycin forms a right-handed cupped structure, with the potential for divalent metal ion coordination at 5'-OH, 8'-OH, and the pseudogalactopyranosyl 7'-O ring oxygen. The formation of tunicamycin complexes with various divalent metal ions was confirmed experimentally by MALDI-TOF mass spectrometry. Our data support the hypothesis that tunicamycin is a structural analogue of the UDP-D-HexNAc substrate and is reversibly coordinated to the divalent metal cofactor in the D-HexNAc-1-P translocase active site.

Binding Sites↗